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10



EDISI



FARMAKOTERAPI PENDEKATAN PATOFISIOLOGI Perhatian Kedokteran adalah ilmu yang selalu berubah. Karena penelitian baru dan pengalaman klinis memperluas pengetahuan kita, perubahan dalam pengobatan dan terapi obat diperlukan. Penulis dan penerbit karya ini telah memeriksa dengan sumber yang dipercaya dapat diandalkan dalam upaya memberikan informasi yang lengkap dan secara umum sesuai dengan standar yang diterima pada saat publikasi. Namun, mengingat kemungkinan kesalahan manusia atau perubahan dalam ilmu kedokteran, baik penulis maupun penerbit atau pihak lain yang telah terlibat dalam persiapan atau publikasi karya ini menjamin bahwa informasi yang terkandung di sini dalam segala hal akurat atau menyelesaikan, dan mereka melepaskan semua tanggung jawab atas kesalahan atau kelalaian atau untuk hasil yang diperoleh dari penggunaan informasi yang terkandung dalam pekerjaan ini. Pembaca didorong untuk mengkonfirmasi informasi yang terkandung di sini dengan sumber lain. Misalnya dan secara khusus, pembaca disarankan untuk memeriksa lembar informasi produk yang termasuk dalam paket setiap obat yang mereka rencanakan untuk diberikan untuk memastikan bahwa informasi yang terkandung dalam pekerjaan ini akurat dan bahwa perubahan tidak dilakukan dalam dosis yang direkomendasikan atau dalam kontraindikasi pemberian. Rekomendasi ini sangat penting sehubungan dengan obat baru atau yang jarang digunakan.



10



farmakoterapi



TH EDITION



A



patofisiologis PENDEKATAN Editor



Joseph T. DiPiro, PharmD



FCCP, FASN,FNAP



Dekan dan Profesor, Archie O. McCalley Ketua Sekolah Farmasi, Virginia Commonwealth University



Profesordan Direktur Pendiri, ACCP / ASHP / VCU Congressional Health Care Policy Fellow Program, Department of Pharmacotherapy and Outcome Sciences, School of Pharmacy, Virginia Universitas Commonwealth, Richmond, Virginia



Robert L. Talbert, PharmD, FCCP, pil KB, faha SmithKline Profesor, College of Pharmacy, Universitas Texas di Austin, Profesor, Sekolah Kedokteran, Pusat Ilmu Kesehatan Universitas Texas di San Antonio, Texas



Gary C. Yee, PharmD, FCCP,BCOP Profesordan Dekan Asosiasi, Departemen Praktek Farmasi, Sekolah Tinggi Farmasi, Universitas Nebraska Medical Center, Omaha, Nebraska



Gary R. Matzke, PharmD, FCP,



Barbara G. Wells, PharmD, FCCP,FASHP Dekan Emeritusdan Profesor Emeritus, Departemen Praktik Farmasi, Universitas Mississippi, Sekolah Farmasi, Oxford, Mississippi



L. Michael Posey, BSPharm, MA President, PENS Pharmacy Editorial & News Services, Arlington, Virginia



Vicki L. Ellingrod, PharmD,FCCP Associate Editor



Thomas D. Nolin, PharmD, PhD, FCCP, Associate Dean for Research dan John Profesor Gideon Searle untuk Farmasi Klinis dan Translasional, Profesor Psikiatri Fakultas Farmasi dan Profesor Tambahan Direktur Asosiasi Psikologi, Institut Michigan untuk Penelitian Klinis dan Kesehatan (MICHR) dan Direktur Grup Pendidikan dan Pendampingan Universitas Michigan



Stuart T. Haines, PharmD , BCPS, BCACP,BC-ADM Profesor, Departemen Praktek dan Direktur Farmasi, Divisi Pengembangan Profesional Farmasi, Universitas Mississippi, Sekolah Farmasi, Jackson, Mississippi



FCP, FASN Associate Professor Departemen Farmasi dan Terapi, Pusat Ilmu Farmasi Klinis , Departemen Kedokteran, Divisi Elektrolit Ginjal, Sekolah Farmasi dan Kedokteran Universitas Pittsburgh, Pittsburgh, Pennsylvania



New York Chicago San Francisco Athena London Madrid Kota Meksiko Milan New Delhi Singapura Sydney Toronto



Hak Cipta © 2017 oleh McGraw-Hill Education. Seluruh hak cipta. Kecuali diizinkan berdasarkan Undang-Undang Hak Cipta Amerika Serikat tahun 1976, tidak ada bagian dari publikasi ini yang boleh direproduksi atau didistribusikan dalam bentuk apa pun atau dengan cara apa pun, atau disimpan dalam database atau sistem pengambilan, tanpa izin tertulis sebelumnya dari penerbit. ISBN: 978-1-25-958749-8 MHID: 1-25-958749-5. Materi dalam eBuku ini juga muncul dalam versi cetak judul ini: ISBN: 978-1-25-958748-1, MHID: 1-25-958748-7. Konversi eBook dengan codeMantra Versi 1.0 Semua merek dagang adalah merek dagang dari pemiliknya masing-masing. Daripada meletakkan simbol merek dagang setelah setiap kemunculan nama merek dagang, kami menggunakan nama hanya dalam gaya editorial, dan untuk kepentingan pemilik merek dagang, tanpa bermaksud melanggar merek dagang. Jika sebutan seperti itu muncul dalam buku ini, maka itu telah dicetak dengan tutup awal. EBook McGraw-Hill Education tersedia dengan diskon kuantitas khusus untuk digunakan sebagai premi dan promosi penjualan atau untuk digunakan dalam program pelatihan perusahaan. Untuk menghubungi perwakilan, silakan kunjungi halaman Hubungi Kami di www.mhprofessional.com. PERSYARATAN PENGGUNAAN Ini adalah karya berhak cipta dan McGraw-Hill Education serta pemberi lisensinya memiliki semua hak dalam dan atas karya tersebut. Penggunaan karya ini tunduk pada persyaratan ini. Kecuali jika diizinkan berdasarkan Undang-Undang Hak Cipta tahun 1976 dan hak untuk menyimpan dan mengambil satu salinan karya, Anda tidak boleh mendekompilasi, membongkar, merekayasa balik, mereproduksi, memodifikasi, membuat karya turunan berdasarkan, mengirimkan, mendistribusikan, menyebarkan, menjual, mempublikasikan atau mensublisensikan karya atau bagian apa pun darinya tanpa persetujuan sebelumnya dari McGraw-Hill Education. Anda dapat menggunakan karya tersebut untuk penggunaan nonkomersial dan pribadi Anda sendiri; Dilarang keras menggunakan karya lain apa pun. Hak Anda untuk menggunakan karya tersebut dapat dihentikan jika Anda gagal mematuhi persyaratan ini. PEKERJAAN DIBERIKAN "SEBAGAIMANA ADANYA". McGRAW-HILL EDUCATION DAN PEMBERI LISENSINYA TIDAK MEMBERIKAN JAMINAN ATAU JAMINAN TERKAIT AKURASI, KECUKUPAN ATAU KELENGKAPAN ATAU HASIL YANG DIPEROLEH DARI PENGGUNAAN KARYA, TERMASUK INFORMASI APA PUN YANG DAPAT DIAKSES MELALUI KERJA MELALUI HYPERLINK ATAU LAINNYA JAMINAN, TERSURAT MAUPUN TERSIRAT, TERMASUK NAMUN TIDAK TERBATAS PADA JAMINAN TERSIRAT ATAS DAPAT DIPERDAGANGKAN ATAU KESESUAIAN UNTUK TUJUAN TERTENTU. McGraw-Hill Education dan pemberi lisensinya tidak menjamin atau menjamin bahwa fungsi yang terkandung dalam pekerjaan akan memenuhi kebutuhan Anda atau bahwa operasinya tidak akan terganggu atau bebas dari kesalahan. Baik McGraw-Hill Education maupun pemberi lisensinya tidak akan bertanggung jawab kepada Anda atau siapa pun atas ketidakakuratan, kesalahan, atau kelalaian, apa pun penyebabnya, dalam pekerjaan atau atas kerusakan apa pun yang



diakibatkannya. McGraw-Hill Education tidak bertanggung jawab atas konten informasi apa pun yang diakses melalui pekerjaan tersebut. Dalam keadaan apa pun McGraw-Hill Education dan / atau pemberi lisensinya tidak akan bertanggung jawab atas segala kerusakan tidak langsung, insidental, khusus, hukuman, konsekuensial, atau serupa yang diakibatkan oleh penggunaan atau ketidakmampuan untuk menggunakan karya tersebut, bahkan jika salah satu dari mereka telah diberitahu. dari kemungkinan kerusakan tersebut. Batasan tanggung jawab ini berlaku untuk setiap klaim atau penyebab apa pun apakah klaim atau sebab tersebut muncul dalam kontrak, wanprestasi atau sebaliknya.



12. Serangan



Isi



Jantung. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23 Jeffrey F. Barletta



13. Hipertensi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Joseph J. Saseen dan Eric J. MacLaughlin



14. Gagal Jantung Kronis. . . . . . . . . . . . . . . . . . . . . . . . . . . . 0,79 Robert B. Parker, Jean M. Nappi, dan Larisa H. Cavallari 15. Gagal Jantung Dekompensasi Akut. . . . . . . . . . . . 117 Jo E. Rodgers dan Brent N. Reed



Kontributor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Kata Pengantar. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxix Kata Pengantar untuk Edisi Pertama. . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxi Kata Pengantar. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxiii



16. Penyakit Jantung Iskemik Stabil. . . . . . . . . . . . . . . . . . 135 Paul P. Dobesh



17. Sindrom Koroner Akut. . . . . . . . . . . . . . . . . . . . 165 Kelly C. Rogers, Simon de Denus, Shannon W. Finks, dan Sarah A. Spinler



18. Aritmia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 BAGIAN



Cynthia A. Sanoski dan Jerry L. Bauman



1 Masalah Dasar 1



19. Tromboemboli Vena. . . . . . . . . . . . . . . . . . . . . 231 Daniel M. Witt, Nathan P. Clark, dan Sara R. Vazquez



Editor Bagian: L. Michael Posey, Thomas D. Nolin dan Gary R. Matzke e1. Literasi Kesehatan dan Penggunaan Obat. . . . . . . . . . . 1 Oralia V. Bazaldua, DeWayne A. Davidson, Ashley Zurek, dan Sunil Kripalani



20. Stroke. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



e2. Kompetensi Budaya. . . . . . . . . . . . . . . . . . . . . . . . . 3



Dislipidemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271 Robert L. Talbert



. . 261 Susan C. Fagan dan David C. Hess



21.



Jeri J. Sias, Amanda M. Loya, José O. Rivera, dan Jessica M. Shenberger-Trujillo



e22. Penyakit Arteri Perifer. . . . . . . . . . . . . . . . . 299 Sheryl



e3. Prinsip dan Praktik Keamanan Obat. . . . 5 Robert J.



L. Chow dan Barbara J. Hoeben



23. Penggunaan Vasopresor dan Inotropik dalam



Weber



Farmakoterapi Syok. . . . . . . . . . . . . . . . . . . . . 301



e4. Farmakokinetik Klinik dan



Robert Maclaren, Scott Mueller, dan Joseph F. Dasta



Farmakodinamik. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Larry A. Bauer



e5. Farmakogenetika. . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Larisa H. Cavallari dan YW Francis Lam



24. Syok Hipovolemik. . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 Brian L. Erstad



e25. PengantarParu Pengujian Fungsi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341



e6. Pediatri. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11



Maria I. Velez, Tamara D. Simpson, Stephanie M. Levine, dan Jay I. Peters



Milap C. Nahata dan Carol Taketomo e7



. Geriatri. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13 Emily R. Hajjar, Shelly L. Gray, Patricia W. Slattum, Lauren R. Hersh, Jennifer G. Naples, dan Joseph T. Hanlon



e8. Perawatan paliatif . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Nina M. Bemben dan Mary Lynn McPherson



BAGIAN



Editor Bagian: Robert L. Talbert



26. Asma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



e9. Toksikologi Klinis. . . . . . . . . . . . . . . . . . . . . . . . . . .17



343 Christine A. Sorkness dan Kathryn V. Blake



Peter A. Chyka



e10. Manajemen KlinisPotensi



3 Gangguan Pernapasan 343 v



vi



Kondisi TerkaitBioterorisme. . . . . . . . . . . . . .19 Colleen M. Terriff, Lisa T. Costanigro, Kimberly C. McKeirnan, dan Barbara J. Hoeben BAGIAN



46. Penyakit Ginjal Akibat Obat. . . . . . . . . . . . . . . . . . 657 27. Penyakit Paru Obstruktif Kronis. . . . . . . . 375 Sharya V. Bourdet dan Dennis M. Williams



2 Gangguan Kardiovaskular 21



28. Hipertensi Arteri Paru. . . . . . . . . . . . . . . 401 Rebecca Moote, Rebecca L. Attridge, dan Deborah J. Levine



Editor Bagian: Robert L. Talbert dan Stuart T. Haines e11.



Pengujian Kardiovaskular. . . . . . . . . . . . . . . . . . . . . . .21



29. Cystic Fibrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Richard A. Lange C



. . 417 Chanin C. Wright dan Yolanda Y. Vera



e30. Penyakit Paru Akibat Obat. . . . . . . . . 431 O



N



Homeostasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759 Rachel W. Flurie dan Donald F. Brophy



Hengameh H. Raissy dan Michelle Harkins



T



E



N



52. Gangguan Asam-Basa. . . . . . . . . . . . . . . . . . . . . . . . . . .



T



S



775 John W. Devlin dan Gary R. Matzke BAGIAN



4 Gastrointestinal Disorders 433 Editor BAGIAN



Bagian: Joseph T. DiPiro



E31. Evaluasi Saluran Pencernaan. . . . . 433 Keith M. Olsen dan Rachael V. McCaleb



6 Gangguan Neurologis 795 Editor



Bagian: Barbara G. Wells dan Vicki L. Ellingrod



e53. Evaluasi Penyakit Neurologis. . . . . . . . . . . . 795 Melody



32. Penyakit Refluks Gastroesofageal. . . . . . . . . . . . . . .



Ryan, Stephen J. Ryan, dan Susan C. Fagan



435 Dianne May, Michael Thiman, dan Satish SC Rao



33. Penyakit Ulkus Peptikum dan Gangguan Terkait. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453



54. Penyakit Alzheimer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797 Emily P. Peron, Patricia W. Slattum,



Bryan L. Love dan Phillip L. Mohorn



Kacie E. Powers, dan Sarah E. Hobgood



55. Multiple Sclerosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



34. Penyakit Radang Usus. . . . . . . . . . . . . . . . . . . 477



815 Jacquelyn L. Bainbridge, Augusto Miravalle, dan Pei Shieen Wong



Brian A. Hemstreet



35. Mual dan Muntah. . . . . . . . . . . . . . . . . . . . . . . . . . 497



56. Epilepsi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Leigh Anne Hylton Gravatt, Krista L. Donohoe, dan Cecily V. DiPiro



837 Viet-Huong V. Nguyen, Christine B. Baca, Jack J. Chen, dan Susan J. Rogers



36. Diare, Sembelit, dan Irritable Bowel Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511



57. Status Epilepticus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 867 Stephanie J. Phelps dan James W. Wheless



Patricia H. Fabel dan Kayce M. Shealy



37. Hipertensi Portal dan Sirosis. . . . . . . . . . . . . . 527



58. Manajemen Akut Pasien Cedera Otak. . . . 881 Bradley



Julie M. Sease dan Jennifer N. Clements



A. Boucher dan G. Christopher Wood



e38. Penyakit Hati Akibat Obat. . . . . . . . . . . . . . . . 543



59. Penyakit



William R. Kirchain dan Rondall E. Allen



Parkinson. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 895 Jack J. Chen dan Khashayar Dashtipour



39.



60. Manajemen Nyeri. . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Pankreatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545 Scott Bolesta dan Patricia A. Montgomery



909 Chris M. Herndon, Jennifer M. Strickland, dan James B. Ray



40. Virus Hepatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



61. Gangguan Sakit Kepala. . . . . . . . . . . . . . . . . . . . . . . . . .



. . 561 Paulina Deming



. . 927 Deborah S. Minor dan T. Kristopher Harrell



41. Penyakit Celiac. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579 Priti N. Patel dan Robert A. Mangione



BAGIAN



BAGIAN



5 Gangguan Ginjal 587



Bagian: Barbara G. Wells dan Vicki L. Ellingrod e62



. Penilaian Gangguan Psikiatri. . . . . . . . 943 Mark E. Schneiderhan, Leigh Anne Nelson, dan Steven J. Bauer



Editor Bagian: Gary R. Matzke dan Thomas D. Nolin



63. Attention Deficit / Hyperactivity Disorder. . . . . . . . 945



e42. Evaluasi Fungsi Ginjal. . . . . . . . . . . . . 587 Thomas C.



Julie A. Dopheide dan Steven R. Pliszka



Dowling



43. Cedera Ginjal Akut. . . . . . . . . . . . . . . . . . . . . . . . . . . . 589 Jenana Halilovic Maker dan William Dager



44. Penyakit Ginjal Kronis. . . . . . . . . . . . . . . . . . . . . . . . 609 Joanna Q. Hudson dan Lori D. Wazny



45. Hemodialisis dan Dialisis Peritoneal. . . . . . . . . . . 639 Kevin M. Sowinski, Mariann D. Churchwell, dan Brian S. Decker Thomas D. Nolin



47. Glomerulonefritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . 675 Alan H. Lau



48. Individualisasi Terapi Obat untuk Pasien Penyakit Ginjal Kronis. . . . . . . . . . . . . . . . . . . . . . . . 699 Marisa



64. Gangguan Makan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959 Steven C. Stoner dan Valerie L. Ruehter



65. Gangguan Terkait Zat I: Gambaran Umum dan Depresan, Stimulan, dan Halusinogen. . . . 973 Paul L. Doering dan Robin Moorman Li



66. Gangguan Terkait Zat II: Alkohol, Nikotin, dan Kafein. . . . . . . . . . . . . . . . . 993 Paul L. Doering dan Robin Moorman Li



67. Skizofrenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1011 vii



81. Endometriosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1279 Deborah A. Sturpe dan Kathleen J. Pincus



Battistella dan Gary R. Matzke



49. Gangguan Homeostasis Sodium dan Air. . . . 719 Katherine H. Chessman dan Jason Haney



50. GangguanKalsium dan



82. Terapi Hormon pada Wanita. . . . . . . . . . . . . . . . . . 1287 Sophia N. Kalantaridou, Laura M. Borgelt, Devra K. Dang, dan Karim Anton Calis



HomeostasisFosfor. . . . . . . . . . . . . . . . . . . . . . 741 Amy Barton Pai



51. GangguanKalium dan Magnesium



7 Gangguan Psikiatri 943 Editor



BAGIAN



10 Gangguan Urologi 1309 C



O



N



T



M. Lynn Crismon, Rania S. Kattura, dan Peter F. Buckley



Editor Bagian: Gary C. Yee dan Gary R. Matzke



e86. Fungsi dan Evaluasi Sistem Kekebalan Tubuh. . . . . . . . . . . . . . . . . . . . . . . . 1373 Daniel A. Zlott, Nicole Weimert Pilch, dan Geoffrey M. Thiele



68. Gangguan Depresi Mayor. . . . . . . . . . . . . . . . . . . . 1041 Christian J. Teter, Judith C. Kando, dan Barbara G. Wells 69.



87. Systemic Lupus Erythematosus. . . . . . . . . . . . . . . . 1375 Beth H. Resman-Targoff



Gangguan Bipolar. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1063



e88. Alergi obat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1393



Shannon J. Drayton dan Christopher S. Fields



Lynne M. Sylvia



70. Gangguan Kecemasan: Kecemasan Umum,



89. Transplantasi Organ Padat. . . . . . . . . . . . . . . . . . . 1395



Panik, dan Gangguan Kecemasan Sosial. . . . . . . . . . . . 1079 Sarah T. Melton dan Cynthia K. Kirkwood



Heather J. Johnson dan Kristine S. Schonder



71. Gangguan Stres Pascatrauma dan Gangguan Obsesif-Kompulsif. . . . . . . . . . . . . . . 1099 Cynthia K.



BAGIAN



Kirkwood, Sarah T. Melton, dan Barbara G. Wells



72. Gangguan Tidur-Bangun. . . . . . . . . . . . . . . . . . . . . . . .



90. Osteoartritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



1111 John M. Dopp dan Bradley G. Phillips



1419 Lucinda M. Buys dan Sara A. Wiedenfeld



73. Gangguan Terkait denganIntelektual



91. Artritis Reumatoid. . . . . . . . . . . . . . . . . . . . . . . . . . 1439



Cacat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1123 Nancy C. Brahm, Steven R. Erickson,



Kimberly Wahl dan Arthur A. Schuna



92. Osteoporosis dan Osteomalacia. . . . . . . . . . . . . . . 1457



dan Douglas W. Stewart



BAGIAN



12 Gangguan Reumatologi 1419 Editor



Bagian: L. Michael Posey



Mary Beth O'Connell dan Jill S. Borchert



93. Gout dan Hiperurisemia. . . . . . . . . . . . . . . . . . . . . .



8 Gangguan Endokrinologi 1139 Editor



1485 Michelle A. Fravel dan Michael E. Ernst



Bagian: Robert L. Talbert dan Stuart T. Haines



74. Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . .



BAGIAN



1139 Curtis L. Triplitt, Thomas Repas, dan Carlos Alvarez



13 Gangguan Mata dan Otolaringologi 1505



75. Gangguan Tiroid. . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Editor Bagian: L. Michael Posey



1183 Jacqueline Jonklaas dan Michael P. Kane



76. Gangguan Kelenjar Adrenal. . . . . . . . . . . . . . . . . . . . . .



94. Glaukoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



1207 Andrew Y. Hwang, Steven M. Smith, dan John G. Gums e77. Gangguan Kelenjar Hipofisis. . . . . . . . . . . . . . . . . 1227



1505 Richard G. Fiscella, Timothy S. Lesar, Ohoud A. Owaidhah, dan Deepak P. Edward



95. Rinitis Alergi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Joseph K. Jordan, Amy Heck Sheehan, dan Karim Anton Calis



1521 J. Russell May viii



BAGIAN



9 Gangguan Ginekologi dan



113. Infeksi Saluran Pencernaan danEnterotoksigenik



Kebidanan 1229



Keracunan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1799 BAGIAN



Editor Bagian: Barbara G. Wells dan Vicki L. Ellingrod



78. Kehamilan dan Laktasi:Terapeutik



14 Gangguan Dermatologi 1535 Editor Bagian: L. Michael Posey



Pertimbangan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1229 Kristina E. Lingkungan



96. Acne Vulgaris. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1535 Debra Sibbald



79. Kontrasepsi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1247 Sarah P. Shrader dan Kelly R. Ragucci



97.



