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Table of Contents Authors Preface Chapter Introduction Chapter Pharmacodynamics Chapter Pharmacokinetics Chapter Drug Metabolism Chapter Drug Evaluation and Regulation Chapter Introduction to Autonomic Pharmacology Chapter Cholinoceptor-Activating and Cholinesterase-Inhibiting Drugs Chapter Cholinoceptor Blockers and Cholinesterase Regenerators Chapter Sympathomimetics Chapter 10 Adrenoceptor Blockers Chapter 11 Drugs Used in Hypertension Chapter 12 Drugs Used in the Treatment of Angina Pectoris Chapter 13 Drugs Used in Heart Failure Chapter 14 Antiarrhythmic Drugs Chapter 15 Diuretic Agents Chapter 16 Histamine, Serotonin, and the Ergot Alkaloids Chapter 17 Vasoactive Peptides Chapter 18 Prostaglandins and Other Eicosanoids Chapter 19 Nitric Oxide, Donors, and Inhibitors Chapter 20 Bronchodilators and Other Drugs Used in Asthma Chapter 21 Introduction to CNS Pharmacology Chapter 22 Sedative-Hypnotic Drugs Chapter 23 Alcohols Chapter 24 Antiseizure Drugs Chapter 25 General Anesthetics Chapter 26 Local Anesthetics Chapter 27 Skeletal Muscle Relaxants Chapter 28 Drugs Used in Parkinsonism and Other Movement Disorders Chapter 29 Antipsychotic Agents and Lithium Chapter 30 Antidepressants Chapter 31 Opioid Analgesics and Antagonists Chapter 32 Drugs of Abuse Chapter 33 Agents Used in Anemias and Hematopoietic Growth Factors Chapter 34 Drugs Used in Coagulation Disorders Chapter 35 Drugs Used in the Treatment of Hyperlipidemias Chapter 36 NSAIDs, Acetaminophen, and Drugs Used in Rheumatoid Arthritis and Gout Chapter 37 Hypothalamic and Pituitary Hormones Chapter 38 Thyroid and Antithyroid Drugs Chapter 39 Corticosteroids and Antagonists Chapter 40 Gonadal Hormones and Inhibitors Chapter 41 Pancreatic Hormones, Antidiabetic Agents, and Glucagon Chapter 42 Drugs That Affect Bone Mineral Homeostasis Chapter 43 Beta-Lactam Antibiotics and Other Cell Wall Synthesis Inhibitors Chapter 44 Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, Streptogramins, and Linezolid Chapter 45 Aminoglycosides Chapter 46 Sulfonamides, Trimethoprim, and Fluoroquinolones Chapter 47 Antimycobacterial Drugs Chapter 48 Antifungal Agents Chapter 49 Antiviral Chemotherapy and Prophylaxis Chapter 50 Miscellaneous Antimicrobial Agents and Urinary Antiseptics Chapter 51 Clinical Use of Antimicrobials Chapter 52 Antiprotozoal Drugs Chapter 53 Antihelminthic Drugs Chapter 54 Cancer Chemotherapy Chapter 55 Immunopharmacology Chapter 56 Environmental and Occupational Toxicology Chapter 57 Heavy Metals Chapter 58 Management of the Poisoned Patient Chapter 59 Drugs Used in Gastrointestinal Disorders Chapter 60 Dietary Supplements and Herbal Medications Chapter 61 Drug Interactions Appendix I Key Words for Key Drugs Appendix IV Strategies for Improving Test Performance Chemotherapeutic Drugs: Overview Appendix IV Strategies for Improving Test Performance Authors Anthony J Trevor, PhD Professor Emeritus of Pharmacology and Toxicology Department of Cellular & Molecular Pharmacology University of California, San Francisco Bertram G Katzung, MD, PhD Professor Emeritus of Pharmacology Department of Cellular & Molecular Pharmacology University of California, San Francisco Susan B Masters, PhD Professor & Academy Chair of Pharmacology Education Department of Cellular & Molecular Pharmacology University of California, San Francisco Preface This book is designed to help students review pharmacology and to prepare for both regular course examinations and board examinations The ninth edition has been extensively revised to make such preparation as active and efficient as possible As with earlier editions, rigorous standards of accuracy and currency have been maintained in keeping with the book's status as the companion to the Basic & Clinical Pharmacology textbook This review book divides pharmacology into the topics used in most courses and textbooks Major introductory chapters (eg, autonomic pharmacology and CNS pharmacology) are included for integration with relevant physiology and biochemistry The chapter-based approach facilitates use of this book in conjunction with course notes or a larger text We recommend several strategies to make reviewing more effective First, each chapter has a short discussion of the major concepts that underlie its basic principles or drug group, accompanied by explanatory figures and tables The figures are now in full color and many are new to this edition Read the text thoroughly before you attempt to answer the study questions at the back of each chapter If you find a concept difficult or confusing, consult a regular textbook, such as Basic and Clinical Pharmacology Second, each drug-oriented chapter opens with a "Drug Tree" that organizes the group of drugs visually You should practice reproducing the Drug Tree diagram from memory Third, a list of High-Yield Terms to Learn and their definitions is near the front of most chapters Make sure that you can define those terms Fourth, many chapters contain a "Skill Keeper" question that prompts you to review previous material and to see links between related topics Try to answer the Skill Keeper questions on your own before checking the Skill Keeper answers that are provided at the end of the chapter Fifth, each chapter contains sample questions followed by a set of answers with explanations For most effective learning, take each set of sample questions as if it were a real examination After you have answered every question, work through the answers When you are analyzing the answers, make sure that you understand why each choice is either correct or incorrect Sixth, each chapter includes a Checklist of focused tasks that you should be able to once you have finished the chapter Seventh, each drug-oriented chapter ends with a Summary Table that lists the important drugs and includes key information concerning their mechanisms of action, effects, clinical uses, pharmacokinetics, drug interactions, and toxicities Eighth, when preparing for a comprehensive examination, you should review the list of drugs in Appendix I: Key Words for Key Drugs Do this at the same time that you work your way through the chapters so that you can begin to recognize drugs out of the context of a chapter that discusses a restricted set of drugs Ninth, after you have worked your way through most or all of the chapters and have a good grasp of the Key Drugs, you should take the comprehensive examinations presented in Appendices II and III These examinations are followed by a list of answers and the numbers of the chapters in which the answers are explained Again, we recommend that you take an entire examination or a block of questions as if it were a real