Additional Information
Book Details
Abstract
A favorite among nursing students, Pharmacology for Nursing Care, 8th Edition, features a uniquely engaging writing style, clear explanations, and unmatched clinical precision and currency to help you gain a solid understanding of key drugs and their implications -- as opposed to just memorization of certain facts. Compelling features such as a drug prototype approach, use of large and small print to distinguish need-to-know versus nice-to-know content, and a focus on major nursing implications save you study time by directing your attention on the most important, need-to-know information. The new edition also features an abundance of content updates to keep you ahead of the curve in school and in professional practice.
- UNIQUE! Engaging writing style with clear explanations makes content easy to grasp and even enjoyable to learn.
- A drug prototype approach uses one drug within each drug family to characterize all members of its group to help you learn about related drugs currently on the market and drugs that will be released once you begin practice.
- UNIQUE! Special Interest Topic boxes address timely issues in pharmacology and connect pharmacology content with current trends.
- Large print/small print design distinguishes essential "need-to-know" information from "nice-to-know" information.
- Limited discussion of adverse effects and drug interactions keeps your limited study time focused on only the most clinically important information.
- Reliance on up-to-date evidence-based clinical guidelines ensures that therapeutic uses are clinically relevant.
- Integrated and summarized nursing content demonstrates the vital interplay between drug therapy and nursing care.
- Coverage of dietary supplements and herbal interactions equips you to alert patients and caregivers to the potential dangers of certain dietary supplements, including interactions with prescribed and over-the-counter drugs and herbal therapies.
- Additional learning features provide a touchstone for study and review as you complete reading assignments and build a foundation of pharmacologic knowledge.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | Cover | ||
| Table of contents | ifc1 | ||
| Front matter | i | ||
| Pharmacology for nursing care | i | ||
| Copyright | ii | ||
| Dedication | iii | ||
| About the author | iv | ||
| Contributors and reviewers | v | ||
| Welcome to our eighth edition | vi | ||
| What’s new in the book? | vi | ||
| New drugs | vi | ||
| New special interest topics | vi | ||
| Restructured content | vi | ||
| Canadian trade names | vii | ||
| Learning supplements for students | vii | ||
| Evolve student resources | vii | ||
| Pharmacology online | vii | ||
| Study guide | vii | ||
| Teaching supplements for instructors | vii | ||
| Evolve instructor resources | vii | ||
| Please write | vii | ||
| Preface | viii | ||
| Laying foundations in basic principles | viii | ||
| Reviewing physiology and pathophysiology | viii | ||
| Teaching through prototypes | viii | ||
| Large print and small print: A way to focus on essentials | viii | ||
| Using clinical reality to prioritize content | viii | ||
| Nursing implications: Demonstrating the application of pharmacology in nursing practice | ix | ||
| About dosage calculations | ix | ||
| Ways to use this textbook | ix | ||
| Acknowledgments | x | ||
| 1 Orientation to pharmacology | 1 | ||
| Four basic terms | 1 | ||
| Properties of an ideal drug | 1 | ||
| The big three: Effectiveness, safety, and selectivity | 2 | ||
| Additional properties of an ideal drug | 2 | ||
| Because no drug is ideal . . . | 2 | ||
| The therapeutic objective | 3 | ||
| Factors that determine the intensity of drug responses | 3 | ||
| Administration | 3 | ||
| Pharmacokinetics | 3 | ||
| Pharmacodynamics | 3 | ||
| Sources of individual variation | 4 | ||
| Summary | 4 | ||
| Key points | 4 | ||
| 2 Application of pharmacology in nursing practice | 5 | ||
| Evolution of nursing responsibilities regarding drugs | 5 | ||
| Application of pharmacology in patient care | 6 | ||
| Preadministration assessment | 6 | ||
| Dosage and administration | 6 | ||
| Evaluating and promoting therapeutic effects | 7 | ||
| Minimizing adverse effects | 7 | ||
| Minimizing adverse interactions | 7 | ||
| Making PRN decisions | 7 | ||
| Managing toxicity | 8 | ||
| Application of pharmacology in patient education | 8 | ||
| Dosage and administration | 8 | ||
| Promoting therapeutic effects | 8 | ||
| Minimizing adverse effects | 9 | ||
| Minimizing adverse interactions | 9 | ||
| Application of the nursing process in drug therapy | 9 | ||
| Review of the nursing process | 9 | ||
| Applying the nursing process in drug therapy | 9 | ||
| Preadministration assessment | 10 | ||
| Baseline data needed to evaluate therapeutic effects. | 10 | ||
| Baseline data needed to evaluate adverse effects. | 10 | ||
| Identification of high-risk patients. | 10 | ||
| Assessment of the patient’s capacity for self-care. | 10 | ||
| Analysis and nursing diagnoses | 11 | ||
| Planning | 11 | ||
| Defining goals. | 11 | ||
| Setting priorities. | 11 | ||
| Identifying interventions. | 12 | ||
| Establishing criteria for evaluation. | 12 | ||
| Implementation | 12 | ||
| Evaluation | 12 | ||
| Use of a modified nursing process format to summarize nursing implications in this text | 12 | ||
| Summary | 13 | ||
| Key points | 14 | ||
| 3 Drug regulation, development, names, and information | 15 | ||
| Landmark drug legislation | 15 | ||
| New drug development | 16 | ||
| The randomized controlled trial | 16 | ||
| Stages of new drug development | 17 | ||
| Preclinical testing | 17 | ||
| Clinical testing | 17 | ||
| Phase I. | 17 | ||
| Phases II and III. | 17 | ||
| Phase IV: Postmarketing surveillance. | 17 | ||
| Limitations of the testing procedure | 17 | ||
| Limited information in women and children | 17 | ||
| Women. | 17 | ||
| Children. | 18 | ||
| Failure to detect all adverse effects | 18 | ||
| Exercising discretion regarding new drugs | 19 | ||
| Drug names | 19 | ||
| The three types of drug names | 19 | ||
| Which name to use, generic or trade? | 20 | ||
| The little problems with generic names | 20 | ||
| The big problems with trade names | 21 | ||
| A single drug can have multiple trade names. | 21 | ||
| Over-the-counter (OTC) products with the same trade name may have different active ingredients. | 21 | ||
| Trade names can endanger international travelers. | 22 | ||
| What if peas were marketed like drugs? | 22 | ||
| Generic products versus brand-name products | 23 | ||
| Are generic products and brand-name products therapeutically equivalent? | 23 | ||
| Would a difference between brand-name and generic products justify the use of trade names? | 23 | ||
| Conclusion regarding generic names and trade names | 23 | ||
| Over-the-counter drugs | 23 | ||
| Sources of drug information | 24 | ||
| People | 24 | ||
| Published information | 24 | ||
| Text-like books | 24 | ||
| Newsletters | 24 | ||
| Reference books | 25 | ||
| The internet | 25 | ||
| Key points | 25 | ||
| 4 Pharmacokinetics | 26 | ||
| Application of pharmacokinetics in therapeutics | 26 | ||
| A note to chemophobes | 26 | ||
| Passage of drugs across membranes | 27 | ||
| Membrane structure | 27 | ||
| Three ways to cross a cell membrane | 27 | ||
| Channels and pores | 27 | ||
| Transport systems | 27 | ||
| P-glycoprotein. | 28 | ||
| Direct penetration of the membrane | 28 | ||
| Polar molecules | 28 | ||
| Ions | 29 | ||
| Quaternary ammonium compounds | 29 | ||
| pH-dependent ionization | 29 | ||
| Ion trapping (pH partitioning) | 30 | ||
| Absorption | 30 | ||
| Factors affecting drug absorption | 30 | ||
| Characteristics of commonly used routes of administration | 31 | ||
| Intravenous | 32 | ||
| Barriers to absorption. | 32 | ||
| Absorption pattern. | 32 | ||
| Advantages. | 32 | ||
| Rapid onset. | 32 | ||
| Control. | 32 | ||
| Permits use of large fluid volumes. | 32 | ||
| Permits use of irritant drugs. | 32 | ||
| Disadvantages. | 32 | ||
| High cost, difficulty, and inconvenience. | 32 | ||
| Irreversibility. | 32 | ||
| Fluid overload. | 33 | ||
| Infection. | 33 | ||
| Embolism. | 33 | ||
| The importance of reading labels. | 33 | ||
| Intramuscular | 33 | ||
| Barriers to absorption. | 33 | ||
| 5 Pharmacodynamics | 48 | ||
| Dose-response relationships | 48 | ||
| Basic features of the dose-response relationship | 48 | ||
| Maximal efficacy and relative potency | 48 | ||
| Maximal efficacy | 48 | ||
| Relative potency | 49 | ||
| Drug-receptor interactions | 50 | ||
| Introduction to drug receptors | 50 | ||
| The four primary receptor families | 51 | ||
| Receptors and selectivity of drug action | 52 | ||
| Theories of drug-receptor interaction | 53 | ||
| Simple occupancy theory | 53 | ||
| Modified occupancy theory | 53 | ||
| Affinity. | 53 | ||
| Intrinsic activity. | 53 | ||
| Agonists, antagonists, and partial agonists | 53 | ||
| Agonists | 54 | ||
| Antagonists | 54 | ||
| Noncompetitive versus competitive antagonists. | 54 | ||
| Noncompetitive (insurmountable) antagonists. | 54 | ||
| Competitive (surmountable) antagonists. | 54 | ||
| Partial agonists | 55 | ||
| Regulation of receptor sensitivity | 55 | ||
| Drug responses that do not involve receptors | 55 | ||
| Interpatient variability in drug responses | 55 | ||
| The therapeutic index | 57 | ||
| Key points | 58 | ||
| 6 Drug interactions | 59 | ||
| Drug-drug interactions | 59 | ||
| Consequences of drug-drug interactions | 59 | ||
| Intensification of effects | 59 | ||
| Increased therapeutic effects. | 59 | ||
| Increased adverse effects. | 59 | ||
| Reduction of effects | 59 | ||
| Reduced therapeutic effects. | 59 | ||
| Reduced adverse effects. | 60 | ||
| Creation of a unique response | 60 | ||
| Basic mechanisms of drug-drug interactions | 60 | ||
| Direct chemical or physical interactions | 60 | ||
| Pharmacokinetic interactions | 60 | ||
| Altered absorption. | 60 | ||
| Altered distribution. | 60 | ||
| Altered metabolism. | 60 | ||
| Induction of CYP isozymes. | 60 | ||
| Inhibition of CYP isozymes. | 62 | ||
| Altered renal excretion. | 62 | ||
| Interactions that involve p-glycoprotein. | 62 | ||
| Pharmacodynamic interactions | 62 | ||
| Interactions at the same receptor. | 62 | ||
| Interactions resulting from actions at separate sites. | 63 | ||
| Combined toxicity | 63 | ||
| Clinical significance of drug-drug interactions | 63 | ||
| Minimizing adverse drug-drug interactions | 63 | ||
| Drug-food interactions | 63 | ||
| Impact of food on drug absorption | 63 | ||
| Impact of food on drug metabolism: The grapefruit juice effect | 64 | ||
| Impact of food on drug toxicity | 65 | ||
| Impact of food on drug action | 65 | ||
| Timing of drug administration with respect to meals | 65 | ||
| Drug-supplement interactions | 65 | ||
| Key points | 66 | ||
| 7 Adverse drug reactions and medication errors | 67 | ||
| Adverse drug reactions | 67 | ||
| Scope of the problem | 67 | ||
| Definitions | 67 | ||
| Side effect | 67 | ||
| Toxicity | 67 | ||
| Allergic reaction | 67 | ||
| Idiosyncratic effect | 68 | ||
| Iatrogenic disease | 68 | ||
| Physical dependence | 68 | ||
| Carcinogenic effect | 68 | ||
| Teratogenic effect | 68 | ||
| Organ-specific toxicity | 68 | ||
| Hepatotoxic drugs | 68 | ||
| QT interval drugs | 69 | ||
| Identifying adverse drug reactions | 69 | ||
| Adverse reactions to new drugs | 70 | ||
| Ways to minimize adverse drug reactions | 72 | ||
| Medication guides, boxed warnings, and REMS | 72 | ||
| Medication guides | 72 | ||
| Boxed warnings | 72 | ||
| Risk evaluation and mitigation strategies | 73 | ||
| Medication errors | 73 | ||
| What’s a medication error and who makes them? | 73 | ||
| Types of medication errors | 73 | ||
| Causes of medication errors | 73 | ||
| Ways to reduce medication errors | 74 | ||
| How to report a medication error | 76 | ||
| Key points | 78 | ||
| 8 Individual variation in drug responses | 79 | ||
| Body weight and composition | 79 | ||
| Age | 79 | ||
| Pathophysiology | 79 | ||
| Kidney disease | 79 | ||
| Liver disease | 80 | ||
| Tolerance | 80 | ||
| Pharmacodynamic tolerance | 80 | ||
| Metabolic tolerance | 81 | ||
| Placebo effect | 81 | ||
| Variability in absorption | 81 | ||
| Bioavailability | 83 | ||
| Other causes of variable absorption | 83 | ||
| Genetics and pharmacogenomics | 83 | ||
| Genetic variants that alter drug metabolism | 83 | ||
| Genetic variants that alter drug targets | 85 | ||
| Genetic variants that alter immune responses to drugs | 85 | ||
| Gender | 85 | ||
| Race | 86 | ||
| Drug interactions | 86 | ||
| Diet | 86 | ||
| Failure to take medicine as prescribed | 87 | ||
| Key points | 87 | ||
| 9 Drug therapy during pregnancy and breast-feeding | 88 | ||
| Drug therapy during pregnancy: Basic considerations | 88 | ||
| Physiologic changes during pregnancy and their impact on drug disposition and dosing | 88 | ||
| Placental drug transfer | 89 | ||
| Adverse reactions during pregnancy | 89 | ||
| Drug therapy during pregnancy: Teratogenesis | 89 | ||
| Incidence and causes of congenital anomalies | 89 | ||
| Teratogenesis and stage of development | 89 | ||
| Identification of teratogens | 89 | ||
| FDA pregnancy risk categories | 92 | ||
| Minimizing the risk of drug-induced teratogenesis | 92 | ||
| Responding to teratogen exposure | 92 | ||
| Drug therapy during breast-feeding | 93 | ||
| Key points | 94 | ||
| 10 Drug therapy in pediatric patients | 95 | ||
| Pharmacokinetics: Neonates and infants | 95 | ||
| Absorption | 96 | ||
| Distribution | 96 | ||
| Hepatic metabolism | 96 | ||
| Renal excretion | 97 | ||
| Pharmacokinetics: Children 1 year and older | 97 | ||
| Adverse drug reactions | 97 | ||
| Dosage determination | 97 | ||
| Promoting adherence | 98 | ||
| Key points | 98 | ||
| 11 Drug therapy in geriatric patients | 99 | ||
| Pharmacokinetic changes in the elderly | 99 | ||
| Pharmacodynamic changes in the elderly | 100 | ||
| Adverse drug reactions and drug interactions | 100 | ||
| Promoting adherence | 100 | ||
| Key points | 102 | ||
| 12 Basic principles of neuropharmacology | 103 | ||
| How neurons regulate physiologic processes | 103 | ||
| Basic mechanisms by which neuropharmacologic agents ACT | 104 | ||
| Sites of action: Axons versus synapses | 104 | ||
| Axonal conduction | 104 | ||
| Synaptic transmission | 104 | ||
| Receptors | 104 | ||
| Steps in synaptic transmission | 104 | ||
| Effects of drugs on the steps of synaptic transmission | 105 | ||
| Multiple receptor types and selectivity of drug action | 106 | ||
| An approach to learning about peripheral nervous system drugs | 107 | ||
| Key points | 107 | ||
| 13 Physiology of the peripheral nervous system | 109 | ||
| Divisions of the nervous system | 109 | ||
| Overview of autonomic nervous system functions | 109 | ||
| Functions of the parasympathetic nervous system | 109 | ||
| Functions of the sympathetic nervous system | 110 | ||
| Basic mechanisms by which the autonomic nervous system regulates physiologic processes | 110 | ||
| Anatomic considerations | 111 | ||
| Introduction to transmitters of the peripheral nervous system | 112 | ||
| Introduction to receptors of the peripheral nervous system | 112 | ||
| Exploring the concept of receptor subtypes | 113 | ||
| Locations of receptor subtypes | 115 | ||
| Functions of cholinergic and adrenergic receptor subtypes | 115 | ||
| Functions of cholinergic receptor subtypes | 115 | ||
| Functions of adrenergic receptor subtypes | 116 | ||
| Alpha1 receptors | 116 | ||
| Alpha2 receptors | 116 | ||
| Beta1 receptors | 117 | ||
| Beta2 receptors | 117 | ||
| Dopamine receptors | 118 | ||
| Receptor specificity of the adrenergic transmitters | 118 | ||
| Transmitter life cycles | 119 | ||
| Life cycle of acetylcholine | 119 | ||
| Life cycle of norepinephrine | 120 | ||
| Life cycle of epinephrine | 120 | ||
| Key points | 121 | ||
| Introduction to Cholinergic Drugs | 122 | ||
| 14 Muscarinic agonists and antagonists | 124 | ||
| Muscarinic agonists | 124 | ||