80. Gangguan Terkait Menstruasi. . . . . . . . . . . . . . . 1263 Elena M. Umland dan Jacqueline M. Klootwyk Editor Bagian: L. Michael Posey



C



Psoriasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1561 Rebecca M. Law dan Wayne P. Gulliver



E O



N N



98. Dermatitis Atopik. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1579



83. Disfungsi Ereksi. . . . . . . . . . . . . . . . . . . . . . . . . . . 1309



T T E S



Mary Lee dan Roohollah Sharifi



N



Rebecca M. Law dan Po Gin Kwa



T



84. Hiperplasia Prostatik Jinak. . . . . . . . . . . . . . . . . . 1335 Mary Lee dan Roohollah Sharifi



85. Inkontinensia Urinary. . . . . . . . . . . . . . . . . . . . . . . . . . 1353 Eric S. Rovner, Jean Wyman, dan Sum Lam BAGIAN



11 Gangguan Imunologi 1373



e99. Reaksi Obat Dermatologis dan S



Kondisi Kulit Umum. . . . . . . . . . . . . . . . . . . . . 1591 Rebecca M. Law dan David TS Law



BAGIAN



15 Gangguan Hematologi 1593



Editor Bagian: Gary C. Yee



122. Infeksi padaImmunocompromised Pasien. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1943 Scott W. Mueller dan Douglas N. Fish



100. Anemias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1593 Kristen Cook



123. Profilaksis Antimikroba dalam Pembedahan. . . . . . . . . . . 1973 Salmaan Kanji



101. Gangguan Koagulasi. . . . . . . . . . . . . . . . . . . . . . . .



e124. Kesehatan Perjalanan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1989 Douglas



1611 Heidi Trinkman, Donald Beam, dan Tracy M. Hagemann



Slain dan Scott Kincaid



102. Penyakit Sel Sabit. . . . . . . . . . . . . . . . . . . . . . . . . . . .



125. Vaksin dan Imunoglobulin. . . . . . . . . . . . . . . 1991 Mary



1629 CY Jennifer Chan dan Melissa Frei-Jones



S. Hayney



e103. Gangguan Hematologi Akibat Obat. . . . . 1647 Elisa



126. Infeksi Human Immunodeficiency Virus. . . . . 2007



M. Greene dan Tracy M. Hagemann



BAGIAN



Peter L. Anderson, Thomas N. Kakuda, dan Courtney V. Fletcher



16 Penyakit Menular 1649



Editor Bagian: Joseph T. DiPiro



BAGIAN



e104. Tes Laboratorium untuk Mengarahkan Farmakoterapi



17 Gangguan Onkologi 2029



Editor Bagian: Gary C. Yee



Antimikroba. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1649



127. Perawatan Kanker dan Kemoterapi. . . . . . . . . 2029



Michael J. Rybak, Jeffrey R. Aeschlimann, dan Kerry L. LaPlante



Stacy S. Shord dan Lisa M. Cordes



128. Kanker Payudara. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



105. Pemilihan Regimen Antimikroba. . . . . . . . . . . . . .



. . 2077 Chad M. Barnett, Bonnie Lin Boster, dan Laura Boehnke Michaud



1651 Grace C. Lee dan David S. Burgess



106. Infeksi Sistem Saraf Pusat. . . . . . . . . . . . . 1665 Ramy



129. Kanker Paru. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



H. Elshaboury, Aileen S. Ahiskali, Jessica S. Holt, dan John C. Rotschafer



2117 Val R. Adams dan Sarah Scarpace Peters



130. Kanker Kolorektal. . . . . . . . . . . . . . . . . . . . . . . . . . . . .



107. Infeksi Saluran Pernapasan Bawah. . . . . . . . . . . . .



2133 Lisa M. Holle, Jessica M. Clement, dan Lisa E. Davis



1685 Martha G. Blackford, Mark L. Glover, dan Michael D. Reed



131. Kanker Prostat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2165 LeAnn B. Norris dan Jill M. Kolesar



108. Infeksi Saluran Pernapasan Atas. . . . . . . . . . . . . 1709



132. Limfoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



Christopher Frei dan Bradi Frei



2181 Alexandre Chan dan Jolynn Sessions



109. Influenza. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



133. Kanker Ovarium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



. 1721 Jessica C. Njoku



110. Infeksi Kulit dan Jaringan Lunak. . . . . . . . . . . . . . . . 1733 Douglas N. Fish



111. Endokarditis Infektif. . . . . . . . . . . . . . . . . . . . . . . . . 1761 Angie Veverka, Brian L. Odle, dan Jeffrey A. Kyle



112. Tuberkulosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1779 Rocsanna Namdar, Michael Lauzardo, dan Charles A. Peloquin Andrew Roecker, Brittany Bates, dan Steven Martin



114. Infeksi Intra-Abdominal. . . . . . . . . . . . . . . . . . . . 1813 Alan E. Gross, Keith M. Olsen, dan Joseph T. DiPiro



2209 Judith A. Smith dan Elizabeth K. Nugent ix



134. Leukemia Akut. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2225 Amy Hatfield Seung dan Alix A. Dabb BAGIAN



18 Gangguan Gizi 2323



135. Leukemia Kronis. . . . . . . . . . . . . . . . . . . . . . . . . . . . 2247 Patrick J. Kiel dan Christopher A. Fausel



136. Multiple Myeloma. . . . . . . . . . . . . . . . . . . . . . . . . . . . 2265 Kamakshi V. Rao dan Amy M. Pilih



e115. Penyakit Parasit. . . . . . . . . . . . . . . . . . . . . . . . . 1827 e137. Sindrom Myelodysplastic. . . . . . . . . . . . . . 2281 Kristen Jason M. Cota dan JV Anandan



116. Infeksi Saluran Kemih dan Prostatitis. . . . . . . . . 1829 Elizabeth A. Coyle dan Randall A. Prince



117. Penyakit Menular Seksual. . . . . . . . . . . . . . . . . 1845 Leroy C. Knodel, Bryson Duhon, dan Jacqueline Argamany



118. Infeksi Tulang dan Sendi. . . . . . . . . . . . . . . . . . . . . 1865 Marcella N. Honkonen, Ziad Shehab, Edward P. Armstrong



119. Sepsis dan Septic Shock. . . . . . . . . . . . . . . . . . . . . . . 1877 S. Lena Kang-Birken



120. Infeksi Jamur Superfisial. . . . . . . . . . . . . . . . . . 1891 Thomas ER Brown dan Linda D. Dresser



121. Infeksi Jamur Invasif. . . . . . . . . . . . . . . . . . . . . 1911 Peggy L. Carver



B. McCullough dan Julianna A. Merten



e138. Karsinoma Sel Ginjal. . . . . . . . . . . . . . . . . . . . . 2283 Christine M. Walko dan Daniel J. Crona



139. Melanoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2285 Cindy L. O'Bryant dan Jamie C. Poust



140. Transplantasi Sel Punca Hematopoietik. . . . . . 2305 Susanne Liewer dan Janelle Perkins Editor Bagian: Gary R. Matzke



141. Penilaian Status Gizi dan Persyaratan Gizi. . . . . . . . . . . . . . . . . . . 2323 Katherine H. Chessman dan Vanessa J. Kumpf



142. Nutrisi Parenteral. . . . . . . . . . . . . . . . . . . . . . . . . . . 2345 C



O



Todd W. Mattox dan Catherine M. Crill



N



T



143. Nutrisi Enteral. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2367 E



N



144. Obesitas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2385 Amy Heck Sheehan, Judy T. Chen, Jack A. Yanovski, dan Karim Anton Calis



T



Vanessa J. Kumpf dan Katherine H. Chessman S



Indeks 2403



Konversi Satuan SI diproduksi oleh Dr. Ed Randell PhD DCC FCACB, Kepala Divisi dan Profesor Kedokteran Laboratorium, Dept. Lab. Kedokteran, Otoritas Kesehatan Timur & Fakultas Kedokteran, Universitas Memorial



Halaman ini sengaja dikosongkan



Kontributor



Jeffrey R. Aeschlimann,PharmD Profesor Associate Departemen Praktek Farmasi UConn School of Pharmacy Storrs, Connecticut Bab e104



Aileen Ahiskali, PharmD Val R. Adams, PharmD, FCCP, BCOP Associate Professor Departemen Praktek Farmasi dan Fakultas Sains Fakultas Farmasi Universitas Kentucky Lexington, Kentucky Bab 129



Antimicrobial Stewardship Apoteker Hennepin County Medical Center Minneapolis, Minnesota Bab 129



Rondall E. Allen, BS,PharmD Dekandan Profesor Sekolah Farmasi dan Kesehatan Profesi Universitas Maryland Eastern Shore Princess Anne, Maryland



Bab e38A.Alvarez



Carlos, PharmD, MSc, BCPS Associate Professor Texas Tech University Pusat Ilmu Kesehatan Sekolah Farmasi Universitas Texas Barat Daya Dallas, Texas Bab 74 JV Anandan,PharmD Konsultan Rumah Sakit Henry Ford Detroit, Michigan Bab e115



Resident Farmakoterapi/Kandidat MSc Sekolah Tinggi Universitas Texas di Austin Austin, TX Adjoint Assistant Professor Pusat Penelitian & Pendidikan Farmakoterapi Pusat Ilmu Kesehatan Universitas Texas di San Antonio San Antonio, Texas Bab 117



Edward P. Armstrong,PharmD Profesor Emeritus Departemen Praktek dan Ilmu FarmasiFarmasi FakultasUniversitas Arizona Tucson, Arizona Bab 118



Rebecca L. Attridge, PharmD, MSc, BCPS



Peter L. An derson,PharmD Profesor Departemen Ilmu Farmasi Sekolah Skaggs Farmasi dan Ilmu Farmasi Universitas Colorado Kampus Medis Anschutz Aurora, Colorado Bab 126



Jacqueline Argamany,PharmD



Associate Professor Departemen Praktek Farmasi Universitas Inkarnasi Word Feik Sekolah Farmasi Asisten Profesor Divisi Penyakit Paru dan Perawatan Kritis Pusat Ilmu Kesehatan Universitas Texas San Antonio, Texas Bab 28



Christine B. Baca, MD,MSHS AsistenProfesor Departm ent of Neurology University of Colorado School of Medicine Aurora, Colorado Bab 56



xi xii



Sekolah Skaggs Farmasi dan Ilmu Farmasi



Jacquelyn L. Bainbridge, PharmD,FCCP Profesor Departemen Farmasi Klinis dan Neurologi Universitas Colorado Kampus Medis Anschutz C



Aurora, Colorado



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N



Bab 55



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Jerry L. Bauman, PharmD , FCCP, FACC Dekan Fakultas Farmasi Universitas Illinois di Chicago Profesor Departemen Praktek dan Kedokteran Farmasi, Utara Ohio Rumah SakitMemorial Lima Lima, Ohio Bab 113



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Jeffrey F. Barletta, PharmD, FCCM I



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Associate Professor dan Wakil Ketua



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DepartemenPraktik Farmasi



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College of Pharmacy Midwestern University Glendale, Arizona Bab 12



Marisa Battistella, BScPhm, PharmD,ACPR Farmasi Clinician Scientist Asisten Profesor Dan FakultasLeslie Farmasi Universitas Toronto Clinical Apoteker-Nephrology University Network Kesehatan Toronto, Ontario, Kanada Bab 48



Larry A. Bauer, PharmD, FCP, FCCP



Brittany N. Bates, PharmD,BCPS



Profesor DepartemenFarmasi FakultasFakultas Farmasi Asisten Profesor Departemen Laboratorium Kedokteran Fakultas Kedokteran Universitas Washington Seattle, Washington Bab e4



Asisten Profesor Klinikdan Apoteker KlinisUniversitas



Steven J. Bauer, MD



Chad M. Barnett, PharmD, BCOP Spesialis Farmasi Klinis-Onkologi Payudara Divisidari Layanan Farmasi Klinis Farmasi Universitas Texas MD Anderson Cancer Center Houston, Texas Bab 128



Direktur Medis Departemen Psikiatri Pusat Perkembangan Manusia Duluth, Minnesota Bab e62 Bagian Kardiologi Sekolah Tinggi Farmasi dan Kedokteran Universitas dari Illinois di Chicago Chicago, Illinois Bab 18



Oralia V. Bazaldua, PharmD, FCCP, BCPS Associate Professor Departemen Keluarga dan Pengobatan Komunitas Pusat Ilmu Kesehatan Universitas Texas di San Antonio San Antonio, Texas Bab e1



Donald Beam, MDMD Hematologi / Ahli Onkologi Anak Direktur Medis Program Gangguan Pendarahan dan Hemofilia Cook Children's Medical Center Fort Worth, Texas Bab 101



Nina Bemben, PharmD, BCPS Asisten Profesor Departemen Praktek Farmasi dan Sains Sekolah Farmasi Universitas Maryland Baltimore, Maryland Bab e8



Martha Blackford, PharmD, BCPS Farmakolog Klinis & Toksikologi Farmakologi Klinis & Toksikologi, Divisi Perawatan Kritis Departemen Pediatri Rumah Sakit Anak Akron Akron, Ohio Bab 107



Kathryn Blake, PharmD, BCPS,FCCP Direktur, Pusat Penelitian Farmakogenomik dan Penerjemahan Principal Research Scientist Nemours Children's Speciality Care Departemen Riset Biomedis Jacksonville, Florida Bab 26



Scott Bolesta, PharmD , BCPS, FCCM Associate Professor Departemen Praktek Farmasi Nesbitt College of Pharmacy Wilkes University Wilkes-Barre, Pennsylvania DAN Investigator Tamu Pusatuntuk Inovasi Farmasi dan Hasil Sistem Kesehatan Geisinger Danville, Pennsylvania Bab 39 xiii



Jill S. Borchert, PharmD, BCACP, BCPS, FCCP David S. Burgess, PharmD, FCCP Profesor & Wakil Ketua Praktik Farmasi Direktur PGY2 Program Residensi Perawatan Rawat Jalan Universitas Midwestern Chicago College of Pharmacy Bab 92



Laura M. Borgelt, PharmD, FCCP, BCPS, NCMP Associate



Dean for Administration and Operations Professor, Departments of Clinical Farmasi dan Kedokteran Keluarga Skaggs Sekolah Farmasi dan Ilmu Farmasi Universitas Colorado Kampus Medis Anschutz Aurora, Colorado Bab 82



Bonnie Lin Boster, PharmD, BCOP Spesialis Farmasi Klinis Divisidari Farmasi Universitas Texas MD Anderson Cancer Center Houston, Texas Bab 128



Bradley A. Boucher, PharmD, FCCP, FCCM ProfesorFarmasi Klinis Dekan AsosiasiInisiatif Strategis dan Operasi College of Pharmacy University of Tennessee Memphis, Tennessee Bab 58



Sharya Vaughan Bourdet, PharmD, BCPS Perawatan Kritis Apoteker / Manajer Program Rawat Inap Klinis Urusan Veteran Pusat Medis Pusat Ilmu Kesehatan Klinis Asisten Profesor Sekolah Pharm acy University of California San Francisco, California Bab 27



Nancy C.Brahm, PharmD, MS, BCPP, CGP Profesor Klinis Sekolah Tinggi Farmasi Universitas Oklahoma Tulsa, Oklahoma Bab 73



Donald F. Brophy, PharmD, MSc, FCCP, BCPS McFarlane Professor dan Ketua Departemen Farmakoterapi dan Ilmu Hasil Sekolah Farmasi Virginia Commonwealth University Richmond, Virginia Bab 51



Thomas ER Brown,PharmD Profesor Associate Leslie Dan Fakultas Farmasi Universitas Toronto Toronto, Ontario Bab 120



Peter F. Buckley, MD, MS Dekan Profesor Psikiatri , Farmakologi, dan Radiologi Medical College of Georgia Universitas Augusta Augusta, Georgia Bab 67 Profesor dan Ketua FakultasUniversitas Kentucky FarmasiDepartemen Praktek dan Ilmu Farmasi Lexington, Kentucky Bab 105 C



Karim Anton Calis, PharmD, MPH, FASHP, FCCP



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Adjunct Senior Clinical Investigator T



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Office of Clinical Director



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B



Eunice Kennedy Shriver National Institute of Chil d Kesehatan dan U



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PembangunanManusia



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National InstitutesKesehatan Bethesda, Maryland Clinical Professor University of Maryland Baltimore, Maryland Clinical Professor Virginia Commonwealth University Richmond, Virginia Bab E77, 82, dan 144



Peggy L. Carver, PharmD, FCCP Associate ProfessorFarmasiFarmasi DepartemenDepartemenKlinisFarmasi Sekolah TinggiUniversitas Michigan Ann Arbor, Michigan Bab 121



Larisa H. Cavallari,PharmD Profesor Associate Departemen Praktek Farmasi Universitas Illinois di Chicago Chicago, Illinois Bab e5 dan 14



Alexandre Chan, PharmD, MPH, FCCP , pil KB, BCOP Associate Professor dan Asisten Kepala Departemen Farmasi Fakultas Ilmu xiv ProfesorKlinis Departemen Praktik Farmasi Purdue University College of Pharmacy Indianapolis , Indiana Bab 144 C



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Katherine H. Chessman, PharmD, FCCP, BCPS, BCNSP



N



Clinical Assistant Professor of Pharmacy Farmakoterapi Pendidikan dan Pusat Penelitian Universitas Texas di Austin — Co Fakultas Farmasi Adjunct Associate Professor of Pediatrics Department of Pediatrics University of Texas Health Science Center San Antonio, Texas Bab 102



Jack J. Chen,PharmD Profesordan Ketua Departemen Praktek Farmasi Sekolah Tinggi Farmasi Marshall B. Ketchum University Fullerton, California Department of Neurology Fakultas Kedokteran Universitas Loma Linda Loma Linda, California Bab 56 dan 59



Lisa M. Cordes, PharmD, BCACP, BCOP Judy T. Chen, PharmD, BCPS, CDE, FNAPRekanan Nathan P. Clark, PharmD, BCPS Pengawas Farmasi Klinik Pelayanan Farmasi Klinik, Antikoagulasi dan Anemia Kaiser Permanente Aurora, Colorado Bab 19



Jessica M. Clement,MD



Departemen Pelayanan Farmasi



Jennifer N. Clements, PharmD , BCPS, CDE, BCACP Associate Professor



Departemen Farmasi Klinis dan Ilmu Hasil



B



Medical University of South Carolina College of U



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Pediatri



CY Jennifer Chan, PharmD, BCPPS



Pharmacy Spesialis Farmasi Klinis, Bedah Pediatri /



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I



National University of Singapore Specialist Apoteker (Onkologi Farmasi) Departemen Farmasi National Cancer Centre Singapore Singapore Chapter 132



Asisten Profesor Divisi Hematologi / Onkologi Departemen Kedokteran Fakultas Kedokteran UConn Health Farmington, Connecticut Bab 130



Profesor



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Medical University of South Carolina Children's Hospital Charleston, South Carolina Chapters 49, 141, dan 143



Sheryl L. Chow, PharmD, FCCP, FAHA, FHFSA, BCPS AQ-Cardiology College of Pharmacy Universitas Barat Ilmu Kesehatan Pomona, California Bab e22



Mariann D. Churchwell, PharmD, BCPS, FCCP Associate Professor College of Ilmu Farmasi dan Farmasi Universitas Toledo Toledo, Ohio Bab 45



Peter A. Chyka, PharmD, FAACT, DABAT Profesor Farmasi Klinis dan Dekan Asosiasi Sekolah Tinggi Farmasi Universitas Tennessee Pusat Ilmu Kesehatan Knoxville, Tennessee Bab e9



Departemen Praktek Farmasi Presbyterian College School of Pharmacy Clinton, South Carolina Chap ter 37



Kristen Cook, PharmD, BCPS Asisten Profesor Departemen Praktek Farmasi Sekolah Tinggi Farmasi Universitas Nebraska Medical Center Omaha, Nebraska Bab 100 Onkologi Klinik Spesialis Farmasi Pusat Klinik Departemen Farmasi Institut Nasional Kesehatan Bethesda, Maryland Bab 127



Jason M. Cota, PharmD , MS Wakil Ketua dan Profesor Associate Departemen Praktek Farmasi Universitas Penjelmaan Word Feik Sekolah Farmasi San Antonio, Texas Bab e115



Elizabeth A. Coyle, PharmD, FCCM,BCPS Asisten DekanPenilaian Profesor Klinis Universitas Houston College of Pharmacy Houston, Texas Bab 116



Catherine M. Crill, PharmD, BCPS, BCNSP Associate Professor Departemen Farmasi Klinis dan Pediatri Pusat Ilmu Kesehatan Universitas Tennessee Memphis, Tennessee Bab 142



M. Lynn Crismon, PharmD, FCCP,BCPP Dekan James T. Doluisio Bupati Ketua dan Profesor Behrens Centennial University of Texas di Austin — Sekolah Tinggi Farmasi Austin, Texas Bab 67



Daniel J. Crona, PharmD, PhD Asisten Profesor Divisi Farmakoterapi dan Terapi Eksperimental Universitas North Carolina Eshelman School of Pharmacy Chapel Hill, North Carolina Bab e138



Alix A. Dabb,PharmD, Spesialis FarmasiDepartemen Pendukung Keputusan Klinis Onkologi Farmasi Sidney Pusat Kanker Komprehensif Kimmel Rumah Sakit Johns Hopkins Baltimore, Maryland Bab 134



William E. Dager, PharmD, BCPS Spesialis Apoteker Pusat Medis UC Davis Profesor Klinis FarmasiFarmasi SekolahUC San Francisco Profesor Klinis KedokteranKedokteran SekolahUC Davis Profesor Klinik Farmasi Touro Sekolah Farmasi Sacramento, California Bab 43



Devra K. Dang, PharmD, BCPS, CDE Associate Profesor Klinis Sekolah Farmasi Universitas Connecticut Storrs, Connecticut Bab 82



Austin, Texas Bab 23



Dewayne A. Davidson,PharmD Asisten Profesor Departemen Kedokteran Keluarga dan Komunitas Pusat Ilmu Kesehatan Universitas Texas di San Antonio San Antonio, Texas Bab e1



Lisa E. Davis, PharmD, BCPS, BCOP Profesor Departemen Praktek Farmasi & Sains Sekolah Tinggi Farmasi Universitas Arizona Tucson, Arizona Bab 130



Brian S. Decker, MD, PharmD, MS Asisten Profesor Kedokteran Klinik Nephrology Fellowship Program Pelatihan Direktur Indiana University School of Medicine Indianapolis, Indiana Bab 45



Simon de Denus, BPharm, MSC, PhD Peneliti Apoteker, Institut Jantung Montreal, Profesor Associate Facul Badan Farmasi Université de Montréal Université de Montréal Beaulieu-Saucier Chair di Farmakogenomik Montreal, Quebec Bab 17



Paulina Deming,PharmD Profesor Associate Departemen Praktek Farmasi Sekolah Tinggi Farmasi-Universitas New Mexico Pusat Ilmu Kesehatan Albuquerque, New Mexico Bab 40



John W. Devlin, PharmD, FCCP, FCCM, BCPS Profesor Departemen Farmasi dan Ilmu Sistem Kesehatan Sekolah Farmasi Bouve Sekolah Tinggi Profesi Kesehatan Northeastern University Boston, Massachusetts Bab 52 Bab 114 C



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Cecily DiPiro, PharmD T



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Konsultan Apoteker I



B



Midlothian, Virginia U



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Bab 35 O



Khashayar Dashtipour, MD, PhD Profesor Neurologi dan Direktur Ilmu Dasar, Divisi Gangguan Gerakan Departemen Neurologi / Gerakan Dis pesanan Sekolah Kedokteran Universitas Loma Linda xv



Joseph T. DiPiro, PharmD, BCPS Dekan dan Profesor Archie O. McCalley Ketua Sekolah Farmasi Universitas Persemakmuran Virginia Richmond, Virginia Loma Linda, California Bab 59



Joseph F. Dasta, MSc, FCCM, FCCP Adjunct Profesor Universitas Texas Profesor Emeritus Universitas Negeri Ohio



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S



Paul P. Dobesh, PharmD, FCCP, BCPS - AQ Kardiologi Profesor Praktek Farmasi Sekolah Tinggi Farmasi Universitas Nebraska Medical Center Omaha, Nebraska Bab 16



Paul L. Doering, MS Layanan Terhormat Profesor Pelayanan Praktek Farmasi Emeritus Departemen Farmakoterapi dan Sekolah Tinggi Penelitian Terjemahan Farmasi Universitas Florida Gainesville, Flor ida Chapters 65 and 66



Krista L. Donohoe, PharmD, BCPS, CGP Assistant Professor Department of Pharmacotherapy and Outcomes Science



Virginia Commonwealth University School of Pharmacy Richmond, Virginia Chapter 35



Julie A. Dopheide, PharmD, BCPP, FASHP Professor of Clinical Pharmacy, Psychiatry, and the Behavioral Sciences University of Southern California School of Pharmacy and Keck School of Medicine Director, Office of Continuing Professional Development Director, PGY2 Psychiatric Pharmacy Residency Los Angeles, California Chapter 63



John M. Dopp, PharmD, MS Associate Professor School of Pharmacy University of Wisconsin Madison, Wisconsin xvi



Christopher A. Fausel, PharmD, MHA, BCOP Linda Dresser, PharmD, FCSHP Assistant Professor Leslie Dan Faculty of Pharmacy University of Toronto Pharmacotherapy Specialist - Antimicrobial Stewardship University Health Network Toronto, Ontario C



O



Chapter 120 N



Chapter 72



Thomas C. Dowling, PharmD, PhD, FCCP, FCP Professor, Assistant Dean and Head Pharmacy Practice Department College of Pharmacy Ferris State University Grand Rapids, Michigan Chapter e42



Shannon J. Drayton, PharmD Associate Professor Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy Medical University of South Carol ina Charleston, South Carolina Chapter 69 Professor Department of Pharmacy Practice and Science University of Arizona College of Pharmacy Tucson, Arizona Chapter 24



Patricia H. Fabel, PharmD, BCPS Clinical Assistant Professor Department of Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy - University of South Carolina Campus Columbia, South Carolina Chapter 36