examination; commit to answers for the whole set before you check the answers As you work though the answers, make sure you understand why each distracter is either correct or incorrect If you need to, return to the relevant chapter(s) to review the text that covers key concepts and facts that form the basis of the question Tenth, you can use strategies in Appendix IV for improving your test performance General advice for studying and approaching exams includes strategies for several types of questions that follow specific formats We recommend that this book be used with a regular text Basic & Clinical Pharmacology, eleventh edition (McGraw-Hill, 2009), follows the chapter sequence used here However, this review book is designed to complement any standard medical pharmacology text The student who completes and understands Pharmacology: Examination & Board Review will greatly improve his or her performance on examinations and will have an excellent command of pharmacology Because it was developed in parallel with the textbook Basic & Clinical Pharmacology, this review book represents the authors' interpretations of chapters written by contributors to that text We are very grateful to these contributors, to our other faculty colleagues, and to our students—who have taught us most of what we know about teaching We very much appreciate the invaluable contributions to this text afforded by the editorial team of Alison Kelley, Karen Davis, Harriet Lebowitz, Michael Weitz, and Harleen Chopra, and by Dr S Manikandan, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India The authors also thank Alice Camp, for her expert proofreading contributions to this and earlier editions Suggestions and criticisms regarding this study guide should be sent to us at the following address: Department of Cellular & Molecular Pharmacology, Box 0450, University of California School of Medicine, San Francisco, CA 94143-0450, USA Anthony J Trevor, PhD Bertram G Katzung, MD, PhD Susan B Masters, PhD chapter Introduction Introduction Pharmacology is the body of knowledge concerned with the action of chemicals on biologic systems Medical pharmacology is the area of pharmacology concerned with the use of chemicals in the prevention, diagnosis, and treatment of disease, especially in humans Toxicology is the area of pharmacology concerned with the undesirable effects of chemicals on biologic systems Pharmacokinetics describes the effects of the body on drugs, eg, absorption, excretion, etc Pharmacodynamics denotes the actions of the drug on the body, such as mechanism of action and therapeutic and toxic effects This chapter introduces the basic principles of pharmacokinetics and pharmacodynamics that will be applied in subsequent chapters The Nature of Drugs Drugs in common use include inorganic ions, nonpeptide organic molecules, small peptides and proteins, nucleic acids, lipids, and carbohydrates Some are found in plants or animals, but many are partially or completely synthetic Many biologically important endogenous molecules and exogenous drugs are optically active; that is, they contain one or more asymmetric centers and can exist as enantiomers The enantiomers of optically active drugs usually differ, sometimes more than 1000fold, in their affinity for their biologic receptor sites Furthermore, such enantiomers may be metabolized at different rates in the body, with important clinical consequences Size and Molecular Weight Drugs vary in size from molecular weight (MW) (lithium) to over MW 50,000 (thrombolytic enzymes, other proteins) Most drugs, however, have molecular weights between 100 and 1000 Drugs smaller than MW 100 are rarely sufficiently selective in their actions, whereas drugs much larger than MW 1000 are often poorly absorbed and poorly distributed in the body Drug-Receptor Bonds Drugs bind to receptors with a variety of chemical bonds These include very strong covalent bonds (which usually result in irreversible action), somewhat weaker electrostatic bonds (eg, between a cation and an anion), and much weaker interactions (eg, hydrogen, van der Waals, and hydrophobic bonds) High-Yield Terms to Learn Drugs Substances that act on biologic systems at the chemical (molecular) level and alter their functions Drug receptors The molecular components of the body with which drugs interact to bring about their effects Distribution phase The phase of drug movement from the site of administration into the tissues Elimination phase The phase of drug inactivation or removal from the body by metabolism or excretion Endocytosis, exocytosis Endocytosis: Absorption of material across a cell membrane by enclosing it in cell membrane material and pulling it into the cell, where it can be released Exocytosis: Expulsion of material from vesicles in the cell into the extracellular space Permeation Movement of a molecule (eg, drug) through the biologic medium Pharmacodynamics The actions of a drug on the body, including receptor interactions, doseresponse phenomena, and mechanisms of therapeutic and toxic actions Pharmacokinetics The actions of the body on the drug, including absorption, distribution, metabolism, and elimination Elimination of a drug may be achieved by metabolism or by excretion Biodisposition is a term sometimes used to describe the processes of metabolism and excretion Transporter A specialized molecule, usually a protein, that carries a drug, transmitter, or other molecule across a membrane in which it is not permeable, eg, Na+/K+ ATPase, serotonin reuptake transporter, etc Pharmacodynamic Principles Receptors and Receptor Sites Drug actions are mediated through the effects of drug molecules on drug receptors in the body Most receptors are large regulatory molecules that influence important biochemical processes (eg, enzymes involved in glucose metabolism) or physiologic processes (eg, neurotransmitter receptors, neurotransmitter reuptake transporters, and ion transporters) If drug-receptor binding results in activation of the receptor, the drug is termed an agonist; if inhibition results, the drug is considered an antagonist As suggested in Figure 1-1, a receptor molecule may have several binding sites Quantitation of the effects of drug-receptor binding as a function of dose yields dose-response curves that provide information about the nature of the drugreceptor interaction Dose-response phenomena are discussed in more detail in Chapter A few drugs are enzymes themselves (eg, thrombolytic enzymes that dissolve blood clots) These drugs not act on endogenous receptors but on endogenous substrate molecules, such as plasminogen FIGURE 1-1 Potential mechanisms of drug interaction with a receptor Possible effects resulting