| Bethanechol | 124 | ||
| Mechanism of action | 124 | ||
| Pharmacologic effects | 124 | ||
| Therapeutic uses | 124 | ||
| Urinary retention. | 124 | ||
| Adverse effects | 125 | ||
| Cardiovascular system. | 125 | ||
| Alimentary system. | 125 | ||
| Urinary tract. | 125 | ||
| Exacerbation of asthma. | 125 | ||
| Dysrhythmias in hyperthyroid patients. | 125 | ||
| Toxicology of muscarinic agonists | 126 | ||
| Muscarinic antagonists (anticholinergic drugs) | 126 | ||
| Atropine | 126 | ||
| Mechanism of action | 126 | ||
| Pharmacologic effects | 126 | ||
| Heart. | 126 | ||
| Exocrine glands. | 126 | ||
| Smooth muscle. | 126 | ||
| Eye. | 127 | ||
| Central nervous system (cns). | 127 | ||
| Dose dependency of muscarinic blockade. | 127 | ||
| Therapeutic uses | 127 | ||
| Preanesthetic medication. | 127 | ||
| Disorders of the eye. | 127 | ||
| Bradycardia. | 127 | ||
| Intestinal hypertonicity and hypermotility. | 127 | ||
| Muscarinic agonist poisoning. | 127 | ||
| Adverse effects | 127 | ||
| Xerostomia (dry mouth). | 127 | ||
| Blurred vision and photophobia. | 128 | ||
| Elevation of intraocular pressure. | 128 | ||
| Urinary retention. | 128 | ||
| Constipation. | 128 | ||
| Anhidrosis. | 128 | ||
| Tachycardia. | 128 | ||
| Asthma. | 128 | ||
| Drug interactions | 128 | ||
| Muscarinic antagonists for overactive bladder | 128 | ||
| Overactive bladder: Characteristics and overview of treatment | 128 | ||
| Introduction to anticholinergic therapy of OAB | 129 | ||
| Specific anticholinergic drugs for OAB | 129 | ||
| Toxicology of muscarinic antagonists | 132 | ||
| Key points | 133 | ||
| 15 Cholinesterase inhibitors and their use in myasthenia gravis | 135 | ||
| Reversible cholinesterase inhibitors | 135 | ||
| Neostigmine | 135 | ||
| Chemistry | 135 | ||
| Mechanism of action | 135 | ||
| Pharmacologic effects | 135 | ||
| Muscarinic responses. | 136 | ||
| Neuromuscular effects. | 137 | ||
| Central nervous system. | 137 | ||
| Pharmacokinetics | 137 | ||
| Therapeutic uses | 137 | ||
| Myasthenia gravis. | 137 | ||
| Reversal of competitive (nondepolarizing) neuromuscular blockade. | 137 | ||
| Adverse effects | 137 | ||
| Excessive muscarinic stimulation. | 137 | ||
| Neuromuscular blockade. | 137 | ||
| Precautions and contraindications | 137 | ||
| Drug interactions | 137 | ||
| Muscarinic antagonists. | 137 | ||
| Competitive neuromuscular blockers. | 137 | ||
| Depolarizing neuromuscular blockers. | 137 | ||
| Acute toxicity | 137 | ||
| Symptoms. | 137 | ||
| Treatment. | 137 | ||
| Other reversible cholinesterase inhibitors | 138 | ||
| Physostigmine | 138 | ||
| “Irreversible” cholinesterase inhibitors | 138 | ||
| Basic pharmacology | 138 | ||
| Chemistry | 138 | ||
| Mechanism of action | 139 | ||
| Pharmacologic effects | 139 | ||
| Therapeutic uses | 139 | ||
| Toxicology | 139 | ||
| Myasthenia gravis | 139 | ||
| Pathophysiology | 139 | ||
| Treatment with cholinesterase inhibitors | 140 | ||
| Key points | 141 | ||
| 16 Drugs that block nicotinic cholinergic transmission: Neuromuscular blocking agents and ganglionic blocking agents | 143 | ||
| Neuromuscular blocking agents | 143 | ||
| Control of muscle contraction | 143 | ||
| Competitive (nondepolarizing) neuromuscular blockers | 145 | ||
| Group properties | 145 | ||
| Chemistry | 145 | ||
| Mechanism of action | 145 | ||
| Pharmacologic effects | 145 | ||
| Muscle relaxation. | 145 | ||
| Hypotension. | 145 | ||
| Central nervous system. | 145 | ||
| Pharmacokinetics | 145 | ||
| Therapeutic uses | 146 | ||
| Adverse effects | 146 | ||
| Respiratory arrest. | 146 | ||
| Hypotension. | 146 | ||
| Precautions and contraindications | 146 | ||
| Myasthenia gravis. | 146 | ||
| Electrolyte disturbances. | 146 | ||
| Drug interactions | 146 | ||
| General anesthetics. | 146 | ||
| Antibiotics. | 146 | ||
| Cholinesterase inhibitors. | 146 | ||
| Toxicity | 147 | ||
| Properties of individual agents | 147 | ||
| Depolarizing neuromuscular blockers: Succinylcholine | 147 | ||
| Therapeutic uses of neuromuscular blockers | 148 | ||
| Key points | 150 | ||
| 17 Adrenergic agonists | 152 | ||
| Mechanisms of adrenergic receptor activation | 152 | ||
| Overview of the adrenergic agonists | 153 | ||
| Chemical classification: Catecholamines versus noncatecholamines | 153 | ||
| Catecholamines | 153 | ||
| Noncatecholamines | 153 | ||
| Receptor specificity | 153 | ||
| Therapeutic applications and adverse effects of adrenergic receptor activation | 154 | ||
| Clinical consequences of alpha1 activation | 155 | ||
| Therapeutic applications of alpha1 activation | 155 | ||
| Hemostasis. | 155 | ||
| Nasal decongestion. | 155 | ||
| Adjunct to local anesthesia. | 155 | ||
| Elevation of blood pressure. | 155 | ||
| Mydriasis. | 155 | ||
| Adverse effects of alpha1 activation | 156 | ||
| Hypertension. | 156 | ||
| Necrosis. | 156 | ||
| Bradycardia. | 156 | ||
| Clinical consequences of alpha2 activation | 156 | ||
| Clinical consequences of beta1 activation | 156 | ||
| Therapeutic applications of beta1 activation | 156 | ||
| Heart failure. | 156 | ||
| Shock. | 156 | ||
| Atrioventricular heart block. | 156 | ||
| Cardiac arrest caused by asystole. | 156 | ||
| Adverse effects of beta1 activation | 156 | ||
| Altered heart rate or rhythm. | 156 | ||
| Angina pectoris. | 156 | ||
| Clinical consequences of beta2 activation | 156 | ||
| Therapeutic applications of beta2 activation | 156 | ||
| Asthma. | 156 | ||
| Delay of preterm labor. | 157 | ||
| Adverse effects of beta2 activation | 157 | ||
| Hyperglycemia. | 157 | ||
| Tremor. | 157 | ||
| Clinical consequences of dopamine receptor activation | 157 | ||
| Multiple receptor activation: Treatment of anaphylactic shock | 157 | ||
| Properties of representative adrenergic agonists | 157 | ||
| Epinephrine | 157 | ||
| Therapeutic uses | 157 | ||
| Pharmacokinetics | 159 | ||
| Absorption. | 159 | ||
| Inactivation. | 159 | ||
| Adverse effects | 159 | ||
| Hypertensive crisis. | 159 | ||
| Dysrhythmias. | 159 | ||
| Angina pectoris. | 159 | ||
| Necrosis following extravasation. | 159 | ||
| Hyperglycemia. | 159 | ||
| Drug interactions | 159 | ||
| MAO inhibitors. | 159 | ||
| Tricyclic antidepressants. | 159 | ||
| General anesthetics. | 159 | ||
| Alpha-adrenergic blocking agents. | 159 | ||
| Beta-adrenergic blocking agents. | 159 | ||
| Preparations, dosage, and administration | 159 | ||
| Isoproterenol | 160 | ||
| 18 Adrenergic antagonists | 165 | ||
| Alpha-adrenergic antagonists | 165 | ||
| Therapeutic and adverse responses to alpha blockade | 165 | ||
| Therapeutic applications of alpha blockade | 165 | ||
| Adverse effects of alpha blockade | 166 | ||
| Adverse effects of alpha1 blockade | 166 | ||
| Orthostatic hypotension. | 166 | ||
| Reflex tachycardia. | 166 | ||
| Nasal congestion. | 166 | ||
| Inhibition of ejaculation. | 166 | ||
| Properties of individual alpha blockers | 167 | ||
| Prazosin | 167 | ||
| Beta-adrenergic antagonists | 168 | ||
| Therapeutic and adverse responses to beta blockade | 168 | ||
| Therapeutic applications of beta blockade | 168 | ||
| Adverse effects of beta blockade | 169 | ||
| Adverse effects of beta1 blockade | 169 | ||
| Bradycardia. | 169 | ||
| Reduced cardiac output. | 169 | ||
| Precipitation of heart failure. | 169 | ||
| AV heart block. | 169 | ||
| Rebound cardiac excitation. | 169 | ||
| Adverse effects of beta2 blockade | 170 | ||
| Bronchoconstriction. | 170 | ||
| Hypoglycemia from inhibition of glycogenolysis. | 170 | ||
| Adverse effects in neonates from beta1 and beta2 blockade | 170 | ||
| Properties of individual beta blockers | 170 | ||
| Propranolol | 170 | ||
| Pharmacologic effects | 170 | ||
| Pharmacokinetics | 170 | ||
| Therapeutic uses | 170 | ||
| Adverse effects | 170 | ||
| Bradycardia. | 170 | ||
| AV heart block. | 170 | ||
| Heart failure. | 170 | ||
| Rebound cardiac excitation. | 170 | ||
| Bronchoconstriction. | 171 | ||
| Inhibition of glycogenolysis. | 171 | ||
| CNS effects. | 171 | ||
| Effects in neonates. | 171 | ||
| Precautions, warnings, and contraindications | 171 | ||
| Severe allergy. | 171 | ||
| Diabetes. | 171 | ||
| Cardiac, respiratory, and psychiatric disorders. | 172 | ||
| Drug interactions | 172 | ||
| Calcium channel blockers. | 172 | ||
| Insulin. | 172 | ||
| Preparations, dosage, and administration | 172 | ||
| General dosing considerations. | 172 | ||
| Metoprolol | 173 | ||
| Other beta-adrenergic blockers | 173 | ||
| Key points | 174 | ||
| 19 Indirect-acting antiadrenergic agents | 177 | ||
| Centrally acting alpha2 agonists | 177 | ||
| Clonidine | 177 | ||
| Mechanism of antihypertensive action | 177 | ||
| Pharmacologic effects | 177 | ||
| Therapeutic uses | 177 | ||
| Adverse effects | 177 | ||
| Drowsiness. | 177 | ||
| Xerostomia. | 178 | ||
| Rebound hypertension. | 178 | ||
| Use in pregnancy. | 178 | ||
| Abuse. | 178 | ||
| Methyldopa and methyldopate | 178 | ||
| Mechanism of action | 178 | ||
| Pharmacologic effects | 178 | ||
| Therapeutic use | 178 | ||
| Adverse effects | 178 | ||
| Positive Coombs’ test and hemolytic anemia. | 178 | ||
| Hepatotoxicity. | 179 | ||
| Key points | 180 | ||
| 20 Introduction to central nervous system pharmacology | 182 | ||
| Transmitters of the CNS | 182 | ||
| The blood-brain barrier | 182 | ||
| How do CNS drugs produce therapeutic effects? | 183 | ||
| Adaptation of the CNS to prolonged drug exposure | 183 | ||
| Development of new psychotherapeutic drugs | 183 | ||
| Approaching the study of CNS drugs | 183 | ||
| Key points | 184 | ||
| 21 Drugs for Parkinsons disease | 185 | ||
| Pathophysiology that underlies motor symptoms | 185 | ||
| Overview of motor symptom management | 186 | ||
| Pharmacology of the drugs used for motor symptoms | 188 | ||
| Levodopa | 188 | ||
| Use in Parkinson’s disease | 188 | ||
| Beneficial effects. | 188 | ||
| Acute loss of effect. | 188 | ||
| Mechanism of action | 188 | ||
| Pharmacokinetics | 188 | ||
| Adverse effects | 188 | ||
| Nausea and vomiting. | 188 | ||
| Dyskinesias. | 189 | ||
| Cardiovascular effects. | 189 | ||
| Psychosis. | 189 | ||
| Other adverse effects. | 191 | ||
| Drug interactions | 191 | ||
| First-generation antipsychotic drugs. | 191 | ||
| Monoamine oxidase inhibitors. | 191 | ||
| Anticholinergic drugs. | 192 | ||
| Food interactions | 192 | ||
| Levodopa/carbidopa | 192 | ||
| Mechanism of action | 192 | ||
| Advantages of carbidopa | 192 | ||
| Disadvantages of carbidopa | 192 | ||
| Dopamine agonists | 192 | ||
| Pramipexole | 193 | ||
| Actions and uses. | 193 | ||
| Adverse effects and interactions. | 194 | ||
| COMT inhibitors | 195 | ||
| Entacapone | 195 | ||
| Actions and therapeutic use. | 195 | ||
| Adverse effects. | 195 | ||
| MAO-B inhibitors | 196 | ||
| Selegiline | 196 | ||
| Actions and use. | 196 | ||
| Key points | 198 | ||
| 22 Alzheimers disease | 201 | ||
| Pathophysiology | 201 | ||
| Risk factors, symptoms, biomarkers, and diagnosis | 202 | ||
| Drugs for cognitive impairment | 204 | ||
| Cholinesterase inhibitors | 205 | ||
| Group properties | 205 | ||
| Mechanism of action. | 205 | ||
| Therapeutic effect. | 205 | ||
| Adverse effects. | 205 | ||
| Drug interactions. | 206 | ||
| Dosage and duration of treatment. | 206 | ||
| Properties of individual cholinesterase inhibitors | 206 | ||
| Memantine | 206 | ||
| Drugs for neuropsychiatric symptoms | 208 | ||
| Can we prevent Alzheimer’s disease or delay cognitive decline? | 208 | ||
| Key points | 210 | ||
| 23 Drugs for multiple sclerosis | 211 | ||
| Overview of MS and its treatment | 211 | ||
| Pathophysiology | 211 | ||
| Signs and symptoms | 212 | ||
| MS subtypes | 212 | ||
| Diagnosis | 212 | ||
| Drug therapy overview | 214 | ||
| Disease-modifying therapy | 214 | ||
| Relapsing-remitting MS. | 214 | ||
| Secondary progressive MS. | 214 | ||
| Progressive-relapsing MS. | 214 | ||
| Primary progressive MS. | 214 | ||
| Treating an acute episode (relapse) | 215 | ||
| Drug therapy of symptoms | 215 | ||
| Disease-modifying drugs I: Immunomodulators | 215 | ||
| Interferon beta preparations | 215 | ||
| Description and mechanism | 215 | ||
| Therapeutic use | 215 | ||
| Adverse effects and drug interactions | 215 | ||
| Flu-like reactions. | 215 | ||
| Hepatotoxicity. | 215 | ||
| Myelosuppression. | 215 | ||
| Injection-site reactions. | 215 | ||
| Depression. | 216 | ||
| Neutralizing antibodies. | 216 | ||
| Drug interactions. | 216 | ||
| Glatiramer acetate | 216 | ||
| Natalizumab | 216 | ||
| Therapeutic uses | 216 | ||
| Multiple sclerosis. | 216 | ||
| Crohn’s disease. | 216 | ||
| Mechanism of action | 216 | ||
| 24 Drugs for epilepsy | 227 | ||
| Seizure generation | 227 | ||
| Types of seizures | 228 | ||
| Partial seizures | 228 | ||
| Generalized seizures | 228 | ||
| Mixed seizures: Lennox-Gastaut syndrome | 229 | ||
| How antiepileptic drugs work | 229 | ||
| Basic therapeutic considerations | 229 | ||
| Therapeutic goal and treatment options | 229 | ||
| Diagnosis and drug selection | 229 | ||
| Drug evaluation | 231 | ||
| Monitoring plasma drug levels | 231 | ||
| Promoting patient adherence | 231 | ||
| Withdrawing antiepileptic drugs | 231 | ||
| Suicide risk with antiepileptic drugs | 232 | ||
| Classification of antiepileptic drugs | 233 | ||
| Traditional antiepileptic drugs | 233 | ||
| Phenytoin | 233 | ||
| Mechanism of action | 233 | ||
| Pharmacokinetics | 234 | ||
| Absorption. | 234 | ||
| Metabolism. | 234 | ||
| Therapeutic uses | 234 | ||
| Epilepsy. | 234 | ||
| Cardiac dysrhythmias. | 234 | ||
| Adverse effects | 234 | ||
| Effects on the cns. | 234 | ||
| Gingival hyperplasia. | 235 | ||
| Dermatologic effects. | 235 | ||
| Effects in pregnancy. | 235 | ||
| Cardiovascular effects. | 235 | ||
| Drug interactions | 235 | ||
| Interactions resulting from induction of hepatic drug-metabolizing enzymes. | 235 | ||
| Drugs that increase plasma levels of phenytoin. | 235 | ||
| Drugs that decrease plasma levels of phenytoin. | 235 | ||
| CNS depressants. | 235 | ||
| Preparations, dosage, and administration | 235 | ||
| Preparations. | 235 | ||
| Dosage. | 235 | ||
| Carbamazepine | 236 | ||
| Mechanism of action | 236 | ||
| Pharmacokinetics | 236 | ||
| Therapeutic uses | 236 | ||
| Epilepsy. | 236 | ||
| Bipolar disorder. | 236 | ||
| Trigeminal and glossopharyngeal neuralgias. | 236 | ||
| Adverse effects | 236 | ||
| CNS effects. | 236 | ||
| Hematologic effects. | 236 | ||
| Birth defects. | 236 | ||
| Hypo-osmolarity. | 236 | ||
| Dermatologic effects. | 236 | ||
| Drug-drug and drug-food interactions | 237 | ||
| Induction of drug-metabolizing enzymes. | 237 | ||
| Phenytoin and phenobarbital. | 237 | ||
| Grapefruit juice. | 237 | ||
| Valproic acid | 237 | ||
| Nomenclature | 237 | ||
| Therapeutic uses | 237 | ||
| Seizure disorders. | 237 | ||
| Bipolar disorder. | 237 | ||
| Migraine. | 238 | ||
| Adverse effects | 238 | ||
| Gastrointestinal effects. | 238 | ||
| Hepatotoxicity. | 238 | ||
| Pancreatitis. | 238 | ||
| Pregnancy-related harm. | 238 | ||
| Hyperammonemia. | 238 | ||
| Ethosuximide | 238 | ||
| Phenobarbital | 239 | ||
| Newer antiepileptic drugs | 240 | ||
| Oxcarbazepine | 240 | ||
| Management of epilepsy during pregnancy | 245 | ||
| Management of generalized convulsive status epilepticus | 246 | ||
| Key points | 246 | ||
| 25 Drugs for muscle spasm and spasticity | 252 | ||
| Drug therapy of muscle spasm: Centrally acting muscle relaxants | 252 | ||
| Drugs for spasticity | 253 | ||
| Baclofen | 253 | ||
| Mechanism of action | 253 | ||
| Therapeutic use | 253 | ||
| Adverse effects | 253 | ||
| CNS effects. | 253 | ||
| Withdrawal. | 253 | ||
| Diazepam | 254 | ||
| Dantrolene | 254 | ||
| Mechanism of action | 254 | ||
| Therapeutic uses | 254 | ||
| Spasticity. | 254 | ||
| Malignant hyperthermia. | 254 | ||
| Adverse effects | 254 | ||
| Hepatic toxicity. | 254 | ||
| Key points | 255 | ||
| 26 Local anesthetics | 257 | ||
| Basic pharmacology of the local anesthetics | 257 | ||
| Classification | 257 | ||
| Mechanism of action | 257 | ||
| Selectivity of anesthetic effects | 257 | ||