T



R



I



Bryson Duhon, PharmD, BCPS



B



Clinical Assistant Professor U



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The University of Texas College of Pharmacy O



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Austin, Texas S



Chapter 117



Deepak P. Edward, MD Jonas S Friedenwald Professor of Ophthalmology and Pathology Department of Ophthalmology Wilmer Eye Institute Johns Hopkins University Baltimore, Maryland Chapter 94



Ramy Elshaboury, PharmD, BCPS AQ-ID Clinical Pharmacy Coordinator - Infectious Diseases Massachusetts General Hospital Boston, Massachusetts Chapter 106



Steven R. Erickson, PharmD Associate Professor Department of Clinical Pharmacy College of Pharmacy University of Michigan Ann Arbor, Michigan Chapter 73



Michael E. Ernst, PharmD



Susan C. Fagan, PharmD, BCPS, FCCP Jowdy Professor, Assistant Dean College of Pharmacy University of Georgia Athens, Georgia Chapters 20 and e53 Clinical Manager, Oncology Pharmacy Department of Pharmacy Indiana University Simon Cancer Center Indianapolis, Indiana Chapter 135



Christopher S. Fields, MD Assistant Professor Department of Psychiatry and Behavioral Sciences Medical University of South Carolina Charleston, South Carolina Chapter 69



Shan non W. Finks, PharmD, FCCP, BCPS-AQ (Cardiology) Associate Professor College of Pharmacy University of Tennessee Memphis, Tennessee Chapter 17



Richard G. Fiscella, PharmD, MPH Clinical Professor Emeritus Department of Pharmacy Practice University of Illinois at Chicago Chicago, Illinois Chapter 94



Douglas N. Fish, PharmD, BCPS AQ-ID, FCCP, FCCM Professor and Chair



Professor (Clinical) Department o f Pharmacy Practice and Science College of Pharmacy and Department of Family Medicine Carver College of Medicine University of Iowa Iowa City, Iowa Chapter 93



Department of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Sciences Aurora, Colorado Chapters 110 and 122



Brian L. Erstad, PharmD, FCCM, FCCP, FASHP



Dean and Professor College of Pharmacy



Courtney V. Fletcher, PharmD



Elisa M. Greene, PharmD, BCACP



University of Nebraska Medical Center Omaha, Nebraska Chapter 126



Assistant Professor Department of Pharmacy Practice Clinical Pharmacist—Siloam Family Health Center College of Pharmacy Belmont University Nashville, Tennessee Chapter 103



Rachel Flurie, PharmD, BCPS Assistant Professor Department of Pharmacotherapy and Outcomes Science Virginia Commonwealth University School of Pharmacy Richmond, Virginia Chapter 51



Alan E. Gross, PharmD, BCPS AQ-ID Clinical Assistant Professor Department of Pharmacy Practice University of Illinois at Chicago College of Pharmacy Chicago, Illinois Chapter 114



Michelle Fravel, PharmD, BCPS Clinical Assistant Professor Clinical Pharmacy Specialist Applied Clinical Science Department of Pharmacy Practice and Science University of Iowa College of Pharmac y Iowa City, Iowa Ambulatory Care Department of Pharmaceutical Care University of Iowa Health Care Iowa City, Iowa Chapter 93



Wayne P. Gulliver, MD, FRCPC Professor of Dermatology and Medicine Memorial University of Newfoundl and St. John's, Newfoundland and Labrador, Canada Chapter 97 Chapter 76 C



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N



Tracy M. Hagemann, PharmD, FCCP, FPPAG T



Bradi L. Frei, PharmD, MS, BCPS, BCOP



R



Professor and Associate Dean



Associate Professor Feik School of Pharmacy University of the Incarnate Word San Antonio, Texas Chapter 108



I



B



College of Pharmacy U



T



University of Tennessee Health Sciences Center O



R



Nashville, Tennessee



Christopher R. Frei, PharmD, MS, FCCP, BCPS Associate Professor and Division Head Pharmacotherapy Division College of Pharmacy, The University of Texas at Austin Center Director, Pharmacotherapy Education & Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio



John G. Gums, PharmD, FCCP Professor of Pharmacy and Translational Research Department of Family Medicine College of Pharmacy and Medicine University of Florida Gainesville, Florida San Antonio, Texas Chapter 108



S



Chapters 101 and e103



Emily Hajjar, PharmD, BCPS, BCAP, CGP Associate Professor Department of Pharmacy Practice xvii Jefferson School of Pharmacy Thomas Jefferson University Philadelphia, Pennsylvania Chapter e7



Melissa Frei-Jones, MD



Jason S. Haney, PharmD, BCPS Assistant Professor Medical University of South Carolina College of Pharmacy Charleston, South Carolina Chapter 49



Associate Professor Department of Pediatrics Division of Hematology/Oncology School of Medicine University of Texas Health Science Center San Antonio, Texas Chapter 102



Joseph T. Hanlon, PharmD, MS



Mark L. Glove r, PharmD Associate Consultant Eli Lilly and Company Indianapolis, Indiana Chapter 107



Associate Professor of Medicine Department of Internal Medicine University of New Mexico Health Sciences Center Albuquerque, New Mexico Chapter e30



Leigh Anne Hylton Gravatt, PharmD, BCPS Assistant Professor



T. Kristopher Harrell, PharmD, MA, FASHP



Department of Pharmacotherapy and Outcomes Science Virginia Commonwealth University School of Pharmacy Richmond, Virginia Chapter 35



Associate Profes sor Director of Experiential Affairs Department of Pharmacy Practice University of Mississippi School of Pharmacy Jackson, Mississippi Chapter 61



Shelly L. Gray, PharmD, MS Professor and Vice Chair for Curriculum and Instruction Department of Pharmacy Director Geriatric Pharmacy Program and PleinCertifi cate School of Pharmacy University of Washington Seattle, Washington Chapter e7



Professor Department of Medicine, Pharmacy and Therapeutics, and Epidemiology University of Pittsburgh Pittsburgh, Pennsylvania Chapter e7



Michelle S. Harkins, MD



Mary S. Hayney, PharmD, MPH, BCPS Professor of Pharmacy Division of Pharmacy Practice University of Wisconsin --Madison School of Pharmacy



Madison, Wisconsin Chapter 125



Brian A. Hemstreet, PharmD, FCCP, BCPS Assistant Dean for Student Affairs xviii Associate Professor School of Pharmacy Southern Illinois University Edwardsville Edwardsville, Illinois Chapter 60 C



O



Lauren R. Hersh, MD



N



T



Instructor



R



I



Department of Family and Community Medicine



B



Thomas Jefferson University U



T



Philadelphia, Pennsylvania O



Professor of Pharmacy Practice Regis University School of Pharmacy Denver, Colorado Chapter 34



Andrew Y. Hwang, PharmD, BCPS Chris Herndon, PharmD University of Tennessee, Health Sciences Center Memphis, Tennessee Chapter 44 Postdoctoral Fellow, Family Medicine University of Florida College of Pharmacy Department of Pharmacotherapy and Translational Research Gainesville, Florida Chapter 76



Heather J. Johnson, PharmD, BCPS, FASN Assistant Professor Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Clinical Specialist-Transplant, UPMC Pittsburgh, Pennsylvania Chapter 89



R



Chapter e7 S



David C. Hess, MD Professor and Chairman Department of Neurology Medical College of Georgia Augusta, Georgia Chapter 20



Sarah E. Hobgood, MD Assistant Professor Geriatric Medic ine Department of Internal Medicine School of Medicine Virgina Commonwealth University Richmond, Virginia Chapter 54



Barbara J. Hoeben, Lt Col, USAF, PharmD, MSPharm, BCPS Keesler Air Force Base Biloxi, Mississippi Chapter e10



Lisa M. Holle, PharmD, BCOP, FHOPA Associate Clinical Professor Department of Pharmacy Practice School of Pharmacy University of Connecticut Storrs, Connecticut Chapter 130



Jessica Holt, PharmD, BCPS (AQ-ID) Infectious Diseases Pharmacy Coordinator Department of Pharmacy Abbott Northwestern Hospital, Part of Allina Health Minneapolis, Minnesota Chapter 106



Marcella N. Honkonen, PharmD, BCPS Assistant Professor Department of Pharmacy Practice and Science University of Arizona College of Pharmacy Tucson, Arizona Chapter 118



Joanna Q. Hudson, PharmD, BCPS, FASN, FCCP, FNKF Professor Department of Clinical Pharmacy Associate Professor Department of Medicine (Nephrology)



Jacqueline Jonklaas, MD, PhD Associate Professor Division of Endocrinology Department of Medicine Georgetown University Washington, DC Chapter 75



Joseph K. Jordan, PharmD, BCPS Associate Professor Department of Pharmacy Practice Butler University College of Pharmacy and Health Sciences Drug Information Specialist Indiana University Health Indianapolis, Indiana



Thomas Kakuda, PharmD Scientific Director Clinical Pharmacology Alios BioPharma, Inc, part of the Janssen Pharmaceutical Companies of Johnson & Johnson South San Francisco, California Chapter 126



Sophia N. Kalantaridou, MD, PhD Professor of Obstetrics and Gynecology Depart ment of Obstetrics and Gynecology University of Ioannina Medical School Ioannina, Greece Chapter 82



Judith C. Kando, PharmD, BCPP Shire Pharmaceuticals Lead, US Medical, BED Lexington, Massachusetts Chapter 68



Michael P. Kane, PharmD, FCCP, BCPS, BCACP Professor Department of Pharmacy Practice School of Pharmacy and Pharmaceutical Sciences Albany College of Pharmacy and Health Sciences Clinical Pharmacy Specialist Albany Medical Center Division of Community Endocrinology (formerly The Endocrine Group) Albany, New York Chapter 75



S. Lena Kang-Birken, PharmD, FCCP, AAHIVP Associate Professor



Department of Pharmacy Practice Thomas J Long School of Pharmacy and Health Sciences University of the University of Texas at Austin—College of Pharmacy Pacific Stockton, California Austin, Texas xix Chapter 117 Leroy C. Knodel, PharmD [DECEASED] Associate Professor Department of Surgery University of Texas Health Science Center San Antonio, Texas Chapter 119



Salmaan Kanji, PharmD Clinical Pharmacy Specialist The Ottawa Hospital Associate Scientist The Ottawa Hospital Resear ch Institute Ottawa, Ontario, Canada Chapter 123



Rania S. Kattura, PharmD, MS, BCPP Psychiatric Pharmacist Austin State Hospital Adjunct Assistant Professor College of Pharmacy University of Texas at Austin Austin, Texas Chapter 67



Patrick J. Kiel, PharmD, BCPS, BCOP Clinical Pharmacy Specialist Hematology/Oncology - Precision Genomics Program Indiana University Simon Cancer Center Indianapolis, Indiana Chapter 135



Scott E. Kincaid, PharmD, BCPS Director, Clinical Pharmacy Services UK HealthCare Adjunct Assistant Professor Department of Pharmacy Practice and Science University of Kentucky College of Pharmacy Lexington, Kentucky Chapter e124



William R. Kirchain, PharmD, CDE Wilbur and Mildred Robichaux Endowed Professor Division of Clinical and Administrative Sciences Xavier University of Louisiana, College of Pharmacy New Orleans, Louisiana Chapter e38



Cynthia K. Kirkwood, PharmD, BCPP Professor and Executive Associate Dean for Academic Affairs School of Pharmacy Virginia Commonwealth University Richmond, Virginia Chapters 70 and 71



Jacqueline M. Klootwyk, PharmD, BCPS, BCACP, TTS Assistant Professor of Clinical, Social, and Administrative Sciences Mylan School of Pharmacy Duquesne University Pittsburgh, Pennsylvania Chapter 80 Clinical Professor xx Associate Clinical Professor Department of Clinical Pharmacy Practice St. John's University Queens, New York Chapter 85



O



N



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R



I



B



U



T



Jill M. Kolesar, PharmD, MS, FCCP, BCPS



O



R



Professor Department of Pharmacy Practice and Science Department of Internal Medicine Colleges of Pharmacy and Medicine Director, Early Phase Clinical Trials Center Markey Cancer Center University of Kentucky Lexington, Kentucky Chapter 131



Lisa T Costanigro, PharmD Clinical Pharmacist Department of Pharmacy Poudre Valley Hospital - University of Colorado Health Fort Collins, Colorado Chapter e10



Sunil Kripalani, MD, MSc Associate Professor Section of Hospital Medicine Division of General Internal Medicine and Public Health Department of Medicine Vanderbilt University Nashville, Tenness ee Chapter e1



Vanessa J. Kumpf, PharmD, BCNSP Clinical Specialist, Nutrition Support Center for Human Nutrition Vanderbilt University Medical Center Nashville, Tennessee Chapters 141 and 143



Po Gin Kwa, MD, FRCPC Clinical Assistant, Professor of Pediatrics Faculty of Medicine Memorial University of Newfoundland and Pediatrician Eastern Health St. John's, Newfoundland and Labrador, Canada Chapter 98



Jeffrey A. Kyle, PharmD, BCPS Associate Professor of Pharmacy Practice Clinical Pharmacy Specialist, Shelby Baptist Medical Center Department of Pharmacy Practice McWhorter School of Pharmacy Samford University Birmingham, Alabama Chapter 111



YW Francis Lam, PharmD, FCCP Professor Department of Pharmacology (MSC 7764) University of Texas Health Science Center at San Antonio San Antonio, Texas Chapter e5



Grace C. Lee, PharmD, PhD, BCPS Sum Lam, PharmD, CGP, BCPS, FASCP Richard A. Lange, MD, MBA O



N



President T



R



Dean, Paul L. Foster School of Medicine I



C



C



S



B



Rick and Ginger Francis Endowed Professor



Chapters 83 and 84



U



T



El Paso, Texas O



R



Chapter e11 S



Kerry L. Laplante, PharmD, BS Infectious Diseases Pharmacotherapy Specialist Providence Veterans Affairs Medical Center Associate Professor of Pharmacy College of Pharmacy University of Rhode Island Adjunct Associate Professor of Medicine Warren Alpert School of Medicine Brown University Kingston, Rhode Island Chapter e104



Alan H. Lau, PharmD, FCCP Professor Department of Pharmacy Practice Director International Clinical Pharmacy Education College of Pharmacy University of Illinois at Chicago Chicago, Illinois Chapter 47



Michael Lauzardo, MD, MSc Chief Division of Infectious Diseases and Global Medicine Director Southeastern National Tuberculosis Center College of Medicine University of Florida Gainesville, Florida Chapter 112



Rebecca Law, PharmD School of Pharmacy and Discipline of Family Medicine Faculty of Medicine Mem orial University of Newfoundland St. John's Newfoundland, Canada Chapter 98



David TS Law, BSc, MD, PhD, CCFP Assistant Professor Department of Family and Community Medicine Faculty of Medicine University of Toronto Staff, Department of Family Practice The Scarborough Hospital and Rouge Valley Health System Scarborough, Ontario, Canada Chapter e99



Rebecca Law, PharmD



Timothy S. Lesar, PharmD Director of Clinical Pharmacy Services Patient C are Services Director Department of Pharmacy Albany Medical Center Albany, New York Chapter 94



Deborah J. Levine, MD, FCCP Associate Professor of Medicine Division of Pulmonary and Critical Care University of Texas at San Antonio San Antonio, Texas Chapter 28



Stephanie M. Levine, MD Professor of Medicine Division of Pulmonary Diseases and Critical Care Medicine University of Texas Health Science Center San Antonio, Texas Chapter e25



Robin Moorman Li, PharmD, BCACP, CPE Assistant Director Jacksonville Campus Clinical Associate Professor Department of Pharmacotherapy and Translational Research College of Pharmacy University of Florida Gainesville, Florida Chapters 65 and 66



Susanne Liewer, PharmD, BCOP Clinical Pharmacy Coordinator, Stem Cell Transplant Department of Pharmaceutical and Nutrition Care Nebraska Medicine Clinical Associate Professor Department of Pharmacy Practice College of Pharmacy University of Nebraska Medical Center Omaha, Nebraska Chapter 140



Bryan L. Love, PharmD, BC PS-AQ ID Associate Professor Department of Clinical Pharmacy & Outcomes Sciences South Carolina College of Pharmacy University of South Carolina Campus Columbia, South Carolina Chapter 33



Amanda M. Loya Clinical Associate Professor University of Texas at El Paso UT Austin Cooperative Pharmacy Program University of Texas at El Paso College of Health Sciences University of Texas at Austin—College of Pharmacy xxi



School of Pharmacy and Discipline of Family Medicine Faculty of Medicine Memorial University of Newfoundland St. John's Newfoundland, Canada Dianne May, PharmD, FCCP, BCPS Chapters 97 and e99 Clinical Professor Assistant Professor Department of Clinical and Administrative Pharmacy College of Pharmacy, The University of Texas at Austin Campus Director for Pharmacy Practice Experiences Austin, Texas Division of Experience Programs Pharmacotherapy Education and Research Center, School of Medicine, University of Texas Health Science Center at San Antonio University of Georgia College of Pharmacy Adjunct Clinical Assistant Professor San Antonio, Texas Department of Family and Community Medicine Chapter 105 Texas Tech University Health Sciences Center—El Paso Mary Lee, PharmD, BCPS, FCCP El Paso, Texas Professor of Pharmacy Practice Chapter e2 Chicago College of Pharmacy Robert MacLaren, BSc, PharmD, MPH, FCCM, Midwestern University FCCP Professor Downers Grove, Illinois



T



Department of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Denver Aurora, Colorado Chapter 23



School of Pharmacy



E ric J. MacLaughlin, PharmD, FCCP, BCPS



Kristen B. McCullough, PharmD, BCPS, BCOP



University of Arkansas For Medical Sciences Little Rock, Arkansas



Professor and Head of Adult Medicine Department of Pharmacy Practice Professor Departments of Family Medicine and Internal Medicine Texas Tech University Health Sciences Center School of Pharmacy Amarillo, Texas Chapter 13



Hematology/Oncology Clinical Pharmacy Specialist Assistant Professor of Pharmacy Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota Chapter e137



Kimberly McKeirnan, PharmD, BCACP



Jenana Halilovic Maker, PharmD, BCPS



Clinical Assistant Professor Department of Pharmacotherapy Washington State University College of Pharmacy Spokane, Washington Chapter 10



Associate Professor Department of Pharmacy Practice Thomas J Long School of Pharmacy and Health Sciences Stockton, California Chapter 43



Mary Lynn McPherson, PharmD, MA, BCPS, CPE



Robert A. Mangione, PharmD



Professor Executive Director, Advanced Post-Graduate Education in Palliative Care Department of Pharmacy Practice and Science University of Maryland School of Pharmacy Baltimore, Maryland Chapter 8



Provost and Professor of Pharmacy Office of the Provost St. John's University Queens, New York Chapter 41



Steven J. Martin, PharmD, BCPS, FCCP, FCCM Dean and Professor



Sarah T. Melton, PharmD, BCPP, BCACP, FASCP



Rudolph H. Raabe College of Pharmacy Ohio Northern University Ada, Ohio Chapter 142



Profe ssor of Pharmacy Practice Department of Pharmacy Practice Gatton College of Pharmacy at East Tennessee State University Johnson City, Tennessee Chapters 70 and 71



Gary R. Matzke, PharmD, FCP, FCCP, FASN, FNAP Professor and Founding Director



Julianna A. Merten, PharmD, BCPS, BCOP



ACCP/ASHP/VCU Congressional Health Care Policy Fellow Program Department of Pharmacotherapy and Outcome Sciences School of Pharmacy Virginia Commonwealth University Richmond, Virginia Chapters 48, 52



Clinical Pharmacy Specialist - Hematology/Oncology Assistant Professor of Pharmacy Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota Chapter e137



Laura Boehnke Michaud, PharmD, FASHP, BCOP, CMQ Manager, Clinical Pharmacy Services



J. Russ ell May, PharmD Clinical Professor Department of Clinical and Administrative Pharmacy University of Georgia College of Pharmacy Augusta, Georgia Chapter 95 Augusta, Georgia



Division of Pharmacy Clinical Pharmacy Services University of Texas MD Anderson Cancer Center Houston, Texas Chapter 128 C



O



Chapter 32



N



T



R



Rachael McCaleb, PharmD



I



B



Assistant Professor xxii



C



Associate Professor Department of Neurology University of Colorado School of Medicine Associate Director Neurology Residency Program University of Colorado



N



U



Deborah S. Minor, PharmD Professor Department of Medicine University of Mississippi School of Medicine Jackson, Mississippi Chapter 61



Jean Nappi, BS, PharmD, FCCP, BCPS Augusto Miravalle, MD U



T



O



Phillip L . Mohorn, PharmD, BCPS, BCCCP



R



S



Clinical Pharmacy Specialist-Critical Care



Aurora, Colorado



Department of Pharmacy Spartanburg Medical Center Spartanburg Regional Healthcare System Spartanburg, South Carolina Chapter 33



Chapter 55



Patricia A. Montgomery, PharmD, FCSHP



O



Anschutz Medical Campus



T



R



I



B



O



R



S



Clinical Pharmacy Specialist Mercy General Hospital Sacramento, CA Adjunct Professor of Pharmacy University of the Pacific Stockton, California Chapter 39



Department of Pharmacy and Therapeutics Center for Clinical Pharmaceutical Sciences Department of Medicine, Renal-Electrolyte Division University of Pittsburgh Schools of Pharmacy and Medicine Pittsburgh, Pennsylvania Chapter 46



Rebecca Moote, PharmD, MSc, BCPS



Associate Professor Department of Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy Columbia, South Carolina Chapter 131



LeAnn B. Norris, PharmD, BCPS, BCOP



Associate Professor Department of Pharmacy Practice Regis University School of Pharmacy Denver, Colorado Chapter 28



Elizabeth K. Nugent, MD Assistant Professor Department of Obstetrics, Gynecology and Reproductive Sciences University of Texas Health Science Center McGovern Medical School Houston, Texas Chapter 133



Scott W Mueller, PharmD, BCCCP Assistant Professor Department of Clinical Pharmacy University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Aurora, Colorado Chapters 23 and 112



Cindy L. O'Bryant, PharmD, BCOP, FCCP, FHOPA Professor Department of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Sciences Clinical Specialist in Oncology University of Colorado Anschutz Medical Campus Aurora, Colorado Chapter 139



Milap Nahata, PharmD, MS, FCCP Professor of Pharmacy Pediatrics and Internal Medicine Division Chair Pharmacy Practice and Administration College of Pharmacy Ohio State University Associate Director of Pharmacy Ohio State University Medical Center Columb us, Ohio Chapter e6



Mary Beth O'Connell, PharmD, BCPS, FASHP, FCCP Associat e Professor Department of Pharmacy Practice Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University Detroit, Michigan Chapter 92



Rocsanna Namdar PharmD, BCPS, FCCP Medical Science Liaison Medical Affairs Allergan, Inc. Irvine, California Chapter 112



Jennifer Greene Naples Clinical Pharmacist, Pharmacovigilance Pharmacovigilance Center, Office of The Surgeon General, Department of the Army Falls Church, Virginia Chapter e7 Professor of Clinical Pharmacy and Outcome Sciences South Carolina College of Pharmacy—MUSC Campus Professor of Medicine, Medical University of South Carolina Charleston, South Carolina Chapter 14



Leigh Anne Nelson, PharmD, BCPP



Brian Odle, PharmD Associate Professor Department of Pharmacy Practice East Tennessee State University Gatton College of Pharmacy Johnson City, Tennessee Chapter 111 xxiii



Jay Peters, MD Professor and Chief Division of Pulmonary Critical Care University of Texas Health Science Center San Antonio, Texas Chapter e25 C



Keith M. Olsen, PharmD, FCCP, FCCM



Associate Professor Division of Pharmacy Practice and Administration University of Missouri–Kansas City School of Pharmacy Kansas City, Missouri Chapter e62



Dean and Professor College of Pharmacy University of Arkansas for Medical Sciences Little Rock, Arkansas Chapters e31 and 114



Viet-Huong V. Nguyen, PharmD, MPH, MS, BCPS



Oohed A. Owaidhah, MD



Assistant Professor Department of Pharmacy Practice Chapman University School of Pharmacy Irvine, California Chapter 56



Jessica Njoku, PharmD, MPH, BCPS Clinical Director, Pharmacy Services/Antimicrobial Stewardship Good Shepherd Health System Longview, Texas Chapter 109