from these interactions are diagrammed in the dose-response curves at the right The traditional agonist (drug A)-receptor binding process results in the dose-response curve denoted "A alone." B is a pharmacologic antagonist drug that competes with the agonist for binding to the receptor site The dose-response curve produced by increasing doses of A in the presence of a fixed concentration of B is indicated by the curve "A+B." Drugs C and D act at different sites on the receptor molecule; they are allosteric activators or inhibitors Note that allosteric inhibitors not compete with the agonist drug for binding to the receptor, and they may bind reversibly or irreversibly (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 11th ed McGraw-Hill, 2009: Fig 1-3.) Inert Binding Sites Because most drug molecules are much smaller than their receptor molecules (discussed in the text that follows), specific regions of receptor molecules often can be identified that provide the local areas for drug binding Such areas are termed receptor sites In addition, drugs bind to other, nonregulatory molecules in the body without producing a discernible effect Such binding sites are termed inert binding sites In some compartments of the body (eg, the plasma), inert binding sites play an important role in buffering the concentration of a drug because bound drug does not contribute directly to the concentration gradient that drives diffusion Albumin and orosomucoid ( 1-acid glycoprotein) are important plasma proteins with significant drug-binding capacity Pharmacokinetic Principles To produce useful therapeutic effects, most drugs must be absorbed, distributed, and eliminated Pharmacokinetic principles make rational dosing possible by quantifying these processes The Movement of Drugs in the Body To reach its receptors and bring about a biologic effect, a drug molecule (eg, a benzodiazepine sedative) must travel from the site of administration (eg, the gastrointestinal tract) to the site of action (eg, the brain) Permeation Permeation is the movement of drug molecules into and within the biologic environment It involves several processes, the most important of which are discussed next Aqueous Diffusion Aqueous diffusion is the movement of molecules through the watery extracellular and intracellular spaces The membranes of most capillaries have small water-filled pores that permit the aqueous diffusion of molecules up to the size of small proteins between the blood and the extravascular space This is a passive process governed by Fick's law (see later discussion) The capillaries in the brain, testes, and some other organs lack aqueous pores, and these tissues are less exposed to some drugs Lipid Diffusion Lipid diffusion is the passive movement of molecules through membranes and other lipid structures Like aqueous diffusion, this process is governed by Fick's law (see later discussion) Transport by Special Carriers Drugs that not readily diffuse through membranes may be transported across barriers by mechanisms that carry similar endogenous substances A very large number of such transporters have been identified, and many of these are important in the movement of drugs or as targets of drug action Unlike aqueous and lipid diffusion, carrier transport is not governed by Fick's law and is capacitylimited Important examples are transporters for ions (eg, Na+/K+ ATPase), for neurotransmitters (eg, transporters for serotonin, norepinephrine), for metabolites (eg, glucose, amino acids), and for anticancer drugs Selective inhibitors for these carriers may have clinical value; for example, several antidepressants act by inhibiting the transport of amine neurotransmitters back into the nerve endings from which they have been released After release, such amine neurotransmitters (dopamine, norepinephrine, and serotonin) and some other transmitters are recycled into nerve endings by transport molecules Probenecid, which inhibits transport of uric acid, penicillin, and other weak acids in the nephron, is used to increase the excretion of uric acid in gout The family of Pglycoprotein transport molecules, previously identified in malignant cells as one cause of cancer drug resistance, has been identified in the epithelium of the gastrointestinal tract and in the blood-brain barrier Endocytosis, Pinocytosis Endocytosis occurs through binding of the transported molecule to specialized components (receptors) on cell membranes, with subsequent internalization by infolding of that area of the membrane The contents of the resulting intracellular vesicle are subsequently released into the cytoplasm of the cell Endocytosis permits very large or very lipid-insoluble chemicals to enter cells For example, large molecules such as proteins may cross cell membranes by endocytosis Smaller, (rarely used): selective inhibitor of vesicle catecholamine-H+ antiporter (VMAT); used in HTN, causes depletion of catecholamines and 5-HT from their stores Tox: severe depression, suicide, ulcers, diarrhea (6, 11) Rifampin Antimicrobial: inhibitor of DNA-dependent RNA polymerase used in drug regimens for tuberculosis and the meningococcal carrier state Tox: hepatic dysfunction, induction of liver drugmetabolizing enzymes (drug interactions), flu-like syndrome with intermittent dosing Rifabutin similar but associated with fewer drug interactions (47) Ritonavir Antiviral: HIV protease inhibitor (PI) used at low dose as a component of combination regimens in AIDS to inhibit metabolism of other drugs (See indinavir) Tox: implicated in many drug interactions when used as sole PI Rosiglitazone Oral antidiabetic: thiazolidinedione stimulator of peroxisome proliferator-activator receptors (PPAR) and enhances target tissue sensitivity to insulin Less hypoglycemia and weight gain than secretagogue antidiabetics Tox: fluid retention, heart failure, fractures in women Pioglitazone is similar (41) Selegiline MAO-B inhibitor: selective inhibitor of the enzyme that metabolizes dopamine (no tyramine interactions at normal dosage) Used in Parkinson's disease Tox: GI distress, CNS stimulation, dyskinesias, serotonin syndrome if used with selective serotonin reuptake inhibitors Rasagiline similar and used more commonly (28) Sildenafil Inhibits phosphodiesterase (PDE)-5, preventing breakdown of cyclic guanosine monophosphate (cGMP), which promotes vasodilation and smooth muscle relaxation Used for erectile dysfunction and pulmonary hypertension Tadalafil, vardenafil are similar Tox: severe hypotension when combined with nitrates, impaired blue-green color vision (12) Sotalol Group antiarrhythmic prototype: blocks IK channels and receptors Used for atrial and ventricular arrhythmias Tox: torsade