| Time course of local anesthesia | 257 | ||
| Use with vasoconstrictors | 258 | ||
| Fate in the body | 258 | ||
| Adverse effects | 258 | ||
| Properties of individual local anesthetics | 259 | ||
| Procaine | 259 | ||
| Lidocaine | 259 | ||
| Cocaine | 259 | ||
| Other local anesthetics | 260 | ||
| Clinical use of local anesthetics | 260 | ||
| Topical administration | 260 | ||
| Administration by injection | 261 | ||
| Key points | 262 | ||
| 27 General anesthetics | 264 | ||
| Inhalation anesthetics | 264 | ||
| Basic pharmacology | 264 | ||
| Properties of an ideal inhalation anesthetic | 264 | ||
| Balanced anesthesia | 264 | ||
| Molecular mechanism of action | 265 | ||
| Minimum alveolar concentration | 265 | ||
| Pharmacokinetics | 265 | ||
| Uptake and distribution | 265 | ||
| Uptake. | 265 | ||
| Distribution. | 266 | ||
| Elimination | 266 | ||
| Export in the expired breath. | 266 | ||
| Metabolism. | 266 | ||
| Adverse effects | 266 | ||
| Drug interactions | 266 | ||
| Adjuncts to inhalation anesthesia | 266 | ||
| Preanesthetic medications | 266 | ||
| Benzodiazepines. | 266 | ||
| Opioids. | 266 | ||
| Alpha2-adrenergic agonists. | 267 | ||
| Anticholinergic drugs. | 267 | ||
| Neuromuscular blocking agents | 267 | ||
| Postanesthetic medications | 267 | ||
| Analgesics. | 267 | ||
| Antiemetics. | 267 | ||
| Muscarinic agonists. | 267 | ||
| Dosage and administration | 267 | ||
| Classification of inhalation anesthetics | 267 | ||
| Properties of individual inhalation anesthetics | 268 | ||
| Halothane | 268 | ||
| Anesthetic properties | 268 | ||
| Potency. | 268 | ||
| Time course. | 268 | ||
| Analgesia. | 268 | ||
| Muscle relaxation. | 268 | ||
| Adverse effects | 268 | ||
| Hypotension. | 268 | ||
| Respiratory depression. | 268 | ||
| Promotion of dysrhythmias. | 268 | ||
| Malignant hyperthermia. | 268 | ||
| Hepatotoxicity. | 268 | ||
| Elimination | 268 | ||
| Isoflurane | 268 | ||
| Nitrous oxide | 269 | ||
| Intravenous anesthetics | 269 | ||
| Key points | 272 | ||
| 28 Opioid (narcotic) analgesics, opioid antagonists, and nonopioid centrally acting analgesics | 274 | ||
| Opioid analgesics | 274 | ||
| Introduction to the opioids | 274 | ||
| Terminology | 274 | ||
| Endogenous opioid peptides | 274 | ||
| Opioid receptors | 274 | ||
| Classification of drugs that act at opioid receptors | 275 | ||
| Basic pharmacology of the opioids | 275 | ||
| Morphine | 275 | ||
| Overview of pharmacologic actions | 275 | ||
| Therapeutic use: Relief of pain | 275 | ||
| Mechanism of analgesic action. | 276 | ||
| Adverse effects | 277 | ||
| Respiratory depression. | 277 | ||
| Constipation. | 277 | ||
| Orthostatic hypotension. | 277 | ||
| Urinary retention. | 277 | ||
| Cough suppression. | 277 | ||
| Biliary colic. | 277 | ||
| Emesis. | 278 | ||
| Elevation of intracranial pressure. | 278 | ||
| Euphoria/dysphoria. | 278 | ||
| Sedation. | 278 | ||
| Miosis. | 278 | ||
| Birth defects. | 278 | ||
| Neurotoxicity. | 278 | ||
| Adverse effects from prolonged use. | 278 | ||
| Pharmacokinetics | 278 | ||
| Tolerance and physical dependence | 278 | ||
| Tolerance. | 278 | ||
| Physical dependence. | 279 | ||
| Abuse liability | 279 | ||
| Precautions | 279 | ||
| Decreased respiratory reserve. | 279 | ||
| Labor and delivery. | 279 | ||
| Neonatal opioid dependence. | 279 | ||
| Head injury. | 279 | ||
| Other precautions. | 280 | ||
| Drug interactions | 280 | ||
| CNS depressants. | 280 | ||
| Anticholinergic drugs. | 280 | ||
| Hypotensive drugs. | 280 | ||
| Monoamine oxidase inhibitors. | 280 | ||
| Agonist-antagonist opioids. | 280 | ||
| Opioid antagonists. | 280 | ||
| Other interactions. | 280 | ||
| Toxicity | 280 | ||
| Clinical manifestations. | 280 | ||
| Treatment. | 280 | ||
| Dosage and administration | 281 | ||
| General guidelines. | 281 | ||
| Other strong opioid agonists | 281 | ||
| Fentanyl | 281 | ||
| Parenteral. | 281 | ||
| Transdermal system. | 283 | ||
| Transmucosal. | 283 | ||
| Moderate to strong opioid agonists | 285 | ||
| Codeine | 285 | ||
| Oxycodone | 285 | ||
| Hydrocodone | 286 | ||
| Agonist-antagonist opioids | 286 | ||
| Pentazocine | 287 | ||
| Actions and uses. | 287 | ||
| Clinical use of opioids | 288 | ||
| Dosing guidelines | 288 | ||
| Pain assessment | 288 | ||
| Dosage determination | 288 | ||
| Dosing schedule | 289 | ||
| Avoiding a withdrawal reaction | 289 | ||
| Physical dependence, abuse, and addiction as clinical concerns | 289 | ||
| Definitions | 289 | ||
| Physical dependence. | 289 | ||
| Abuse. | 289 | ||
| Addiction. | 290 | ||
| Minimizing fears about physical dependence | 290 | ||
| Minimizing fears about addiction | 290 | ||
| Balancing the need to provide pain relief with the desire to minimize abuse | 290 | ||
| Patient-controlled analgesia | 290 | ||
| Using opioids for specific kinds of pain | 291 | ||
| REMS to reduce opioid-related morbidity, mortality, and abuse | 292 | ||
| Opioid antagonists | 292 | ||
| Key points | 296 | ||
| 29 Pain management in patients with cancer | 300 | ||
| Pathophysiology of pain | 300 | ||
| Management strategy | 301 | ||
| Assessment and ongoing evaluation | 301 | ||
| Comprehensive initial assessment | 303 | ||
| Assessment of pain intensity and character: The patient self-report | 303 | ||
| Physical and neurologic examinations | 303 | ||
| Diagnostic tests | 303 | ||
| Psychosocial assessment | 303 | ||
| Pain intensity scales | 303 | ||
| Ongoing evaluation | 303 | ||
| Barriers to assessment | 304 | ||
| Drug therapy | 305 | ||
| Nonopioid analgesics | 305 | ||
| Nonsteroidal anti-inflammatory drugs | 305 | ||
| Acetaminophen | 306 | ||
| Opioid analgesics | 307 | ||
| Mechanism of action and classification | 307 | ||
| Tolerance and physical dependence | 307 | ||
| Tolerance. | 307 | ||
| Physical dependence. | 308 | ||
| Addiction | 308 | ||
| Drug selection | 308 | ||
| Preferred opioids. | 308 | ||
| Opioid rotation. | 308 | ||
| Opioids to use with special caution. | 309 | ||
| Opioids to avoid. | 309 | ||
| Dosage | 309 | ||
| Routes of administration | 309 | ||
| Oral. | 309 | ||
| Rectal. | 309 | ||
| Transdermal. | 309 | ||
| Intravenous and subcutaneous. | 309 | ||
| Intramuscular. | 310 | ||
| Intraspinal. | 310 | ||
| Intraventricular. | 310 | ||
| Patient-controlled analgesia. | 310 | ||
| Managing breakthrough pain | 310 | ||
| Managing side effects | 310 | ||
| Respiratory depression. | 310 | ||
| Constipation. | 311 | ||
| Sedation. | 311 | ||
| Nausea and vomiting. | 311 | ||
| Other side effects. | 311 | ||
| Adjuvant analgesics | 311 | ||
| Antidepressants | 311 | ||
| Tricyclic antidepressants. | 311 | ||
| Other antidepressants. | 311 | ||
| Antiseizure drugs | 311 | ||
| Local anesthetics/antidysrhythmics | 312 | ||
| CNS stimulants | 312 | ||
| Antihistamines | 312 | ||
| Glucocorticoids | 312 | ||
| Bisphosphonates | 313 | ||
| Nondrug therapy | 313 | ||
| Invasive procedures | 313 | ||
| Neurolytic nerve block | 313 | ||
| Neurosurgery | 313 | ||
| Tumor surgery | 313 | ||
| Radiation therapy | 313 | ||
| Physical and psychosocial interventions | 313 | ||
| Physical interventions | 313 | ||
| Heat. | 313 | ||
| Cold. | 314 | ||
| Massage. | 314 | ||
| Exercise. | 314 | ||
| Acupuncture and transcutaneous electrical nerve stimulation. | 314 | ||
| Psychosocial interventions | 314 | ||
| Relaxation and imagery. | 314 | ||
| Cognitive distraction. | 314 | ||
| Peer support groups. | 314 | ||
| Pain management in special populations | 314 | ||
| The elderly | 314 | ||
| Young children | 315 | ||
| Assessment | 315 | ||
| Verbal children. | 315 | ||
| Preverbal and nonverbal children. | 315 | ||
| Treatment | 315 | ||
| Opioid abusers | 315 | ||
| Patient education | 316 | ||
| The joint commission pain management standards | 316 | ||
| Key points | 317 | ||
| 30 Drugs for headache | 319 | ||
| Migraine headache | 320 | ||
| Characteristics, pathophysiology, and overview of treatment | 320 | ||
| Abortive therapy | 321 | ||
| Analgesics | 321 | ||
| Aspirin-like drugs | 321 | ||
| Opioid analgesics | 321 | ||
| Ergot alkaloids | 321 | ||
| Ergotamine | 321 | ||
| Mechanism of antimigraine action. | 321 | ||
| Therapeutic uses. | 321 | ||
| Pharmacokinetics. | 322 | ||
| Adverse effects. | 322 | ||
| Overdose. | 322 | ||
| Drug interactions. | 322 | ||
| Triptans. | 322 | ||
| CYP3A4 inhibitors. | 322 | ||
| Physical dependence. | 322 | ||
| Contraindications. | 322 | ||
| Dihydroergotamine | 323 | ||
| Therapeutic uses. | 323 | ||
| Pharmacologic effects. | 323 | ||
| 31 Antipsychotic agents and their use in schizophrenia | 332 | ||
| Schizophrenia: Clinical presentation and etiology | 332 | ||
| First-generation (conventional) antipsychotics | 334 | ||
| Group properties | 334 | ||
| Classification | 334 | ||
| Classification by potency | 334 | ||
| Chemical classification | 334 | ||
| Mechanism of action | 334 | ||
| Therapeutic uses | 334 | ||
| Adverse effects | 336 | ||
| Extrapyramidal symptoms | 337 | ||
| Acute dystonia. | 337 | ||
| Parkinsonism. | 337 | ||
| Akathisia. | 338 | ||
| Tardive dyskinesia. | 338 | ||
| Other adverse effects | 338 | ||
| Neuroleptic malignant syndrome. | 338 | ||
| Anticholinergic effects. | 338 | ||
| Orthostatic hypotension. | 338 | ||
| Sedation. | 339 | ||
| Neuroendocrine effects. | 339 | ||
| Seizures. | 339 | ||
| Sexual dysfunction. | 339 | ||
| Agranulocytosis. | 339 | ||
| Severe dysrhythmias. | 339 | ||
| Effects in elderly patients with dementia. | 339 | ||
| Signs of withdrawal and extrapyramidal symptoms in neonates. | 339 | ||
| Physical and psychologic dependence | 339 | ||
| Drug interactions | 339 | ||
| Toxicity | 340 | ||
| Properties of individual agents | 340 | ||
| High-potency agents | 340 | ||
| Haloperidol | 340 | ||
| Actions and uses. | 340 | ||
| Adverse effects. | 340 | ||
| Second-generation (atypical) antipsychotics | 341 | ||
| Depot antipsychotic preparations | 346 | ||
| Management of schizophrenia | 346 | ||
| Key points | 348 | ||
| 32 Antidepressants | 354 | ||
| Major depression: Clinical features, pathogenesis, and treatment overview | 354 | ||
| Drugs used for depression | 356 | ||
| Basic considerations | 357 | ||
| Selective serotonin reuptake inhibitors (SSRIs) | 358 | ||
| Fluoxetine | 358 | ||
| Mechanism of action | 358 | ||
| Therapeutic uses | 359 | ||
| Pharmacokinetics | 359 | ||
| Adverse effects | 360 | ||
| Sexual dysfunction. | 360 | ||
| Weight gain. | 360 | ||
| Serotonin syndrome. | 360 | ||
| Withdrawal syndrome. | 360 | ||
| Neonatal effects from use in pregnancy. | 360 | ||
| Teratogenesis. | 360 | ||
| Suicide risk. | 360 | ||
| Drug interactions | 361 | ||
| MAOIs and other drugs that increase the risk of serotonin syndrome. | 361 | ||
| Tricyclic antidepressants and lithium. | 361 | ||
| Antiplatelet drugs and anticoagulants. | 361 | ||
| Other SSRIs | 362 | ||
| Tricyclic antidepressants (TCAs) | 364 | ||
| Monoamine oxidase inhibitors (MAOIs) | 367 | ||
| Oral MAOIs | 367 | ||
| Mechanism of action | 367 | ||
| Therapeutic uses | 368 | ||
| Depression. | 368 | ||
| Other psychiatric uses. | 368 | ||
| Adverse effects | 368 | ||
| CNS stimulation. | 368 | ||
| Orthostatic hypotension. | 368 | ||
| Hypertensive crisis from dietary tyramine. | 368 | ||
| Drug interactions | 370 | ||
| Indirect-acting sympathomimetic agents. | 370 | ||
| Interactions secondary to inhibition of hepatic MAO. | 370 | ||
| Tricyclic antidepressants. | 370 | ||
| Serotonergic drugs. | 370 | ||
| Antihypertensive drugs. | 370 | ||
| Meperidine. | 370 | ||
| Transdermal MAOI: Selegiline | 370 | ||
| Atypical antidepressants | 371 | ||
| Bupropion | 371 | ||
| Mirtazapine | 372 | ||
| Somatic (nondrug) therapies for depression | 373 | ||
| Key points | 374 | ||
| 33 Drugs for bipolar disorder | 380 | ||
| Characteristics of bipolar disorder | 380 | ||
| Types of mood episodes seen in BPD | 380 | ||
| Patterns of mood episodes | 380 | ||
| Etiology | 381 | ||
| Treatment of bipolar disorder | 381 | ||
| Drug therapy | 381 | ||
| Types of drugs employed | 381 | ||
| Mood stabilizers. | 381 | ||
| Antipsychotics. | 381 | ||
| Antidepressants. | 381 | ||
| Drug selection | 382 | ||
| Acute therapy: Manic episodes. | 382 | ||
| Acute therapy: Depressive episodes. | 382 | ||
| Long-term preventive treatment. | 382 | ||
| Promoting adherence | 382 | ||
| Nondrug therapy | 382 | ||
| Education and psychotherapy | 382 | ||
| Electroconvulsive therapy | 383 | ||
| Mood-stabilizing drugs | 383 | ||
| Lithium | 383 | ||
| Chemistry | 383 | ||
| Therapeutic uses | 383 | ||
| Bipolar disorder. | 383 | ||
| Mechanism of action | 384 | ||
| Pharmacokinetics | 384 | ||
| Absorption and distribution. | 384 | ||
| Excretion. | 384 | ||
| Monitoring plasma lithium levels. | 384 | ||
| Adverse effects | 384 | ||
| Adverse effects that occur when lithium levels are excessive. | 384 | ||
| Adverse effects that occur at therapeutic levels of lithium. | 385 | ||
| Early adverse effects. | 385 | ||
| Tremor. | 385 | ||
| Polyuria. | 385 | ||
| Renal toxicity. | 385 | ||
| Goiter and hypothyroidism. | 385 | ||
| Teratogenesis. | 385 | ||
| Use in lactation. | 385 | ||
| Drug interactions | 385 | ||
| Diuretics. | 385 | ||
| Nonsteroidal anti-inflammatory drugs (NSAIDs). | 385 | ||
| Anticholinergic drugs. | 385 | ||
| Preparations, dosage, and administration | 385 | ||
| Preparations and administration. | 385 | ||
| Dosing. | 386 | ||
| Antiepileptic drugs | 386 | ||
| Divalproex sodium (valproate) | 386 | ||
| Carbamazepine | 387 | ||
| Antipsychotic drugs | 387 | ||
| Key points | 387 | ||
| 34 Sedative-hypnotic drugs | 390 | ||
| Benzodiazepines | 390 | ||
| Benzodiazepine-like drugs | 394 | ||
| Zolpidem | 394 | ||
| Zaleplon | 395 | ||
| Eszopiclone | 395 | ||
| Ramelteon: A melatonin agonist | 395 | ||
| Barbiturates | 397 | ||
| Management of insomnia | 400 | ||
| Sleep phases | 400 | ||
| Basic principles of management | 400 | ||
| Cause-specific therapy | 400 | ||
| Nondrug therapy | 400 | ||
| Therapy with hypnotic drugs | 401 | ||
| Major hypnotics used for treatment | 401 | ||
| Benzodiazepines | 401 | ||
| Benzodiazepine-like drugs: Zolpidem, zaleplon, and eszopiclone | 402 | ||
| Ramelteon | 402 | ||
| Key points | 403 | ||
| 35 Management of anxiety disorders | 406 | ||
| Generalized anxiety disorder | 407 | ||
| Characteristics | 407 | ||
| Treatment | 407 | ||
| Benzodiazepines | 407 | ||
| Buspirone | 408 | ||
| Actions and therapeutic use. | 408 | ||
| Adverse effects. | 408 | ||
| Drug and food interactions. | 408 | ||
| Tolerance, dependence, and abuse. | 408 | ||
| Antidepressants: Venlafaxine, paroxetine, escitalopram, and duloxetine | 409 | ||
| Panic disorder | 409 | ||
| Characteristics | 409 | ||
| Treatment | 409 | ||
| Antidepressants | 409 | ||
| Selective serotonin reuptake inhibitors. | 409 | ||
| Obsessive-compulsive disorder | 410 | ||
| Characteristics | 410 | ||
| Treatment | 410 | ||
| Selective serotonin reuptake inhibitors | 410 | ||
| Social anxiety disorder (social phobia) | 412 | ||
| Characteristics | 412 | ||
| Treatment | 412 | ||
| Post-traumatic stress disorder | 414 | ||
| Characteristics | 414 | ||
| Treatment | 414 | ||
| Key points | 414 | ||
| 36 Central nervous system stimulants and attention-deficit/hyperactivity disorder | 416 | ||
| Central nervous system stimulants | 416 | ||
| Amphetamines | 416 | ||
| Methylphenidate and dexmethylphenidate | 418 | ||
| Methylphenidate | 418 | ||
| Preparations, dosage, and administration | 419 | ||
| Methylxanthines | 419 | ||
| Caffeine | 420 | ||
| Dietary sources | 420 | ||
| Mechanism of action | 420 | ||
| Pharmacologic effects | 420 | ||
| Central nervous system. | 420 | ||
| Heart. | 420 | ||
| Blood vessels. | 420 | ||
| Bronchi. | 420 | ||
| Kidney. | 420 | ||
| Reproduction. | 420 | ||
| Pharmacokinetics | 420 | ||
| Therapeutic uses | 420 | ||
| Neonatal apnea. | 420 | ||
| Promoting wakefulness. | 421 | ||
| Attention-deficit/hyperactivity disorder | 423 | ||
| Basic considerations | 423 | ||
| ADHD in children | 423 | ||
| Signs and symptoms | 423 | ||
| Etiology | 423 | ||
| Management overview | 423 | ||