Thomas D. Nolin, PharmD, PhD, FCCP, FCP, FASN Associate Professor



Glaucoma King Khaled Eye Specialist Hospital Riyadh, Saudi Arabia Chapter 94



Amy Barton Pai, PharmD, BCPS, FASN, FCCP, FNKF Associate Professor Department of Clinical Pharmacy College of Pharmacy University of Michigan Ann Arbor, Michigan Chapter 50



Robert B. Parker, PharmD, FCCP



Stephanie J. Phelps, PharmD



Professor Department of Clinical Pharmacy College of Pharmacy Uni versity of Tennessee Memphis, Tennessee Chapter 14



Associate Dean Academic Affairs Professor Clinical Pharmacy and Pediatrics College of Pharmacy University of Tennessee Health Science Center Memphis, Tennessee Chapter 57



Priti N. Patel, PharmD, BCPS Clinical Associate Professor Assistant Campus Director, St. Petersburg Campus Department of Pharmacotherapy and Translational Science University of Florida College of Pharmacy St. Petersburg, Florida Chapter 41



Bradley G. Phillips, PharmD, BCPS, FCCP Milliken-Reeve Professor and Head Department of Clinic al and Administrative Pharmacy University of Georgia College of Pharmacy Athens, Georgia Chapter 72



Charles Peloquin, PharmD, FCCP Professor, and Director, Infectious Disease Pharmacokinetics Lab. College of Pharmacy, and Emerging Pathogens Institute University of Florida Gainesville, Florida Chapter 112



Amy M. Pick, PharmD, BCOP Director of Faculty and Staff Development Associate Professor Department of Pharmacy Practice School of Pharmacy and Health Professions Creighton University Omaha, Nebraska Chapter 136



Janelle Perkins, PharmD, BCOP Associate Professor Department of Pharmacotherapeutics and Clinical Research College of Pharmacy University of South Florida Tampa, Florida Chapter 140



Nicole Weimert Pilch, PharmD, MSCR, BCPS, FAST Quality and Outcomes Director, Transplant ICCE Clinical Associate Professor Department of Pharmacy and Clinical Sciences South Carolina College of Pharmacy - MUSC Campus Medical University of South Carolina Charleston, South Carolina Chapter 86



Emily P. Peron, PharmD, MS, BCPS, FASCP Assistant Professor Geriatric Pharmacotherapy Program Department of Pharmacotherapy & Outcomes Science School of Pharmacy Virginia Commonwealth University Richmond, Virginia Chapter 54



Sarah Scarpace Peters, PharmD, MPH, BCOP



Kathleen J. Pincus, PharmD, BCPS



O



N



Associate Professor T



R



Department of Pharmacy Practice



I



B



Albany College of Pharmacy and Health Sciences U



T



Albany, New York



O



R



Chapter 129 xxiv



C



Oncology & Palliative Care Pharmacy Specialist Department of Pharmacy University of Colorado Hospital Anschutz Inpatient Pavilion Aurora, Colorado Chapter 139



N



Kacie E. Powers, PharmD, BCPS



R



I



Steven R. Pliszka, MD Division of Child and Adolescent Psychiatry Dielmann Distinguished Professor and Chair Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio, Texas Chapter 63



B rent N. Reed, PharmD, BCPS Jamie C. Poust, PharmD, BCOP Randall A. Prince, PharmD, FCCP, FCP, FIDSA Professor Department of Pharmacy Practice and Translational Research University of Houston College of Pharmacy Houston, Texas Chapter 116



Kelly Ragucci, PharmD, FCCP, BCPS, CDE



O



T



S



Assistant Professor Department of Pharmacy Practice and Science School of Pharmacy University of Maryland Baltimore, Maryland Chapter 81



Assistant Professor



B



Geriatric Pharmacotherapy Program U



T



Department of Pharmacotherapy and Outcomes Science O



R



School of Pharmacy S



Virginia Commonwealth University Richmond, Virginia Chapter 54



Professor and Chair Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy Medical University of South Carolina Campus Charleston, South Carolina Chapter 79



Hengameh H. Raissy, PharmD Research Associate Professor of Pediatrics Pulmonary Division School of Medicine University of New Mexico Albuquerque, New Mexico Chapter e30



Satish SC Rao, MD, PhD, FRCP Georgia Health Sciences University Medical College of Georgia Professor of Medicine, Chief, Section of Gastroenterology/Hepatology Director Digestive Health Center Augusta, Georgia Chapter 32



Kamakshi V. Rao, PharmD, BCOP, CPP, FASHP Clinical Pharmacist Practitioner, Bone Marrow Transplant University of North Carolina Hospitals and Clinics Associate Professor of Clinical Education University of North Carolina Eshelman School of Pharmacy Chapel Hill, North Carolina Chapter 136



James B. Ray, PharmD, CPE James A. Otterbeck OnePoint Patient Care Clinical Associate Professor in Hospice and Palliative Care Department of Pharmacy Practice and Science/Division of Applied Clinical Sciences College of Pharmacy University of Iowa Iowa City, Iowa Chapter 60 Assistant Professor Department of Pharmacy Practice and Science School of Pharmacy University of Maryland Clinical Pharmacy Specialist Department of Pharmacy University of Maryland Medical Cen ter Baltimore, Maryland Chapter 15



Michael D. Reed, PharmD, FCCP, FCP Medical Writer PPD Wilmington, North Carolina Chapter 107



Thomas Repas, DO, FACP, FACOI, FNLA, FACE, CDE Clinical Associate Professor Department of Internal Medicine Sanford School of Medicine University of South Dakota Sioux Falls, South Dakota Chapter 74



Beth H. Resman-Targoff, PharmD, FCCP Clinical Professor Department of Pharmacy Clinical and Administrative Sciences College of Pharmacy University of Oklahoma Oklahoma City, Oklahoma Chapter 87



José O. Rivera, PharmD Director and Clinical Professor UT Austin Cooperative Pharmacy Program College of Health Sciences University of Texas at El Paso College of Health Sciences Assistant Dean and Clinical Professor University of Texas at Austin College of Pharmacy El Paso, Texas Chapter e2



Jo E. Rodgers, PharmD, FCCP, BCPS Clinical Associate Professor Department of Pharmacotherapy and Experimental Therapeutics Eshelman School of Pharmacy University of North Carolina at Cha pel Hill



Chapel Hill, North Carolina Chapter 15



Andrew M. Roecker, PharmD, BCPS Professor and Chair Department of Pharmacy Practice Rudolph H. Raabe College of Pharmacy Ohio Northern University Ada, Ohio Chapter 113



Kelly C. Rogers, PharmD, FCCP Professor of Clinical Pharmacy UTHSC Campus AED Program Coordinator College of Pharmacy University of Tennessee Memphis, Tennessee Chapter 17



Susan J. Rogers, PharmD Assistant Clinical Professor (Retired) University of Texas College of Pharmacy (Austin) Clinical Pharmacy Specialist Neurology (Retired) South Texas Healthcare System Audie L. Murphy Memorial Veterans Hospital xxv



Mark E. Schneiderhan, PharmD, BCPP Associate Professor Human Development Center, Psychiatry Department Mental Health Provider University of Minnesota College of Pharmacy—Duluth San Antonio, Texas Chapter 56



John C. Rotschafer, PharmD, FCCP Professor Experimental and Clinical Pharmacology University of Minnesota College of Pharmacy Minneapolis, Minnesota Chapter 106



Eric S . Rovner, MD Professor of Urology Department of Urology Medical University of South Carolina Charleston, South Carolina Chapter 85



Valerie L. Ruehter, PharmD, BCPP Clinical Associate Professor Director of Experiential Learning University of Missouri-Kansas City School of Pharmacy Kansas City, Missouri Chapter 64



Melody Ryan, PharmD, MPH, BCPS, CGP Professor College of Pharmacy University of Kentucky Lexington, Kentucky Chapter e53



Stephen J. Ryan, MD, MS Clinical Professor College of Medicine University of Kentucky Lexington, Kentucky Chapter e53



Michael J. Rybak, PharmD, MPH Professor of Pharmacy & Medicine Anti-Infective Research Laboratory Department of Pharmacy Practice Eugene Applebaum College of Pharmacy & Health Sciences Wayne State University



Detroit, Michigan Chapter e104



Chapter 91



Cynthia A. Sanoski, PharmD, BCPS, FCCP Chair and Associate



Associate Dean for Academic Affairs and Professor of Pharmacy Practice Presbyterian College School of Pharmacy Clinton, South Carolina Chapter 37



Professor Department of Pharmacy Practice Jefferson School of Pharmacy Thomas Jefferson University Philadelphia, Pennsylvania Chapter 18



Joseph J. Sa seen, PharmD Professor Clinical Pharmacy and Family Medicine Vice Chair Department of Clinical Pharmacy Anschutz Medical Campus University of Colorado Aurora, Colorado Chapter 13 Duluth, Minnesota C



O



Chapter e62 N



T



R



Kristine S. Schonder, PharmD I



B



Assistant Professor U



T



Department of Pharmacy and Therapeutics O



R



School of Pharmacy S



University of Pittsburgh Clinical Specialist-Transplantation, UPMC Pittsburgh, Pennsylvania Chapter 89



Arthur Schuna, MS, BCACP, FASHP Clinical Professor University of Wisconsin School of Pharmacy Madison, Wisconsin xxvi



C



Jessica M. Shenberger-Trujillo, PhD O



N



Clinical Assistant Professor T



R



Director of Assessment and Evaluation I



B



University of Texas at El Paso



T



O



El Paso, Texas



R



S



Jolynn Sessions, PharmD, BCOP Clinical Pharmacist in Oncology Mission Health System Associate Professor of Clinical Education University of North Carolina Eshelman School of Pharmacy Asheville, North Carolina Chapter 132



Amy Hatfield Seun g, PharmD, BCOP Senior Director, Clinical Initiatives Physician Resource Management/Caret Cary, North Carolina Chapter 134



Roohollah Sharifi, MD, FACS Professor of Surgery/Urology University of Illinois at Chicago College of Medicine Chicago, Illinois Chapters 83 and 84



Kayce Shealy, PharmD, BCPS, BCACP, CDE Associate Professor Department of Pharmacy Practice Presbyterian College School of Pharmacy Clinton, South Carolina Chapter 36



Amy Heck Sheehan, PharmD Associate Professor Department of Pharmacy Practice Purdue University College of Pharmacy Indianapolis, Indiana Chapters 77 and 144



Patricia W. Slattum, PharmD, PhD, CGP Ziad Shehab, MD Professor Departments of Pediatrics and Pathology University of Arizona College of Medicine Tucson, Arizona Chapter 118



U



Julie M. Sease, Pharm D, FCCP, BCPS, CDE, BCACP



Chapter e2



Department of Pharmacy Practice University of Kansas School of Pharmacy Lawrence, Kansas Chapter 79



Jeri J. Sias, PharmD, MPH Clinical Associate Professor University of Texas at El Paso UT Austin Cooperative Pharmacy Program University of Texas at El Paso College of Health Sciences, University of Texas at Austin College of Pharmacy Adjunct Clinical Assistant Professor Department of Family and Community Medicine Texas Tech University Health Sciences Center—El Paso El Paso, Texas Chapter e2



Debra Sibbald, BScPhm, RPh, ACPR, MA, PhD



Reviewer Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring, Maryland Chapter 127



Senior Lecturer Division of Pharmacy Practice Leslie Dan Faculty of Pharmacy University of Toronto Director Department of Assessment Services Centre for the Evaluation of Health Professionals Educated Abroad Toronto, Ontario Chapte r 96



Sarah P. Shrader, PharmD, BCPS



Tamara Simpson, MD



Stacy S. Shord, PharmD, FCCP, BCOP



Clinical Associate Professor



Clinical Associate Professor



Division of Pulmonary Diseases and Critical Care Medicine University of Texas Health Science Center at San Antonio San Antonio, Texas Chapter e25



Douglas Slain, PharmD, BCPS, FCCP, FASHP Professor Infectious Diseases Clinical Specialist West Virginia University Health Sciences Center Morgantown, West Virginia Chapter e124 Director Geriatric Pharmacotherapy Program Department of Pharmacotherapy and Outcomes Science School of Pharmacy Virginia Commonwealth University Richmond, Virginia Chapters e7 and 54



Jennifer M. Strickland, PharmD, BCPS Millennium Health Senior Vice President/General Manager, Medication Monitoring and Genetic Testing Clinical Assistant Professor University of Florida College of Pharmacy xxvii



Michael L. Thiman, PharmD, BCPS Clinical Assistant Professor Department of Clinical and Administrative Pharmacy University of Georgia College of Pharmacy Athens, Georgia Chapter 32 C



Lakeland, Florida Chapter 60



Deborah A. Sturpe, PharmD, MA, BCPS Associate Clinical



Professor College of Pharmacy Director, Women's Health Integrative Medicine Research Program University of New England Department of Obstetrics, Gynecology, and Reproductive Sciences Portland, Maine Chapter 81 University of Texas Health Science Center McGovern Medical School Lynne M. Sylvia, PharmD Houston, Texas Senior Clinical Pharmacy Specialist - Cardiology Department of Pharmacy Chapter 133 Tufts Medical Center



Judith A. Smith, PharmD, BCOP, CPHQ, FCCP, FISOPP Associate Professor



Steven M. Smith, PharmD, MPH Assistant Professor Department of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Aurora, Colorado Chapter 76



Christine A. Sorkness, PharmD Professor of Pharmacy and Medicine University of Wisconsin Madison, Wisconsin Chapter 26



Kevin M. Sowinski, PharmD, FCCP Professor and Associate Head for Faculty Affairs Department of Pharmacy Practice Purdue University, College of Pharmacy Adjunct Professor Indiana University, School of Medicine Indianapolis, Indiana Chapter 45



Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS-AQ (Cardiology) Professor of Clinical Pharmacy Philadelphia College of Pharmacy University of the Sciences in Philadelphia Philadelphia, Pennsylvania Chapter 17



Douglas W. Stewart, DO, MPH Associate Professor Department of Pediatrics School of Community Medicine University of Oklahoma Tulsa, Oklahoma Chapter 73



Steven C. Stoner, PharmD, BCPP Chair and Clinical Professor Division of Pharmacy Practice and Administration UMKC School of Pharmacy Kansas City, Missouri Chapter 64



Clinical Professor School of Pharmacy Northeastern University Boston, Massachusetts Chapter e88



Carol Taketomo, PharmD Director of Pharmacy and Clinical Nutrition Children's Hospital of Los Angeles Adjunct Assistant Professor of Pharmacy Practice School of Pharmacy University of Southern California Los Angeles, California Chapter e6



Robert L. Talbert, PharmD, FCCP, BCPS, FAHA SmithKli ne Professor College of Pharmacy The University of Texas at Austin Professor School of Medicine, University of Texas Health Science Center San Antonio, Texas Chapter 21



Colleen M. Terriff, PharmD Antimicrobial Stewardship Program Coordinator Deaconess Hospital Spokane, Washington Chapter 10



Christian J. Teter, PharmD, BCPP Associate Professor Psychopharmacology College of Pharmacy Center for Excellence in the Neurosciences University of New England Portland, Maine Chapter 68



Geoffrey M. Thiele, PhD Professor Division of Rheumatology and Immunology Department of Medicine College of Medicine University of Nebraska Medical Center Omaha, Nebraska Chapter 86



Heidi Trinkman, PharmD O



N



Pediatric Clinical Pharmacy Specialist T



R



Hematology/Oncology and Stem Cell Transplantation I



B



Cook Children's Medical Center



Department of Pharmacy Services, University of Utah Health Care, Salt Lake City, Utah Chapter 19



U



Yolanda Y. Vera, PharmD, BCPS



T



Fort Worth, Texas



Pediatric Patient Care Pharmacist Department of Pharmacy The Children's Hospital at Scott & White Temple, Texas Chapter 29



O



R



Chapter 101 S



Curtis Triplitt, PharmD, CDE Clinical Associate Professor Department of Medicine Division of Diabetes University of Texas Health Science Center at San Antonio Texas Diabetes Institute University Health System San Antonio, Texas Chapter 74



Elena M. Umland, PharmD Associate Dean for Academic Affairs Professor of Pharmacy Practice Jefferson College of Pharmacy Thomas Jefferson University Philadelphia, Pennsylvania Chapter 80



Sara R. Vazquez, PharmD, BCPS Clinical Pharmacist, xxviii



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Maria I. Velez Assistant Professor of Medicine Division of Pulmonary Diseases and Critical Care Medicine University of Texas Health Science Center- San Antonio San Antonio, Texas



Angie Veverka, PharmD, BCPS Clinical Pharmacist Educator RxPrep, Inc. Manhattan Beach, California Chapter 111



Kimberly Wahl, PharmD Ambulatory Care Clinical Pharmacist Department of Pharmacy Ralph H. Johnson VA Medical Center Myrtle Beac h CBOC Myrtle Beach, South Carolina Chapter 91 Department of Pharmacy Salt Lake City, Utah The Ohio State University Wexner Medical Center Chapter 19 Columbus, Ohio Pei Shieen Wong, BSc (Pharm) (Hons), Chapter e3 BCPS Principal Pharmacist Barbara G. Wells, PharmD, FCCP, FASHP Pharmacy Department S ingapore General Hospital Dean Emeritus and Professor Emeritus SingHealth University of Mississ ippi School of Pharmacy Singapore Department of Pharmacy Practice Chapter 55 Oxford, Mississippi Chapters 68 and 71



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James W. Wheless, MD



Professor and Chief of Pediatric Neurology LeBonheur Chair in Pediatric Neurology University of Tennessee Health Science Center Christine M. Walko, PharmD, FCCP, Director BCOP LeBonheur Comprehensive Epilepsy Program Personalized Medicine Specialist and Neuroscience Institute DeBartolo Family Personalized Medicine Institute LeBonheur Children's Hospital Moffitt Cancer Center Memphis, Tennessee Tampa, Florida Chapter 57 Chapter 138 T



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Kristina E. Ward, BS, PharmD, BCPS Clinical Professor Director Drug Information Services College of Pharmacy University of Rhode Island Kingston, Rhode Island Chapter 78



Lori Wazny, BSc (Pharm), PharmD, EPPh



Sara A. Wiedenfeld, PharmD, BCPS Clinical Assistant Professor Department of Pharmacy Practice and Science Division of Applied Clinical Sciences College of pharmacy The University of Iowa Iowa City, Iowa Chapter 90



Dennis M. Williams, PharmD, BCPS



Associate Professor Clinical Pharmacist - Manitoba Renal Program Eshelman School of Pharmacy Clinical Assistant Professor - Colleges of University of North Carolina Pharmacy, University of Manitoba and University Chapel Hill, North Carolina of Florida Working Professional PharmD program Chapter 27 Department of Pharmaceutical Services Health Sciences Centre Daniel M. Witt, PharmD, FCCP, BCPS Winnipeg, Manitoba, Canada Professor (Clinical) and Vice Chair Chapter 44 Department of Pharmacotherapy Robert J. Weber, PharmD, MS University of Utah Senior Director, Pharmaceutical Services College of Pharmacy



G. Christopher Wood, PharmD, FCCP, FCCM, BCPS (AQ-ID) Associate Professor of Clinical Pharmacy College of Pharmacy University of Tennessee Memphis, Tennessee Chapter 58



Chanin Clark Wright, PharmD Director of Pharmacy McLane Children's Hospital Assistant Professor Department of Pediatrics Texas A&M College of Medicine Temple Texas Adjunct Clinical Assistant Professor University of Texas college of Pharmacy Austin, Texas Chapter 29



Jean Wyman, MN, PhD Professor Cora Meidl Siehl Chair in Nursing Research Adult and Gerontological Health Cooperative School of Nursing University of Minnesota Minneapolis, Minnesota Chapter 85



Jack A. Yanovski, MD, PhD Chief Section on Growth and Obesity Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National



Institute of Child Health and Human Development Clinical Center Pharmacy Department Ashley M. Zurek, PharmD National Institutes of Health National Cancer Institute Surgery and Clinical Pharmacist, Internal Medicine Service Immunotherapy Programs National Institutes of San Antonio Military Medical Center Bethesda, Maryland Health Chapter 144 Fort Sam Houston, Texas Bethesda, Maryland Chapter e1 Daniel A. Zlott, PharmD, BCOP Chapter e86 Clinical Pharmacy Specialist Extensive efforts are now underway to enhance access to and coordinate electronic health records within and between hospitals, physicians' offices, and pharmacies. As the health care environment has changed, so too has the pharmacy profession. When the 1st edition of Pharmacotherapy was published in 1988, the Board of Pharmacy Specialties (BPS; formerly called the Board of Pharmaceutical Specialties) had not yet approved Pharmacotherapy as a specialty within pharmacy, although they had acknowledged that the petition for approval of the specialty did doc ument a specialist who did exist within the practice of pharmacy and whose expertise could be differentiated from the performance char Publication of the 10th edition of Pharmacotherapy: A Pathophysi ologic acteristics of those in general practice. BPS approval came later that Approach represents a milestone, in that almost 30 years have passed year and signified that the pharmacotherapy specialist had taken since publication of the 1st edition. Accordingly, this is a logical time to unprecedented responsibilities in the collaborative management of pause and reflect upon the mission and changes in Pharmacotherapy, patient-specific pharmacotherapy problems. That same year BPS health care delivery systems, and our profession. Hopefully, this recognized Nutrition Support as a specialty within pharmacy prac tice, reflection is not simply an academic exercise, but instead an opportunity bringing the number of recognized specialties to three. Since that time, to think about what the future may hold and how we might be able to five more specialties have been approved. Today more lead the future such that clinical, humanis than 25,000 pharmacists worldwide are BPS certified. The 2nd edition of tic, and economic outcomes of our patients are improved. These are Pharmacotherapy came in the early 1990s when pharmaceutical care times of unprecedented change in health care. Since publication of the emerged as the future mission for phar macy practice. Pharmaceutical 1st edition, there has been growth and consolida tion (through mergers) care emphasized the pharmacist's role to accept shared responsibility within health care systems, the pharmaceutical industry, and community with other health care profes sionals for patients' drug therapy outcomes. pharmacy, especially within chain pharmacy. Managed health care has Also of note, pharmacy practice and specialty practice residency become an increasingly stronger influ ence on how clinicians practice in programs were beginning to proliferate. The expansion of residencies in an effort to ensure delivery of high quality but cost conscious care. the 1990s and growth in demand for pharmacists in community and Patient-centered medical homes and accountable care organizations hospital settings resulted in substantial increases in pharmacist salaries appear to be promising approaches to achieving higher-quality and costand a phar macist workforce shortage. effective care while improving medi cation-related outcomes. In 2003, President George W. Bush signed the Medicare Pre Pharmacists will need to be integral members of the collaborative teams scription Drug, Improvement, and Modernization Act which pro vided within patient-centered medical homes in order to maximize these prescription drug benefits (Medicare Part D) to America's seniors starting improvements in patient outcomes. In 2001, the National Academy of in 2006. Medicine (NAM; formerly the Institute of Medicine) brought to the In 2004, the Joint Commission of Pharmacy Practitioners and the 11 nation's attention the gap between the excellent care some patients national pharmacy organizations that comprise its member ship received and the average care that most patients received. They also endorsed a future vision of pharmacy practice as follows: reported that our health care system is fragmented and uncoordinated, and that more than 43 million people at that time lacked health Pharmacists will be the health care professionals responsible for insurance. They called upon practitioners, health care organizations, and providing patient care that ensures optimal medication therapy Congress to address these pressing deficiencies. Although some outcomes. advances have been made, health care remains poorly coordinated, Over the course of the last 30 years, pharmacy has matured into a there are varia tions in quality, and limited progress has been made in clinical profession. Medication management is no longer provided only integrating team based approaches. Additionally, medication adverse by pharmacists in tertiary care settings. Although the transfor mation is events continue to contribute to poor quality of care and high costs. not complete, pharmacists provide evidence-based medi cation Passage of the Affordable Care Act in 2010 expanded access to health management and immunizations in many primary care and community insurance coverage, including medications and medication therapy pharmacy settings, and many pharmacists practice col laboratively with management. About 90% of Americans now have health insurance, but physicians and other health care professionals. significant problems remain. In 1985 spending for prescription drugs in the United States was just over $22 billion. IMS Health Holdings Inc. recently esti mated that by 2020, that spending will climb to as high as $400 bil lion. These numbers do not include the ancillary costs of treatment failure, morbidity, and mortality associated with these drug thera pies. Today the increasing cost of new drugs is garnering great media and even Congressional attention, as is the escalating costs of old drugs. Calls are being made for manufacturers to provide transpar ency in pricing and in some cases to justify pricing based on out comes achieved.