de pointes arrhythmias Others in group: ibutilide, dofetilide (14) Spironolactone Aldosterone receptor antagonist: K+-sparing diuretic action in the collecting tubules; used in aldosteronism, HTN, and female hirsutism (androgen receptor-blocking action) Tox: hyperkalemia, gynecomastia Eplerenone, used in HTN and heart failure, is a more selective aldosterone antagonist (13, 15, 39, 40) Streptogramins Antibiotics: Synercid is the combination of quinupristin and dalfopristin; bactericidal inhibitors of protein synthesis Intravenous use for drug-resistant gram-positive cocci including MRSA (methicillin-resistant S aureus), VRE (vancomycin-resistant enterococci), and pneumococci Tox: infusion-related pain, arthralgia, myalgia Linezolid is another inhibitor of protein synthesis used for drug-resistant gram-positive cocci, including PRSP (penicillin-resistant S pneumoniae) strains (44) Succinylcholine Depolarizing neuromuscular relaxant prototype: short duration (5 min) if patient has normal plasma cholinesterase (genetically determined) No antidote (compare with tubocurarine) Implicated in malignant hyperthermia (7, 27) Sulfasalazine 5Aminosalicylate (5-ASA) anti-inflammatory drug: used for inflammatory bowel disease (IBD) and rheumatoid arthritis Tox: rash, GI disturbances, leukopenia Other 5-ASA drugs used for IBD are mesalamine, balsalazide, olsalazine (36, 59) Sumatriptan 5-HT1D receptor agonist: used to abort migraine attacks Tox: coronary vasospasm, chest pain or pressure Six other "triptans" are currently available (16) Tamoxifen Selective estrogen receptor modulator (SERM): blocks estrogen receptors in breast tissue; activates endometrial receptors Used in estrogen receptor-positive cancers, possibly prophylactic in high-risk patients Toremifene is similar Raloxifene, approved for osteoporosis, activates bone estrogen receptors but is an antagonist of breast and endometrial receptors (40, 54) Terbinafine Antifungal: fungicidal inhibitor of squalene epoxidase Most effective agent in onychomycosis, oral and topical forms Tox: GI upsets, headache, and rash (48) Tetracycline Antibiotic: tetracycline prototype; bacteriostatic inhibitor of protein synthesis (30S) Broad spectrum, but many resistant organisms Used for mycoplasmal, chlamydial, rickettsial infections, chronic bronchitis, acne, cholera; a backup drug in syphilis Tox: GI upset and superinfections, Fanconi's syndrome, photosensitivity, dental enamel dysplasia Other tetracyclines include doxycycline (see above) and tigecycline (IV) used for multidrug-resistant nosocomial pathogens (44) Theophylline Methylxanthine derivative found in tea; used in asthma Bronchodilator, mild CNS stimulant Caffeine (coffee), theobromine (cocoa) are similar Tox: seizures (20) Trimethoprimsulfamethoxazole (TMP-SMZ) Antimicrobial drug combination: causes synergistic sequential blockade of folic acid synthesis Active against many gram-negative bacteria, including Aeromonas, Enterobacter, H influenzae, Klebsiella, Moraxella, Salmonella, Serratia, and Shigella Tox: mainly due to sulfonamide; includes hypersensitivity, myelotoxicity, kernicterus, and drug interactions caused by competition for plasma protein binding (46, 52) Tubocurarine Nondepolarizing neuromuscular blocking agent prototype: competitive nicotinic blocker Analogs: pancuronium, atracurium, vecuronium, and other "-curiums" and "-oniums." Tox: respiratory paralysis Releases histamine and may cause hypotension, therefore rarely used Antidote: cholinesterase inhibitor, for examples, neostigmine (8, 26) Tyramine Indirect-acting sympathomimetic prototype: releases or displaces norepinephrine from stores in nerve endings Presence in certain foods may cause potentially lethal hypertensive responses in patients taking MAO inhibitors (6, 27) Valproic acid Anticonvulsant: primary drug in absence, clonic-tonic, and myoclonic seizure states Also used commonly for bipolar disorder Tox: GI distress, hepatic necrosis (rare), teratogenic (spina bifida), inhibits drug metabolism (24, 29) Vancomycin Glycopeptide bactericidal antibiotic: inhibits synthesis of cell wall precursor molecules A drug of choice for methicillin-resistant staphylococci and effective in antibiotic-induced colitis Dose reduction required in renal impairment (or hemodialysis) Tox: ototoxicity, hypersensitivity, renal dysfunction (rare) (43, 51) Verapamil Calcium channel blocker prototype: blocks L-type channels; cardiac depressant and vasodilator; used in HTN, angina, and arrhythmias (group 4) Tox: AV block, HF, constipation Diltiazem, like verapamil, has more depressant effect on heart than dihydropyridines (eg, nifedipine) (11, 12, 14) Vincristine Antineoplastic: cell cycle (M phase)-specific plant alkaloid; inhibits mitotic spindle formation Tox: peripheral neuropathy Vinblastine, a congener, causes myelosuppression (54) Warfarin Oral anticoagulant prototype: causes synthesis of nonfunctional versions of the vitamin K-dependent clotting factors (II, VII, IX, X) Tox: bleeding, teratogenic Antidote: vitamin K, fresh plasma (34) Zidovudine (ZDV) Antiviral: prototype NRTI used in combinations for HIV infections and in prophylaxis for needlesticks and vertical transmission Tox: severe myelosuppression Other NRTIs: abacavir, didanosine (ddI), lamivudine (3TC), stavudine (d4T), and zalcitabine (ddC) (49) Zolpidem Nonbenzodiazepine hypnotic: acts via the BZ1 receptor subtype and is reversed by flumazenil; less amnesia and muscle relaxation and lower dependence liability than benzodiazepines Zaleplon and eszopiclone are similar (22) Appendix IV Strategies for Improving Test Performance Introduction There are many strategies for studying and exam taking, and decisions about which ones to use are partly a function of individual habit and preference However, basic study rules may be applied to any learning exercise; test-taking strategies depend on the type of examination For those interested in test-writing strategies, the Case and Swanson reference is strongly recommended (see References) Five Basic Study Rules When studying dense textual material, stop after a few pages to write out the gist of it from memory If necessary, refer to the material just read After finishing a chapter, construct your own tables of the major drugs, receptor types, mechanisms, and so on, and fill in as many of the blanks as you can Refer to tables and figures in the book as needed to complete your notes Create your own mnemonics if possible Look up other mnemonics in books if you can't think of one yourself These are all active learning techniques; mere reading is passive and far less effective unless you happen to have a photographic memory Your notes should be legible or typed on a