| ADHD in adults | 423 | ||
| Drugs used for ADHD | 423 | ||
| CNS stimulants | 423 | ||
| Nonstimulants | 426 | ||
| Atomoxetine, a norepinephrine uptake inhibitor | 426 | ||
| Description and therapeutic effects. | 426 | ||
| Mechanism of action. | 426 | ||
| Pharmacokinetics. | 426 | ||
| Adverse effects. | 426 | ||
| Drug interactions. | 427 | ||
| Role in ADHD therapy. | 427 | ||
| Alpha2-adrenergic agonists | 427 | ||
| Guanfacine. | 427 | ||
| Key points | 428 | ||
| 37 Drug abuse I: Basic considerations | 430 | ||
| Definitions | 430 | ||
| APA diagnostic criteria regarding drugs of abuse | 431 | ||
| Factors that contribute to drug abuse | 431 | ||
| Neurobiology of addiction | 433 | ||
| Principles of addiction treatment | 434 | ||
| The controlled substances act | 434 | ||
| Key points | 437 | ||
| 38 Drug abuse II: Alcohol | 438 | ||
| Basic pharmacology of alcohol | 438 | ||
| Alcohol use disorder | 443 | ||
| Drugs for alcohol use disorder | 445 | ||
| Drugs used to facilitate withdrawal | 446 | ||
| Benzodiazepines | 446 | ||
| Adjuncts to benzodiazepines | 446 | ||
| Drugs used to maintain abstinence | 446 | ||
| Disulfiram aversion therapy | 446 | ||
| Therapeutic effects. | 446 | ||
| Mechanism of action. | 446 | ||
| Pharmacologic effects. | 446 | ||
| Patient selection. | 447 | ||
| Patient education. | 447 | ||
| Naltrexone | 447 | ||
| Acamprosate | 447 | ||
| Therapeutic use. | 447 | ||
| Mechanism of action. | 447 | ||
| Pharmacokinetics. | 447 | ||
| Adverse effects and drug interactions. | 448 | ||
| Key points | 448 | ||
| 39 Drug abuse III: Nicotine and smoking | 450 | ||
| Basic pharmacology of nicotine | 450 | ||
| Pharmacologic aids to smoking cessation | 452 | ||
| Nicotine replacement therapy | 454 | ||
| Nicotine chewing gum (nicotine polacrilex) | 454 | ||
| Nicotine lozenges (nicotine polacrilex) | 454 | ||
| Nicotine transdermal systems (patches) | 455 | ||
| Nicotine inhaler | 455 | ||
| Nicotine nasal spray | 455 | ||
| Bupropion SR | 455 | ||
| Varenicline | 456 | ||
| Key points | 457 | ||
| 40 Drug abuse IV: Major drugs of abuse other than alcohol and nicotine | 458 | ||
| Heroin, oxycodone, and other opioids | 458 | ||
| General CNS depressants | 463 | ||
| Barbiturates | 463 | ||
| Benzodiazepines | 465 | ||
| Psychostimulants | 465 | ||
| Cocaine | 465 | ||
| Methamphetamine | 466 | ||
| Marijuana and related preparations | 467 | ||
| Psychedelics | 469 | ||
| D-lysergic acid diethylamide (LSD) | 469 | ||
| Salvia | 470 | ||
| Mescaline, psilocin, psilocybin, and dimethyltryptamine | 471 | ||
| Dissociative drugs | 471 | ||
| Phencyclidine | 471 | ||
| Chemistry and pharmacokinetics | 471 | ||
| Chemistry. | 471 | ||
| Pharmacokinetics. | 471 | ||
| Mechanism of action | 471 | ||
| Subjective and behavioral effects | 471 | ||
| Effects of low to moderate doses. | 471 | ||
| High-dose (toxic) effects. | 471 | ||
| Managing toxicity. | 471 | ||
| Ketamine | 472 | ||
| Dextromethorphan | 472 | ||
| 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) | 472 | ||
| Inhalants | 473 | ||
| Anabolic steroids | 473 | ||
| Key points | 474 | ||
| 41 Diuretics | 476 | ||
| Review of renal anatomy and physiology | 476 | ||
| Anatomy | 476 | ||
| Physiology | 476 | ||
| Overview of kidney functions | 476 | ||
| The three basic renal processes | 476 | ||
| Filtration. | 476 | ||
| Reabsorption. | 476 | ||
| Active tubular secretion. | 477 | ||
| Processes of reabsorption that occur at specific sites along the nephron | 477 | ||
| Proximal convoluted tubule. | 477 | ||
| Loop of henle. | 477 | ||
| Distal convoluted tubule (early segment). | 477 | ||
| Distal nephron: Late distal convoluted tubule and collecting duct. | 478 | ||
| Sodium-potassium exchange. | 478 | ||
| Introduction to diuretics | 478 | ||
| How diuretics work | 478 | ||
| Adverse impact on extracellular fluid | 479 | ||
| Classification of diuretics | 479 | ||
| High-ceiling (loop) diuretics | 479 | ||
| Furosemide | 479 | ||
| Mechanism of action | 479 | ||
| Pharmacokinetics | 479 | ||
| Therapeutic uses | 479 | ||
| Adverse effects | 479 | ||
| Hyponatremia, hypochloremia, and dehydration. | 479 | ||
| Hypotension. | 480 | ||
| Hypokalemia. | 480 | ||
| Ototoxicity. | 480 | ||
| Drug interactions | 480 | ||
| Digoxin. | 480 | ||
| Ototoxic drugs. | 480 | ||
| Potassium-sparing diuretics. | 480 | ||
| Thiazides and related diuretics | 481 | ||
| Hydrochlorothiazide | 481 | ||
| Mechanism of action | 481 | ||
| Pharmacokinetics | 481 | ||
| Therapeutic uses | 481 | ||
| Essential hypertension. | 481 | ||
| Edema. | 481 | ||
| Adverse effects | 481 | ||
| Hyponatremia, hypochloremia, and dehydration. | 481 | ||
| Hypokalemia. | 481 | ||
| Use in pregnancy and lactation. | 481 | ||
| Drug interactions | 482 | ||
| Potassium-sparing diuretics | 482 | ||
| Spironolactone | 483 | ||
| 42 Agents affecting the volume and ion content of body fluids | 488 | ||
| Disorders of fluid volume and osmolality | 488 | ||
| Volume contraction | 488 | ||
| Isotonic contraction | 488 | ||
| 43 Review of hemodynamics | 493 | ||
| Overview of the circulatory system | 493 | ||
| Components of the circulatory system | 493 | ||
| Distribution of blood | 493 | ||
| What makes blood flow? | 493 | ||
| How does blood get back to the heart? | 494 | ||
| Regulation of cardiac output | 494 | ||
| Determinants of cardiac output | 494 | ||
| Control of stroke volume by venous return | 495 | ||
| Starling’s law of the heart | 495 | ||
| Factors that determine venous return | 496 | ||
| Starling’s law and maintenance of systemic-pulmonary balance | 496 | ||
| Regulation of arterial pressure | 497 | ||
| Overview of control systems | 497 | ||
| Steady-state control by the ANS | 497 | ||
| Rapid control by the ANS: The baroreceptor reflex | 497 | ||
| The Renin-Angiotensin-Aldosterone system | 497 | ||
| Renal retention of water | 497 | ||
| Postural hypotension | 497 | ||
| Natriuretic peptides | 498 | ||
| Key points* | 498 | ||
| 44 Drugs acting on the Renin-Angiotensin-Aldosterone system | 500 | ||
| Physiology of the Renin-Angiotensin-Aldosterone system | 500 | ||
| Types of angiotensin | 500 | ||
| Actions of angiotensin II | 500 | ||
| Actions of aldosterone | 502 | ||
| Formation of angiotensin II by renin and angiotensin-converting enzyme | 502 | ||
| Renin | 502 | ||
| Regulation of renin release. | 502 | ||
| Angiotensin-converting enzyme (kinase II) | 502 | ||
| Regulation of blood pressure by the Renin-Angiotensin-Aldosterone system | 502 | ||
| Tissue (local) angiotensin II production | 502 | ||
| Angiotensin-converting enzyme inhibitors | 503 | ||
| Angiotensin II receptor blockers | 507 | ||
| Aliskiren, a direct renin inhibitor | 509 | ||
| Aldosterone antagonists | 509 | ||
| Eplerenone | 510 | ||
| Mechanism of action | 510 | ||
| Therapeutic use | 510 | ||
| Hypertension. | 510 | ||
| Heart failure. | 510 | ||
| Adverse effects | 510 | ||
| Hyperkalemia. | 510 | ||
| Drug interactions | 510 | ||
| Key points | 511 | ||
| 45 Calcium channel blockers | 515 | ||
| Calcium channels: Physiologic functions and consequences of blockade | 515 | ||
| Vascular smooth muscle | 515 | ||
| Heart | 515 | ||
| Calcium channel blockers: Classification and sites of action | 515 | ||
| Verapamil and diltiazem: Agents that act on vascular smooth muscle and the heart | 516 | ||
| Verapamil | 516 | ||
| Hemodynamic effects | 517 | ||
| Direct effects. | 517 | ||
| Indirect (reflex) effects. | 517 | ||
| Net effect. | 517 | ||
| Pharmacokinetics | 517 | ||
| Therapeutic uses | 517 | ||
| Angina pectoris. | 517 | ||
| Essential hypertension. | 517 | ||
| Cardiac dysrhythmias. | 517 | ||
| Adverse effects | 518 | ||
| Common effects. | 518 | ||
| Cardiac effects. | 518 | ||
| Drug and food interactions | 518 | ||
| Digoxin. | 518 | ||
| Beta-adrenergic blocking agents. | 518 | ||
| Grapefruit juice. | 518 | ||
| Dihydropyridines: Agents that act mainly on vascular smooth muscle | 519 | ||
| Nifedipine | 519 | ||
| Hemodynamic effects | 519 | ||
| Direct effects. | 519 | ||
| Indirect (reflex) effects. | 519 | ||
| Net effect. | 520 | ||
| Therapeutic uses | 520 | ||
| Angina pectoris. | 520 | ||
| Hypertension. | 520 | ||
| Adverse effects | 520 | ||
| Drug interactions | 520 | ||
| Beta-adrenergic blockers. | 520 | ||
| Toxicity | 520 | ||
| Key points | 521 | ||
| 46 Vasodilators | 524 | ||
| Basic concepts in vasodilator pharmacology | 524 | ||
| Selectivity of vasodilatory effects | 524 | ||
| Overview of therapeutic uses | 524 | ||
| Adverse effects related to vasodilation | 525 | ||
| Postural hypotension | 525 | ||
| Reflex tachycardia | 525 | ||
| Expansion of blood volume | 525 | ||
| Pharmacology of individual vasodilators | 525 | ||
| Hydralazine | 525 | ||
| Cardiovascular effects | 525 | ||
| Pharmacokinetics | 525 | ||
| Absorption and time course of action. | 525 | ||
| Metabolism. | 525 | ||
| 47 Drugs for hypertension | 529 | ||
| Basic considerations in hypertension | 529 | ||
| Classification of blood pressure | 529 | ||
| Types of hypertension | 530 | ||
| Consequences of hypertension | 531 | ||
| Management of chronic hypertension | 531 | ||
| Basic considerations | 531 | ||
| Lifestyle modifications | 533 | ||
| Drug therapy | 534 | ||
| Review of blood pressure control | 534 | ||
| Principal determinants of blood pressure | 534 | ||
| Cardiac output. | 534 | ||
| Peripheral vascular resistance. | 534 | ||
| Systems that help regulate blood pressure | 534 | ||
| Sympathetic baroreceptor reflex. | 534 | ||
| Renin-Angiotensin-Aldosterone system. | 534 | ||
| Renal regulation of blood pressure. | 534 | ||
| Antihypertensive mechanisms: Sites of drug action and effects produced | 535 | ||
| Classes of antihypertensive drugs | 537 | ||
| Diuretics | 537 | ||
| Thiazide diuretics. | 537 | ||
| High-ceiling (loop) diuretics. | 537 | ||
| Potassium-sparing diuretics. | 540 | ||
| Sympatholytics (antiadrenergic drugs) | 540 | ||
| Beta-adrenergic blockers. | 540 | ||
| Alpha1 blockers. | 540 | ||
| Alpha/beta blockers: Carvedilol and labetalol. | 540 | ||
| Centrally acting alpha2 agonists. | 540 | ||
| Adrenergic neuron blockers. | 540 | ||
| Direct-acting vasodilators: Hydralazine and minoxidil | 541 | ||
| Calcium channel blockers | 541 | ||
| Drugs that suppress the RAAS | 541 | ||
| ACE inhibitors. | 541 | ||
| Angiotensin II receptor blockers. | 541 | ||
| Direct renin inhibitors. | 541 | ||
| Aldosterone antagonists. | 541 | ||
| Fundamentals of hypertension drug therapy | 541 | ||
| Treatment algorithm | 541 | ||
| Initial drug selection | 543 | ||
| Patients without compelling indications. | 543 | ||
| Patients with compelling indications. | 543 | ||
| Adding drugs to the regimen | 543 | ||
| Rationale for drug selection. | 543 | ||
| Benefits of multidrug therapy. | 543 | ||
| Dosing | 544 | ||
| Step-down therapy | 544 | ||
| Individualizing therapy | 544 | ||
| Patients with comorbid conditions | 544 | ||
| Renal disease. | 544 | ||
| Diabetes. | 544 | ||
| Patients in special populations | 544 | ||
| African americans. | 544 | ||
| Children and adolescents. | 545 | ||
| The elderly. | 545 | ||
| Minimizing adverse effects | 546 | ||
| Promoting adherence | 546 | ||
| Why adherence is often hard to achieve | 546 | ||
| Ways to promote adherence | 546 | ||
| Patient education. | 546 | ||
| Teach self-monitoring. | 546 | ||
| Minimize side effects. | 546 | ||
| Establish a collaborative relationship. | 546 | ||
| Simplify the regimen. | 546 | ||
| Other measures. | 546 | ||
| Drugs for hypertensive emergencies | 547 | ||
| Drugs for hypertensive disorders of pregnancy | 547 | ||
| Chronic hypertension | 547 | ||
| Preeclampsia and eclampsia | 547 | ||
| Key points | 548 | ||
| 48 Drugs for heart failure | 551 | ||
| Pathophysiology of heart failure | 551 | ||
| Overview of drugs used to treat heart failure | 553 | ||
| Diuretics | 553 | ||
| Drugs that inhibit the RAAS | 554 | ||
| ACE inhibitors | 554 | ||
| Hemodynamic benefits. | 554 | ||
| Impact on cardiac remodeling. | 555 | ||
| Adverse effects. | 555 | ||
| Dosage. | 555 | ||
| Angiotensin II receptor blockers | 555 | ||
| Aldosterone antagonists | 555 | ||
| Direct renin inhibitors | 556 | ||
| Beta blockers | 556 | ||
| Digoxin | 556 | ||
| Digoxin, a cardiac glycoside | 557 | ||
| Management of heart failure | 562 | ||
| Stage A | 563 | ||
| Stage B | 563 | ||
| Stage C | 563 | ||
| Drug therapy | 563 | ||
| Diuretics. | 563 | ||
| ACE inhibitors and arbs. | 563 | ||
| Aldosterone antagonists. | 563 | ||
| Beta blockers. | 563 | ||
| Digoxin. | 563 | ||
| Isosorbide dinitrate/hydralazine. | 563 | ||
| Drugs to avoid | 564 | ||
| Device therapy | 564 | ||
| Implanted cardioverter-defibrillators. | 564 | ||
| Cardiac resynchronization. | 564 | ||
| Exercise training | 564 | ||
| Evaluating treatment | 564 | ||
| Stage D | 564 | ||
| Key points | 565 | ||
| 49 Antidysrhythmic drugs | 568 | ||
| Introduction to cardiac electrophysiology, dysrhythmias, and the antidysrhythmic drugs | 568 | ||
| Electrical properties of the heart | 568 | ||
| Impulse conduction: Pathways and timing | 569 | ||
| Cardiac action potentials | 569 | ||
| Fast potentials | 569 | ||
| Phase 0. | 569 | ||
| Phase 1. | 569 | ||
| Phase 2. | 569 | ||
| Phase 3. | 569 | ||
| Phase 4. | 570 | ||
| Slow potentials | 570 | ||
| Phase 0. | 571 | ||
| Phases 1, 2, and 3. | 571 | ||
| Phase 4. | 571 | ||
| The electrocardiogram | 571 | ||
| Generation of dysrhythmias | 571 | ||
| Disturbances of automaticity | 571 | ||
| Disturbances of conduction | 571 | ||
| Classification of antidysrhythmic drugs | 573 | ||
| Prodysrhythmic effects of antidysrhythmic drugs | 573 | ||
| Overview of common dysrhythmias and their treatment | 574 | ||
| Supraventricular dysrhythmias | 574 | ||
| Ventricular dysrhythmias | 574 | ||
| Principles of antidysrhythmic drug therapy | 575 | ||
| Pharmacology of the antidysrhythmic drugs | 576 | ||
| Class I: Sodium channel blockers | 577 | ||
| Class IA agents | 577 | ||
| Quinidine | 577 | ||
| Chemistry and source. | 577 | ||
| Effects on the heart. | 577 | ||
| Effects on the ECG. | 577 | ||
| Therapeutic uses. | 577 | ||
| Adverse effects. | 577 | ||
| Diarrhea. | 577 | ||
| Cinchonism. | 577 | ||
| Cardiotoxicity. | 577 | ||
| Arterial embolism. | 577 | ||
| Other adverse effects. | 577 | ||
| Drug interactions. | 577 | ||
| Digoxin. | 577 | ||
| Class IB agents | 578 | ||
| Lidocaine | 578 | ||
| Effects on the heart and ECG. | 578 | ||
| Pharmacokinetics. | 578 | ||
| Antidysrhythmic use. | 578 | ||
| Adverse effects. | 578 | ||
| Preparations, dosage, and administration. | 579 | ||
| Class II: Beta blockers | 579 | ||
| Class III: Potassium channel blockers (drugs that delay repolarization) | 580 | ||
| Amiodarone | 580 | ||
| Oral therapy | 580 | ||
| Therapeutic use. | 580 | ||
| Effects on the heart and ECG. | 580 | ||
| Pharmacokinetics. | 580 | ||
| 50 Prophylaxis of coronary heart disease: Drugs that help normalize cholesterol and triglyceride levels | 590 | ||
| Cholesterol | 591 | ||
| Plasma lipoproteins | 591 | ||
| Structure and function of lipoproteins | 591 | ||
| Classes of lipoproteins | 591 | ||
| Very-low-density lipoproteins | 592 | ||
| Low-density lipoproteins | 592 | ||
| High-density lipoproteins | 592 | ||
| LDL cholesterol versus HDL cholesterol | 592 | ||
| Role of LDL cholesterol in atherosclerosis | 593 | ||
| Detection, evaluation, and treatment of high cholesterol: Recommendations from ATP III | 593 | ||
| Cholesterol screening | 593 | ||
| Adults | 593 | ||
| Children and adolescents | 593 | ||
| CHD risk assessment | 595 | ||
| Factors in risk assessment | 595 | ||
| Identifying CHD risk factors. | 595 | ||
| Calculating 10-year CHD risk. | 595 | ||
| Identifying CHD risk equivalents. | 597 | ||
| Identifying an individual’s CHD risk category | 597 | ||
| Final note: Each type of dyslipidemia a patient has contributes independently to CHD risk | 597 | ||
| Treatment of high LDL cholesterol | 599 | ||
| Therapeutic lifestyle changes | 599 | ||
| The TLC diet. | 599 | ||
| Weight control. | 599 | ||
| Exercise. | 599 | ||