Foreword



xxx Today, the pace of entry of new drugs onto the market, limited efficacy, and potential toxicity create great complexity in selection and management of optimal medications for individual patients. Even when treatment guidelines are available for many specific dis eases, far too many patients continue to receive suboptimal treat ment. A 2000 NAM report documented that in the United States adverse drug effects are the sixth leading cause of death. Overuse of



xxix Health Literacy, Pharmacogenetics, Palliative Care, and Clinical Management of Potential Bioterrorism-related Conditions. Several pedagogical features have also been added to facilitate learning. Rec ognizing a need to provide students and practitioners a mechanism to grow their clinical problem-solving skills, Pharmacotherapy Case book: A Patient Focused Approach was introduced as a companion textbook in 1997. antibiotics and underuse of vaccines continue to challenge practi tioners involved in delivery and oversight of drug therapy. These F



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only a few of the critical challenges that we must continue to address W



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to improve the health of our nation. It is increasingly important that all patients have access to the expertise of a clinically trained phar macist and that all pharmacists ensure that patients receive the most effective, safe, and economical pharmacotherapy. These contribu tions to patient care must be shared with other health care profes sionals and the resulting change in clinical outcomes documented to inform health policy decision makers of the value that pharmacists bring to patient care. When the 1st edition of Pharmacotherapy was published in 1988, the PharmD was not the entry level degree, and 74 US schools and colleges graduated only about 1000 PharmD graduates (in addition to approximately 5300 BS in pharmacy graduates). In 2015, 125 schools and colleges graduated approximately 14,000 first professional degree PharmD graduates, and 273 post-BS PharmD degrees were also con ferred. The pharmacy education enterprise continues to grow, but at a slower pace than in the last decade of the 20th century and the first decade of the 21st century. In the early 1990s, the American Association of Colleges of Pharmacy Commission to Implement Change in Pharmaceutical Education recommended a process to establish entry-level profes sional doctoral programs designed to produce graduates competent to provide pharmaceutical care upon entry into the pharmacy pro fession. The Commission also recommended curricular change to emphasize problem solving, communications, and improved prac tice skills. Responding to this, many colleges of pharmacy enhanced the practice component of the curriculum and are now delivering a significant portion of the curriculum using a problem-based, active learning format. Many schools and colleges are now experimenting with peer teaching and flipped classrooms. Curriculums continue to evolve to ensure that pharmacy students not only have a good grasp of the pharmaceutical sciences and pharmacotherapy, but that they can also think critically, communicate effectively, solve complex problems, and work effectively in teams. Pharmacy educators recognize that information about preven tion, diagnosis, and treatment is emerging more rapidly than ever before, largely due to our increasing knowledge of pharmacoge netics, pharmacogenomics, proteomics, and bioinformatics. This knowledge and information from other basic sciences will enable greater individualization of treatment and eventually precision med icine. It is very difficult to predict the pace of these advances, but relevant information from these disciplines is continuously being incorporated into the pharmacy curriculum. The 1st edition of Pharmacotherapy included 111 chapters. In response to many of the advances and challenges noted above, the 10th edition includes 144 chapters. Chapters added to the Founda tional Issues section include Medication Safety, Cultural



Competency, Pharmacotherapy has evolved to provide much more informa tion to support provision of medication management in ambulatory and community pharmacy settings, as pharmacy has evolved into a truly clinical profession. The selection of cases for the Casebook, the Clinical Controversies section, and other features in Pharmaco therapy have been critical in expanding this focus. As stated in the Preface to the 1st edition, the book's purpose was to “provide a basis of principles and information that reflects the breadth and depth of knowledge appropriate for today's pharmacy student and practitioner. The Preface goes on to explain that “the sections on treatment attempt to place drug therapy in its proper perspective with other modalities” and also that “The pathophysiol ogy sections are the key to imparting a way of thinking for the devel oping practitioner.” Today, 30 years after those precepts were crafted, they are as true for the 10th edition as they were for the first. Each edition of the book provides the scientific knowledge foundation for the clinician who manages the drug therapy of patients. Building on this foundation, the clinician must stay abreast of new developments and advance his/her competence by interpretation and assimilation of new information in the primary literature. We believe that over the last 30 years Pharmacotherapy has had a critical role in preparing pharmacy students and those already in practice to become medication managers and to define new clinical roles, thus helping to evolve our profession into a truly clinical one. Pharmacy practitioners, students, teachers, and researchers must accept responsibility to help expand pharmacists' roles as pro viders of patient focused, comprehensive medication management. This includes providing the highest quality of care in our own prac tices and increasing awareness of pharmacists' roles and abilities by government, researchers, third-party payers, and the public. It is clear that we also have a responsibility to continue to define new and innovative models for the provision of medication management in all practice settings, including community pharmacies, commu nity health clinics, managed care settings, and physician practices. Pharmacists will be key players in transformation of our medication use systems. Resources, including pharmacists, must be deployed more efficiently and effectively, taking advantage of their full scope of practice and breadth and depth of education and training. Strong leadership will be required to advance both generalist and specialty practices in pharmacy. Patient care of the future will be patient cen tered and will use a team based approach. Only when we optimize medication use will we be able to make meaningful improvements in the quality of care and decrease the costs of care. We are confident the evolution and maturation of our profession will not only con tinue, but that it will gain momentum in the years to come. Barbara G. Wells Robert L. Talbert Gary R. Matzke



Foreword to the First Edition Evidence of the maturity of a profession is not unlike that character izing the maturity of an individual; a child's utterances and behavior typically reveal an unrealized potential for attainment, eventually, of those attributes characteristic of an appropriately confident, inde pendently competent, socially responsible, sensitive, and productive member of society. Within a period of perhaps 15 or 20 years, we have witnessed a profound maturation within the profession of pharmacy. The utter ances of the profession, as projected in its literature, have evolved from mostly self-centered and self-serving issues of trade protection to a composite of expressed professional interests that prominently include responsible



explorations of scientific/technological ques tions and ethical issues that promote the best interests of the clientele served by the profession. With the publication of Pharmacotherapy: A Pathophysiologic Approach, pharmacy's utterances bespeak a matured practitioner who is able to call upon unique knowledge and skills so as to function as an appropriately confident, independently competent pharmacotherapeutics expert. In 1987, the Board of Pharmaceutical Specialties (BPS), in denying the petition filed by the American College of Clinical Phar macy (ACCP) to recognize “clinical pharmacy” as a specialty, con ceded nonetheless that the petitioning party had documented in its petition a specialist who does in fact exist within the practice of pharmacy and whose expertise



clearly can be extricated from the performance characteristics of those in general practice. A refiled petition from ACCP requests recognition of “pharmacotherapy” as a Specialty Area of Pharmacy Practice. While the BPS had issued no decision when this book went to press, it is difficult to comprehend the basis for a rejection of the second petition. Within this book one will find the scientific foundation for the essential knowledge required of one who may aspire to specialty practice as a pharmacotherapist. As is the case with any such pub lication, its usefulness to the practitioner or the future practitioner is limited to providing such a foundation. To be socially and profes sionally responsible in practice, the pharmacotherapist's foundation must be continually supplemented and complemented by the flow of information appearing in the primary literature. Of course this is not unique to the general or specialty practice of pharmacy; it is essential to the fulfillment of obligations to clients in any occupation operat ing under the code of professional ethics. Because of the growing complexity of pharmacotherapeutic agents, their dosing regimens, and techniques for delivery, pharmacy is obligated to produce, recognize, and remunerate specialty practi tioners who can fulfill the profession's responsibilities to society for service expertise where the competence required in a particular case exceeds that of the general practitioner. It simply is a component of our covenant with society and is as important as any other facet of that relationship existing between a profession and those it serves. The recognition by BPS of pharmacotherapy as an area of spe cialty practice in pharmacy will serve as an important statement by the profession that we have matured sufficiently to be competent and willing to take unprecedented responsibilities in the collaborative, pharmacotherapeutic management of patient-specific problems. It commits pharmacy to an intention that will not be uniformly or rap idly accepted within the established health care community. None theless, this formal action places us on the road to an avowed goal, and



xxxii F



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acceptance will be gained as the pharmacotherapists proliferate and establish their importance in the provision of optimal, costeffec tive drug therapy. Suspecting that other professions in other times must have faced similar quests for recognition of their unique knowledge and skills I once searched the literature for an example that might paral lel pharmacy's modern-day aspirations. Writing in the Philadelphia Medical Journal, May 27, 1899, DH Galloway, MD, reflected on the need for specialty training and practice in a field of medicine lacking such expertise at that time. In an article entitled “The Anesthetizer as a Speciality,” Galloway commented: The anesthetizer will have to make his own place in medicine: the profession will not make a place for him, and not until he has demonstrated the value of his services will it concede him the position which the importance of his duties entitles him to occupy. He will be obliged to define his own rights, duties and privileges, and he must not expect that his own estimate of the importance of his position will be conceded without opposi tion. There are many surgeons who are unwilling to share either the credit or the emoluments of their work with anyone, and their opposition will be overcome only when they are shown that the importance of their work will not be lessened, but enhanced, by the increased safety and dispatch with which operations may be done. . . . It has been my experience that, given the opportunity for one-onone, collaborative practice with physicians and other health professionals, pharmacy practitioners who have been educated and trained to perform at the level of pharmacotherapeutics specialists almost invariably have convinced the former that “the importance of their work will not be lessened, but enhanced, by the increased safety and dispatch with which” individualized problems of drug therapy could be managed in collaboration with clinical pharmacy practitioners.



xxxi contents of this book, and the intraprofessional recognition and acceptance of a higher level of



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responsibility in the safe, effective, and economical use of drugs and drug products, bode well for the future of the profession and for the improvement of patient care with drugs.



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Preface



It is fortuitous—the coinciding of the release of Pharmacother apy: A Pathophysiologic Approach with ACCP's petitioning of BPS for recognition of the pharmacotherapy specialist. The utterances Charles A. Walton, PhD San Antonio, Texas of a maturing profession as revealed in the many hours spent identifying the best ways of conveying complicated disease patho physiologic and pharmacotherapeutic concepts. The continuing Editors also welcome our new colleagues, all of whom are already contributing much to our editorial development and production processes. As with the previous nine editions, the founding precepts for PAPA continue to guide our content decisions:



With publication of the 10th edition of Pharmacotherapy: A Patho physiologic Approach (PAPA), this textbook reaches a milestone that none of us on the original editorial team ever dreamed possible. It is thus appropriate that the changes with this edition are more focused on the team itself than on the specific elements readers have found useful over the past three decades. With this edition of PAPA, readers will notice the addition of three Associate Editors to the editorial team. These individu als—Stuart T. Haines, Thomas D. Nolin, and Vicki L. Ellingrod, respectively—will replace three of our Editors beginning with the 11th edition: Robert L. Talbert (Founding Editor), Gary R. Matzke (Section Editor in the 1st edition and Editor beginning with the 2nd edition), and Barbara G. Wells (Author in the first two editions and Editor beginning with the 3rd edition). As the Editors transition to Editor Emeritus status, we thank them for the



• Advance the quality of patient care through evidence-based medication therapy management based on sound pharma cotherapeutic principles. • Enhance the health of our communities by incorporating contemporary health promotion and disease-prevention strategies in our practice environments. • Motivate young practitioners to enhance the breadth, depth, and quality of care they provide to their patients. • Challenge established pharmacists and other primary-care providers to learn new concepts and refine their understand ing of the pathophysiologic tenets that undergird the devel opment of individualized therapeutic regimens. • Present the pharmacy and health care communities with innovative patient assessment, triage, and pharmacotherapy management skills.



Within these pages and in the online version of PAPA on the Access Pharmacy website (www.accesspharmacy.com), readers will find material that builds on and expands the foundation of previ ous editions. Key Concepts guide the student through each chapter, and material is always evidence based. When available, ratings of the level of evidence support the key therapeutic approaches. Per sonalized pharmacotherapy is emphasized in a special section, and diseasespecific chapters have diagnostic flow diagrams, treatment algorithms, dosing guideline recommendations, and monitoring approaches with color codes to clearly distinguish treatment path ways. Drug dosing and monitoring tables provide both students and practitioners with a one-stop reference point in each chapter. New in the 10th edition is a chapter on Travel Health (Chapter 124), added in recognition of the importance of emerging diseases and the travel vaccine services increasingly provided in pharma cies and alternative care settings. More content has been shifted from print to online presentation on our Access Pharmacy (www. accesspharmacy.com) digital home. Users of Access Pharmacy will find many features to enhance their learning and information retrieval.



Thoughtful and provocative updates to PAPA chapters are added as new information mandates to keep our readers relevant in these times of rapid advancements. Also, the site has many new features such as education guides, Goodman & Gilman's animations, virtual cases, and many other textbooks. As in previous editions, the text coordinates well with Pharmacotherapy: A Patient-Focused Approach, which includes indepth patient cases with questions and answers. In closing, we acknowledge the many hours that Pharmaco therapy's more than 300 authors contributed to this labor of love. Without their devotion to the cause of improved pharmacotherapy and dedication in maintaining the accuracy, clarity, and relevance of their chapters, this text would unquestionably not be possible. In addition, we thank Michael Weitz, Brian Kearns, James Shanahan, and their colleagues at McGrawHill for their consistent support of the Pharmacotherapy family of resources, insights into trends in publishing and higher education, and the critical attention to detail so necessary in pharmacotherapy. The Editors December 2016



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In Memoriam Leroy C. Knodel (1954-2015), the author of “Sexually Transmitted Diseases” chapter in Pharmacotherapy since its first edition in 1989, received his BS and PharmD degrees from the University of Kentucky in 1977 and 1980, respectively. He served as a faculty member for The University of Texas at Austin and the University of Texas Health Science Center at San Antonio for more than 30 years. His chief aca demic responsibility was to coordinate experiential pharmacy education in the San Antonio region, a role he thoroughly embraced and enjoyed. He also directed the Drug Information Service for many years and held prominent service roles with state agencies, local health care institutions, and charitable organizations. Leroy was an outstanding educator and tireless mentor who was universally loved by faculty, staff, students, and professional colleagues. He was a warm and caring person, known for his quick wit, great humor, and empathy. He was gifted in his ability to let those he encountered know they were important and appreciated. His contagious smile and laugh could brighten any room. Student pharmacists frequently cited him as one of the faculty members who made the biggest impact on their personal and professional development during their time in pharmacy school. Leroy touched many lives, and gave of himself unselfishly both professionally and personally. The thou sands of students he helped educate and encourage during his academic career are his living legacy.



SECTION



1



FOUNDATION ISSUES



Health Literacy and Medication Use



e1



Oralia V. Bazaldua, DeWayne A. Davidson, Ashley Zurek, and Sunil Kripalani



KEY CONCEPTS



1 Limited health literacy is common and must be considered when providing medication management services. 2 Some groups of people are at higher risk for having limited literacy skills, but in general, you cannot tell by looking. 3 Patients with limited health literacy are more likely to misunderstand medication instructions and have difficulty demonstrating the correct dosing regimen. 4 Limited health literacy is associated with increased healthcare



costs and worse health outcomes, including increased mortality. 5 Despite numerous efforts to improve safe medication practices,



current strategies have been inadequate, and this may have a



larger impact in patients with limited literacy. 6 Most printed materials are written at higher comprehension levels



than most adults can read. 7 The United States Pharmacopeia has set new standards for



prescription medication labeling to minimize patient confusion. 8 Several instruments exist to measure health literacy, but some



experts advocate “universal precautions” under which all patients are assumed to benefit from plain language and clear communication. 9 Obtaining a complete medication history and providing medication



counseling are vital components in the medication management of patients with limited health literacy.



INTRODUCTION Every day, thousands of patients are not taking their medications correctly. Some take too much. Others take too little. Some use a tablespoon instead of a teaspoon. Parents pour an oral antibiotic suspension in their child's ear instead of giving it by mouth because it was prescribed for an ear infection. Others are in the emergency department because they did not know how to use their asthma inhaler. It is not a deliberate revolt against the doctor's orders but rather a likely and an unfortunate result of a hidden risk factor— limited health literacy. 1 Literacy, at the basic level, is simply the ability to read and write. When these skills are applied to a health context, it is called health literacy, but health literacy is more than just reading and writ ing. Health literacy, as defined by the Institute of Medicine (IOM), is “the degree to which individuals have the capacity to obtain, pro cess, and understand basic health information and services needed to make appropriate health decisions.” A growing body of evidence associates low health literacy with less understanding, worse out comes, and increased cost. These poor outcomes have led this topic to receive national attention. Health literacy has been made “a pri ority area for national action” by the IOM1,2 and Healthy People 2020.3 As a result,



federal policy initiatives promoting health liter acy continue to be highlighted in Healthy People 2020, the Patient Protection and Affordable Care Act of 2010, and the Plain Writing Act of 2010.4 A National Action Plan to Improve Health Literacy (Table e1-1) has also been developed by the Department of Health and Human Services (HHS).5 Likewise, the Agency for Healthcare Research and Quality (AHRQ),6,7 the National Institutes of Health (NIH),8 and Centers for Disease Control and Prevention (CDC)9 have each dedicated websites to this topic and have provided funding to support studies and interventions that are specifically relevant to health literacy. Additionally, state and private sector organizations, such as America's Health Insurance Plans (AHIP) and the American College of Physicians (ACP) Foundation, have led efforts to improve health literacy following the IOM's call to action.10 Indeed, health literacy should be a national priority for the medical community as its consequences are far-reaching and cross-cutting. More than one of every three American adults has difficulty understanding and acting on health information.11 Patients with limited health literacy have less knowledge about how to manage their disease;12 they misunderstand dosing instructions and warn ing labels on medication containers;13,14 they are less likely to read or even look at medication guides;15 their ability for medication management is limited as these persons are less able to identify or distinguish their medications from one another;16,17 and they are less able to use a metered-dose inhaler (MDI) properly.18 Limited health literacy skills have also been documented in caregivers of seniors19 and in parents of children.20 There is no question that limited health literacy is associated with adverse health outcomes21 including an increased mortality rate22 and increased healthcare costs.23



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



1



Cultural Competency Jeri J. Sias, Amanda M. Loya, José O. Rivera, and Jessica M. Shenberger-Trujillo



KEY CONCEPTS



1 Healthcare providers should strive toward cultural competency to



improve care and access unique resources for patients and communities from diverse cultures and backgrounds. 2 Changes in demographics in the United States, health disparities,



and patient safety are among the reasons that cultural competency should be emphasized in healthcare. 3 A variety of models recognize cultural competency as a process,



not an achievement. 4 Legal and regulatory issues surrounding cultural competency



e2



include understanding and interpreting accreditation standards for healthcare organizations and Title VI of the Civil Rights Act. 5 Patients may enter the healthcare setting with a different



explanation of their illnesses than found in the Western biomedical model (WBM). 6 Cultural values and beliefs influence decisions and attitudes about



healthcare, including race, ethnicity, age, gender, sexual orientation, and religious beliefs. 7 Developing communication skills to interact with diverse population



involves recognizing personal styles and cultural values of communication as well as barriers to patient understanding. 8 Linguistic competency encompasses understanding the capacity



of organizations and providers to communicate well with diverse populations such as patients with limited English proficiency



(LEP), low literacy, or hearing impairments.



health insurance and her city public pol icy includes no indoor smoking in public places and state policies include special low-emission 9 Before practitioners can understand other cultures, they should requirements on vehicles. Weekend activities with the family include understand personal and organizational values and beliefs. sports and dance for the kids along with others from the community 10 Skills for working with patients from diverse cultures include being center that serves a number of Asian-American families. able to listen to the patient's perception of health, Patient 2 is a 27-year-old single African American, Muslim upperacknowledging differences, being respectful, and negotiating middle-class man living in a major city in the Eastern Coast of the United treatment options. States. Having just finished his graduate school degree, he lives in a high-rise apartment and walks or rides the subway to his work at a major corporation. In his leisure time, he enjoys read ing and going to major sporting events with his college friends who come CULTURE, COMMUNITY, AND SOCIAL from diverse backgrounds. During the week, he also frequents the local DETERMINANTS OF HEALTH mosque and community events that are supported by his neighborhood. Patient 3 is a 55-year-old European American, Protestant mid dle Culture defines us.1 Although our genetic makeup, which is largely class man living in the Midwest. His family moved from the rural South 2 nonmodifiable and affects our physical state of being, social deter years ago for a new full-time job. Due to recent economic changes in the minants of health are also of great influence. Determinants of health community, he now has to work three part-time jobs (two in food industry describe the factors that affect the health of individuals. At the core of and one in construction) so that he can help support his wife who is each person are their inherited traits as well as the choices that they undergoing breast cancer treatment. As a result of his high work make about their lifestyles (eg, diet, exercise, leisure activities). Their demands, he is not able to shop for grocer ies or exercise and so the health is further marked by their exposure to healthy or risky couple often eats away from the home or they prepare quick and behaviors based on the places where they live, work, worship, or go processed meals at home. He notices that he has gained about 10 during the day and their built environment (eg, sidewalks, expo sure to pounds (4.5 kg) in the past 6 months and has difficulty sleeping. The 2 clean air, policies for healthy choices). Basically, our socio economic status, race and ethnicity, gender, age, and communities (environments), family also has not had time to connect with their church or other friends due to his work and doctor appoint ments for his wife. as part of our cultures, shape us.3 Consider the following brief descriptions of three individuals and the determinants of health that influence them. Patient 1 is a 42-year-old bilingual Vietnamese American, Buddhist woman liv ing on the West Coast whose family immigrated to the United States 35 years ago. Her lifestyle choices include a vegetarian diet, garden ing, and daily meditation. She lives in a suburban community with her husband and three children, drives a hybrid electric/gas car to her work as a school teacher, and purchases food from a local farmer's market. She has



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



3



e3



Medication Safety Principles



and Practices Robert J. Weber



KEY CONCEPTS 1 Medication errors (MEs) are defined as any mistake at any stage of



the medication-use process; adverse drug events (ADEs) are the result of an injury as a result of an ME. 2 All MEs can be prevented, while ADEs can be categorized as



preventable and potential. 3 MEs occur at an alarmingly high rate, with ADEs having fatal



outcomes for patients. 4 MEs can occur at any step of the medication-use process: selection



and procurement, storage, ordering and transcribing, preparing and dispensing, administration, or monitoring. 5 Determining the actual and potential root causes of MEs helps to



correct future errors in the medication-use system. 6 Quality improvement methods that prevent MEs and thereby minimize ADEs include identifying the ME and/ or ADE, understanding the reasons for the ME and/or ADE, designing and implementing changes to prevent an ADE or ME, and checking the outcome of that change. 7 Healthcare organizations have implemented various measures to



reduce the incidence of MEs and ADEs, such as computerized physician order entry (CPOE), automated drug distribution systems, bar-code scanning, and “smart” infusion pumps with decision support and where information is passed in a bidirectional manner between the pump and the patient's electronic medical record (EMR).



8 Medication reconciliation or comparing a patient's current medication



orders to all of the medications that the patient had been taking before any care transition (hospital admission, transfer, or discharge) is a vital process in preventing MEs and ADEs. 9 A “just culture” of medication safety cultivates trust in the workplace



that makes personnel feel comfortable sharing safety information (eg, unsafe situations) and assuming personal responsibility and accountability for complying with safe medication practices.