computer, and saved for ready access when reviewing for exams Experiment with other study methods until you find out what works for you This may involve solo study or group study, flash cards, or text reading You won't know how effective these techniques are until you have tried them Don't scorn "cramming," but don't rely on it either Some steady, day-by-day reading and digestion of conceptual material is usually needed to avoid last-minute indigestion Similarly, don't substitute memorization of lists (eg, the Key Words list, Appendix I) for more substantive understanding If you are preparing for a course examination, make every effort to attend all the lectures The lecturer's view of what is important may be different from that of the author of a course textbook, and chances are good that exam questions will be based on the instructor's own lecture notes If old test questions are legitimately available (as they are for the USMLE and courses in most medical schools), make use of these guides to study By definition, they are a strong indicator of what the examination writers have considered core information in the recent past (also see Point 4) Strategies Applicable to All Examinations Three general rules apply to all examinations When starting the examination, scan the entire question set before answering any If the examination has several parts, allot time to each part in proportion to its length and difficulty Within each part, answer the easy questions first, placing a mark in the margin by the questions to which you will return Practice saving enough time for the more difficult questions by scheduling or less for each question on practice examinations such as those in Examinations and in the SelfAssessment (The time available in the USMLE examination is approximately 55-60 sec per question.) Students are often advised to avoid changing their first guess on multiple-choice questions However, research has shown that students who are unsure of the answer to a question make a change from the incorrect answer to the correct answer about 55% of the time So if you are unsure of your first choice for a particular question and on further reflection see an answer that looks better, research supports your making one—but only one—change Understand the method for scoring wrong answers The USMLE does not penalize for wrong answers; it scores you only on the total number of correct answers Therefore, even if you have no idea as to the correct answer, make a guess anyway; there is no penalty for an incorrect answer In other words, not leave any blanks on a USMLE answer sheet or computer screen Note that this may not be true for some local examinations; some scoring algorithms penalize for incorrect answers Make sure you understand the rules for such local examinations Strategies for Specific Question Formats A certain group of students—often characterized as "good test-takers"—may not know every detail about the subject matter being tested but seem to perform extremely well most of the time The strategy used by these people is not a secret, although few instructors seem to realize how easy it is to break down their questions into much simpler ones Lists of these strategies are widely available (eg, in the descriptive material distributed by the National Board of Medical Examiners to its candidates) A paraphrased compendium of this advice is presented next Strategies for the "Choose the One Best Answer" (of Choices) Type Question Many of the newer "clinical correlation" questions on the Board exam have an extremely long stem that provides a great deal of clinical data Much of the data presented may be irrelevant The challenge becomes one of finding out what is being asked One method for rapidly narrowing the search, especially when confronted with a long stem, is to just read the last sentence of the stem, then scan the answer list The nature of the last sentence and the answers provide a clue to the parts of the stem that are relevant and those that are not If statements are contradictory (ie, only can be correct), chances are good that of the is the correct answer (ie, the other choices may be distracters) For example, consider the following: In treating quinidine overdose, the best strategy would be to (A) Acidify the urine (B) Administer a calcium chelator such as EDTA (C) Alkalinize the urine (D) Give potassium chloride (E) Give procainamide The correct answer is A: acidify the urine In the pair of contradictory distractors (choices A and C), the instructor revealed what was being tested and then used the other three as "filler." Therefore, if you don't know the answer, you are better off guessing A or C (a 50% success probability) than A or B or C or D or E (a 20% success probability) Note that this strategy is valid only if you must guess; many instructors now introduce contradictory pairs as distracters Another "rule" that should be used only if you must guess is the "longest choice" rule When all the answers in a multiple-choice question are relatively long, the correct answer is often the longest one Note again that sophisticated question writers may introduce especially long incorrect choices to foil this strategy Statements that contain the words "always," "never," "must," and so on are usually false For example, Acetylcholine always increases the heart rate when given intravenously because it lowers blood pressure and evokes a strong baroreceptor-mediated reflex tachycardia The statement is false because, although acetylcholine often increases the heart rate, it can also cause bradycardia (When given as a bolus, it may reach the sinus node in high enough concentration to cause initial bradycardia.) The use of trigger words such as "always" and "must" suggests that the instructor had some exception in mind However, be aware that there are a few situations in which the statement with a trigger word is correct Choices that not fit the stem grammatically are usually wrong For example: A drug that acts on a -receptor and produces a maximal effect that is equal to one half the effect of a large dose of isoproterenol is called a (A) Agonist (B) Analog of isoproterenol (C) Antagonist (D) Partial agonist The use of the article a at the end of the stem rather than an implies that the answer must start with a consonant (ie, choice D) Similar use may be made of disagreements in number Note that careful question writers avoid this problem by placing the articles in the choice list, not in the stem A statement is not false just because changing a few words will make it somewhat more true than you think it is now "Choose the one best answer" does not mean "Choose the only correct statement." Strategies for "All of the