| Smoking cessation. | 599 | ||
| Drug therapy | 600 | ||
| Secondary treatment targets | 600 | ||
| Metabolic syndrome | 600 | ||
| High triglycerides | 602 | ||
| Drugs and other products used to improve plasma lipid levels | 602 | ||
| HMG-CoA reductase inhibitors (statins) | 603 | ||
| Beneficial actions | 603 | ||
| Reduction of LDL cholesterol. | 603 | ||
| Elevation of HDL cholesterol. | 603 | ||
| Reduction of triglyceride levels. | 603 | ||
| Nonlipid beneficial cardiovascular actions. | 603 | ||
| Mechanism of cholesterol reduction | 604 | ||
| Clinical trials | 604 | ||
| Therapeutic uses | 605 | ||
| Hypercholesterolemia. | 605 | ||
| Primary and secondary prevention of CV events. | 605 | ||
| Primary prevention in people with normal LDL levels. | 605 | ||
| Post-MI therapy. | 605 | ||
| Diabetes. | 605 | ||
| Potential uses. | 605 | ||
| Pharmacokinetics | 605 | ||
| Adverse effects | 606 | ||
| Myopathy/rhabdomyolysis. | 606 | ||
| Hepatotoxicity. | 606 | ||
| Drug interactions | 606 | ||
| With other lipid-lowering drugs. | 606 | ||
| With drugs that inhibit cyp3a4. | 606 | ||
| Use in pregnancy | 607 | ||
| Preparations, dosage, and administration | 607 | ||
| Drug selection | 607 | ||
| LDL goal. | 607 | ||
| Drug interactions. | 607 | ||
| Kidney function. | 607 | ||
| Safety in asians. | 607 | ||
| Price. | 607 | ||
| Niacin (nicotinic acid) | 607 | ||
| Bile-acid sequestrants | 608 | ||
| Colesevelam | 609 | ||
| Effect on plasma lipoproteins. | 609 | ||
| Pharmacokinetics. | 609 | ||
| Mechanism of action. | 609 | ||
| Therapeutic use. | 609 | ||
| Adverse effects. | 609 | ||
| Drug interactions. | 609 | ||
| Ezetimibe | 609 | ||
| Fibric acid derivatives (fibrates) | 610 | ||
| Gemfibrozil | 610 | ||
| Effect on plasma lipoproteins. | 610 | ||
| Therapeutic use. | 610 | ||
| Adverse effects. | 610 | ||
| Gallstones. | 610 | ||
| Myopathy. | 610 | ||
| Liver injury. | 610 | ||
| Drug interactions. | 610 | ||
| Key points | 613 | ||
| 51 Drugs for angina pectoris | 617 | ||
| Determinants of cardiac oxygen demand and oxygen supply | 617 | ||
| Angina pectoris: Pathophysiology and treatment strategy | 617 | ||
| Chronic stable angina (exertional angina) | 617 | ||
| Variant angina (Prinzmetal’s angina, vasospastic angina) | 619 | ||
| Unstable angina | 619 | ||
| Organic nitrates | 620 | ||
| Nitroglycerin | 620 | ||
| Vasodilator actions | 620 | ||
| Mechanism of antianginal effects | 620 | ||
| Stable angina. | 620 | ||
| Variant angina. | 620 | ||
| Pharmacokinetics | 620 | ||
| Absorption. | 620 | ||
| Metabolism. | 620 | ||
| Adverse effects | 620 | ||
| Headache. | 620 | ||
| Orthostatic hypotension. | 620 | ||
| Reflex tachycardia. | 621 | ||
| Drug interactions | 621 | ||
| Hypotensive drugs. | 621 | ||
| Phosphodiesterase type 5 inhibitors. | 621 | ||
| Beta blockers, verapamil, and diltiazem. | 621 | ||
| Tolerance | 621 | ||
| Preparations and routes of administration | 621 | ||
| Sublingual tablets. | 621 | ||
| Sustained-release oral capsules. | 622 | ||
| Transdermal delivery systems. | 622 | ||
| Discontinuing nitroglycerin | 623 | ||
| Summary of therapeutic uses | 623 | ||
| Acute therapy of angina. | 623 | ||
| Sustained therapy of angina. | 623 | ||
| Intravenous therapy. | 623 | ||
| Beta blockers | 623 | ||
| Calcium channel blockers | 624 | ||
| Ranolazine | 624 | ||
| Revascularization therapy: CABG and PCI | 624 | ||
| Summary of treatment measures | 625 | ||
| Guidelines for management of chronic stable angina | 625 | ||
| Drugs used to prevent myocardial infarction and death | 625 | ||
| Antiplatelet drugs. | 626 | ||
| Cholesterol-lowering drugs. | 626 | ||
| Angiotensin-converting enzyme (ACE) inhibitors. | 626 | ||
| Antianginal agents: Drugs used to reduce anginal pain | 626 | ||
| Reduction of risk factors | 627 | ||
| Smoking. | 628 | ||
| High cholesterol. | 628 | ||
| Hypertension. | 628 | ||
| Diabetes. | 628 | ||
| Obesity. | 628 | ||
| Physical inactivity. | 628 | ||
| Management of variant angina | 628 | ||
| Key points | 628 | ||
| 52 Anticoagulant, antiplatelet, and thrombolytic drugs | 631 | ||
| Coagulation: Physiology and pathophysiology | 631 | ||
| Overview of drugs for thromboembolic disorders | 635 | ||
| Anticoagulants | 635 | ||
| Heparin and its derivatives: Drugs that activate antithrombin | 635 | ||
| Heparin (unfractionated) | 636 | ||
| Chemistry | 636 | ||
| Mechanism of anticoagulant action | 636 | ||
| Pharmacokinetics | 636 | ||
| Absorption and distribution. | 636 | ||
| Protein and tissue binding. | 636 | ||
| Metabolism and excretion. | 636 | ||
| Time course. | 636 | ||
| Therapeutic uses | 636 | ||
| Adverse effects | 636 | ||
| Hemorrhage. | 636 | ||
| Spinal/epidural hematoma. | 636 | ||
| Heparin-induced thrombocytopenia. | 636 | ||
| Hypersensitivity reactions. | 638 | ||
| Warnings and contraindications | 638 | ||
| Warnings. | 638 | ||
| Contraindications. | 638 | ||
| Drug interactions | 638 | ||
| Protamine sulfate for heparin overdose | 638 | ||
| Laboratory monitoring | 638 | ||
| Unitage and preparations | 638 | ||
| Unitage. | 638 | ||
| Dosage and administration | 638 | ||
| General considerations. | 638 | ||
| Low-molecular-weight heparins | 639 | ||
| Group properties | 639 | ||
| Production. | 639 | ||
| Mechanism of action. | 639 | ||
| Therapeutic use. | 639 | ||
| Pharmacokinetics. | 639 | ||
| Administration, dosing, and monitoring. | 639 | ||
| Adverse effects and interactions. | 639 | ||
| Cost. | 640 | ||
| Individual preparations | 640 | ||
| Enoxaparin. | 640 | ||
| Warfarin, a vitamin K antagonist | 641 | ||
| Direct thrombin inhibitors | 645 | ||
| Dabigatran etexilate | 645 | ||
| Mechanism of action | 645 | ||
| Therapeutic use | 645 | ||
| Atrial fibrillation. | 645 | ||
| Knee or hip replacement. | 645 | ||
| Pharmacokinetics | 645 | ||
| Adverse effects | 646 | ||
| Bleeding. | 646 | ||
| Gastrointestinal disturbances. | 646 | ||
| Drug interactions | 646 | ||
| Rivaroxaban, a direct factor Xa inhibitor | 648 | ||
| Clinical trials | 648 | ||
| Knee and hip replacement patients. | 648 | ||
| Nonvalvular atrial fibrillation patients. | 648 | ||
| Pharmacokinetics | 648 | ||
| Adverse effects | 648 | ||
| Bleeding. | 648 | ||
| Spinal/epidural hematoma. | 648 | ||
| Drug interactions | 648 | ||
| Precautions | 648 | ||
| Renal impairment. | 648 | ||
| Hepatic impairment. | 649 | ||
| Pregnancy. | 649 | ||
| Antiplatelet drugs | 649 | ||
| Thrombolytic (fibrinolytic) drugs | 654 | ||
| Key points | 657 | ||
| 53 Management of ST-elevation myocardial infarction | 662 | ||
| Pathophysiology of STEMI | 662 | ||
| Diagnosis of STEMI | 662 | ||
| Management of STEMI | 663 | ||
| Routine drug therapy | 663 | ||
| Oxygen | 663 | ||
| Aspirin | 664 | ||
| Nonaspirin NSAIDs | 664 | ||
| Morphine | 664 | ||
| Beta blockers | 664 | ||
| Nitroglycerin | 664 | ||
| Reperfusion therapy | 664 | ||
| Primary percutaneous coronary intervention | 665 | ||
| Fibrinolytic therapy | 665 | ||
| Adjuncts to reperfusion therapy | 665 | ||
| Heparin | 665 | ||
| Antiplatelet drugs | 666 | ||
| Thienopyridines: Clopidogrel and prasugrel. | 666 | ||
| Glycoprotein (GP) IIb/IIIa inhibitors. | 666 | ||
| Aspirin. | 666 | ||
| Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers | 666 | ||
| Complications of STEMI | 666 | ||
| Secondary prevention of STEMI | 667 | ||
| Key points | 667 | ||
| 54 Drugs for hemophilia | 668 | ||
| Basic considerations | 668 | ||
| Pathophysiology | 668 | ||
| Inheritance pattern | 669 | ||
| Clinical features | 669 | ||
| Overview of therapy | 669 | ||
| Pain management | 670 | ||
| Immunization | 670 | ||
| Preparations used to treat hemophilia | 670 | ||
| Factor VIII concentrates | 670 | ||
| Production methods and product safety | 670 | ||
| Plasma-derived factor VIII. | 670 | ||
| Recombinant factor VIII. | 670 | ||
| Adverse effects: Allergic reactions | 671 | ||
| 55 Drugs for deficiency anemias | 676 | ||
| Red blood cell development | 676 | ||
| Iron deficiency | 676 | ||
| Biochemistry and physiology of iron | 676 | ||
| Iron deficiency: Causes, consequences, and diagnosis | 678 | ||
| Oral iron preparations | 679 | ||
| Ferrous iron salts | 679 | ||
| Ferrous sulfate | 679 | ||
| Indications. | 679 | ||
| Adverse effects. | 679 | ||
| GI disturbances. | 679 | ||
| Staining of teeth. | 679 | ||
| Toxicity. | 679 | ||
| Drug interactions. | 679 | ||
| Preparations. | 680 | ||
| Dosage and administration. | 680 | ||
| General considerations. | 680 | ||
| Use in iron deficiency anemia. | 680 | ||
| Prophylactic use. | 680 | ||
| Carbonyl iron | 680 | ||
| Parenteral iron preparations | 681 | ||
| Iron dextran | 681 | ||
| Indications | 681 | ||
| Adverse effects | 681 | ||
| Anaphylactic reactions. | 681 | ||
| Guidelines for treating iron deficiency | 682 | ||
| Vitamin B12 deficiency | 682 | ||
| Biochemistry and physiology of vitamin B12 | 682 | ||
| Vitamin B12 deficiency: causes, consequences, and diagnosis | 683 | ||
| Vitamin B12 preparations: cyanocobalamin | 684 | ||
| Guidelines for treating vitamin B12 deficiency | 685 | ||
| Folic acid deficiency | 685 | ||
| Physiology and biochemistry of folic acid | 685 | ||
| Folic acid deficiency: Causes, consequences, and diagnosis | 686 | ||
| Folic acid preparations | 686 | ||
| Guidelines for treating folic acid deficiency | 687 | ||
| Key points | 687 | ||
| 56 Hematopoietic agents | 691 | ||
| Hematopoietic growth factors | 691 | ||
| Erythropoietic growth factors | 691 | ||
| Epoetin alfa (erythropoietin) | 692 | ||
| Physiology | 692 | ||
| Therapeutic uses | 692 | ||
| Anemia of chronic renal failure. | 692 | ||
| Chemotherapy-induced anemia. | 692 | ||
| HIV-infected patients taking zidovudine. | 692 | ||
| Anemia in patients facing surgery. | 692 | ||
| Pharmacokinetics | 692 | ||
| Adverse effects and interactions | 692 | ||
| Hypertension. | 692 | ||
| Cardiovascular events. | 693 | ||
| Warnings | 693 | ||
| Excessive dosage. | 693 | ||
| 57 Drugs for diabetes mellitus | 702 | ||
| Diabetes mellitus: Basic considerations | 702 | ||
| Insulin | 709 | ||
| Physiology | 709 | ||
| Preparations and administration | 711 | ||
| Sources of insulin | 711 | ||
| Types of insulin | 711 | ||
| Short duration: Rapid acting | 711 | ||
| Insulin lispro. | 712 | ||
| Insulin aspart. | 712 | ||
| Insulin glulisine. | 713 | ||
| Short duration: Slower acting | 713 | ||
| Regular insulin injection. | 713 | ||
| Intermediate duration | 714 | ||
| Neutral protamine hagedorn (NPH) insulin suspension. | 714 | ||
| Insulin detemir. | 714 | ||
| Long duration | 714 | ||
| Insulin glargine. | 714 | ||
| Appearance | 714 | ||
| Concentration | 714 | ||
| Mixing insulins | 714 | ||
| Administration | 715 | ||
| Subcutaneous injection | 715 | ||
| Preparing for injection. | 715 | ||
| Injection sites. | 715 | ||
| Injection devices. | 715 | ||
| Syringe and needle. | 715 | ||
| Pen injectors. | 715 | ||
| Jet injectors. | 715 | ||
| Subcutaneous infusion | 716 | ||
| Portable insulin pumps. | 716 | ||
| Intravenous infusion | 716 | ||
| Storage | 716 | ||
| Therapeutic use | 716 | ||
| Indications | 716 | ||
| Insulin therapy of diabetes | 716 | ||
| Dosage | 716 | ||
| Dosing schedules | 717 | ||
| Conventional therapy. | 717 | ||
| Intensive conventional therapy (ICT). | 717 | ||
| Continuous subcutaneous insulin infusion. | 717 | ||
| Achieving tight glucose control | 717 | ||
| Complications of insulin treatment | 718 | ||
| Hypoglycemia | 718 | ||
| Drug interactions | 718 | ||
| Drugs for type 2 diabetes | 718 | ||
| Oral drugs | 719 | ||
| Biguanides: Metformin | 720 | ||
| Sulfonylureas | 721 | ||
| Thiazolidinediones (glitazones) | 723 | ||
| Pioglitazone | 723 | ||
| Actions and use. | 723 | ||
| Pharmacokinetics. | 723 | ||
| Adverse effects. | 723 | ||
| 58 Drugs for thyroid disorders | 738 | ||
| Thyroid physiology | 738 | ||
| Thyroid function tests | 740 | ||
| Thyroid pathophysiology | 740 | ||
| Hypothyroidism | 740 | ||
| Hypothyroidism in adults | 740 | ||
| Clinical presentation. | 740 | ||
| 59 Drugs related to hypothalamic and pituitary function | 750 | ||
| Overview of hypothalamic and pituitary endocrinology | 750 | ||
| Growth hormone | 751 | ||
| Physiology | 751 | ||
| Regulation of release | 751 | ||
| Biologic effects | 751 | ||
| Promotion of growth. | 751 | ||
| Promotion of protein synthesis. | 752 | ||
| Effect on carbohydrate metabolism. | 752 | ||
| Pathophysiology | 752 | ||
| Growth hormone deficiency | 752 | ||
| Pediatric. | 752 | ||
| Adult. | 752 | ||
| Growth hormone excess | 752 | ||
| Consequences. | 752 | ||
| Treatment overview. | 753 | ||
| Clinical pharmacology | 753 | ||
| Therapeutic uses | 753 | ||
| Pediatric growth hormone deficiency. | 753 | ||
| Pediatric non–growth-hormone-deficient (NGHD) short stature. | 753 | ||
| Pediatric short stature associated with Prader-Willi syndrome. | 753 | ||
| Growth hormone deficiency in adults. | 753 | ||
| Adverse effects and interactions | 753 | ||
| Hyperglycemia. | 753 | ||
| Neutralizing antibodies. | 753 | ||
| Fatality in PWS patients. | 753 | ||
| Interaction with glucocorticoids. | 753 | ||
| Preparations, dosage, and administration | 753 | ||
| Preparations: Somatropin. | 753 | ||
| Administration. | 753 | ||
| Prolactin | 754 | ||
| Antidiuretic hormone (vasopressin) | 755 | ||
| Key points | 757 | ||
| 60 Drugs for disorders of the adrenal cortex | 760 | ||
| Physiology of the adrenocortical hormones | 760 | ||
| Glucocorticoids | 760 | ||
| Physiologic effects | 760 | ||
| Carbohydrate metabolism. | 760 | ||
| Protein metabolism. | 760 | ||
| Fat metabolism. | 760 | ||
| Cardiovascular system. | 760 | ||
| Skeletal muscle. | 761 | ||
| Central nervous system. | 761 | ||
| Stress. | 761 | ||
| Respiratory system in neonates. | 761 | ||
| Regulation of synthesis and secretion | 761 | ||
| Mineralocorticoids | 762 | ||
| Adrenal androgens | 762 | ||
| Pathophysiology of the adrenocortical hormones | 762 | ||
| Adrenal hormone excess | 762 | ||
| Cushing’s syndrome | 762 | ||
| Causes. | 762 | ||
| Clinical presentation. | 762 | ||
| Treatment. | 762 | ||
| Primary hyperaldosteronism | 763 | ||
| Clinical presentation, causes, and diagnosis. | 763 | ||
| 61 Estrogens and progestins: Basic pharmacology and noncontraceptive applications | 768 | ||
| The menstrual cycle | 768 | ||
| Estrogens | 769 | ||
| Biosynthesis and elimination | 769 | ||
| Physiologic and pharmacologic effects | 770 | ||
| Effects on primary and secondary sex characteristics of females | 770 | ||
| Metabolic actions | 770 | ||
| Bone. | 770 | ||
| Cholesterol. | 770 | ||
| Blood coagulation. | 770 | ||
| Clinical pharmacology | 770 | ||
| Adverse effects | 770 | ||
| Endometrial hyperplasia and carcinoma. | 770 | ||
| Breast cancer. | 770 | ||
| Ovarian cancer. | 771 | ||
| Cardiovascular events. | 771 | ||
| Nausea. | 771 | ||
| Therapeutic uses | 771 | ||
| Menopausal hormone therapy. | 771 | ||
| Female hypogonadism. | 771 | ||
| Acne. | 771 | ||
| Selective estrogen receptor modulators (SERMs) | 771 | ||
| Progestins | 772 | ||
| Biosynthesis | 772 | ||
| Physiologic and pharmacologic effects | 772 | ||
| Clinical pharmacology | 772 | ||
| Adverse effects | 772 | ||
| Teratogenic effects. | 772 | ||
| Gynecologic effects. | 772 | ||
| Breast cancer. | 772 | ||
| Other adverse effects. | 772 | ||
| Therapeutic uses | 772 | ||
| Menopausal hormone therapy. | 772 | ||
| Menopausal hormone therapy | 775 | ||
| Landmark studies: WHI and HERS | 775 | ||
| Benefits and risks of hormone therapy | 776 | ||
| Benefits of hormone therapy | 776 | ||
| Relief of vasomotor symptoms. | 776 | ||
| Management of urogenital atrophy. | 776 | ||
| Prevention of osteoporosis and related fractures. | 776 | ||
| Cardioprotection. | 777 | ||
| Improved quality of life? | 777 | ||
| Prevention of colorectal cancer? | 777 | ||
| Adverse effects of hormone therapy | 777 | ||
| Cardiovascular events. | 777 | ||
| Endometrial cancer. | 778 | ||
| Breast cancer. | 778 | ||
| Ovarian cancer. | 778 | ||
| Lung cancer. | 778 | ||
| Gallbladder disease. | 778 | ||
| Dementia. | 778 | ||
| Urinary incontinence. | 779 | ||