INTRODUCTION Medical errors are not a new phenomenon. Medical errors caus ing harm may lead to devastating effects on patients. In 1991, the Harvard Medical Practice Study showed that a significant number of people are victims of medication errors (MEs). This landmark study reviewed the incidence of adverse events and negligence in hospital ized patients in the state of New York showing that almost 4% of patients experienced an iatrogenic injury (one caused by healthcare practices or procedures), prolonging their hospital stays.1 Impor tantly, nearly 14% of those mistakes were fatal. Examples of mistakes noted in the Harvard study included renal failure from angiographic dye and a missed diagnosis of colon cancer. Drug complications were the most common type of outcome attributed to negligence, accounting for 19% of these preventable adverse events.1 The goal of medication therapy is achieving defined thera peutic goals to improve a patient's quality of life while minimizing harm.2 There are both known and unknown risks associated with the therapeutic use of prescription and nonprescription drugs and drug administration devices.3 Mishaps related to medication therapy include both adverse drug events (ADEs) and MEs.4 Medication errors negatively affect patients' confidence in the



healthcare system and increase healthcare costs. Research con ducted by the American Society of Health-System Pharmacists (ASHP) showed that 61% of patients surveyed reported that they were “very concerned” about being given the wrong medicine dur ing a hospital stay.5 MEs are also very costly—to healthcare systems, patients and their families, and healthcare workers. The emotional cost of an ME is also significant, including the burden on the family for grieving loss or injury to the healthcare worker involved in an ME that caused harm. Many MEs are not detected by standard reporting systems and often do not cause patient harm. According to the “Fourth Annual Report on Medication Errors in US Hospitals” by the United States Pharmacopeia (USP), 49% of MEs never reach the patient. 6 Many MEs have little to no clinical importance or have minimal impact on patient care. According to the 2002 USP study of the anonymous Web-based reporting system MEDMARx, 98% of reported MEs (n = ~190,000) resulted in no harm to the patient. Tragically, how ever, MEs do sometimes result in serious patient morbidity and mor tality.7 In fact, preliminary data from the Centers for Disease Control and Prevention (CDC) list accidents (of which MEs are included) as the fifth leading cause of death in the United States in 2010.8



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



5



e4



Clinical Pharmacokinetics and



Pharmacodynamics Larry A. Bauer



KEY CONCEPTS 1 Clinical pharmacokinetics is the discipline that describes the



absorption, distribution, metabolism, and elimination of drugs in patients requiring drug therapy. 2 Clearance is the most important pharmacokinetic parameter because



it determines the steady-state concentration for a given dosage rate. Physiologically, clearance is determined by blood flow to the organ that metabolizes or eliminates the drug and the efficiency of the organ in extracting the drug from the bloodstream. 3 The volume of distribution is a proportionality constant that relates the



amount of drug in the body to the serum concentration. The volume of distribution is used to calculate the loading dose of a drug that will



immediately achieve a desired steady-state concentration. The value of the volume of distribution is determined by the physiologic volume of blood and tissues and how the drug binds in blood and tissues. 4 Half-life is the time required for serum concentrations to decrease by



one-half after absorption and distribution are complete. It is important because it determines the time required to reach steady state and the dosage interval. Half life is a dependent kinetic variable because its value depends on the values of clearance and volume of distribution. 5 The fraction of drug absorbed into the systemic circulation after



extravascular administration is defined as its bioavailability.



6 Most drugs follow linear pharmacokinetics, whereby steady state



serum drug concentrations change proportionally with long-term daily dosing. 7 Some drugs do not follow the rules of linear



pharmacokinetics. Instead of steady-state drug concentration changing proportionally with the dose, serum concentration changes more or less than expected. These drugs follow nonlinear pharmacokinetics. 8 Pharmacokinetic models are useful to describe data sets, to predict



serum concentrations after several doses or different routes of administration, and to calculate pharmacokinetic constants such as clearance, volume of distribution, and half-life. The simplest case uses a single compartment to represent the entire body. 9 Factors to be taken into consideration when deciding on the best drug



dose for a patient include age, gender, weight, ethnic background, other concurrent disease states, and other drug therapy. 10 Cytochrome P450 is a generic name for the group of enzymes



that are responsible for most drug metabolism oxidation reactions. Several P450 isozymes have been identified, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. 11 Membrane transporters are protein molecules concerned with the active transport of drugs across cell membranes. The importance of transport proteins in drug bioavailability, elimination, and distribution is continuing to evolve. A principal transport protein involved in the movement of drugs across biologic membranes is Pglycoprotein. P-glycoprotein is present in many organs, including the gastrointestinal (GI) tract, liver, and kidney. Other transport protein families include the organic cation transporters, the organic anion transporters, and the organic anion transporting polypeptides. 12 When deciding on initial doses for drugs that are renally eliminated, the patient's renal function should be assessed. A common, useful way to do this is to measure the patient's serum creatinine



concentration and convert this value into an estimated creatinine clearance (CLcr est). For drugs that are eliminated primarily by the kidney (more than or equal to 60% of the administered dose), some agents will need minor dosage adjustments for CLcr est between 30 and 60 mL/min (0.50 and 1.00 mL/s), moderate dosage adjustments for CLcr est between 15 and 30 mL/min (0.25 and 0.50 mL/s), and major dosage adjustments for CLcr est less than 15 mL/min (0.25 mL/s). For drugs approved after 2010, renal drug dosing adjustments may also include recommendations using estimated glomerular filtration rate (eGFR) in addition to CLcr est. Supplemental doses of some medications also may be needed for patients receiving hemodialysis if the drug is removed by the artificial kidney or for patients receiving hemoperfusion if the drug is removed by the hemofilter. 13 When deciding on initial doses for drugs that are hepatically



eliminated, the patient's liver function should be assessed. The Child-Pugh score can be used as an indicator of a patient's ability to metabolize drugs that are eliminated by the liver. In the absence of specific pharmacokinetic dosing guidelines for a medication, a Child-Pugh score equal to 8 or 9 is grounds for a moderate decrease (~25%) in the initial daily drug dose for agents that are metabolized primarily hepatically (more than or equal to 60%), and a score of 10 or greater indicates that a significant decrease in the initial daily dose (~50%) is required for drugs that are metabolized mostly hepatically.



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com. 7



Pharmacogenetics Larisa H. Cavallari and YW Francis Lam



KEY CONCEPTS 1 Genetic variation contributes to pharmacokinetic and



pharmacodynamic drug properties. 2 Genetic variation occurs for drug metabolism, drug transporter,



and drug target proteins, as well as disease associated proteins. 3 Single-nucleotide polymorphisms are the most common gene



variations associated with drug response. 4 Genetic polymorphisms may influence drug effectiveness and risk



for toxicity. 5 Pharmacogenetics is the study of the impact of genetic



polymorphisms on drug response. 6 The goals of pharmacogenetics are to optimize drug efficacy and limit drug toxicity based on an individual's DNA. 7 Gene therapy aims to cure



disease caused by genetic defects by changing gene expression. 8 Inadequate gene delivery and expression and serious adverse



effects are obstacles to successful gene therapy.



PHARMACOGENETICS: INTRODUCTION Great variability exists among individuals in response to drug therapy, and it is difficult to predict how effective or safe a medica tion will be for a particular patient. For example, when treating a patient with hypertension, it may be necessary to try several agents or a combination of agents before achieving adequate blood pressure control with acceptable tolerability. A number of clinical factors are known to influence drug response, including age, body size, renal and hepatic function, and concomitant drug use. However, consid ering these factors alone is often insufficient in predicting the like lihood of drug efficacy or safety for a given patient. For example, identical antihypertensive therapy in two patients of similar age, sex, race, and with similar medical histories and concomitant drug ther apy may produce inadequate blood pressure reduction in one patient and symptomatic hypotension in the other. 1 2 The observed interpatient variability in drug response may result largely from genetically determined differences in drug metabolism, drug distribution, and drug target proteins. The influ ence of heredity on drug response was demonstrated as early as 1956 with the discovery that an inherited deficiency of glucose 6-phosphate dehydrogenase (G6PD) was responsible for hemolytic reactions to the antimalarial drug primaquine. Variations in genes encoding cytochrome P450 (CYP) and other drugmetabolizing enzymes are now well recognized as causes of interindividual differ ences in plasma concentrations of certain drugs. These variations may have serious implications for narrow-therapeuticindex drugs such as warfarin, phenytoin, and mercaptopurine. Other variations associ ated with drug response occur in genes for drug transporters such as the solute carrier organic anion transporter (OAT)



family member



pharmacogenomics. However, pharmacogenetics generally refers to monogenetic variants that affect drug response, whereas pharma cogenomics refers to the entire spectrum of genes that interact to determine drug efficacy and safety. For example, a pharmacogenetic study would be one that examines the influence of the CYP2C9 gene on warfarin dose requirements. A pharmacogenomic study might examine the interaction between the CYP2C9, vitamin K oxido reductase complex subunit 1 (VKORC1), and CYP4F2 genes on war farin dose requirements. Given that multiple proteins are involved in determining the ultimate response to most drugs, many investiga tors are taking a more pharmacogenomic approach to elucidating genetic contributions to drug response. For simplicity, this chapter treats pharmacogenetics and pharmacogenomics as synonymous. 5 The goals of pharmacogenetics are to optimize drug therapy and limit drug toxicity based on an individual's genetic profile. Thus, pharmacogenetics aims to use genetic information to choose a drug, drug dose, and treatment duration that will have the greatest likeli hood for achieving therapeutic outcomes with the least potential for harm in a given patient. 1B1 (SLCO1B1) and organic cation transporter 1 (OCT1), as well as Pharmacogenetic discoveries have provided opportunities for clinicians drug targets such as receptors, enzymes, and proteins involved in to use genetic tests to predict individual responses to drug treatments intracellular signal transduction. Genetic variations for drug metabolizing and specifically select medications for patients based on DNA profiles. enzymes and drug transporter proteins may influence drug disposition, Genotype-guided therapy is already a reality for some diseases, such as thus altering pharmacokinetic drug properties. Drug target genes may cancer and cystic fibrosis, where novel drugs have been developed to alter pharmacodynamic mechanisms by affecting sensitivity to a drug at target specific mutations. Clini cal implementation of pharmacogenetics its target site. Finally, genes associated with dis ease severity have been is beginning to emerge in other therapeutic areas, such as cardiology, correlated with drug efficacy despite having no direct effect on neurology, pain manage ment, and infectious disease. pharmacokinetic or pharmacodynamic mechanisms.



e5



PHARMACOGENETICS: A DEFINITION



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



3 4 Pharmacogenetics involves the search for genetic varia tions that



lead to interindividual differences in drug response. The term pharmacogenetics often is used interchangeably with the term



9



e6



Pediatrics Milap C. Nahata and Carol



Taketomo



KEY CONCEPTS 1 Children are not just “little adults,” and lack of data on



important pharmacokinetic and pharmacodynamic differences has led to several disastrous situations in pediatric care. 2 Variations in absorption of medications from the gastrointestinal



tract, intramuscular injection sites, and skin are important in pediatric patients, especially in premature and other newborn infants. 3 The rate and extent of organ function development and the



distribution, metabolism, and elimination of drugs differ not only between pediatric versus adult patients but also among pediatric age groups. 4 The effectiveness and safety of drugs may vary among age groups



and from one drug to another in pediatric versus adult patients. 5 Concomitant diseases may influence dosage requirements to achieve a targeted effect for a specific disease in children. 6 Use of weight-based dosing of medications for obese children may result in



suboptimal drug therapy. 7 The myth that neonates and young infants do not experience pain



has led to inadequate pain management in this pediatric population. 8 Special methods of drug administration are needed for infants



and young children. 9 Many medicines needed for pediatric patients are not available in



appropriate dosage forms; thus, the dosage forms of drugs marketed for adults may require modification for use in infants and children, necessitating assurance of potency and safety of drug use. 10 The pediatric medication-use process is complex and error prone



because of the multiple steps required in calculating, verifying, preparing, and administering doses.



INTRODUCTION Remarkable progress has been made in the clinical management of diseases in pediatric patients. This chapter highlights important principles of pediatric pharmacotherapy that must be considered when the diseases discussed in other chapters of this book occur in pediatric patients, defined as those younger than 18 years. Newborn infants born before 37 weeks of gestational age are termed prema ture; those between 1 day and 1 month of age are neonates; 1 month to 1 year are infants; 1 to 11 years are children; and 12 to 16 years are adolescents. This chapter covers notable examples of problems in pediatrics, pharmacokinetic differences in pediatric patients, drug efficacy and toxicity in this patient group, and various factors affecting pediatric pharmacotherapy. Specific examples of problems and special considerations in pediatric patients are cited to enhance understanding. 1 Infant mortality up to 1 year of age has declined from 200 per 1,000 births in the 19th century to 75 per 1,000 births in 1925 and to 5.96 per 1,000 births in 2013.1 This success has resulted largely from improvements in identification, prevention, and treatment of diseases once common during delivery and the infancy period. Although most marketed drugs are used in pediatric patients, only approximately onefourth of the drugs approved by the US Food and Drug Administration (FDA) have indications specific for use in the pediatric population. Data on the pharmacokinetics, phar macodynamics, efficacy, and safety of drugs in infants and children are scarce. Lack of this type of information led to disasters such as gray baby syndrome from chloramphenicol, phocomelia from tha lidomide, and kernicterus from sulfonamide therapy. Gray baby syn drome was first reported in two neonates who died after excessive doses



of chloramphenicol (100-300 mg/kg/day); the serum concen trations of chloramphenicol immediately before death were 75 and 100 mcg/mL (mg/L; 232 and 309 μmol/L). Patients with gray baby syndrome usually have abdominal distension, vomiting, diarrhea, a characteristic gray color, respiratory distress, hypotension, and pro gressive shock. Thalidomide is well known for its teratogenic effects. Clearly implicated as the cause of multiple congenital fetal abnormalities (particularly limb deformities), thalidomide also can cause polyneu ritis, nerve damage, and mental retardation. Isotretinoin (Accutane) is another teratogen, because it is used to treat severe acne vulgaris, which is common in teenage patients who may be sexually active but not willing to acknowledge that activity to healthcare professionals; isotretinoin has presented a difficult problem in patient education since its marketing in the 1980s. Kernicterus was reported in neonates receiving sulfonamides, which displaced bilirubin from protein-binding sites in the blood to cause hyperbilirubinemia. This results in deposition of bilirubin in the brain and induces encephalopathy in infants.



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



11



e7



Geriatrics



Emily R. Hajjar, Shelly L. Gray, Patricia W. Slattum Jr, Lauren R. Hersh, Jennifer G. Naples, and Joseph T. Hanlon



KEY CONCEPTS 1 The population of persons age 65 years and older is



physical functioning (eg, activities of daily living), psychological functioning (eg, cognition, depression), social func tioning (eg, social activities, support systems), and overall health (eg, 2 Age-related changes in physiology can affect the general health perception).1 pharmacokinetics and pharmacodynamics of numerous drugs. Despite the benefits of pharmacotherapy, HRQOL can be com 3 Improving and maintaining functional status is a promised by drug-related problems. Prevention of drug-related adverse cornerstone of care for older adults. consequences in older adults requires that health profes sionals become 4 Drug-related problems in older adults are common and cause knowledgeable about a number of age-specific issues. To address these considerable morbidity. knowledge needs, this chapter discusses the epidemiology of aging; physiologic changes associated with aging, with emphasis on changes 5 Pharmacists can play a major role in optimizing drug therapy and that can affect the pharmacokinetics and pharmacodynamics of drugs; preventing drug-related problems in older adults. clinical conditions commonly seen in older adult patients; epidemiology of drug-related problems in older adults; and an approach to reducing drug-related problems through the provision of comprehensive geriatric Pharmacotherapy for older adults can cure or palliate disease as well as assessment. enhance health-related quality of life (HRQOL). Health-related quality of life considerations for older adults include focusing on improvements in increasing.



the higher post-World War II birth rate but also by the declin ing mortality rate and overall improved health status among older adults.3 The decline in early death and the better health of older adults arises from a variety 1 The older American population is highly diverse and heteroge neous of reasons: (a) public health measures affect ing all age groups (eg, with respect to health status. The demographics and health immunizations, prenatal care), (b) advances in medical technology, (c) characteristics of persons age 65 to 74 years differ from those of per promotion of a healthy lifestyle, and (d) improvements in living sons 85 years of age and older, as do those of persons who are insti conditions.4 More relevant to health pro fessionals providing care to older tutionalized compared with those living in the community. Teasing apart Americans is the steadily increasing life expectancy at 65 and 85 years the various threads of wellness and illness, independence and of age. In 2009, women 65 years of age could expect an average dependence, and function and dysfunction makes the available additional 20.30 years of life, and men could expect to live 17.6 demographic and health status data relevant for clinical practice. additional years. Life expectancies are lower for black men and women.2 Understanding the diversity and growth of older populations will allow society to plan for the training, research, and resources needed for Upon reaching 85 years of life, women may expect to live another 7.0 years and men another 5.9 years.2 Nonetheless, the life expectancy at future clinical practice and adequate healthcare. The proportion of the population age 65 and older is increasing. In age 65 in the United States remains lower than that of many other 2010, persons age 65 and older accounted for 13.0% (40 million) of the industrialized countries. Interestingly, the number of centenarians (n = total US population, up from 12.4% in 2006. Among those older than 65 53,364) increased by 5.8% between 2000 and 2010. years, women accounted for 57% of this segment of the population. The gender gap widens with increasing age, with women accounting for 67% of the cohort 85 years and older.2 In 2011, the first baby boomers turned 65 years old; this marked the beginning of a rapid increase in the older population. By 2030, this older popula tion is projected to almost double in size; one in five Americans will be older than 65 years. This 20% projection will remain relatively stable through 2050. However, the The complete chapter, proportion of the “oldest old” (greater than 85 years) will continue to learning objectives, and other grow; by 2050, almost one in four older adults will be 85 years or older. resources can be found at The increase in the number of older persons is caused not only by



EPIDEMIOLOGY OF AGING



www.pharmacotherapyonline.com.



13



Palliative Care Nina M. Bemben and Mary Lynn McPherson



KEY CONCEPTS 1 Palliative care may be provided to any patient with a serious illness,



at any point in the course of the illness, including while a patient receives curative or disease-focused therapy. 2 Hospice is a form of palliative care, which has been defined by Medicare to encompass care solely focused on comfort and quality of life during the last 6 months of a patient's life. 3 Pain is a common symptom among patients receiving palliative care and may be managed safely and effectively using nonopioid, adjuvant, and/or opioid therapies. 4 Opioids are the drug of choice for the management of dyspnea. 5 Constipation, nausea, vomiting, anxiety, and delirium are common



symptoms among patients receiving palliative care and may be managed effectively with drug and nondrug therapies. 6 End-of-life care can be provided to patients in the last days of their



lives through palliative or hospice care, and provides management of common terminal symptoms. 7 Identifying a patient's goals and structuring care to achieve those



goals is a key component of palliative care. Identifying a patient's



goals of care involves communication with patients, their families and/or caregivers, as well as other healthcare professionals. 8 Addressing nonphysical needs, such as spirituality and faith, are key



components of providing quality palliative care.



1 Palliative care, or palliative medicine, is specialized care pro vided to



patients with serious illness with a goal of managing symp toms and helping patients to cope with their illnesses.1 It is provided by an interdisciplinary team of healthcare professionals, including physicians, pharmacists, nurses, nurse practitioners, social workers, chaplains, and others.2 Palliative care is appropriate for any patient with a serious or potentially life-limiting illness, at any point during the time course of that illness. Common diseases for which palliative care is appropriate include cancer, heart failure, advanced lung dis ease such as chronic obstructive pulmonary disease (COPD), organ failure such as liver or renal failure, and neurologic diseases such as dementia and Parkinson disease.2 Patients may receive palliative care throughout the course of a serious illness, including while the patient receives treatment aimed at managing or curing the disease. If or when the serious illness progresses and disease-focused thera pies are no longer helpful or desired, palliative care continues to be provided to manage symptoms and maximize quality of life. Provision of palliative and hospice care to patients with lim ited prognoses has been shown to improve patient and caregiver satisfaction,3-5 reduce healthcare utilization,3,4 and decrease health care costs.3,4,6 In addition to providing symptom management,



e8 improving patient and caregiver satisfaction, and reducing health care costs, early integration of palliative care has been shown to increase survival among patients with advanced cancer.7,8 Because of the evidence supporting the benefits of palliative care, clinical practice guidelines for serious illnesses incorporate pal liative care into treatment recommendations. The American Society of Clinical Oncology and National Comprehensive Cancer Net work both recommend palliative care as a component of oncology management.9,10 In addition, the American College of Cardiology Foundation/American Heart Association practice guideline for the management of heart failure supports the incorporation of palliative care into the management of patients with advanced heart failure due to its effectiveness in increasing quality of life.11



WHAT IS HOSPICE?



2 In the United States, hospice care is a Medicare-defined benefit and is a form of palliative care that is focused on caring for patients with a life expectancy of 6 months or less.12 While palliative care may be provided at any stage in the course of serious disease, including alongside curative, or disease-focused therapy, hospice care is gener ally provided when a patient is no longer pursuing disease-focused therapies and the decision has been made to focus solely on comfort and quality of life.12,13 Although commonly associated with end-stage cancer, the frequency of noncancer diagnoses among hospice patients more than doubled between 1998 and 2008. 14 In 2014, the most recent year for which data are available, the most common hospice diagno ses were: non-cancer diagnoses (63.4% of hospice admissions) such as dementia (14.8%), heart disease (14.7%), and lung disease (9.3%). Cancer diagnoses accounted for 36.6% of hospice admissions.14



SYMPTOM MANAGEMENT IN PALLIATIVE CARE Based on the diseases frequently encountered in hospice and palliative care, the most common symptoms managed by palliative care practitio ners include pain, dyspnea, constipation, nausea and vomiting, anxiety, and delirium. The management of these symptoms is discussed below.



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



15



Clinical Toxicology



7 Anticholinesterase insecticides may produce life-threatening



Peter A. Chyka



8 An overdose of calcium channel antagonists will produce severe



KEY CONCEPTS 1 Poisoning can result from exposure to excessive doses of any



chemical, with medicines being responsible for most childhood and adult poisonings. 2 The total number and rate of poisonings have been increasing, but



preventive measures, such as child-resistant containers, have reduced mortality in young children. 3 Immediate first aid may reduce the development of serious



poisoning, and consultation with a poison control center may indicate the need for further therapy.



respiratory distress and paralysis by all routes of exposure and can be treated with symptomatic care, atropine, and pralidoxime. hypotension and bradycardia and can be treated with supportive care, calcium, insulin with supplemental dextrose, and glucagon. 9 Poisoning with iron-containing drugs produces vomiting, gross



gastrointestinal bleeding, shock, metabolic acidosis, and coma and can be treated with supportive care and deferoxamine. 10 Acute opioid poisoning and overdose can produce life threatening



respiratory depression that can be treated with assisted ventilation and naloxone. 11 Chemicals can be used for mass poisonings by acts of terrorism and



warfare and typically produce life-threatening effects within minutes to hours, which warrant emergency preparedness at healthcare facilities and communities.



4 The use of ipecac syrup, gastric lavage, whole bowel irrigation,



and cathartics has fallen out of favor as routine therapies, whereas activated charcoal remains useful for gastric decontamination of appropriate patients. 5 Antidotes can prevent or reduce the toxicity of certain poisons, but



symptomatic and supportive care is essential for all patients. 6 Acute acetaminophen poisoning produces severe liver injury and



occasionally kidney failure. A determination of serum acetaminophen concentration may indicate whether there is risk of hepatotoxicity and the need for acetylcysteine therapy.



Poisoning is an adverse effect from a chemical that has been taken in excessive amounts. The body is able to tolerate and, in some cases, detoxify a certain dose of a chemical; however, toxicity ensues once a



e9



emergency department visits, and over 1.3 million nonfatal poisoning injuries each year in the United States. 1,2 Approximately 0.2% of poi soning deaths involve children younger than 5 years.1 Of emergency department visits for drug-related poisoning, typically 1.1 million visits are made each year (3.5 per 100,000 population) with the highest rate observed for patients 20 to 34 years of age. One-fourth of emergency department visits for drug-related poisonings were hospitalized, which is twice the rate of other types of visits. 2 The age-adjusted death rates from poisonings from all circumstances have been increasing steadily, with a 224% increase from 2000 to 2014, representing 51,966 deaths in 2014 of which 91% were drug-related poisonings. This increasing mortality trend has placed poisoning since 2008 as the leading cause of injury death in the United States.1



critical exposure threshold is exceeded. Poisoning can produce minor local effects that may be treated readily in the outpatient setting or systemic life-threatening effects that require intensive medical inter vention. Virtually any chemical can become a poison when taken in sufficient quantity, but the potency of some compounds leads to seri ous toxicity with small quantities (Table e9-1). Poisoning by chemi cals includes exposure to drugs, industrial chemicals, household products, plants, venomous animals, agrochemicals, and weapons for warfare and terrorism. This chapter describes some examples of the spectrum of toxicity, outlines means to recognize poisoning risk, and presents principles of treatment.



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



EPIDEMIOLOGY Poisonings account for approximately 52,000 deaths, at least 2.3 million



17



e10



Clinical Management of



Potential Bioterrorism related Conditions Colleen M. Terriff, Lisa T. Costanigro, Kimberly C. McKeirnan, and Barbara J. Hoeben



KEY CONCEPTS 1 The majority of emerging pathogens associated with public health



outbreaks are zoonotic infections, passed from animals to humans. 2 Due to the high mortality rates with inhalation anthrax, postexposure



prophylaxis may need to be rapidly offered to all people who were potentially exposed. 3 Pneumonic plague, one of the most lethal forms of plague, develops



through primary (direct inhalation of infected droplets) or secondary exposure. 4 Rapid recognition of Ebola virus disease (EVD) is essential to initiate



supportive care and infection control procedures. 5 While the incidence of measles-related deaths has, overall,



significantly declined as the result of major global vaccination



efforts, vigilance is still critical, since measles is extremely contagious and there are some gaps in vaccine coverage. 6 Middle Eastern Respiratory Syndrome (MERS) is an emerging viral



respiratory illness, which can cause severe respiratory distress and has been fatal in one third of all patients who have contracted the disease. 7 A pertussis vaccination booster is recommended for all women



during weeks 27 to 36 of gestation of each pregnancy to allow maximal maternal antibody response and passive in utero transfer of antibodies. 8 Infectious disease outbreaks following a natural disaster are



common and usually attributable to critical infrastructure damage, limited access to quality healthcare, displacement, environmental and human condition changes, and vulnerability to pathogens.