Following Are Accurate Except" Questions This type of question is avoided now on the USMLE because of problems with ambiguity; however, this type still is used in many local examinations because question-writers perceive them to be relatively easier to construct When faced with this type of question, approach it as a nested set of true/false questions in which (hopefully) only one is true It may help to mark each choice as either "T" or "F" as you read through them If statements are contradictory, then of them is certain to be the correct (false) answer because they cannot both be accurate statements, and yet this type of question cannot have false answers For example, consider the following: All of the following may result from the use of thiazide diuretics EXCEPT (A) Hyperglycemia (B) Hypernatremia (C) Hyponatremia (D) Hyperuricemia (E) Metabolic alkalosis The correct answer is B: hypernatremia The possibility that thiazide diuretics not affect serum sodium concentrations is not tenable because that would produce false choices It is also somewhat unlikely that a drug could cause opposite effects: therefore, the probability that of the opposites is the correct (false) answer is high If the choices contain drugs that are highly similar, then neither is likely to be the correct (false) answer For example, consider the following: A young man who had become physiologically dependent after illicit use of secobarbital is undergoing severe withdrawal symptoms, including nausea, vomiting, delirium, and periodic seizures Which one of the following drugs will NOT alleviate these symptoms? (A) Buspirone (B) Chlordiazepoxide (C) Diazepam (D) Midazolam (E) Phenobarbital The correct answer is A: buspirone If you recognize that chlordiazepoxide, diazepam, and midazolam all are benzodiazepine drugs with virtually identical pharmacologic effects, then you can quite safely rule out all three of them Strategies for Matching Type Questions Matching questions usually test name recognition, and the most efficient approach consists of reading each stem item and then scanning the list of choices from the start and picking the first clear "hit." This is especially important on extended matching questions in which just reading the list can be time consuming (Note, however, that the strategy suggested by the National Board of Medical Examiners for the USMLE differs from the above; see their General Instructions publication.) Occasionally, the strategies described above for the single best answer type question can be applied to the matching and extended matching type Strategies for the "Answer A if 1, 2, and Are Correct" Type Question This type of question, known as the "K type," has been dropped from the USMLE and therefore is no longer represented among the practice questions provided in this Review However, it is still used in many local examinations For this type of question, one rarely must know the truth about all statements to arrive at the correct answer The instructions are to select (A) if only (1), (2), and (3) are correct; (B) if only (1) and (3) are correct; (C) if only (2) and (4) are correct; (D) if only (4) is correct; (E) if all are correct Useful strategies include the following: If statement is correct and is wrong, the answer must be B (ie, and are correct) You don't need to know anything about or If statement is wrong, then answers A, B, and E are automatically excluded Concentrate on statements and The converse of above: If choice is wrong and is correct, the answer must be C (ie, and are correct) If statement is correct and is wrong, the answer is A (ie, and must be correct and you need not even look at them) (See example below.) If statements 1, 2, and are correct, the answer must be E You need not know anything about Similarly, if statements and are correct and is wrong, the answer must be A, and statement must be correct If statements 2, 3, and are correct, then the answer must be E, and statement must be correct No doubt, more of these rules exist In general, if you know whether or of the statements in each question are right or wrong (ie, 50-75% the material), you should achieve a perfect score on this kind of question The best way to learn these rules is to apply them to practice questions until the principles are firmly ingrained Consider the following question Using the above rules, you should be able to answer it correctly even though there is no reason why you should know anything about the information contained in of the statements The answer follows Which of the following statements is (are) correct? The "struck bushel" is equal to 2150.42 cubic inches Medicine is one of the health sciences The fresh meat of the Atlantic salmon contains 220 IU of vitamin A per 100 g edible portion Hippocrates was the founder of modern psychoanalysis The answer is A Because statement is clearly correct and is just as patently incorrect (let's give Freud the credit), the answer can only be A, and statements and must be correct (The data are from Lentner C, editor: Geigy Scientific Tables, 8th ed Vol Ciba-Geigy, 1981.) References Le T, et al: First Aid for the USMLE STEP 2010 McGraw-Hill, 2010 Case SM, Swanson DB: Constructing Written Test Questions for the Basic and Clinical Sciences, 2nd ed National Board of Medical Examiners, 1998 Available only from the World Wide Web (www.nbme.org/Publications; Item-Writing Manual) Fischer MR, Herrmann S, Kopp V: Answering multiple-choice questions in high-stakes medical examinations Medical Education 2005;39:890 [PMID: 16150028] Step content description and sample test materials National Board of Medical Examiners Available annually from the USMLE World Wide Web page at www.usmle.org Chemotherapeutic Drugs: Overview Introduction The emergence of microbial resistance poses a constant challenge to the use of antimicrobial drugs Mechanisms underlying microbial resistance to cell wall synthesis inhibitors include the production of antibiotic-inactivating enzymes, changes in the structure of target receptors, increased efflux via drug transporters, and decreases in the permeability of microbes’ cellular membranes to antibiotics Strategies designed to combat microbial resistance include the use of adjunctive agents that can protect against antibiotic inactivation, the use of antibiotic combinations, the introduction of new (and often expensive) chemical derivatives of established antibiotics, and efforts to avoid the indiscriminate use or misuse of antibiotics AppendixIV Strategies for Improving Test Performance Strategies for Improving Test Performance: Introduction There are many strategies for studying and exam taking, and decisions about which ones to use are partly a function of