| Minor adverse effects. | 779 | ||
| Warnings | 779 | ||
| Recommendations on hormone therapy use | 779 | ||
| General recommendations | 779 | ||
| Use for approved indications | 779 | ||
| Treatment of vasomotor symptoms. | 780 | ||
| Treatment of symptoms of vulvar and vaginal atrophy. | 780 | ||
| Prevention of osteoporosis. | 780 | ||
| Inappropriate uses: Attempted prevention of heart disease and dementia | 780 | ||
| Heart disease. | 780 | ||
| Alzheimer’s disease. | 781 | ||
| Safety in younger women who don’t have a uterus | 781 | ||
| Discontinuing hormone therapy | 781 | ||
| Open questions | 782 | ||
| Drug products for hormone therapy | 782 | ||
| Preparations | 782 | ||
| Dosing schedules | 783 | ||
| Key points | 783 | ||
| 62 Birth control | 786 | ||
| Effectiveness of birth control methods | 786 | ||
| Selecting a birth control method | 787 | ||
| Oral contraceptives | 788 | ||
| Combination oral contraceptives | 788 | ||
| Mechanism of action | 788 | ||
| Components | 788 | ||
| Estrogens. | 788 | ||
| Progestins. | 788 | ||
| Effectiveness | 788 | ||
| Overall safety | 789 | ||
| Adverse effects | 789 | ||
| Thromboembolic disorders. | 789 | ||
| Cancer. | 790 | ||
| Hypertension. | 790 | ||
| Abnormal uterine bleeding. | 790 | ||
| Use in pregnancy and lactation. | 790 | ||
| Stroke in women with migraine. | 790 | ||
| Benign hepatic adenoma. | 790 | ||
| Effects related to estrogen or progestin imbalance. | 790 | ||
| Noncontraceptive benefits of OCs | 791 | ||
| Drug interactions | 791 | ||
| Drugs and herbs that reduce the effects of OCs. | 791 | ||
| Drugs whose effects are reduced by OCs. | 791 | ||
| Drugs whose effects are increased by OCs. | 791 | ||
| Preparations | 791 | ||
| Dosing schedules | 794 | ||
| 28-day-cycle schedules. | 794 | ||
| Extended-cycle and continuous schedules. | 794 | ||
| What to do in the event of missed doses | 794 | ||
| Progestin-only oral contraceptives | 794 | ||
| Combination contraceptives with novel delivery systems | 795 | ||
| Long-acting contraceptives | 795 | ||
| Subdermal etonogestrel implant | 795 | ||
| Depot medroxyprogesterone acetate | 796 | ||
| Key points | 801 | ||
| 63 Drug therapy of infertility | 805 | ||
| Infertility: Causes and treatment strategies | 805 | ||
| Female infertility | 805 | ||
| Anovulation and failure of follicular maturation | 805 | ||
| Unfavorable cervical mucus | 805 | ||
| Hyperprolactinemia | 805 | ||
| Endometriosis | 806 | ||
| Polycystic ovary syndrome | 806 | ||
| Male infertility | 806 | ||
| Hypogonadotropic hypogonadism | 806 | ||
| Erectile dysfunction | 806 | ||
| Idiopathic male infertility | 806 | ||
| Drugs used to treat female infertility | 806 | ||
| Drugs for controlled ovarian stimulation | 806 | ||
| Clomiphene | 806 | ||
| Therapeutic use. | 806 | ||
| Mechanism of fertility promotion. | 806 | ||
| Monitoring. | 807 | ||
| Adverse effects. | 807 | ||
| Menotropins | 808 | ||
| Therapeutic actions and uses. | 808 | ||
| Anovulatory women. | 808 | ||
| Ovulatory women. | 808 | ||
| Men. | 808 | ||
| 64 Drugs that affect uterine function | 813 | ||
| Drugs for preterm labor | 813 | ||
| Drugs used to suppress preterm labor | 813 | ||
| Control of myometrial contraction and mechanisms of tocolytic drug action | 813 | ||
| Specific tocolytic drugs | 814 | ||
| Terbutaline, a beta2-adrenergic agonist | 814 | ||
| Nifedipine, a calcium channel blocker | 814 | ||
| Indomethacin, a cyclooxygenase inhibitor | 815 | ||
| Drugs used to prevent preterm labor | 816 | ||
| Hydroxyprogesterone caproate | 816 | ||
| Drugs for cervical ripening and induction of labor | 817 | ||
| Drugs for postpartum hemorrhage | 819 | ||
| Drugs for menorrhagia | 821 | ||
| Key points | 822 | ||
| 65 Androgens | 824 | ||
| Testosterone | 824 | ||
| Biosynthesis and secretion | 824 | ||
| Mechanism of action | 825 | ||
| Physiologic and pharmacologic effects | 825 | ||
| Effects on sex characteristics in males | 825 | ||
| Pubertal transformation. | 825 | ||
| Spermatogenesis. | 825 | ||
| Effects on sex characteristics in females | 825 | ||
| Anabolic effects | 825 | ||
| Erythropoietic effects | 825 | ||
| Clinical pharmacology of the androgens | 825 | ||
| Classification | 825 | ||
| Therapeutic uses | 825 | ||
| Adverse effects | 826 | ||
| Androgen (anabolic steroid) abuse by athletes | 830 | ||
| Key points | 832 | ||
| 66 Drugs for erectile dysfunction and benign prostatic hyperplasia | 834 | ||
| Erectile dysfunction | 834 | ||
| Physiology of erection | 834 | ||
| Oral drugs for ED: PDE5 inhibitors | 834 | ||
| Sildenafil | 834 | ||
| Mechanism of action | 835 | ||
| Pharmacokinetics | 835 | ||
| Sexual benefits | 835 | ||
| In men with ED. | 835 | ||
| In men without ED. | 835 | ||
| In women. | 835 | ||
| Adverse effects | 835 | ||
| Hypotension. | 835 | ||
| Priapism. | 837 | ||
| Nonarteritic ischemic optic neuropathy (NAION). | 837 | ||
| Sudden hearing loss. | 837 | ||
| Other adverse effects. | 837 | ||
| Drug interactions | 837 | ||
| Nitrates. | 837 | ||
| Alpha blockers. | 837 | ||
| Inhibitors of CYP3A4. | 837 | ||
| Is sildenafil safe for men with CHD? | 837 | ||
| Benign prostatic hyperplasia | 839 | ||
| Pathophysiology and overview of treatment | 839 | ||
| Drug therapy of BPH | 839 | ||
| Key points | 842 | ||
| 67 Review of the immune system | 844 | ||
| Introduction to the immune system | 844 | ||
| Natural immunity versus specific acquired immunity | 844 | ||
| Cell-mediated immunity versus antibody-mediated (humoral) immunity | 844 | ||
| Introduction to cells of the immune system | 844 | ||
| Antibodies | 846 | ||
| Antigens | 847 | ||
| Characteristic features of immune responses | 848 | ||
| Phases of the immune response | 848 | ||
| Major histocompatibility complex molecules | 848 | ||
| Cytokines, lymphokines, and monokines | 849 | ||
| Antibody-mediated (humoral) immunity | 849 | ||
| Production of antibodies | 849 | ||
| Overview of antibody production | 849 | ||
| Specific cellular events in antibody production | 849 | ||
| B cells. | 849 | ||
| Antigen-presenting cells. | 850 | ||
| Helper T cells (CD4 cells). | 850 | ||
| Antibody effector mechanisms | 851 | ||
| Opsonization of bacteria | 851 | ||
| Activation of the complement system | 851 | ||
| Neutralization of viruses and bacterial toxins | 851 | ||
| Cell-mediated immunity | 851 | ||
| Delayed-type hypersensitivity | 851 | ||
| Cytolytic T lymphocytes | 852 | ||
| Key points | 853 | ||
| 68 Childhood immunization | 855 | ||
| General considerations | 855 | ||
| Definitions | 855 | ||
| Public health impact of immunization | 856 | ||
| Reporting vaccine-preventable diseases | 856 | ||
| Immunization records | 857 | ||
| Adverse effects of immunization | 857 | ||
| Vaccine information statements | 858 | ||
| Childhood immunization schedule | 858 | ||
| Target diseases | 858 | ||
| Measles, mumps, and rubella | 858 | ||
| Diphtheria, tetanus, and pertussis | 858 | ||
| Poliomyelitis | 859 | ||
| Haemophilus influenzae type b | 859 | ||
| Varicella (chickenpox) | 859 | ||
| Hepatitis B | 859 | ||
| Hepatitis A | 860 | ||
| Pneumococcal infection | 860 | ||
| Meningococcal infection | 860 | ||
| Influenza | 860 | ||
| Rotavirus gastroenteritis | 860 | ||
| Genital human papillomavirus infection | 860 | ||
| Specific vaccines and toxoids | 861 | ||
| Measles, mumps, and rubella virus vaccine (MMR) | 861 | ||
| Diphtheria and tetanus toxoids and acellular pertussis vaccine | 863 | ||
| Poliovirus vaccine | 864 | ||
| Haemophilus influenzae type b conjugate vaccine | 864 | ||
| Varicella virus vaccine | 865 | ||
| Hepatitis B vaccine | 866 | ||
| Hepatitis A vaccine | 866 | ||
| Pneumococcal conjugate vaccine | 866 | ||
| Meningococcal conjugate vaccine | 867 | ||
| Influenza vaccine | 868 | ||
| Rotavirus vaccine | 868 | ||
| Human papillomavirus vaccine | 869 | ||
| Quadrivalent HPV vaccine: Gardasil | 869 | ||
| Composition. | 869 | ||
| Indications. | 869 | ||
| Cancers and precancerous lesions in females. | 869 | ||
| Genital warts in females and males. | 869 | ||
| Anal cancer in females and males. | 869 | ||
| Efficacy. | 869 | ||
| Is a pap test still needed? | 869 | ||
| Safety. | 869 | ||
| Who should be vaccinated? | 870 | ||
| Females: Routine vaccination. | 870 | ||
| Males: Routine vaccination. | 870 | ||
| Females and males: Catch-up vaccination. | 870 | ||
| 69 Immunosuppressants | 874 | ||
| Calcineurin inhibitors | 874 | ||
| Cyclosporine | 874 | ||
| Therapeutic uses | 874 | ||
| Pharmacokinetics | 875 | ||
| Adverse effects | 875 | ||
| Nephrotoxicity. | 875 | ||
| Infection. | 875 | ||
| Drug and food interactions | 875 | ||
| Drugs that can decrease cyclosporine levels. | 875 | ||
| Drugs that can increase cyclosporine levels. | 875 | ||
| Nephrotoxic drugs. | 875 | ||
| Grapefruit juice. | 875 | ||
| Repaglinide. | 875 | ||
| Tacrolimus | 876 | ||
| Glucocorticoids | 877 | ||
| Cytotoxic drugs | 878 | ||
| Antibodies | 878 | ||
| Key points | 879 | ||
| 70 Antihistamines | 881 | ||
| Histamine | 881 | ||
| Distribution, synthesis, storage, and release | 881 | ||
| Physiologic and pharmacologic effects | 881 | ||
| Effects of H1 stimulation | 881 | ||
| Vasodilation. | 881 | ||
| Increased capillary permeability. | 881 | ||
| Bronchoconstriction. | 881 | ||
| CNS effects. | 882 | ||
| Other effects. | 882 | ||
| Effects of H2 stimulation | 882 | ||
| Role of histamine in allergic responses | 882 | ||
| The two types of antihistamines: H1 antagonists and H2 antagonists | 882 | ||
| H1 antagonists I: basic pharmacology | 882 | ||
| H1 antagonists II: preparations | 885 | ||
| First-generation H1 antagonists | 885 | ||
| Second-generation (nonsedating) H1 antagonists | 886 | ||
| Key points | 887 | ||
| 71 Cyclooxygenase inhibitors: Nonsteroidal anti-inflammatory drugs and acetaminophen | 889 | ||
| Mechanism of action | 889 | ||
| Classification of cyclooxygenase inhibitors | 890 | ||
| First-generation NSAIDs | 890 | ||
| Aspirin | 890 | ||
| Chemistry | 890 | ||
| Mechanism of action | 891 | ||
| Pharmacokinetics | 891 | ||
| Absorption. | 891 | ||
| Metabolism. | 891 | ||
| Distribution. | 891 | ||
| Excretion. | 891 | ||
| Plasma drug levels. | 891 | ||
| Therapeutic uses | 891 | ||
| Suppression of inflammation. | 891 | ||
| Analgesia. | 892 | ||
| Reduction of fever. | 892 | ||
| Dysmenorrhea. | 892 | ||
| Suppression of platelet aggregation. | 892 | ||
| Cancer prevention. | 892 | ||
| Colorectal cancer. | 892 | ||
| Other cancers. | 893 | ||
| Adverse effects | 893 | ||
| Gastrointestinal effects. | 893 | ||
| Bleeding. | 893 | ||
| Renal impairment. | 894 | ||
| Salicylism. | 894 | ||
| Reye’s syndrome. | 894 | ||
| Adverse effects associated with use during pregnancy. | 894 | ||
| Hypersensitivity reactions. | 894 | ||
| Cardiovascular events. | 894 | ||
| Erectile dysfunction. | 894 | ||
| Summary of precautions and contraindications | 894 | ||
| Drug interactions | 895 | ||
| Anticoagulants: Warfarin, heparin, and others. | 895 | ||
| Glucocorticoids. | 895 | ||
| Alcohol. | 895 | ||
| Nonaspirin NSAIDs. | 895 | ||
| ACE inhibitors and ARBs. | 895 | ||
| Vaccines. | 895 | ||
| Acute poisoning | 895 | ||
| Signs and symptoms. | 895 | ||
| Nonaspirin first-generation NSAIDs | 896 | ||
| Second-generation NSAIDs (COX-2 inhibitors, coxibs) | 900 | ||
| Celecoxib | 900 | ||
| Therapeutic use | 900 | ||
| Mechanism of action | 901 | ||
| Adverse effects | 901 | ||
| Gastroduodenal ulceration. | 901 | ||
| Cardiovascular events. | 901 | ||
| Renal impairment. | 901 | ||
| Sulfonamide allergy. | 901 | ||
| Use in pregnancy. | 901 | ||
| Drug interactions | 901 | ||
| Warfarin. | 901 | ||
| Acetaminophen | 902 | ||
| AHA statement on COX inhibitors in chronic pain | 904 | ||
| Key points | 905 | ||
| 72 Glucocorticoids in nonendocrine disorders | 909 | ||
| Review of glucocorticoid physiology | 909 | ||
| Physiologic effects | 909 | ||
| Control of synthesis and secretion | 910 | ||
| Pharmacology of the glucocorticoids | 910 | ||
| Molecular mechanism of action | 910 | ||
| Pharmacologic effects | 910 | ||
| Effects on metabolism and electrolytes | 910 | ||
| Anti-inflammatory and immunosuppressant effects | 911 | ||
| Therapeutic uses in nonendocrine disorders | 911 | ||
| Adverse effects | 912 | ||
| Use in pregnancy and lactation | 914 | ||
| Drug interactions | 914 | ||
| Summary of precautions and contraindications | 914 | ||
| Adrenal suppression | 914 | ||
| Preparations and routes of administration | 915 | ||
| Preparations | 915 | ||
| Routes of administration | 915 | ||
| Dosage | 915 | ||
| General guidelines for dosing | 915 | ||
| Alternate-day therapy | 915 | ||
| Key points | 916 | ||
| 73 Drug therapy of rheumatoid arthritis | 919 | ||
| Pathophysiology of rheumatoid arthritis | 919 | ||
| Overview of therapy | 919 | ||
| Nondrug measures | 919 | ||
| Drug therapy | 920 | ||
| Classes of antiarthritic drugs | 920 | ||
| Drug selection | 920 | ||
| Nonsteroidal anti-inflammatory drugs | 921 | ||
| Glucocorticoids | 922 | ||
| Nonbiologic (traditional) DMARDs | 922 | ||
| Methotrexate | 922 | ||
| Sulfasalazine | 922 | ||
| Biologic DMARDs | 923 | ||
| Tumor necrosis factor antagonists | 923 | ||
| Etanercept | 924 | ||
| Mechanism of action. | 924 | ||
| Therapeutic uses. | 924 | ||
| Adverse effects. | 924 | ||
| Mild effects. | 924 | ||
| Serious infections. | 924 | ||
| Severe allergic reactions. | 925 | ||
| Heart failure. | 925 | ||
| Cancer. | 925 | ||
| Hematologic disorders. | 925 | ||
| Liver injury. | 925 | ||
| Central nervous system (CNS) demyelinating disorders. | 925 | ||
| Drug interactions. | 925 | ||
| Key points | 928 | ||
| 74 Drug therapy of gout | 930 | ||
| Pathophysiology of gout | 930 | ||
| Overview of drug therapy | 930 | ||
| Drugs for acute gouty arthritis | 930 | ||
| Nonsteroidal anti-inflammatory drugs | 930 | ||
| Glucocorticoids | 930 | ||
| Drugs for hyperuricemia (urate-lowering therapy) | 931 | ||
| Xanthine oxidase inhibitors: Allopurinol and febuxostat | 931 | ||
| Allopurinol | 932 | ||
| Therapeutic uses. | 932 | ||
| Mechanism of action. | 932 | ||
| Probenecid, a uricosuric agent | 933 | ||
| Pegloticase, a recombinant form of uric acid oxidase | 933 | ||
| Key points | 933 | ||
| 75 Drugs affecting calcium levels and bone mineralization | 935 | ||
| Calcium physiology | 935 | ||
| Drugs for disorders involving calcium | 938 | ||
| Calcium salts | 938 | ||
| Oral calcium salts | 938 | ||
| Therapeutic uses. | 938 | ||
| Adverse effects. | 938 | ||
| Vitamin D | 939 | ||
| Physiologic actions | 939 | ||
| Health benefits | 939 | ||
| Sources and daily requirements | 939 | ||
| Sources. | 939 | ||
| Requirements. | 939 | ||
| Vitamin D deficiency | 939 | ||
| Calcitonin-salmon | 941 | ||
| Actions | 941 | ||
| Therapeutic uses | 941 | ||
| Osteoporosis. | 941 | ||
| Bisphosphonates | 941 | ||
| Alendronate | 942 | ||
| Pharmacokinetics. | 942 | ||
| Mechanism of action. | 942 | ||
| Therapeutic use. | 942 | ||
| Osteoporosis in postmenopausal women. | 942 | ||
| Osteoporosis in men. | 942 | ||
| Glucocorticoid-induced osteoporosis. | 942 | ||
| Paget’s disease of bone. | 942 | ||
| Adverse effects. | 942 | ||
| Esophagitis. | 943 | ||
| Atypical femoral fractures. | 943 | ||
| Administration. | 943 | ||
| Zoledronate | 944 | ||
| Actions and uses. | 944 | ||
| Adverse effects. | 945 | ||
| Drug interactions. | 945 | ||
| Raloxifene | 945 | ||
| Mechanism of action | 945 | ||
| Therapeutic uses | 946 | ||
| Postmenopausal osteoporosis. | 946 | ||
| Breast cancer. | 946 | ||
| Adverse effects and interactions | 946 | ||
| Venous thromboembolism. | 946 | ||
| Fetal harm. | 946 | ||
| Hot flushes. | 946 | ||
| Comparison with estrogen | 946 | ||
| Teriparatide | 946 | ||
| Denosumab | 947 | ||
| Therapeutic uses | 947 | ||
| Clinical trials | 947 | ||
| Osteoporosis in postmenopausal women. | 947 | ||
| Prevention of skeletal-related events in patients with bone metastases. | 948 | ||
| Mechanism of action | 948 | ||
| Pharmacokinetics | 948 | ||
| Adverse effects | 948 | ||
| Hypocalcemia. | 948 | ||
| Serious infections. | 948 | ||