Bioterrorism is characterized by an intentional exposure to animals or humans of an organism or toxin, which subsequently causes dis ease and/or death. Historically, these acts were planned and carried out against military personnel or directed towards select segments of the civilian population. Examples include diseased bodies flung over city walls, poisons added to drinking water, bacteria used to taint salad bars, and weaponized ricin and anthrax.1,2 In general, while there is no catastrophic destruction of property associated with most acts of bioterrorism, there usually is fear, anxiety and confusion, some ensuing morbidity and mortality, economic disruption, and definite pressure on healthcare and public health systems. After the intentional release of anthrax in 2001 public health officials, first responders, healthcare workers, employers, school officials, parents and community members incorporated the term bioterrorism in their emergency and disaster preparedness and response vocabulary. Subsequently, these groups wrote plans, con ducted response exercises for potential scenarios, such as small pox outbreaks and mass exposures of plague, that have, thankfully, not occurred. While these traditional bioterrorism agents are still threats, public health officials and healthcare professionals are start ing to turn their focus on



new or re-emerging concerns, many tied to Mother Nature or unintentional human acts. 1 Similar to intentional acts of bioterrorism, disease out breaks of Ebola and Middle Eastern Respiratory Syndrome Coro navirus (MERS) are a threat to global health security, associated with social unrest or instability and major economic disruption, in addition to significant morbidity and mortality.3 The emer gence and spread of these infectious diseases (ID) and the grow ing prevalence of drug resistance; ease of trade and travel; and rise of laboratories capable of creating dangerous microbes have heightened public concern.3 Through a partnership of the Centers for Disease Control and Prevention (CDC), private and public stakeholders, and international organizations, The Global Health Security Agenda which focuses on efforts to prevent and reduce outbreaks, detect threats early to save lives, and rapidly and effec tively respond to potential infectious disease threats has become a reality.4 It is estimated that 75% of recently emerging infections are zoonotic, or passed between animals and humans.5 The CDC recognizes the strong connection between humans, animals and the environment and has created the One Health Program to move forward an action agenda with both domestic and global activities. Initiatives of One Health are focused on improvements in research; detection or biosurveillance; clinical assessment, pre vention and treatment; education and communication.5 Many of these outbreaks, from pathogens like SARS and West Nile Virus, caused serious financial, political and public health ramifications, while eroding public confidence in the government's ability to anticipate and respond to these events.5 Healthcare professionals are on the front lines of detection, clinical management and edu cation related to these emerging zoonotic threats.



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com.



19



SECTION



2



CARDIOVASCULAR



DISORDERS



Cardiovascular Testing



e11



Richard A. Lange



1 A careful history and physical examination are extremely



KEY CONCEPTS



2 Elevated jugular venous pressure (JVP) is an important sign of



important in diagnosing cardiovascular disease; they should be performed before any testing. heart failure and may be used to assess its severity and the response to therapy. 3 Heart sounds and heart murmurs are important in identifying



heart valve abnormalities and other structural cardiac defects. 4 Electrocardiography is useful for determining rhythm



disturbances (tachy- or bradyarrhythmias).



5 Exercise stress testing provides important information



concerning the presence and severity of coronary artery disease; changes in heart rate, blood pressure, and the electrocardiogram (ECG) are used to assess the response to exercise. 6 Echocardiography is used to assess valve structure and



function as well as ventricular wall motion; transesophageal echocardiography is more sensitive than transthoracic echocardiography for detecting thrombus and vegetations. 7 Radionuclides, such as technetium-99m and thallium-201, are



used to assess myocardial ischemia and myocardial viability in patients with suspected coronary artery disease. 8 When patients cannot exercise, pharmacologic stress testing is used to assess the likelihood of coronary artery disease. 9 Cardiac catheterization and angiography are used to assess coronary anatomy and ventricular performance.



INTRODUCTION In the United States, cardiovascular disease (CVD) afflicts an estimated 85.6 million people (ie, greater than 1 in 3 adults) and accounts for 31% of all deaths. By 2030, 44% of the US population is projected to have some form of CVD. In 2011, the estimated direct and indirect cost of CVD—which includes hypertension, coronary heart disease, heart failure, and stroke—was $320.1 billion.1 Atherosclerosis, the cause of most CVD events, is typically present for decades before symptoms appear. With a thorough his tory, comprehensive physical examination, and appropriate testing, the individual with subclinical CVD usually can be identified, and the subject with symptomatic CVD can be assessed for the risk of an adverse event and can be managed appropriately.



describe his or her current symptoms, including their duration, quality, frequency, severity, progression, precipitating and relieving factors, associated symptoms, and impact on daily activities. The medical history may reveal previous cardiovascular prob lems, conditions that predispose the patient to develop CVD (ie, hypertension, hyperlipidemia, or diabetes mellitus) (Table e11-1), or comorbid conditions that influence the identification or management of CVD. The patient should be asked about social habits that affect the cardiovascular system, including diet, amount of regular physical activity, tobacco use, alcohol intake, and illicit drug use. At present, family history of early onset CVD is the best available screening tool to identify patients with a genetic predisposition for CVD.



Cardiovascular History 1 Chest pain is a frequent symptom and may occur as a result of



myocardial ischemia (angina pectoris) or infarction or a variety of noncardiac conditions, such as esophageal, pulmonary, or mus culoskeletal disorders. The quality of chest pain, its location and duration, and the factors that provoke or relieve it are important in ascertaining its etiology. Typically, patients with angina describe a sensation of heavi ness or pressure in the retrosternal area that may radiate to the jaw, left shoulder, back, or left arm. It is precipitated by exertion, emo tional stress, eating, smoking a cigarette, or exposure to cold, and it is usually relieved within minutes with rest or a sublingual nitroglyc erin, although the latter also is effective in relieving chest pain due to esophageal spasm. Angina that is increasing in severity, longer in duration, or occurring at rest is called unstable angina; it should prompt the patient to seek medical attention expeditiously.



THE HISTORY The elements of a comprehensive history include the chief com plaint, current symptoms, medical history, family history, social his tory, and review of systems. The chief complaint is a brief statement describing the rea son the patient is seeking medical attention. The patient is asked to



The complete chapter, learning objectives, and other resources can be found at www.pharmacotherapyonline.com. 21



12



Cardiac Arrest Jeffrey F. Barletta



KEY CONCEPTS 1 High quality cardiopulmonary resuscitation (CPR) with minimal



interruptions in chest compressions should be emphasized in all patients following cardiac arrest. 2 The AHA algorithm for basic life support following cardiac arrest emphasizes circulation, airway, and breathing forming the pneumonic “CAB” versus the historic pneumonic “ABC.”



5 Amiodarone remains the preferred antiarrhythmic during cardiac arrest with lidocaine considered as an alternative. 6 Successful treatment of both pulseless electrical activity (PEA) and asystole depends almost entirely on diagnosis of the underlying cause. 7 Intraosseous administration is the preferred alternative route for



administration if IV access cannot be achieved.



3 The purpose of using vasopressor therapy following cardiac arrest is



to augment low coronary and cerebral perfusion pressures encountered during CPR. 4 Vasopressin appears to offer no benefit as a substitute over



epinephrine.



CARDIAC ARREST Cardiac arrest is defined as the cessation of cardiac mechanical activ ity



as confirmed by the absence of signs of circulation (eg, a detectable pulse, unresponsiveness, and apnea).1 While there is wide variation in the reported incidence of cardiac arrest, it is estimated that there are more than 320,000 people in the United States who experience emergency medical services (EMS)-assessed out-of-hospital cardiac arrest.2 Survival to hospital discharge following out-of-hospital car diac arrest is only 10.6% and survival with good neurologic function is only 8.3%.2 While there has been minimal improvement in survival over the past 40 years, recent data have shown some progress from 2005 to 2012 (adjusted rate ratio = 1.47 [1.26-1.7]).3 This improvement was attributed to both improved pre-hospital and in-hospital survival. In-hospital cardiac arrests occur in roughly 200,000 patients in the United States annually and this rate may be increasing.4 Simi lar to outof-hospital arrests, some progress has been made over the past decade with survival rates to hospital discharge being 13.7% in 2000 and 22.3% in 2009.5 Survival rates are substantially higher in victims with a shockable first documented rhythm as one study reported survival rates of 49% with ventricular fibrillation/pulseless ventricular tachycardia (VF/PVT) versus 11% with pulseless electri cal activity (PEA)/asystole.6



heart disease and heart failure may account for the increased occurrence of non-VF/PVT rhythms.9 Nonetheless, this declining incidence is particularly concerning as survival rates are substantially higher with shockable rhythms such as VF and PVT compared to nonshockable rhythms such as PEA and asystole. Sur vival rates with VF/PVT are roughly 27% versus 2% with asystole.8 A similar finding has been observed with in-hospital cardiac arrest. One study using the “Get with the Guidelines-Resuscitation” registry reported 79% of patients had an initial rhythm of asystole or PEA and 21% had VF or PVT.5 Survival rates were 12.2% for asystole/PEA and 35% for VF/PVT. Similarly, a second study used the National Registry of CPR and noted the incidence of VF/PVT, PEA and asystole to be 24%, 37%, and 39%, respectively.13 Survival rates were 37% for VF/PVT compared to 12% for PEA and 11% for asystole. Patients with VF/PVT were more likely to have myocardial infarction as the immediate factor pre-arrest while acute respiratory failure and hypotension were the immediate factors more commonly found in patients with PEA/asystole. In pediatric patients, cardiac arrest typically results from respi ratory failure and asphyxiation. As such, the initial rhythm most often encountered in out-of-hospital arrest is PEA or asystole.14 Survival rates with out-of-hospital pediatric arrests range between 1% and 12% with lower rates in infants compared to children and adolescents.15 Survival following in-hospital cardiac arrest appears higher with an overall rate of 34%.16 Similar to the adult population, risk-adjusted survival rates have increased over the past decade from 14% in 2000 to 43% in 2009.16



EPIDEMIOLOGY In adult patients, cardiac arrest usually results from the develop ment of an arrhythmia.7 Historically, VF and PVT have been the most common initial rhythm accounting for 40% to 60% of out-of hospital arrests but their incidence now is estimated to be only about 24%.8,9 In fact, data from the Cardiac Arrest Registry to Enhance Survival (CARES) project reported asystole to be the most com mon presenting rhythm (45%) which is similar to other registry data whereby nonshockable rhythms were more prevalent.8,10,11 The rea son for this change has not been firmly established. Possible expla nations include the influence of noncardiac causes of arrest that typically present with apnea leading to bradycardia and then PEA or asystole. A second explanation is the increasing role of implantable pacemakers and defibrillators.12 Finally, it has been suggested that beta-blockers and angiotensin-converting enzyme (ACE) inhibitors may shorten the duration of VF and the expanded use of these drug classes for ischemic



ETIOLOGY The most common clinical finding in adult patients who suffer car diac arrest is coronary artery disease accounting for roughly 80% of sudden cardiac deaths.7 Approximately 10% to 15% of sudden car diac deaths occur in patients with cardiomyopathies (eg, hypertro phic cardiomyopathy, dilated cardiomyopathy) and the remaining 5% to 10% are composed of either structurally abnormal congenital cardiac conditions or patients with structurally normal but electri cally abnormal heart. Unfortunately, in many patients (approxi mately two-thirds), cardiac arrest is the first clinical sign of coronary artery disease with no preceding signs or symptoms.17 23



24 In pediatric patients, cardiac arrest is often the terminal event of causes of arrest, anxiety, crushing chest pain, nausea, vomiting, and respiratory failure or progressive shock.18 Out-of-hospital arrests fre quently are associated with trauma, sudden infant death syndrome, drowning, poisoning, choking, severe asthma, and diaphoresis can precede the event. Following an arrest, individuals pneumonia. In hospital arrests, on the other hand, are associated are unresponsive, apneic, hypotensive and do not have a with sepsis, respi ratory failure, drug toxicity, metabolic disorders, and arrhythmias.detectable D



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pulse. Extremities are cold and clammy and cyanosis is common.



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PATHOPHYSIOLOGY OF CARDIAC ARREST



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ciated with cardiac arrest. The first is primary cardiac arrest whereby arterial blood is typically fully oxygenated at the time of arrest. The



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second is cardiac arrest secondary to respiratory failure in which lack of ventilation leads to severe hypoxemia, hypotension, and second ary cardiac arrest. It is important to understand the specific condi tion at hand as different treatment approaches are likely C



necessary.19



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CLINICAL PRESENTATION v



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Cardiac arrest is characterized by the cessation of cardiac mechani



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cal activity therefore signs and symptoms are consistent with those



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encountered when there is no circulation. In the setting of cardiac



TREATMENT Cardiopulmonary resuscitation (CPR) is an attempt to restore spon taneous circulation by performing chest compressions (to restore threshold blood flows, particularly to the heart and brain) with or without ventilations. There are two proposed theories describing the mechanism of blood flow during CPR.20 The original theory is known as the cardiac pump theory and is based on the active com pression of the heart between the sternum and vertebrae thereby creating forward flow. Echocardiography, however, has revealed that left ventricular size does not always change with compressions and the mitral valve may in fact be open.20 The second theory is the tho racic pump theory. This theory is based on intrathoracic pressure alterations induced by chest compressions and the differential com pressibility of the arteries and veins. In this model, the heart merely acts as a passive conduit for flow. It is likely that both models con tribute to the mechanism of blood flow with CPR. High-quality CPR continues to be emphasized in the latest guidelines published by the American Heart Association. Clinicians must focus on proper technique, including adequate rate and depth of compressions, allowance of chest recoil after



each compression, avoid ing excessive ventilation, and minimizing interruptions.21 One study, in patients suffering out-of-hospital VF, reported an increased chance of survival as chest compression fraction increased (eg, the propor tion of resuscitation time without spontaneous circulation where chest compressions were administered).22 Unfortunately, the provi sion of high-quality CPR is frequently suboptimal particularly when rescuers become fatigued.23 There are several devices available that provide prompts and/or feedback in “real time”; however, data illus trating improvement in survival are lacking.23 Additionally, mechani cal devices designed to improve hemodynamics have been studied but inconsistent results limit their applicability in routine practice.24



Desired Outcome



Out of hospital 1. Immediate recognition of cardiac arrest and activation of EMS. 2. Early CPR with an emphasis on chest compressions. 3. Rapid defibrillation. 4. Effective advanced life support. 5. Integrated postcardiac arrest care. In-hospital 1. Appropriate surveillance and prevention of cardiac arrest. 2. Prompt notification and response by a multidisciplinary team of professional providers.



3. High-quality CPR. The global goals of resuscitation are to preserve life, restore 25 health, relieve suffering, limit disability, and respect the individual's 4. Prompt defibrillation and advanced life support when deci sions, rights, and privacy.25 This can be accomplished via CPR by the by mouth-to-mouth, or preferentially by bag-mask ventilation. The appropriate. return of spontaneous circulation (ROSC) with effective perfusion 5. Integrated postcardiac arrest care. and ventilation as quickly as possible to minimize hypoxic damage to vital organs. Survival to hospital discharge with good neurologic While all five links of the chain of survival are important, basic function should be considered the primary treatment outcome life support (BLS) is the foundation for saving lives after cardiac sought by clinicians. Survival to hospital discharge in a vegetative or arrest (ie, immediate recognition, early CPR, and rapid comatose state cannot be classified as a success and can impose a defibrillation).21 In fact, one large observational study compared the tremendous economic burden on the healthcare system. Addition effects of BLS and advanced cardiac life support (ACLS) on ally, most patients would choose not to continue living in a outcomes following out-of-hospital cardiac arrest and survival to massively disabled state.26 hospital discharge was greater among patients receiving BLS The presence of a healthcare advanced directive allows (13.1% vs 9.2%).33 CPR pro vides critical blood flow to the heart and patients to communicate their wishes and preferences regarding brain, prolongs the time VF is present (prior to the deterioration to medical care and may lead to a “do not attempt resuscitation asystole) and increases the likelihood that a shock will terminate VF (DNAR)” order. As many cardiac arrests occur following terminal resulting in a rhythm compatible with life. 21 For every minute that illnesses and end-of elapsed from collapse to successful defibrillation during witnessed life care, “allow natural death (AND)” has become a preferred term VF arrests, survival rates decrease by 7 % to 10% if no CPR is to replace DNAR.27 These orders should explicitly state the resusci provided.34 If immediate CPR is added, the decrease in survival is tation interventions that are to be performed and have clearly been more gradual (down to 3%-4% per minute post-collapse). 35 In effect, communicated by the patient, their family or a surrogate decision CPR can increase the likelihood of survival threefold from arrest to maker. survival. Basic CPR alone, however, is not likely to terminate VF and lead to ROSC. General Approach to Treatment 1 As in previous AHA guidelines for CPR and ECC, the AHA continues to emphasize the provision of high-quality CPR with min Cardiopulmonary Resuscitation imal interruptions in chest compressions. In addition, algorithms Resuscitation techniques have been studied for many years. The continue to be more simplified, with emphasis on the use of end tidal first landmark article was published in 1960 and described the carbon dioxide (ETCO2) to guide resuscitation.36 Furthermore, there outcome of 20 patients who were given closed chest compressions is growing importance of post-arrest care, reflecting that opti at a rate of 60 per minute.28 Artificial ventilation was used to augment mization of many organ systems may help improve outcomes.37 The the com use of drug therapy and airway adjuncts, on the other hand, have pressions, and three patients were given defibrillation for ventricular continued to devolve to a minimal role as survival to hospital dis fibrillation. In this landmark article, all 20 patients had ROSC, and 14 charge does not appear to be impacted. lived for an extended period of time, with reported good neu rologic status. Initial descriptions after this started to integrate the Basic Life Support The pneumonic for the CPR sequence is approach to cardiac arrest, including three phases.29 In 1966, the “CAB” which stands for circulation, airway, and breathing. 2 His American Heart Association (AHA) first published guidelines for the torically, BLS and ACLS providers have been taught the pneumonic, treatment of cardiac arrest.30 Since then, national conferences and “ABC.” This change was made upon recognition of the importance of organized committees have played a major role in encouraging maintaining blood flow to the heart and brain and the consequences widespread competency in CPR technique. There have been of delays or interruptions with chest compressions. tremendous revisions of the guidelines over the years, and this is When first encountering a victim of cardiac arrest, the initial action is 31 true of the most recent guidelines, published in 2015. The 2015 to determine responsiveness of the patient. If there is no response, guidelines represent a new era for the AHA Guidelines for CPR and the rescuer should immediately activate the emergency med ical Emergency Cardiovascular Care (ECC) because they will transition response team, and obtain (or call for) an automated external defi from a 5-year cycle of periodic revisions to a web-based format that brillator (AED) (if one is available) and them immediately start CPR is continuously updated. The intent is that this will allow for more with chest compressions. A true cardiac arrest victim will be rapid application of new research findings into daily patient care. unrespon sive, and agonal respirations can be confused with normal The 2015 guidelines continue to emphasize the “chain of sur vival” breathing. Thus, the “look, listen, and feel” for respirations is not to highlight the treatment approach and illustrate the impor tance of recommended as part of the initial assessment.21 Similarly, pulse a timely response. The updated guidelines however now includes recognition is often inaccurate, and it is recommended that lay two separate chains; one for out of hospital cardiac arrest and one rescuers not check for a pulse. Healthcare providers should assess for in-hospital cardiac arrest.32 This has been done to reflect the for a pulse but take no more than 10 seconds to do so. If one is not differences in the steps needed to respond to a cardiac arrest in the detected within this short time frame, then chest compressions in-patient and out-patient setting. The two chains converge in the should be initiated immediately.21,38 hospital with post-cardiac arrest care as the last link. In summary, The prompt provision of chest compressions is thus of para the five links in each chain of survival are as follows: mount importance, and rescuers should attempt them regardless of



rescuer experience or skill level. The teaching of BLS now focuses on delivering high quality CPR with a rate of 100 to 120 beats/min, ade quate depth (at least 2 inches in an adult), allowing full chest recoil, minimizing interruptions in compressions, and avoiding excessive ventilation. While it is true that opening the airway has the potential to improve oxygenation and allow for better attempts at ventilation, this can be very challenging, especially if the rescuer is alone and is a novice. Thus, the simplified adult BLS algorithm calls for the initiation of CPR, with rhythm check every 2 minutes, shocking if indicated, with continued repetition. Once chest compressions have been started, it is then appropri ate for a trained rescuer to attempt to deliver rescue breaths, either current guidelines recommend delivering a breath over one second, use enough volume to elicit a visible chest rise, and to use a compres sion to ventilation ratio of 30 to 2 for one rescuer.21 The 2015 AHA guidelines for CPR and ECC continue to stress that there should be minimal interruptions in chest compressions. If there is no AED available, then cycles of compressions/breaths should continue, with pulse checks every 2 minutes until help arrives or the patient regains spontaneous circulation. If there is an AED



States is only 26%.39 This has led to further educational interventions in an attempt to increase quality of CPR, and EMS dispatchers will often attempt to give instructions over the phone when EMS is activated. There is now a push for hands-only CPR for lay persons, given data that show similar survival compared to the addition of rescue breaths. There has been reluctance on many bystanders to consider mouth-to-mouth, though one data set cites panic as a reason not to pursue bystander CPR rather than actual reluctance.40



Advanced Cardiac Life Support Once ACLS providers arrive,



then further definitive therapy is given. An advanced airway (endo tracheal tube, laryngeal mask airway, or even bag-valve mask) can be used to provide ventilation. When this occurs, the rescuers no lon ger need to provide the cycles of 30:2 compressions to ventilations. Instead, continuous chest compressions are recommended without pauses for ventilations, and the rescuer providing the ventilations needs to deliver a breath once every 6 to 8 seconds. Monitoring during CPR has also evolved over time. Animal and human studies have shown that monitoring of ETCO 2, coronary perfusion pressure, and central venous oxygen saturation can pro vide valuable information as to the success of resuscitation.36 Sur prisingly, no study has ever shown the validity of checking a pulse available, then the rhythm should be checked to determine if defibril is the concentration of carbon diox during ongoing CPR. ETCO2 ide lation is advised. If so, then one shock should be delivered with thein exhaled air at the end of expiration. During cardiac arrest, the immediate resumption of chest compressions (and rescue breaths, 12level of ETCO2 decreases because there is no flow through the if being provided). After 2 minutes (5 cycles of 30:2 compression to pulmonary circulation. Thus, a persistently low ETCO2 (ie, less ventilation), the rhythm should be reevaluated to determine the need for than 10 mm Hg) during CPR in intubated patients suggests that 36 defibrillation. This algorithm should be repeated until help ROSC is unlikely. In fact, one systematic review reported a mean ETCO of 26 mm Hg in patients who achieved ROSC compared to 2 arrives, or the rhythm is no longer “shockable.” If the rhythm is not 13 mm Hg in those who did not.41 In patients without ROSC and persistently decreased ETCO2, it is advised to evaluate the shockable, then chest compressions—rescue breath cycles should be effectiveness of CPR, since good chest compressions can increase ETCO2 agak. The latest guidelines recommend ETCO2 continued until help arrives, or the victim recovers spontaneous cir monitoring during CPR if at all possible.36 Monitoring of coronary perfusion pressure and central venous oxygen saturation require more invasive monitoring and will not be culation (Fig. 12-1). covered. If the cardiac rhythm is not deemed to be shockable, then it is Despite widespread dissemination of cardiac arrest guidelines likely to be either asystole or PEA ( Fig. 12-2). For PEA, the rescuer must consider reversible causes. If the person is in VF or and the ongoing education even of health care providers, there is PVT, then one shock should be delivered (appropriate to the ample evidence that chest compression quality remains poor in available electri gen eral. Furthermore, it have been reported that the rate of cal device), with the immediate resumption of chest compressions bystander CPR with out-of-hospital cardiac arrest in the United C



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Verify scene safety



Nonresponsive victim No Pulse Activate EMS via mobile device/Get AED Healthcare provider: Begin cycles of 30 compressions and two breaths until AED arrives Healthcare provider: Check pulse (take noLay rescuer: Hands-only CPR (chest compressions only)



• Give one breath every 5 to 6 s • Recheck pulse every 2 min



Shockable Not shockable



• Give one shock • Resume CPR immediately for 2 min



• Resume CPR immediately for 2 min • Check rhythm every 2 min



FIGURE 12-1 Treatment algorithm for adult cardiac arrest: Basic life support (BLS).