individual habit and preference However, basic study rules may be applied to any learning exercise; test-taking strategies depend on the type of examination For those interested in test-writing strategies, the Case and Swanson reference is strongly recommended (see References) Five Basic Study Rules When studying dense textual material, stop after a few pages to write out the gist of it from memory If necessary, refer to the material just read After finishing a chapter, construct your own tables of the major drugs, receptor types, mechanisms, and so on, and fill in as many of the blanks as you can Refer to tables and figures in the book as needed to complete your notes Create your own mnemonics if possible Look up other mnemonics in books if you can't think of one yourself These are all active learning techniques; mere reading is passive and far less effective unless you happen to have a photographic memory Your notes should be legible or typed on a computer, and saved for ready access when reviewing for exams Experiment with other study methods until you find out what works for you This may involve solo study or group study, flash cards, or text reading You won't know how effective these techniques are until you have tried them Don't scorn "cramming," but don't rely on it either Some steady, day-by-day reading and digestion of conceptual material is usually needed to avoid last-minute indigestion Similarly, don't substitute memorization of lists (eg, the Key Words list, Appendix I) for more substantive understanding If you are preparing for a course examination, make every effort to attend all the lectures The lecturer's view of what is important may be different from that of the author of a course textbook, and chances are good that exam questions will be based on the instructor's own lecture notes If old test questions are legitimately available (as they are for the USMLE and courses in most medical schools), make use of these guides to study By definition, they are a strong indicator of what the examination writers have considered core information in the recent past (also see Point 4) Strategies Applicable to All Examinations Three general rules apply to all examinations When starting the examination, scan the entire question set before answering any If the examination has several parts, allot time to each part in proportion to its length and difficulty Within each part, answer the easy questions first, placing a mark in the margin by the questions to which you will return Practice saving enough time for the more difficult questions by scheduling or less for each question on practice examinations such as those in Examinations and in the SelfAssessment (The time available in the USMLE examination is approximately 55–60 sec per question.) Students are often advised to avoid changing their first guess on multiple-choice questions However, research has shown that students who are unsure of the answer to a question make a change from the incorrect answer to the correct answer about 55% of the time So if you are unsure of your first choice for a particular question and on further reflection see an answer that looks better, research supports your making one—but only one—change Understand the method for scoring wrong answers The USMLE does not penalize for wrong answers; it scores you only on the total number of correct answers Therefore, even if you have no idea as to the correct answer, make a guess anyway; there is no penalty for an incorrect answer In other words, not leave any blanks on a USMLE answer sheet or computer screen Note that this may not be true for some local examinations; some scoring algorithms penalize for incorrect answers Make sure you understand the rules for such local examinations Strategies for Specific Question Formats A certain group of students—often characterized as "good test-takers"—may not know every detail about the subject matter being tested but seem to perform extremely well most of the time The strategy used by these people is not a secret, although few instructors seem to realize how easy it is to break down their questions into much simpler ones Lists of these strategies are widely available (eg, in the descriptive material distributed by the National Board of Medical Examiners to its candidates) A paraphrased compendium of this advice is presented next Strategies for the "Choose the One Best Answer" (of Choices) Type Question Many of the newer "clinical correlation" questions on the Board exam have an extremely long stem that provides a great deal of clinical data Much of the data presented may be irrelevant The challenge becomes one of finding out what is being asked One method for rapidly narrowing the search, especially when confronted with a long stem, is to just read the last sentence of the stem, then scan the answer list The nature of the last sentence and the answers provide a clue to the parts of the stem that are relevant and those that are not If statements are contradictory (ie, only can be correct), chances are good that of the is the correct answer (ie, the other choices may be distracters) For example, consider the following: In treating quinidine overdose, the best strategy would be to (A) Acidify the urine (B) Administer a calcium chelator such as EDTA (C) Alkalinize the urine (D) Give potassium chloride (E) Give procainamide The correct answer is A: acidify the urine In the pair of contradictory distractors (choices A and C), the instructor revealed what was being tested and then used the other three as "filler." Therefore, if you don't know the answer, you are better off guessing A or C (a 50% success probability) than A or B or C or D or E (a 20% success probability) Note that this strategy is valid only if you must guess; many instructors now introduce contradictory pairs as distracters Another "rule" that should be used only if you must guess is the "longest choice" rule When all the answers in a multiple-choice question are relatively long, the correct answer is often the longest one Note again that sophisticated question writers may introduce especially long incorrect choices to foil this strategy Statements that contain the words "always," "never," "must," and so on are usually false For example, Acetylcholine always increases the heart rate when given intravenously because it lowers blood pressure and evokes a strong baroreceptor-mediated reflex tachycardia The statement is false because, although acetylcholine often increases the heart rate, it can also cause bradycardia (When given as a bolus, it may reach the sinus node in high enough concentration to cause initial bradycardia.) The use of trigger words such as "always" and "must" suggests