| Dermatologic reactions. | 948 | ||
| Osteonecrosis of the jaw. | 948 | ||
| Cinacalcet | 948 | ||
| Osteoporosis | 949 | ||
| General considerations | 949 | ||
| Bone mass | 949 | ||
| Primary prevention: Calcium, vitamin D, and lifestyle | 950 | ||
| Diagnosing osteoporosis and assessing fracture risk | 950 | ||
| Who should be treated? | 950 | ||
| Treating osteoporosis in women | 950 | ||
| Antiresorptive therapy | 951 | ||
| Estrogen. | 951 | ||
| Raloxifene. | 951 | ||
| Bisphosphonates. | 951 | ||
| Alendronate. | 951 | ||
| Risedronate, ibandronate, and zoledronate. | 952 | ||
| Calcitonin-salmon. | 952 | ||
| Denosumab. | 952 | ||
| Bone-forming therapy: Teriparatide | 952 | ||
| Treating osteoporosis in men | 952 | ||
| Key points | 953 | ||
| 76 Drugs for asthma | 958 | ||
| Basic considerations | 958 | ||
| Pathophysiology of asthma | 958 | ||
| Overview of drugs for asthma | 958 | ||
| Administering drugs by inhalation | 959 | ||
| Anti-inflammatory drugs | 960 | ||
| Glucocorticoids | 960 | ||
| Bronchodilators | 965 | ||
| Beta2-adrenergic agonists | 965 | ||
| Glucocorticoid/laba combinations | 968 | ||
| Management of asthma | 969 | ||
| Key points | 973 | ||
| 77 Drugs for allergic rhinitis, cough, and colds | 977 | ||
| Drugs for allergic rhinitis | 977 | ||
| Intranasal glucocorticoids | 977 | ||
| Antihistamines | 978 | ||
| Oral antihistamines | 978 | ||
| Intranasal antihistamines | 978 | ||
| Intranasal cromolyn sodium | 979 | ||
| Sympathomimetics (decongestants) | 979 | ||
| Actions and uses | 979 | ||
| Adverse effects | 979 | ||
| Rebound congestion. | 979 | ||
| Central nervous system stimulation. | 980 | ||
| Cardiovascular effects. | 980 | ||
| Abuse. | 980 | ||
| Factors in topical administration | 981 | ||
| General considerations. | 981 | ||
| Drops. | 981 | ||
| Sprays. | 981 | ||
| Summary of contrasts between oral and topical agents | 981 | ||
| Comparison of phenylephrine, ephedrine, and pseudoephedrine | 981 | ||
| Drugs for cough | 982 | ||
| Antitussives | 982 | ||
| Opioid antitussives | 982 | ||
| Codeine. | 982 | ||
| Nonopioid antitussives | 982 | ||
| Dextromethorphan. | 982 | ||
| Cold remedies: Combination preparations | 983 | ||
| Key points | 984 | ||
| 78 Drugs for peptic ulcer disease | 985 | ||
| Pathogenesis of peptic ulcers | 985 | ||
| Defensive factors | 985 | ||
| Aggressive factors | 985 | ||
| Summary | 986 | ||
| Overview of treatment | 986 | ||
| Drug therapy | 986 | ||
| Classes of antiulcer drugs | 986 | ||
| Drug selection | 987 | ||
| Helicobacter pylori–associated ulcers. | 987 | ||
| NSAID-induced ulcers. | 987 | ||
| Prophylaxis. | 987 | ||
| Treatment. | 987 | ||
| Evaluation | 987 | ||
| Nondrug therapy | 988 | ||
| Antibacterial drugs | 988 | ||
| Tests for helicobacter pylori | 988 | ||
| Antibiotics employed | 988 | ||
| Antibiotic regimens | 988 | ||
| Histamine2 receptor antagonists | 989 | ||
| Cimetidine | 989 | ||
| Mechanism of action | 989 | ||
| Pharmacokinetics | 989 | ||
| Therapeutic uses | 990 | ||
| Gastric and duodenal ulcers. | 990 | ||
| Gastroesophageal reflux disease (GERD). | 990 | ||
| Zollinger-Ellison syndrome. | 990 | ||
| Aspiration pneumonitis. | 990 | ||
| Heartburn, acid indigestion, and sour stomach. | 990 | ||
| Adverse effects | 990 | ||
| Antiandrogenic effects. | 990 | ||
| CNS effects. | 990 | ||
| Pneumonia. | 990 | ||
| Drug interactions | 991 | ||
| Interactions related to inhibition of drug metabolism. | 991 | ||
| Antacids. | 991 | ||
| Ranitidine | 991 | ||
| Proton pump inhibitors | 992 | ||
| Omeprazole | 992 | ||
| Other antiulcer drugs | 994 | ||
| Sucralfate | 994 | ||
| Misoprostol | 995 | ||
| Antacids | 995 | ||
| Beneficial actions | 995 | ||
| Key points | 997 | ||
| 79 Laxatives | 1001 | ||
| General considerations | 1001 | ||
| Basic pharmacology of laxatives | 1003 | ||
| Bulk-forming laxatives | 1003 | ||
| Surfactant laxatives | 1003 | ||
| Stimulant laxatives | 1004 | ||
| Osmotic laxatives | 1005 | ||
| Laxative salts | 1005 | ||
| Actions and uses. | 1005 | ||
| Preparations. | 1005 | ||
| Adverse effects. | 1005 | ||
| Polyethylene glycol | 1005 | ||
| Other laxatives | 1005 | ||
| Lubiprostone | 1005 | ||
| Bowel cleansing products for colonoscopy | 1006 | ||
| Polyethylene glycol–electrolyte solutions | 1006 | ||
| Sodium phosphate products | 1007 | ||
| Laxative abuse | 1007 | ||
| Key points | 1007 | ||
| 80 Other gastrointestinal drugs | 1009 | ||
| Antiemetics | 1009 | ||
| The emetic response | 1009 | ||
| Antiemetic drugs | 1010 | ||
| Serotonin receptor antagonists | 1010 | ||
| Ondansetron. | 1010 | ||
| Glucocorticoids | 1011 | ||
| Substance p/neurokinin1 antagonists | 1012 | ||
| Aprepitant. | 1012 | ||
| Actions and use. | 1012 | ||
| Pharmacokinetics. | 1012 | ||
| Adverse effects. | 1012 | ||
| Drug interactions. | 1012 | ||
| Benzodiazepines | 1012 | ||
| Dopamine antagonists | 1012 | ||
| Phenothiazines. | 1012 | ||
| Butyrophenones. | 1012 | ||
| Metoclopramide. | 1013 | ||
| Cannabinoids | 1013 | ||
| Therapeutic uses. | 1013 | ||
| Adverse effects and drug interactions. | 1013 | ||
| Abuse potential. | 1013 | ||
| Chemotherapy-induced nausea and vomiting | 1013 | ||
| Nausea and vomiting of pregnancy | 1013 | ||
| Drugs for motion sickness | 1014 | ||
| Antidiarrheal agents | 1014 | ||
| Nonspecific antidiarrheal agents | 1015 | ||
| Opioids | 1015 | ||
| Diphenoxylate. | 1015 | ||
| Loperamide. | 1015 | ||
| Management of infectious diarrhea | 1016 | ||
| Drugs for irritable bowel syndrome | 1016 | ||
| Nonspecific drugs | 1017 | ||
| IBS-specific drugs | 1017 | ||
| Alosetron | 1017 | ||
| Indications. | 1017 | ||
| Mechanism of action and clinical effects. | 1017 | ||
| Pharmacokinetics. | 1017 | ||
| Drug interactions. | 1017 | ||
| Adverse effects and contraindications. | 1017 | ||
| Risk management program. | 1017 | ||
| Drugs for inflammatory bowel disease | 1019 | ||
| Prokinetic agents | 1021 | ||
| Palifermin | 1022 | ||
| Key points | 1024 | ||
| 81 Vitamins | 1025 | ||
| Basic considerations | 1025 | ||
| Dietary reference intakes | 1025 | ||
| Classification of vitamins | 1025 | ||
| Should we take multivitamin supplements? | 1026 | ||
| Fat-soluble vitamins | 1026 | ||
| Vitamin A (retinol) | 1026 | ||
| Vitamin D | 1027 | ||
| Vitamin E (alpha-tocopherol) | 1027 | ||
| Vitamin K | 1031 | ||
| Water-soluble vitamins | 1032 | ||
| Vitamin C (ascorbic acid) | 1032 | ||
| Niacin (nicotinic acid) | 1032 | ||
| Riboflavin (vitamin B2) | 1033 | ||
| Thiamin (vitamin B1) | 1033 | ||
| Pyridoxine (vitamin B6) | 1033 | ||
| Cyanocobalamin (vitamin B12) and folic acid | 1034 | ||
| Key points | 1035 | ||
| 82 Drugs for weight loss | 1036 | ||
| Assessment of weight-related health risk | 1036 | ||
| Overview of obesity treatment | 1038 | ||
| Weight-loss drugs for long-term use | 1039 | ||
| Orlistat, a lipase inhibitor | 1039 | ||
| Actions and use | 1039 | ||
| Adverse effects | 1040 | ||
| Gastrointestinal effects. | 1040 | ||
| Possible liver damage. | 1040 | ||
| Other adverse effects. | 1040 | ||
| Contraindications. | 1040 | ||
| Drug and nutrient interactions | 1040 | ||
| Reduced absorption of vitamins. | 1040 | ||
| Warfarin. | 1040 | ||
| Levothyroxine. | 1040 | ||
| Key points | 1043 | ||
| 83 Basic principles of antimicrobial therapy | 1044 | ||
| Selective toxicity | 1044 | ||
| Classification of antimicrobial drugs | 1045 | ||
| Acquired resistance to antimicrobial drugs | 1046 | ||
| Microbial mechanisms of drug resistance | 1046 | ||
| Mechanisms by which resistance is acquired | 1048 | ||
| Relationships between antibiotic use and emergence of drug-resistant microbes | 1048 | ||
| Suprainfection (superinfection) | 1048 | ||
| Delaying the emergence of resistance in hospitals | 1049 | ||
| Selection of antibiotics | 1051 | ||
| Empiric therapy prior to completion of laboratory tests | 1051 | ||
| Identifying the infecting organism | 1051 | ||
| Determining drug susceptibility | 1051 | ||
| Host factors that modify drug choice, route of administration, or dosage | 1054 | ||
| Host defenses | 1054 | ||
| Site of infection | 1055 | ||
| Other host factors | 1055 | ||
| Dosage size and duration of treatment | 1055 | ||
| Therapy with antibiotic combinations | 1055 | ||
| Antimicrobial effects of antibiotic combinations | 1055 | ||
| Indications for antibiotic combinations | 1056 | ||
| Disadvantages of antibiotic combinations | 1056 | ||
| Prophylactic use of antimicrobial drugs | 1056 | ||
| Misuses of antimicrobial drugs | 1057 | ||
| Monitoring antimicrobial therapy | 1057 | ||
| Key points | 1058 | ||
| 84 Drugs that weaken the bacterial cell wall I: Penicillins | 1059 | ||
| Introduction to the penicillins | 1059 | ||
| Mechanism of action | 1059 | ||
| Mechanisms of bacterial resistance | 1059 | ||
| The gram-negative cell envelope | 1059 | ||
| Penicillinases (beta-lactamases) | 1060 | ||
| Altered penicillin-binding proteins | 1060 | ||
| Chemistry | 1060 | ||
| Classification | 1061 | ||
| Properties of individual penicillins | 1061 | ||
| Penicillin G | 1061 | ||
| Antimicrobial spectrum | 1061 | ||
| Pharmacokinetics | 1062 | ||
| Absorption. | 1062 | ||
| Oral. | 1062 | ||
| Intramuscular. | 1062 | ||
| Intravenous. | 1062 | ||
| Distribution. | 1062 | ||
| Metabolism and excretion. | 1062 | ||
| Side effects and toxicities | 1063 | ||
| Penicillin allergy | 1063 | ||
| General considerations. | 1063 | ||
| Types of allergic reactions. | 1063 | ||
| Development of penicillin allergy. | 1064 | ||
| Skin tests for penicillin allergy. | 1064 | ||
| Management of patients with a history of penicillin allergy. | 1064 | ||
| Drug interactions | 1064 | ||
| Aminoglycosides. | 1064 | ||
| Penicillinase-resistant penicillins (antistaphylococcal penicillins) | 1064 | ||
| Broad-spectrum penicillins (aminopenicillins) | 1065 | ||
| Ampicillin | 1065 | ||
| Amoxicillin | 1067 | ||
| Extended-spectrum penicillins (antipseudomonal penicillins) | 1067 | ||
| Penicillins combined with a beta-lactamase inhibitor | 1067 | ||
| Key points | 1068 | ||
| 85 Drugs that weaken the bacterial cell wall II: cephalosporins, carbapenems, vancomycin, telavancin, aztreonam, teicoplanin, and fosfomycin | 1070 | ||
| Cephalosporins | 1070 | ||
| Carbapenems | 1075 | ||
| Imipenem | 1075 | ||
| Other inhibitors of cell wall synthesis | 1076 | ||
| Vancomycin | 1076 | ||
| Key points | 1080 | ||
| 86 Bacteriostatic inhibitors of protein synthesis: tetracyclines, macrolides, and others | 1083 | ||
| Tetracyclines | 1083 | ||
| Macrolides | 1086 | ||
| Erythromycin | 1086 | ||
| Mechanism of action | 1086 | ||
| Acquired resistance | 1086 | ||
| Antimicrobial spectrum | 1086 | ||
| Therapeutic uses | 1086 | ||
| Pharmacokinetics | 1087 | ||
| Absorption and bioavailability. | 1087 | ||
| Distribution. | 1087 | ||
| Elimination. | 1087 | ||
| Adverse effects | 1087 | ||
| Gastrointestinal effects. | 1087 | ||
| QT prolongation and sudden cardiac death. | 1087 | ||
| Drug interactions | 1087 | ||
| Other bacteriostatic inhibitors of protein synthesis | 1088 | ||
| Clindamycin | 1088 | ||
| Mechanism of action | 1088 | ||
| Antimicrobial spectrum | 1088 | ||
| Therapeutic use | 1088 | ||
| 87 Aminoglycosides: bactericidal inhibitors of protein synthesis | 1095 | ||
| Basic pharmacology of the aminoglycosides | 1095 | ||
| Properties of individual aminoglycosides | 1100 | ||
| Gentamicin | 1100 | ||
| Therapeutic use | 1100 | ||
| Adverse effects and interactions | 1100 | ||
| Tobramycin | 1100 | ||
| Amikacin | 1100 | ||
| Key points | 1101 | ||
| 88 Sulfonamides and trimethoprim | 1103 | ||
| Sulfonamides | 1103 | ||
| Basic pharmacology | 1103 | ||
| Chemistry | 1103 | ||
| Mechanism of action | 1103 | ||
| Therapeutic uses | 1103 | ||
| Urinary tract infections. | 1103 | ||
| Adverse effects | 1104 | ||
| Hypersensitivity reactions. | 1104 | ||
| Hematologic effects. | 1105 | ||
| Kernicterus. | 1105 | ||
| Renal damage from crystalluria. | 1105 | ||
| Drug interactions | 1105 | ||
| Metabolism-related interactions. | 1105 | ||
| Cross-hypersensitivity. | 1105 | ||
| Sulfonamide preparations | 1105 | ||
| Systemic sulfonamides | 1105 | ||
| Sulfamethoxazole. | 1105 | ||
| Trimethoprim | 1106 | ||
| Trimethoprim/sulfamethoxazole | 1106 | ||
| Key points | 1108 | ||
| 89 Drug therapy of urinary tract infections | 1111 | ||
| Organisms that cause urinary tract infections | 1111 | ||
| Specific urinary tract infections and their treatment | 1111 | ||
| Acute cystitis | 1111 | ||
| Acute uncomplicated pyelonephritis | 1112 | ||
| Complicated urinary tract infections | 1113 | ||
| Recurrent urinary tract infection | 1113 | ||
| Acute bacterial prostatitis | 1113 | ||
| Urinary tract antiseptics | 1113 | ||
| Nitrofurantoin | 1114 | ||
| Mechanism of action | 1114 | ||
| Antimicrobial spectrum | 1114 | ||
| Therapeutic use | 1114 | ||
| Adverse effects | 1114 | ||
| Gastrointestinal effects. | 1114 | ||
| Pulmonary reactions. | 1114 | ||
| Hematologic effects. | 1114 | ||
| Peripheral neuropathy. | 1114 | ||
| Hepatotoxicity. | 1114 | ||
| Birth defects. | 1114 | ||
| CNS effects. | 1114 | ||
| Key points | 1115 | ||
| 90 Antimycobacterial agents: Drugs for tuberculosis, leprosy, and complex infection | 1116 | ||
| Drugs for tuberculosis | 1116 | ||
| Clinical considerations | 1116 | ||
| Pathogenesis | 1116 | ||
| Primary infection | 1116 | ||
| Reactivation | 1117 | ||
| Diagnosis and treatment of active tuberculosis | 1117 | ||
| Diagnosis | 1117 | ||
| Drug resistance | 1117 | ||
| The prime directive: Always treat tuberculosis with two or more drugs | 1117 | ||
| Determining drug sensitivity | 1118 | ||
| Treatment regimens | 1118 | ||
| Drug-sensitive tuberculosis. | 1118 | ||
| Isoniazid- or rifampin-resistant tuberculosis. | 1118 | ||
| Multidrug-resistant TB and extensively drug-resistant TB. | 1118 | ||
| Patients with TB plus HIV infection. | 1118 | ||
| Duration of treatment | 1119 | ||
| Promoting adherence: Directly observed therapy combined with intermittent dosing | 1119 | ||
| Evaluating treatment | 1119 | ||
| Diagnosis and treatment of latent tuberculosis | 1119 | ||
| Who should be tested for latent tuberculosis? | 1119 | ||
| How do we test for latent tuberculosis? | 1120 | ||
| Tuberculin skin test. | 1120 | ||
| Interferon gamma release assays. | 1120 | ||
| How do we treat latent tuberculosis? | 1121 | ||
| Isoniazid. | 1121 | ||
| Isoniazid plus rifapentine. | 1121 | ||
| Pharmacology of individual antituberculosis drugs | 1121 | ||
| Isoniazid | 1121 | ||
| Antimicrobial spectrum and mechanism of action | 1121 | ||
| Resistance | 1122 | ||
| Therapeutic use | 1122 | ||
| Adverse effects | 1122 | ||
| Hepatotoxicity. | 1122 | ||
| Peripheral neuropathy. | 1122 | ||
| Drug interactions | 1122 | ||
| Interactions from inhibiting drug metabolism. | 1122 | ||
| Alcohol, rifampin, rifapentine, rifabutin, and pyrazinamide. | 1122 | ||
| Rifampin | 1123 | ||
| Antimicrobial spectrum | 1123 | ||
| Mechanism of action and bacterial resistance | 1123 | ||
| Pharmacokinetics | 1123 | ||
| Absorption and distribution. | 1123 | ||
| Elimination. | 1123 | ||
| Therapeutic use | 1123 | ||
| Tuberculosis. | 1123 | ||
| Leprosy. | 1123 | ||
| Adverse effects | 1123 | ||
| Hepatotoxicity. | 1123 | ||
| Discoloration of body fluids. | 1123 | ||
| Drug interactions | 1123 | ||
| Accelerated metabolism of other drugs. | 1123 | ||
| Isoniazid and pyrazinamide. | 1123 | ||
| Pyrazinamide | 1124 | ||
| Antimicrobial activity and therapeutic use | 1124 | ||
| Adverse effects and interactions | 1124 | ||
| Hepatotoxicity. | 1124 | ||
| Nongouty polyarthralgias. | 1124 | ||
| Ethambutol | 1125 | ||
| Antimicrobial action | 1125 | ||
| Therapeutic use | 1125 | ||
| Adverse effects | 1125 | ||
| Optic neuritis. | 1125 | ||
| Key points | 1128 | ||
| 91 Miscellaneous antibacterial drugs: Fluoroquinolones, metronidazole, daptomycin, rifampin, rifaximin, bacitracin, and polymyxins | 1131 | ||
| Fluoroquinolones | 1131 | ||
| Ciprofloxacin | 1131 | ||
| Mechanism of action | 1131 | ||
| Therapeutic uses | 1131 | ||
| Adverse effects | 1132 | ||
| Drug and food interactions | 1132 | ||
