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Pharmacology Step I Pharmacology 'WSMU~ is a ~aint program 0~the lfederatlan° a"• State Meaieal Boaras a~the I!Jntitea States • lne, and the Natianal Baara a1 Medieal Examiners. USMLE·Step 1 Pharmacology Lecture Notes 2006-2007 Edition KAPLA~. I meulca • USMLE is a joint program of the Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners. ©2006 Kaplan, Inc. All rights reserved. No part of this book may be reproduced in any form, by photostat, microfilm, xerography or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc. Not for resale. Author Lionel P. Rayman, Pharm.D., Ph.D. Department of Pathology Forensic Toxicology Laboratory University of Miami School of Medicine Miami, FL Contributing Authors Director of Medical Curriculum Sonia Reichert, M.D. Craig Davis, Ph.D. Associate Professor Editorial Director University of South Carolina School of Medicine Department of Pharmacology, Physiology, and Neuroscience Kathlyn McGreevy Columbia, SC Production Manager Maris Victor Nora, Pharm.D., Ph.D. Michael Wolff Associate Professor Rush Medical College Production Editor Chicago.Tl. William Ng Anthony Trevor, Ph.D. Cover Design Professor Emeritus Joanna Myllo Department of Cellular and Molecular Pharmacology University of California Cover Art San Francisco, CA Christine Schaar Steven R. Harris, Ph.D. Associate Dean for Basic Sciences Associate Professor of Pharmacology Pikeville College School of Osteopathic Medicine Pikeville, KY Contributor Kenneth H. Ibsen, Ph.D. Director of Academic Development Kaplan Medical Professor Emeritus Biochemistry University of California-Irvine Irvine, CA • Contents Preface ix Sedion I: General Principles Chapter 1: Pharmacokinetics 3 Chapter 2: Pharmacodynamics 21 Chapter 3: Practice Questions 31 Sedion II: Autonomic Pharmacology Chapter 1: The Autonomic Nervous System (ANS) 41 Chapter 2: Cholinergic Pharmacology 47 Chapter 3: Adrenergic Pharmacology 57 Chapter 4: Autonomic Drugs: Glaucoma Treatment and ANS Practice Problems 65 Chapter 5: Autonomic Drug Listand Practice Questions 73 Sedion III: cardiac and Renal Pharmacology Chapter 1: Fundamental Concepts 87 Chapter 2: Antiarrhythmic Drugs 93 Chapter 3: Antihypertensive Drugs 97 Chapter 4: Drugs for Heart Failure 103 lllVU~~~Ica.'·'1''· •;:·v ----==..,.......----""""=== ---"""""-=- ..-.-------_1 Chapter 5: Antianginal Drugs 107 Chapter 6: Diuretics . .. .. .. 111 Chapter 7: Antihyperlipidemics . .. 117 Chapter 8: Cardiac and Renal Drug list and Practice Questions . .. 121 Sedion IV: eNS Pharmacology Chapter 1: Sedative-Hypnotic-Anxiolytic Drugs 133 Chapter 2: Alcohols . .. 139 Chapter 3: Anticonvulsants 141 Chapter 4: Drugs Used in Anesthesia 145 Chapter 5: Opioid Analgesics 151 Chapter 6: Drugs Used in Parkinson Disease and Psychosis 155 Chapter 7: Drugs Used for Depression, Bipolar Disorders, and Attention Deficit Hyperactivity Disorder (ADHD) 161 Chapter 8: Drugs of Abuse 165 Chapter 9: CNS Drug list and Practice Questions 169 Sedion V. Antimicrobial Agents Chapter 1: Antibacterial Agents 181 Chapter 2: Antifungal Agents 197 Chapter 3: Antiviral Agents 201 Chapter 4: Antiprotoloal Agents 209 Chapter 5: Antimicrobial Drug list and Practice Questions 213 vi m8CIical Sedion VI. Drugs for Inflammatory and Related Disorders Chapter 1: Histamine and Antihistamines 227 Chapter 2: Drugs Used in Gastrointestinal Dysfunction .•... ; ........•.. 229 Chapter 3: Drugs Acting on Serotonergic Systems ................•.... 235 Chapter 4: Eicosanoid Pharmacology ......................•......... 239 Chapter 5: Drugs Used for Treatment of Rheumatoid Arthritis 245 Chapter 6: Drugs Used for Treatment of Gout ............•......••.... 247 Chapter 7: Glucocorticoids ........................•.......•.......• 249 Chapter 8: Drugs Used for Treatment of Asthma 251 Chapter 9: list of Drugs for Inflammatory Disorders and PracticeQuestions... 255 Sedion VII: Drugs Used in Blood Disorders Chapter 1: Anticoagulants 269 Chapter 2: Thrombolytics ......................•........•........•. 273 Chapter 3: Antiplatelet Drugs .........................•............ 275 Chapter 4: list of Drugs Used in Blood Disorders and PracticeQuestions ..... 277 Sedion VIII: Endocrine Pharmacology Chapter 1: Drugs Used in Diabetes ....................••............ 283 Chapter 2: Steroid Hormones ...............................•...... 287 Chapter 3: Antithyroid Agents ........................•...•......... 293 Chapter 4: Drugs Related to Hypothalamic and Pituitary Hormones 295 Chapter 5: Drugs Used for Bone and Mineral Disorders 297 Chapter 6: Endocrine Drug list and Practice Questions ...........•..... 299 2!