that the instructor had some exception in mind However, be aware that there are a few situations in which the statement with a trigger word is correct Choices that not fit the stem grammatically are usually wrong For example: A drug that acts on a -receptor and produces a maximal effect that is equal to one half the effect of a large dose of isoproterenol is called a (A) Agonist (B) Analog of isoproterenol (C) Antagonist (D) Partial agonist The use of the article a at the end of the stem rather than an implies that the answer must start with a consonant (ie, choice D) Similar use may be made of disagreements in number Note that careful question writers avoid this problem by placing the articles in the choice list, not in the stem A statement is not false just because changing a few words will make it somewhat more true than you think it is now "Choose the one best answer" does not mean "Choose the only correct statement." Strategies for "All of the Following Are Accurate Except" Questions This type of question is avoided now on the USMLE because of problems with ambiguity; however, this type still is used in many local examinations because question-writers perceive them to be relatively easier to construct When faced with this type of question, approach it as a nested set of true/false questions in which (hopefully) only one is true It may help to mark each choice as either "T" or "F" as you read through them If statements are contradictory, then of them is certain to be the correct (false) answer because they cannot both be accurate statements, and yet this type of question cannot have false answers For example, consider the following: All of the following may result from the use of thiazide diuretics EXCEPT (A) Hyperglycemia (B) Hypernatremia (C) Hyponatremia (D) Hyperuricemia (E) Metabolic alkalosis The correct answer is B: hypernatremia The possibility that thiazide diuretics not affect serum sodium concentrations is not tenable because that would produce false choices It is also somewhat unlikely that a drug could cause opposite effects: therefore, the probability that of the opposites is the correct (false) answer is high If the choices contain drugs that are highly similar, then neither is likely to be the correct (false) answer For example, consider the following: A young man who had become physiologically dependent after illicit use of secobarbital is undergoing severe withdrawal symptoms, including nausea, vomiting, delirium, and periodic seizures Which one of the following drugs will NOT alleviate these symptoms? (A) Buspirone (B) Chlordiazepoxide (C) Diazepam (D) Midazolam (E) Phenobarbital The correct answer is A: buspirone If you recognize that chlordiazepoxide, diazepam, and midazolam all are benzodiazepine drugs with virtually identical pharmacologic effects, then you can quite safely rule out all three of them Strategies for Matching Type Questions Matching questions usually test name recognition, and the most efficient approach consists of reading each stem item and then scanning the list of choices from the start and picking the first clear "hit." This is especially important on extended matching questions in which just reading the list can be time consuming (Note, however, that the strategy suggested by the National Board of Medical Examiners for the USMLE differs from the above; see their General Instructions publication.) Occasionally, the strategies described above for the single best answer type question can be applied to the matching and extended matching type Strategies for the "Answer A if 1, 2, and Are Correct" Type Question This type of question, known as the "K type," has been dropped from the USMLE and therefore is no longer represented among the practice questions provided in this Review However, it is still used in many local examinations For this type of question, one rarely must know the truth about all statements to arrive at the correct answer The instructions are to select (A) if only (1), (2), and (3) are correct; (B) if only (1) and (3) are correct; (C) if only (2) and (4) are correct; (D) if only (4) is correct; (E) if all are correct Useful strategies include the following: If statement is correct and is wrong, the answer must be B (ie, and are correct) You don't need to know anything about or If statement is wrong, then answers A, B, and E are automatically excluded Concentrate on statements and The converse of above: If choice is wrong and is correct, the answer must be C (ie, and are correct) If statement is correct and is wrong, the answer is A (ie, and must be correct and you need not even look at them) (See example below.) If statements 1, 2, and are correct, the answer must be E You need not know anything about Similarly, if statements and are correct and is wrong, the answer must be A, and statement must be correct If statements 2, 3, and are correct, then the answer must be E, and statement must be correct No doubt, more of these rules exist In general, if you know whether or of the statements in each question are right or wrong (ie, 50–75% the material), you should achieve a perfect score on this kind of question The best way to learn these rules is to apply them to practice questions until the principles are firmly ingrained Consider the following question Using the above rules, you should be able to answer it correctly even though there is no reason why you should know anything about the information contained in of the statements The answer follows Which of the following statements is (are) correct? The "struck bushel" is equal to 2150.42 cubic inches Medicine is one of the health sciences The fresh meat of the Atlantic salmon contains 220 IU of vitamin A per 100 g edible portion Hippocrates was the founder of modern psychoanalysis The answer is A Because statement is clearly correct and is just as patently incorrect (let's give Freud the credit), the answer can only be A, and statements and must be correct (The data are from Lentner C, editor: Geigy Scientific Tables, 8th ed Vol Ciba-Geigy, 1981.) ... Professor Emeritus of Pharmacology and Toxicology Department of Cellular & Molecular Pharmacology University of California, San Francisco Bertram G Katzung, MD, PhD Professor Emeritus of Pharmacology. .. Clinical Pharmacology textbook This review book divides pharmacology into the topics used in most courses and textbooks Major introductory chapters (eg, autonomic pharmacology and CNS pharmacology) ... Cellular & Molecular Pharmacology University of California, San Francisco Susan B Masters, PhD Professor & Academy Chair of Pharmacology Education Department of Cellular & Molecular Pharmacology University
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