(using 30 compressions to 2 breaths for 5 cycles, or 2 minutes con tinuous compressions with assisted ventilations) prior to rechecking the rhythm or pulse. If there is still a shockable rhythm, then one shock should be delivered, and at this time pharmacologic interven tion can be considered. Vasopressors are the initially recommended pharmacologic intervention at this point. After another unsuccessful shock, antiarrhythmics can be considered. Two minutes (five cycles of chest compressions: breaths) should be performed in between attempts at defibrillation. This algorithm will repeat until either a pulse is obtained with effective circulation, the rhythm changes, or the patient expires. For completeness, please refer to the guidelines published by the AHA.36



Cardiocerebral Resuscitation In lieu of the relative lack of progress with survival rates following out-ofhospital cardiac arrest, an alternative approach for resuscita tion was proposed called cardiocerebral resuscitation (CCR).19 CCR has been embraced by the AHA guidelines, and is composed of three major components: a community component, an EMS component, and a hospital component. The community component consists of prompt recognition (check), activation of EMS (call), and chest compression only CPR



(compress). Chest compressions deliver a small but critical amount of oxygen to the brain and myocardium. Cerebral and coronary per fusion pressures, however, build up slowly once chest compressions are begun. These perfusion pressures are lost if chest compressions are stopped to deliver mouth-to-mouth ventilation. In fact, in earlier studies, approximately 16 seconds were required to deliver 2 breaths as recommended by earlier ECC guidelines.42 The loss of perfusion during this time period has been shown to be extremely detrimental as ROSC is closely related to perfusion pressures generated during chest compressions.43 The EMS component of CCR consists of a revised ACLS algo rithm. This protocol is based on the three-phase time-sensitive model of cardiac arrest.44 The first phase is the electrical phase (0-5 minutes), where prompt defibrillation is the most impor tant intervention. The second phase is the hemodynamic phase (5-15 minutes), where adequate coronary and cerebral perfusion pres sures, before and after defibrillation, are crucial. In fact, defibrillation prior to CPR in this phase commonly leads asystole or PEA. This is likely due to the presence of global tissue ischemia and the need for blood flow (via chest compressions) to “flush out” deleterious meta bolic factors that have accumulated during ischemia. The third phase is the metabolic phase (beyond 15 minutes) in which survival is very 27



Pulseless arrest victim • Start CPR • Assess for shockable rhythm Yes No C



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resume CPR immediately and Administer epinephrine 2 min Recheck rhythm Persisten VF/PVT One shock Resume CPR immediately and Consider amiodarone



Treat reversible causes 2 min



Recheck rhythm



Go to appropriate algorithm Recheck rhythm



If patient develops return of spontaneous circulation, begin post-resuscitation care



Go to appropriate algorithm



FIGURE 12-2 Treatment algorithm for adult cardiac arrest: Advanced cardiac life support (ACLS).



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low and hypothermia may be the most beneficial approach. In situa tions where EMS personnel witness the arrest, immediate defibrilla tion is attempted.45 Alternatively, the EMS protocol of CCR emphasizes prompt initiation of 2 minutes of continuous chest compressions before and immediately after a single indicated direct current shock. The third component of CCR is the hospital which calls for aggressive postresuscitation care. This consists of the use of hypo thermia for all comatose patients and emergent cardiac catheteriza tion and percutaneous coronary intervention (PCI) for patients with myocardial ischemia as a potential cause of their arrest. This would entail the designation of cardiac receiving centers or hospitals with a commitment and expertise in postresuscitative care. Since its conception in 2003, clinical studies evaluating CCR have demonstrated an improvement in survival of 250% to 300% compared to conventional CPR.19 One systematic review com pared CCR with CPR (as per the 2005 AHA Guidelines) and the odds ratio (OR) for survival was 2.26 (95% confidence interval [CI] 1.64-3.12).46 A registry study demonstrated better survival with CCR which was observed across multiple age groups.47 The greatest differ ence was noted in those who were younger than 40 years (OR 5.94; [95% CI] 1.82-19.26). Additionally, patients who received CCR had better neurologic outcomes.



nessed VF using a modified resuscitation protocol which included D



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preceded by 200 uninterrupted chest compressions.51 An increase in r



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total survival (57% [19/33] vs 20% [18/92], p = 0.001) and neurologi



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Ventricular Fibrillation/Pulseless Ventricular Tachycardia Nonpharmacologic Therapy Electrical defibrillation is the only effective method of restoring a perfusing cardiac rhythm in either VF or PVT; therefore, it is a cru cial link in the “chain of survival,” especially for a witnessed arrest.36 The probability of successful defibrillation is directly related to the time interval between the onset of VF and the delivery of the first shock.35 In one study, a 23% relative improvement in survival was observed with each 1 minute reduction in the time to defibrillation 28 (OR 0.77; [95% CI] 0.73-0.81).48 If fact, survival decreases an esti mated 7% to 10% for each minute after arrest to defibrillation if no CPR is given.34 When bystander CPR is delivered, this decrease in survival is cut almost in half.35 Although early defibrillation is crucial for survival follow ing cardiac arrest, several studies have suggested that CPR prior to defibrillation (consistent with the CCR model) may lead to more S



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successful outcomes. For in-hospital cardiac arrest, if an AED is available, CPR should begin while the AED is being placed. With C



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200 preshock chest compressions.50 Finally, a pre-post study evalu



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out-of-hospital cardiac arrest, there is some evidence that CPR



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before defibrillation may be beneficial.49-52 One randomized con



trolled trial revealed higher survival rates in patients with response 2 intervals greater than 5 minutes when 3 minutes of CPR was admin istered prior to defibrillation (22% vs 4%; p = 0.006).52 These find ings were not confirmed in other randomized controlled trials.53-56 An observational study found the provision of roughly 90 seconds



cally normal survival (48% [16/33] vs 15% [14/92], p = 0.001) was reported. Nevertheless, meta-analyses have failed to demonstrate benefit with a delayed defibrillation approach. 57-59 Thus, this is an issue of ongoing debate and study. The latest guidelines state for a witnessed adult cardiac arrest, when an AED is immediately avail able, the defibrillator should be used as soon as possible. For adults with unmonitored arrests or when an AED is not immediately avail able, it is reasonable that CPR be initiated while the defibrillator is being retrieved but defibrillation be attempted as soon as the device is ready for use.21 The current guidelines continue to recommend one shock for VF or PVT (as opposed to stacked shocks) with the immedi ate resumption of chest compressions.36 This is largely due to the prolonged time noted (approximately 55 seconds) to deliver three stacked shocks without providing adequate chest compressions.60 The defibrillation attempt should be with 120 to 200 J (biphasic defi brillator) or 360 J (monophasic defibrillator). Defibrillators using biphasic waveforms are preferred to monophasic defibrillators. If an AED is available, it should be used as soon as possible. However, CPR should be started immediately (after EMS activation) while the AED is being prepared. After defibrillation is attempted, CPR should be immediately restarted and continued for 2 minutes without checking a pulse. The omission of the pulse check after defibrillation is related to myocar dial stunning with resultant poor perfusion and diminished cardiac output immediately after electrical therapy. 36 After 2 minutes of chest compressions, the rhythm should be rechecked and if there is still evidence of VF or PVT, pharmacologic therapy with repeat attempts at single-discharge defibrillation should be attempted. Endotracheal intubation and intravenous (IV) access should be obtained when feasible, but not at the expense of stopping chest compressions. The 2015 AHA guidelines for CPR and ECC continue to strongly stress the need for uninterrupted CPR.21 Once an airway is achieved, patients should be ventilated with 100% oxygen. There are several airway adjuncts that are potentially available, such as laryngeal mask airways and esophagealtracheal combination tubes. However, the definitive airway is an endotracheal tube placed with direct laryngoscopy. Other interventions are also being evaluated as nonpharma cologic therapy. In a porcine model of VF arrest, a percutaneously



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of CPR prior to defibrillation was associated with an increased rate



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of hospital survival (compared with a historical control group)



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when response intervals were 4 minutes or longer (27% vs 17%; a



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p = 0.01).49 A second observational study noted an improvement in



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hospital survival (from 22% to 44%, p = 0.0024) in patients with wit



placed left ventricular assist device (LVAD) was shown to sustain vital organ perfusion.61 As well, the performance of angiography and percutaneous coronary intervention during suspected myocar dial infarction has been studied in both animals and anecdotally in humans refractory to traditional ACLS protocol without ROSC. A review of this topic suggests that this intervention is feasible and that further investigation is warranted.62 Extracorporeal membrane oxygenation (ECMO) has also been evaluated and has been shown to improve outcomes in some series, but the logistics of widespread implementation is daunting.63



Pharmacologic Therapy



cated in a second study whereby a significant decrease in survival was noted with each minute increase in the time to epinephrine administration (adjusted OR [95% CI] = 0.95 [0.92-0.97]).75 The time to epinephrine administration may therefore be a key factor associated with survival and future studies must consider this as a potential confounding variable.



Sympathomimetics Sympathomimetics continue to be the first pharmacologic agents administered in the setting of cardiac arrest despite limited evidence demonstrating their ability to increase neu rologically intact survival to hospital discharge. Nevertheless sym pathomimetics have been associated with an increased rate of ROSC and play a major role in the pharmacotherapy of cardiac arrest. 3 The primary goal of sympathomimetic therapy is to aug ment low coronary and cerebral perfusion pressures encountered during The time to epinephrine administration may be an important CPR. Chest compressions (via CPR) can provide some degree of confounding factor for the value of epinephrine during out-ofblood flow to the heart and the brain but it is only about 25% of that hospital cardiac arrest. 64 encountered under basal conditions. In fact, even with prop erly performed chest compressions, coronary perfusion pressures are only 10 to 15 mm Hg and systolic arterial pressure is rarely above Given the disparate results with epinephrine in published 80 mm Hg.65 Clinical data have indicated that ROSC is unlikely when research, it can be considered both a cure and a curse in cardiac coronary perfusion pressure is less than 15 mm Hg and ani mal arrest. One possible explanation for the negative effects of epineph studies have demonstrated higher rates of ROSC when coronary perfusion pressure was 31 versus 14 mm Hg.66,67 Sympathomimetics rine is related to its mechanism of action. Epinephrine causes alpha mediated vasoconstriction which increases coronary perfusion but therefore work to increase these pressures through their vasocon can decrease perfusion to other vital organs. In fact, animal research strictive properties. Epinephrine continues to be a drug of first choice for the treat has linked epinephrine to a decrease in cerebral microvascular ment of VF, PVT, asystole, and PEA. Epinephrine is an alpha- and blood80flow and increase in brain tissue ischemia during and after beta-receptor agonist causing both vasoconstriction and increased CPR. Epinephrine also stimulates beta-receptors which can increase myo cardial oxygen demand, impair lactate clearance and inotropic/chronotrophic activity on the heart. Its effectiveness advance the severity of post resuscitation myocardial dysfunction.81 however is primarily through its alpha effects, particularly alpha-2 68 This has led some investigators to evaluate simultaneous adrenergic activity. Prospective data evaluating epinephrine in the setting of out of- antagonist administration in conjunction with epinephrine therapy 82 hospital cardiac arrest are limited. In one study, patients were (thereby isolating the alpha-2 effects) using an animal model. This approach has not been extensively studied in humans. randomized to receive standard ACLS with IV drug administration or Several studies have compared epinephrine with other adren standard ACLS without IV drug administration. 69 There were 851 patients analyzed and VF/PVT was the initial rhythm in 34%. IV ergic agonists such as pure alpha-1 agonists (phenylephrine and and agents with more potent alpha-activity (norepi medications administered included epinephrine (79%), atropine methoxamine) 83 nephrine). When compared to pure alpha-1 agonists, no advantage (46%), and amiodarone (17%). A significant increase in ROSC (40% vs 25%, p < 0.001) and hospital admission (43% vs. 29%, p < 0.001) in long-term survival could be reported. One potential reason could was noted in patients who received IV therapy. This difference was be the potent alpha-2 effects with epinephrine and the fact that these mak primarily observed in patients with initial rhythms other than VF/PVT. receptors lie extrajunctionally in the intima of the blood vessels 84 The role of epinephrine (vs other IV medications) in the contribution ing them more accessible to circulating catecholamines. Further more, during ischemia, the number of postsynaptic alpha-1of these outcomes was not assessed. A second random suggests a greater role for alpha-2 ized, controlled trial compared epinephrine with placebo in 534 receptors decreases which 85 patients.70 Ventricular fibrillation or PVT was the initial rhythm in 44% agonists during CPR. Epinephrine has also been compared with and 48% of patients in the epinephrine and placebo groups, norepinephrine, a potent alpha-agonist (both alpha-1 and alpha-2) respectively. Return of spontaneous circulation (23.5% vs 8.4%, p < with some beta-1 effects. In the only large-scale randomized, 0.001) and survival to hospital admission (25.4% vs 13%, p < 0.001) double-blind, prospective trial in out-of-hospital cardiac arrest, there were no significant differ ences in ROSC, hospital admission or was significantly higher with epinephrine but there was no differ 86 ence in survival to hospital discharge (4% vs 1.9%, p = 0.15). While discharge. A second, smaller study demonstrated higher epinephrine was effective in achieving ROSC in both shockable (OR resuscitation rates with norepinephrine compared to epinephrine 87 [95% CI] = 2.5 [1.2-4.5]) and nonshockable (OR [95% CI] = 6.9 [2.6- (64% vs 32%) but no significant differ ence in hospital discharge. 18.4]) rhythms, its effect was more pronounced in the latter cohort. Since the use of epinephrine has been established for many Several large observational studies have evaluated the impact decades in evidence-based guidelines, strong outcome-related data of epinephrine on survival. One large registry study of over 400,000 (eg, survival to hospital discharge) would be required for an patients failed to demonstrate a survival benefit with prehospital alternative to replace it. Consequently, epinephrine remains the firstadministration of epinephrine.71 Despite a significant improvement in line sympathomimetic for CPR. 36 ROSC with epinephrine (adjusted OR [95% CI] = 2.36 [2.22-2.5]), 1- tered by IV or intraosseous (IO) injection every 3 to 5 minutes month survival (adjusted OR [95% CI] = 0.46 [0.42-0.51]) and (Table 12-1). The recommended dose for epinephrine was derived from animal studies (0.1 mg/kg in a 10-kg dog) and equates to survival with good neurologic function (adjusted OR [95% CI] approximately 0.015 mg/kg for a 70-kg human.88 Both animal and 29 human studies have demonstrated a positive dose-response rela = 0.31 [0.26-0.36]) were both lower in patients who received epi tionship with epinephrine suggesting that higher doses might be necessary to improve hemodynamics and achieve successful resus The recommended dose for epinephrine is 1 mg adminis citation.83 These results, however, have not been replicated in human nephrine. A second study of evaluated outcomes of patients with



Clinical Controversy…



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witnessed out-of-hospital cardiac arrest.72 After propensity match ing, epinephrine was associated with improvements in survival at 1 month or discharge (17% vs 13.4%) in patients with VF/PVT but no difference in neurologically intact survival (6.6% vs 6.6%). The lack of agreement between these two studies may be related to the fact that epinephrine administration occurred earlier in the latter study (ie, within 10 minutes). The influence of timing of epinephrine has been described in other analyses and earlier administration appears to be more ben eficial than later.73-78 One study though found an adverse association between epinephrine and intact survival which worsened as epi nephrine administration was delayed.79 These findings were repli



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studies. In fact, some studies have reported increased morbidity E



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with high epinephrine doses, indicative of catecholamine toxicity, including decreased cardiac indices, left ventricular dysfunction, 12 and decreased oxygen consumption and delivery. This discrepancy between animal and human studies could be related to most victims of cardiac arrest having coronary artery disease, which is not encoun tered in an animal model. Additionally, atherosclerotic plaques (in C



a



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d



humans) can aggravate the balance between myocardial oxygen sup i



a



ply and demand and the interval from arrest to treatment is longer in



c



A



human studies than that encountered in an animal model. High dose



r



r



e



epinephrine is not recommended for routine use in cardiac arrest.



s



t



Vasopressin Vasopressin, also known as antidiuretic hormone, is a potent, nonadrenergic vasoconstrictor that increases blood pres sure and systemic vascular resistance. Although it acts on various receptors throughout the body, its vasoconstrictive receptor. properties are due primarily to its effects on the V1 Measurement of vaso pressin levels in patients undergoing CPR has shown a high corre lation between the levels of endogenous vasopressin released and the potential for ROSC.89 In fact, in one study, plasma vasopressin concentrations were approximately three times as high in survivors compared with nonsurvivors, suggesting that vasopressin is released as an adjunct vasopressor to epinephrine in life-threatening events such as cardiac arrest.90 Vasopressin may have several advantages over epinephrine. First, the metabolic acidosis that frequently accompanies cardiac arrest can blunt the vasoconstrictive effect of adrenergic agents such as epinephrine. This effect does not occur with vasopressin. Second, the stimulation of beta-receptors caused by epinephrine can increase myocardial oxygen demand and complicate the postresuscitative phase of CPR. Because vasopressin does not 30



act on beta-receptors, this effect does not occur with its use. Vasopressin also may have a beneficial effect on renal blood flow by stimulating V2-receptors in the kidney, causing vasodilation and increased water reabsorption. With regard to splanchnic blood flow, however, vasopressin has a detrimental effect when compared to epinephrine.89 Despite these theoretical advantages with vasopressin, clinical trials have not consistently demonstrated superior results over that achieved with epinephrine (Table 12-2). In one large trial of out ofhospital arrest, no significant differences were noted in ROSC, hospital admission rate or discharge rate.91 Although, when patients were stratified according to their initial rhythm, patients with asys tole had a significantly higher rate of hospital admission (29% vs 20%; p = 0.02) and discharge (4.7% vs 1.5%; p = 0.04) with vaso pressin compared to epinephrine. In addition, a subgroup analysis of 732 patients who required additional epinephrine therapy despite the two doses of study drug revealed significant benefits in ROSC (37% vs 26%; p = 0.002), hospital admission rate (26% vs 16%; p = 0.002), and discharge rate (6.2% vs 1.7%; p = 0.002) with vasopres sin. There was a trend, however, toward a poorer neurologic state or coma among the patients who survived to discharge and received vasopressin. The favorable results observed in the subgroup analysis led to a prospective study evaluating the combination of vasopressin and epi nephrine versus epinephrine alone.92 In this study, patients were ran domized to receive either 1 mg of epinephrine followed by 40 units of vasopressin (in less than 10 seconds) or 1 mg of epinephrine plus



TABLE 12-1 Evidence-Based Recommendations Recommendations Recommendation Grades a Epinephrine Standard dose epinephrine (1 mg IV/IO every 3-5 minutes) may be reasonable for patients with cardiac arrest



Class IIb, LOE BR



High dose epinephrine is not recommended for routine use in cardiac arrest Class III: No benefit, LOE BR



S



E



It may be reasonable to administer epinephrine as soon as feasible after the onset of cardiac arrest due to an initial nonshockable rhythm



I



Vasopressin O



C



T



N



Class IIb, LOE C-LD



Vasopressin offers no advantage as a substitute over epinephrine Class III: No benefit, LOE BR Vasopressin in combination with epinephrine offers no advantage as a substitute for standard



s



c



Lidocaine may be considered as alternative to amiodarone for VF/PVT that is unresponsive CPR,



2



u



dose epinephrine



l



For in-hospital cardiac arrest, the combination of intra-arrest vasopressin, epinephrine and defibrillation, and a vasopressor. methylprednisolone with post-arrest hydrocortisone may be considered a



r



C



Amiodarone



Magnesium



a



r



D



d



Amiodarone may be considered in patients with VF/PVT unresponsive to CPR, defibrillation, and



i



s



Class IIb, LOE BR Class IIb, LOE C-LD



i



o



a vasopressor. v



a



Class IIb, LOE BR Class IIb, LOE C-LD



Lidocaine



Magnesium is not routinely recommended for VF/PVT. Class III: No benefit, LOE BR



o



r



Thrombolysis d



e



Thrombolysis may be considered when cardiac arrest is suspected to be caused by pulmonary embolism. Class IIb, LOE C-LD r



s



Targeted Temperature Management Comatose adult patients with ROSC after cardiac arrest should have targeted temperature management. Class I, LOE BR (VF/PVT) Class I, LOE C-EO (non-VF/PVT and in-hospital arrests) A constant temperature between 32°C and 36°C should be maintained. Class I, LOE BR It is reasonable that targeted temperature management be maintained for at least 24 hours after achieving target temperature. Routine prehospital cooling of patients after ROSC with rapid infusion of cold intravenous



fluids is not recommended. Miscellaneous



Avoiding and immediately correcting hypotension (SBP > Risk Class IIa (Moderate). Benefit >> Risk Class IIb (Weak). Benefit ≥ Risk Class III: No Benefit (Moderate). Benefit = Risk Class III: Harm (Strong). Risk > Benefit Levels of evidence (LOE): Level A: High-quality evidence from more than 1 RCT, meta-analyses of high-quality RCTs, one or more RCT corroborated by high-quality registry studies. Level BR (Randomized): Moderate-quality evidence form 1 or more RCTs, meta-analyses of moderate-quality RCTs. Level B-NR (Nonrandomized): Moderate-quality evidence from 1 or more well-designed nonrandomized studies, observational studies or registry studies, metaanalyses of such studies. Level C-LD (Limited data): Randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analyses of such studies, physiological or mechanistic studies in human subjects. Level C-EO (Expert opinion): Consensus of expert opinion based on clinical experience.



saline placebo. Unfortunately, there were no significant differences between the combination therapy group and epinephrine only group in any of the outcome measures studied (ROSC, survival to hospital admission, survival to hospital discharge, 1-year survival, and good neurologic recovery at discharge). In contrast, a post-hoc subgroup analysis revealed a lower rate of survival (0% vs 5.8%, p = 0.02) with combination therapy when the initial rhythm was PEA. The utility of a multidrug regimen that also included corticoste roids has been evaluated in the setting of in-hospital cardiac arrest.93,94



The rationale is based on the hemodynamic effects of steroids along with their potential to impact the intensity of the postresuscitation systemic inflammatory response and organ dysfunction. In a single center trial, patients were randomized to receive either epineph rine alone or 20 units of vasopressin plus 1 mg of epinephrine and 40 mg of methylprednisolone (followed by hydrocortisone in the postresuscitative phase). Vasopressin 20 units plus epinephrine 1 mg were repeated during each of four subsequent CPR cycles. Signifi cant benefits were observed in ROSC (81% vs 52%, p = 0.003) and 31



TABLE 12-2 Prospective, Randomized, Controlled Trials with Vasopressin in Cardiac Arrest Initial Resuscitation Hospital Discharge Author Setting Initial rhythm Intervention N Vasopressin Epinephrine Vasopressin Epinephrine Lindner et al94a (1997) OOH VF: 100% Vasopressin 40 units vs epinephrine 1 mg for initial drug treatment 40 16/20 (80%) 11/20 (55%) 8/20 (40%) 3/20 (15%) Wenzel et al (2004) OOH VF/PVT: 40% PEA: 16% Asystole: 45% Vasopressin 40 units vs epinephrine 1 mg for two doses as initial drug treatment 1186 145/589 (25%) 167/597 (28%) Gueugniaud et al92 (2008) Asystole: OOH VF: 9% PEA: 8% 83% 91



C



H



Stiell et al94b (2001) IH VF/PVT: 21% PEA: 48% Asystole: 31% Vasopressin 40 units vs epinephrine 1 mg for initial drug



57/578 (10%) 58/588 (10%)



12 Callaway et al (2006) OOH VF: 15% PEA: 22% 94c



treatment 200 62/104 (60%) 57/96 (59%) 12/104 (12%) 13/96 (14%) P



T



E



R



Asystole: 50% Vasopressin 40 units or placebo as soon as possible after the first dose of epinephrine 1 mg 325 52/167 (31%) 48/158 (30%) NR NR



a



r



d



i



a



c



A



r



C



Epinephrine 1 mg 40 units (