~!aIIInni'ca'"'." :,VlI•• Sedion IX: Anticancer Drugs . Chapter 1: Anticancer Drugs 307 Chapter 2: Anticancer Drug Practice Questions 311 Sedion X: Immunopharmacology Chapter 1: Immunopharmacology 315 Chapter 2: Immunopharmacology Practice Questions . .. 317 Sedion XI: Toxicology Chapter 1: Toxicology 321 Chapter 2: Toxicology Practice Questions 327 Index " 329 UP~~,; I viii mvulC8 Preface These seven volumes of Lecture Notes represent a yearlong effort on the part of the Kaplan Medical faculty to update our curriculum to reflect the most-likely-to-be-tested material on the current USMLE Step 1 exam. Please note that these are Lecture Notes, not review books. The Notes were designed to be accompanied by faculty lectures-live, on video, or on the web. Reading these Notes without accessing the accompanying lectures is not an effective way to review for the USMLE. To maximize the effectiveness of these Notes, annotate them as you listen to lectures. To facilitate this process, we've created wide, blank margins. While these margins are occasionally punctuated by faculty high-yield "margin notes," they are, for the most part, left blank for your notations. Many students find that previewing the Notes prior to the lecture is a very effective way to prepare for class. This allows you to anticipate the areas where you'll need to pay particular attention. It also affords you the opportunity to map out how the information is going to be presented and what sorts of study aids (charts, diagrams, etc.) you might want to add. This strategy works regardless of whether you're attending a live lecture or watching one on video or the web. Finally, we want to hear what you think. What do you like about the notes? What do you think could be improved? Please share your feedback by [email protected]. Thank you for joining Kaplan Medical, and best of luck on your Step 1 exam! Kaplan Medical UP~~. I mvulC8 ix " SECTION I General Principles ,. Pharmacokinetics Pharmacokinetic characteristics of drug molecules concern the processes of absorption, distri- bution, metabolism, and excretion. The biodisposition of a drug involves its permeation across cellular membrane barriers. Absorption into Plasma Drug Excretion Drug Metabolism (Renal," Biliary, (Liver, Lung, Blood, etc.) Exhalation, etc.) Figure 1-1-1. Drug Blodlsposltion m.,.UP~~.,.lC8 I 3 USMLE Step 1: Pharmacology PERMEATION Drug permeation is dependent on: Solubility. Ability to diffuse through lipid bilayers (lipid solubility) is important for most drugs; however, water solubility Can influence permeation through aqueous phases. - Concentration gradient. Diffusion down a concentration gradient--only free, unionized drug forms contribute to the concentration gradient. Surface area and vascularity. Important with regard to absorption of drugs into the systemic circulation. The larger the surface area and the greater the vascularity, In A Nutshell the better is the absorption of the drug. • Ionization For Weak Acids and Weak Bases Many drugs are weak acids or weak bases and can exist in either nonionized or ionized forms in an equilibrium, depending on the pH of the environment and Ionized = Water soluble the pKa (the pH at which the molecule is 50% ionized and 50% nonionized) Nonionized = Lipid soluble - Only the nonionized (uncharged) form of a drug crosses biomembranes. - The ionized form is better renally excreted because it is water soluble. Weak Acid R-COOH ~---" R-COO-+H+ (crosses membranes) (better cleared) Weak Base R-NH~ ~---" R-NH +H+ 2 (better cleared) (crosses membranes) :rJ E 80 ~CD .. !. 0 LL 0 '1:J III 60 iD N III ·2 iil ~ 0 n ·2 40 CD 0 z a ~ C 0 20 ~ c (Q -2 -1 0 +1 +2 pH-pKa Figure 1·1·2.Degree of Ionization and Clearance Versus pH Deviation from pKa 4 lMCIical Pharmacokinetics Ionization Increases Renal Clearance of Drugs Only free, unbound drug is filtered. Clinical Correlate • Both ionized and nonionized forms of a drug are filtered. ~ • Only nonionized forms undergo active secretion and active or passive reabsorption. To Change Urinary pH Ionized forms of drugs are "trapped" in the filtrate. • Acidify:NH4C1,vitamin C, Acidification of urine ~ increases ionization of weak bases ~ increases renal cranberry juice elimination. • Alkalinize: NaHCOy aceta- Alkalinization of urine ~ increases ionization of weak adds ~ increases renal zolamide (historically) elimination. • See Aspirin Overdose and Management in Section VI. Glomerulus \ p_rO_x_im_a_l_li_ub_u_'_e _ Free Drug I Excreted (unbound to Filtered protein) U Reabsorption I = ionized drug U = unionized drug Figure 1-1-3. Renal Clearance of Drug Modes of Drug Transport Across a Membrane Bridge to Physiology Table 1-1-1. The Three Basic Modes of Drug Transport Across a Membrane ;;'::':;:;;(w ••••••_ w::: 11 .- <-" Energy I Ion and molecolar transport
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