| Cationic compounds. | 1132 | ||
| Elevation of drug levels. | 1132 | ||
| Additional antibacterial drugs | 1133 | ||
| Metronidazole | 1133 | ||
| Daptomycin | 1134 | ||
| Key points | 1135 | ||
| 92 Antifungal agents | 1137 | ||
| Drugs for systemic mycoses | 1137 | ||
| Amphotericin B, a polyene antibiotic | 1137 | ||
| Mechanism of action | 1138 | ||
| Microbial susceptibility and resistance | 1138 | ||
| Therapeutic uses | 1138 | ||
| Pharmacokinetics | 1138 | ||
| Absorption and distribution. | 1138 | ||
| Adverse effects | 1138 | ||
| Infusion reactions. | 1138 | ||
| Nephrotoxicity. | 1138 | ||
| Hypokalemia. | 1138 | ||
| Hematologic effects. | 1139 | ||
| Drug interactions | 1139 | ||
| Nephrotoxic drugs. | 1139 | ||
| Flucytosine. | 1139 | ||
| Azoles | 1139 | ||
| Itraconazole | 1139 | ||
| Mechanism of action. | 1139 | ||
| Therapeutic use. | 1139 | ||
| Adverse effects. | 1139 | ||
| Cardiac suppression. | 1139 | ||
| Liver injury. | 1139 | ||
| Drug interactions. | 1139 | ||
| Inhibition of hepatic drug-metabolizing enzymes. | 1139 | ||
| Drugs that raise gastric pH. | 1140 | ||
| Flucytosine, a pyrimidine analog | 1143 | ||
| Drugs for superficial mycoses | 1143 | ||
| Overview of drug therapy | 1143 | ||
| Dermatophytic infections (ringworm) | 1143 | ||
| Tinea pedis. | 1143 | ||
| Tinea corporis. | 1143 | ||
| Tinea cruris. | 1144 | ||
| Tinea capitis. | 1144 | ||
| Candidiasis | 1144 | ||
| Vulvovaginal candidiasis. | 1144 | ||
| Oral candidiasis. | 1144 | ||
| Onychomycosis (fungal infection of the nails) | 1144 | ||
| Oral therapy. | 1145 | ||
| Topical therapy with ciclopirox. | 1145 | ||
| Azoles | 1145 | ||
| Clotrimazole | 1145 | ||
| Therapeutic uses. | 1145 | ||
| Adverse effects. | 1145 | ||
| Griseofulvin | 1146 | ||
| Polyene antibiotics | 1147 | ||
| Nystatin | 1147 | ||
| Actions, uses, and adverse effects. | 1147 | ||
| Key points | 1147 | ||
| 93 Antiviral agents I: Drugs for non-HIV viral infections | 1150 | ||
| Drugs for infection with herpes simplex viruses and varicella-zoster virus | 1151 | ||
| Drugs for cytomegalovirus infection | 1153 | ||
| Drugs for hepatitis | 1156 | ||
| Hepatitis C | 1156 | ||
| Interferon alfa | 1156 | ||
| Ribavirin (oral) | 1157 | ||
| Protease inhibitors: Boceprevir and telaprevir | 1158 | ||
| Boceprevir | 1158 | ||
| Therapeutic use. | 1158 | ||
| Mechanism of action. | 1159 | ||
| Pharmacokinetics. | 1159 | ||
| Adverse effects. | 1159 | ||
| Effect in pregnancy. | 1159 | ||
| Drug interactions. | 1159 | ||
| Hepatitis B | 1161 | ||
| Interferon alfa | 1161 | ||
| Nucleoside analogs | 1162 | ||
| Lamivudine | 1162 | ||
| Drugs for influenza | 1163 | ||
| Key points | 1168 | ||
| 94 Antiviral agents II: Drugs for HIV infection and related opportunistic infections | 1170 | ||
| Pathophysiology | 1171 | ||
| Characteristics of HIV | 1171 | ||
| Target cells | 1171 | ||
| Structure of HIV | 1171 | ||
| Replication cycle of HIV | 1171 | ||
| Replication rate | 1173 | ||
| Mutation and drug resistance | 1173 | ||
| Transmission of HIV | 1173 | ||
| Clinical course of HIV infection | 1173 | ||
| Classification of antiretroviral drugs | 1174 | ||
| Nucleoside/nucleotide reverse transcriptase inhibitors | 1174 | ||
| Zidovudine | 1174 | ||
| Mechanism of antiviral action | 1174 | ||
| Therapeutic use | 1174 | ||
| Adverse effects | 1174 | ||
| Anemia and neutropenia from bone marrow suppression. | 1174 | ||
| Lactic acidosis with hepatic steatosis. | 1175 | ||
| Drug interactions | 1176 | ||
| Non-nucleoside reverse transcriptase inhibitors | 1180 | ||
| Efavirenz | 1180 | ||
| Protease inhibitors | 1184 | ||
| Group properties | 1184 | ||
| Adverse effects | 1184 | ||
| Hyperglycemia/diabetes. | 1184 | ||
| Fat maldistribution. | 1184 | ||
| Hyperlipidemia. | 1184 | ||
| Increased bleeding in people with hemophilia. | 1184 | ||
| Reduced bone mineral density. | 1184 | ||
| Elevation of serum transaminases. | 1184 | ||
| Drug interactions | 1185 | ||
| P450 inhibitors. | 1185 | ||
| P450 inducers. | 1185 | ||
| P450 substrates. | 1185 | ||
| Protease inhibitor combinations: Ritonavir boosting. | 1185 | ||
| Herb interactions | 1185 | ||
| St. John’s wort. | 1185 | ||
| Garlic. | 1185 | ||
| Lopinavir/ritonavir | 1185 | ||
| Raltegravir, an integrase strand transfer inhibitor | 1193 | ||
| Enfuvirtide, an HIV fusion inhibitor | 1194 | ||
| Maraviroc, a CCR5 antagonist | 1195 | ||
| Management of HIV infection | 1195 | ||
| Screening and diagnosis | 1196 | ||
| Laboratory tests | 1196 | ||
| CD4 T-cell counts | 1196 | ||
| Viral load (plasma HIV RNA) | 1196 | ||
| HIV drug resistance | 1197 | ||
| HLA-B*5701 screening | 1197 | ||
| CCR5 tropism | 1198 | ||
| Therapeutic drug monitoring | 1198 | ||
| Treatment of adult and adolescent patients | 1198 | ||
| Symptomatic HIV disease | 1198 | ||
| Chronic asymptomatic HIV disease | 1199 | ||
| Acute HIV disease | 1200 | ||
| Changing the regimen | 1200 | ||
| Treatment failure. | 1201 | ||
| Drug toxicity. | 1201 | ||
| Promoting patient adherence | 1201 | ||
| Patient- and medication-related strategies | 1201 | ||
| Clinician- and healthcare team–related strategies | 1201 | ||
| Treatment of infants and young children | 1202 | ||
| Treatment of pregnant patients | 1202 | ||
| Basic principles | 1202 | ||
| Mitochondrial toxicity from NRTIs | 1202 | ||
| Preconception counseling and care | 1203 | ||
| Preventing HIV infection with drugs | 1203 | ||
| Treatment as prevention | 1203 | ||
| Pre-exposure prophylaxis | 1203 | ||
| Postexposure prophylaxis | 1204 | ||
| Nonoccupational postexposure prophylaxis | 1204 | ||
| Occupational postexposure prophylaxis | 1204 | ||
| Preventing perinatal HIV transmission | 1204 | ||
| Prophylaxis and treatment of opportunistic infections | 1204 | ||
| HIV vaccines | 1208 | ||
| Keeping current | 1209 | ||
| Key points | 1209 | ||
| 95 Drug therapy of sexually transmitted diseases | 1218 | ||
| Chlamydia trachomatis infections | 1218 | ||
| Gonococcal infections | 1221 | ||
| Nongonococcal urethritis | 1222 | ||
| Pelvic inflammatory disease | 1222 | ||
| Acute epididymitis | 1223 | ||
| Syphilis | 1223 | ||
| Acquired immunodeficiency syndrome | 1223 | ||
| Bacterial vaginosis | 1223 | ||
| Trichomoniasis | 1224 | ||
| Chancroid | 1224 | ||
| Herpes simplex virus infections | 1224 | ||
| Proctitis | 1224 | ||
| Venereal warts | 1225 | ||
| Key points | 1225 | ||
| 96 Antiseptics and disinfectants | 1226 | ||
| General considerations | 1226 | ||
| Properties of individual antiseptics and disinfectants | 1227 | ||
| Alcohols | 1227 | ||
| Ethanol | 1227 | ||
| Aldehydes | 1227 | ||
| Glutaraldehyde | 1227 | ||
| Iodine compounds: Iodine solution and iodine tincture | 1228 | ||
| Chlorine compounds | 1228 | ||
| Oxychlorosene sodium | 1228 | ||
| Miscellaneous agents | 1229 | ||
| Chlorhexidine | 1229 | ||
| Hand hygiene for healthcare workers | 1230 | ||
| Specific CDC hand-hygiene recommendations | 1230 | ||
| Indications for hand washing and hand antisepsis | 1230 | ||
| Hand-hygiene technique | 1231 | ||
| Surgical hand antisepsis | 1231 | ||
| Other aspects of hand hygiene | 1232 | ||
| Administrative measures regarding hand hygiene | 1232 | ||
| Key points | 1232 | ||
| 97 Anthelmintics | 1233 | ||
| Key points | 1237 | ||
| 98 Antiprotozoal drugs I: Antimalarial agents | 1238 | ||
| Life cycle of the malaria parasite | 1238 | ||
| Types of malaria | 1238 | ||
| Vivax malaria | 1239 | ||
| Falciparum malaria | 1239 | ||
| Principles of antimalarial therapy | 1240 | ||
| Therapeutic objectives | 1240 | ||
| Drug selection | 1240 | ||
| Pharmacology of the major antimalarial drugs | 1241 | ||
| Chloroquine | 1241 | ||
| Primaquine | 1242 | ||
| Quinine | 1242 | ||
| Quinidine gluconate | 1243 | ||
| Mefloquine | 1243 | ||
| Artemisinin derivatives | 1243 | ||
| Artemether/lumefantrine | 1244 | ||
| Indications and efficacy. | 1244 | ||
| Mechanism of action. | 1244 | ||
| Pharmacokinetics. | 1244 | ||
| Why do we combine artemether with lumefantrine? | 1244 | ||
| Adverse effects. | 1244 | ||
| Drug interactions. | 1244 | ||
| Artesunate | 1244 | ||
| Atovaquone/proguanil | 1244 | ||
| Key points | 1245 | ||
| 99 Antiprotozoal drugs II: Miscellaneous agents | 1246 | ||
| Protozoal infections | 1246 | ||
| Drugs of choice for protozoal infections | 1247 | ||
| Iodoquinol | 1247 | ||
| Metronidazole | 1248 | ||
| Nitazoxanide | 1249 | ||
| Key points | 1251 | ||
| 100 Ectoparasiticides | 1252 | ||
| Ectoparasitic infestations | 1252 | ||
| Pediculosis (infestation with lice) | 1252 | ||
| Head lice | 1252 | ||
| Body lice | 1252 | ||
| Pubic lice | 1252 | ||
| Scabies (infestation with mites) | 1253 | ||
| Pharmacology of ectoparasiticides | 1253 | ||
| Permethrin | 1253 | ||
| Basic pharmacology | 1253 | ||
| Actions and uses. | 1253 | ||
| Resistance. | 1254 | ||
| Pharmacokinetics. | 1254 | ||
| Adverse effects. | 1254 | ||
| Pyrethrins plus piperonyl butoxide | 1254 | ||
| Malathion | 1254 | ||
| Benzyl alcohol | 1254 | ||
| Ivermectin | 1255 | ||
| Key points | 1256 | ||
| 101 Basic principles of cancer chemotherapy | 1257 | ||
| What is cancer? | 1257 | ||
| The growth fraction and its relationship to chemotherapy | 1259 | ||
| Obstacles to successful chemotherapy | 1260 | ||
| Toxicity to normal cells | 1260 | ||
| Cure requires 100% cell kill | 1260 | ||
| Absence of truly early detection | 1261 | ||
| Solid tumors respond poorly | 1262 | ||
| Drug resistance | 1263 | ||
| Heterogeneity of tumor cells | 1263 | ||
| Limited drug access to tumor cells | 1263 | ||
| Strategies for achieving maximum benefits from chemotherapy | 1263 | ||
| Intermittent chemotherapy | 1263 | ||
| Combination chemotherapy | 1264 | ||
| Benefits of drug combinations | 1264 | ||
| Suppression of drug resistance. | 1264 | ||
| Increased cancer cell kill. | 1264 | ||
| Reduced injury to normal cells. | 1264 | ||
| Guidelines for drug selection | 1265 | ||
| Optimizing dosing schedules | 1265 | ||
| Regional drug delivery | 1265 | ||
| Major toxicities of chemotherapeutic drugs | 1265 | ||
| Bone marrow suppression | 1265 | ||
| Neutropenia | 1265 | ||
| Thrombocytopenia | 1266 | ||
| Anemia | 1266 | ||
| Digestive tract injury | 1266 | ||
| Nausea and vomiting | 1267 | ||
| Other important toxicities | 1267 | ||
| Making the decision to treat | 1268 | ||
| Looking ahead | 1269 | ||
| Key points | 1269 | ||
| 102 Anticancer drugs I: Cytotoxic agents | 1271 | ||
| Introduction to the cytotoxic anticancer drugs | 1271 | ||
| Mechanisms of cytotoxic action | 1271 | ||
| Cell-cycle phase specificity | 1271 | ||
| Toxicity | 1274 | ||
| Dosage, handling, and administration | 1274 | ||
| Alkylating agents | 1274 | ||
| Shared properties | 1274 | ||
| Properties of individual alkylating agents | 1276 | ||
| Nitrogen mustards | 1276 | ||
| Cyclophosphamide. | 1276 | ||
| Nitrosoureas | 1276 | ||
| Carmustine (BCNU). | 1276 | ||
| Platinum compounds | 1277 | ||
| Antimetabolites | 1277 | ||
| Folic acid analogs | 1277 | ||
| Methotrexate | 1278 | ||
| Mechanism of action. | 1278 | ||
| Toxicity. | 1278 | ||
| Pyrimidine analogs | 1279 | ||
| Cytarabine | 1279 | ||
| 103 Anticancer drugs II: Hormonal agents, targeted drugs, and other noncytotoxic anticancer drugs | 1288 | ||
| Drugs for breast cancer | 1288 | ||
| Drugs for prostate cancer | 1294 | ||
| Androgen deprivation therapy | 1294 | ||
| Gonadotropin-releasing hormone agonists | 1294 | ||
| Leuprolide | 1295 | ||
| Therapeutic use. | 1295 | ||
| Mechanism of action. | 1295 | ||
| Co-treatment with an androgen receptor blocker. | 1295 | ||
| Adverse effects. | 1296 | ||
| Gonadotropin-releasing hormone antagonists | 1296 | ||
| Degarelix | 1296 | ||
| Androgen receptor blockers | 1296 | ||
| Flutamide | 1296 | ||
| Abiraterone, a CYP17 inhibitor | 1297 | ||
| Other drugs for prostate cancer | 1298 | ||
| Sipuleucel-T | 1298 | ||
| Targeted anticancer drugs | 1298 | ||
| Kinase inhibitors | 1299 | ||
| EGFR tyrosine kinase inhibitors | 1299 | ||
| Cetuximab | 1299 | ||
| Mechanism of action. | 1299 | ||
| Therapeutic uses. | 1299 | ||
| Colorectal cancer. | 1299 | ||
| Head and neck cancer. | 1299 | ||
| Adverse effects. | 1299 | ||
| BCR-ABL tyrosine kinase inhibitors | 1302 | ||
| Imatinib | 1302 | ||
| Indications. | 1302 | ||
| CML and its treatment. | 1303 | ||
| Mechanism of action and clinical effects. | 1303 | ||
| Pharmacokinetics. | 1303 | ||
| Adverse effects. | 1303 | ||
| Effects in pregnancy and breast-feeding. | 1303 | ||
| Drug interactions. | 1303 | ||
| Vemurafenib, a BRAF V600E kinase inhibitor | 1305 | ||
| Other targeted drugs | 1305 | ||
| CD20-directed antibodies | 1305 | ||
| Rituximab | 1306 | ||
| Actions, use, and dosage. | 1306 | ||
| Adverse effects. | 1306 | ||
| Infusion reactions. | 1306 | ||
| Tumor lysis syndrome (TLS). | 1306 | ||
| Mucocutaneous reactions. | 1306 | ||
| Hepatitis B reactivation. | 1306 | ||
| Progressive multifocal leukoencephalopathy (PML). | 1306 | ||
| Other adverse effects. | 1306 | ||
| Brentuximab vedotin, an antibody-drug conjugate | 1307 | ||
| Angiogenesis inhibitors | 1307 | ||
| Bevacizumab | 1307 | ||
| Mechanism of action. | 1307 | ||
| Therapeutic use. | 1307 | ||
| Adverse effects. | 1309 | ||
| Effect in pregnancy. | 1309 | ||
| Other noncytotoxic anticancer drugs | 1312 | ||
| Key points | 1314 | ||
| 104 Drugs for the eye | 1317 | ||
| Drugs for glaucoma | 1317 | ||
| Pathophysiology and treatment overview | 1317 | ||
| Primary open-angle glaucoma | 1317 | ||
| Characteristics. | 1317 | ||
| Risk factors. | 1318 | ||
| Screening. | 1318 | ||
| Management. | 1318 | ||
| Angle-closure glaucoma | 1318 | ||
| Drugs used to treat glaucoma | 1319 | ||
| Beta-adrenergic blocking agents | 1319 | ||
| Actions and use in glaucoma. | 1319 | ||
| Adverse effects. | 1319 | ||
| Local. | 1319 | ||
| Systemic. | 1319 | ||
| Prostaglandin analogs | 1320 | ||
| Latanoprost. | 1320 | ||
| Alpha2-adrenergic agonists | 1320 | ||
| Brimonidine. | 1320 | ||
| Cycloplegics and mydriatics | 1322 | ||
| Anticholinergic agents | 1322 | ||
| Effects on the eye | 1322 | ||
| Adverse effects | 1322 | ||
| Blurred vision and photophobia. | 1322 | ||
| Precipitation of angle-closure glaucoma. | 1322 | ||
| Systemic effects. | 1322 | ||
| Phenylephrine (an adrenergic agonist) | 1323 | ||
| Therapeutic and diagnostic applications | 1323 | ||
| Adverse effects | 1323 | ||
| Effects on the eye. | 1323 | ||
| Drugs for allergic conjunctivitis | 1323 | ||
| Drugs for age-related macular degeneration | 1323 | ||
| Pathophysiology of ARMD | 1323 | ||
| Management of dry ARMD | 1324 | ||
| Management of wet (neovascular) ARMD | 1324 | ||
| Angiogenesis inhibitors | 1325 | ||
| Actions and benefits. | 1325 | ||
| Adverse effects. | 1325 | ||
| Pegaptanib, ranibizumab, aflibercept, and bevacizumab: Comparisons and contrasts. | 1325 | ||
| Molecular structure. | 1325 | ||
| Approved usage and cost. | 1325 | ||
| Efficacy. | 1325 | ||
| Key points | 1326 | ||
| 105 Drugs for the skin | 1328 | ||
| Anatomy of the skin | 1328 | ||
| Topical glucocorticoids | 1328 | ||
| Keratolytic agents | 1329 | ||
| Acne | 1330 | ||
| Pathophysiology | 1330 | ||
| Overview of treatment | 1331 | ||
| Nondrug therapy | 1331 | ||
| Drug therapy | 1331 | ||
| Topical drugs for acne | 1331 | ||
| Antibiotics | 1331 | ||
| Benzoyl peroxide. | 1331 | ||
| Clindamycin and erythromycin. | 1331 | ||
| Retinoids | 1332 | ||
| Tretinoin. | 1332 | ||
| Use for acne. | 1332 | ||
| Use for fine wrinkles. | 1332 | ||
| Adverse effects. | 1332 | ||
| Oral drugs for acne | 1332 | ||
| Antibiotics | 1332 | ||
| Isotretinoin | 1333 | ||
| Actions and use. | 1333 | ||
| Adverse effects. | 1333 | ||
| Common effects. | 1333 | ||
| Rare effect: Depression. | 1333 | ||
| Drug interactions. | 1333 | ||
| Contraindication: Pregnancy. | 1333 | ||
| iPLEDGE program. | 1333 | ||
| Requirements for female patients. | 1333 | ||
| Requirements for prescribers. | 1333 | ||
| Hormonal agents | 1334 | ||
| Oral contraceptives. | 1334 | ||
| Spironolactone. | 1334 | ||
| Sunscreens | 1334 | ||
| Key points | 1344 | ||
| 106 Drugs for the ear | 1346 | ||
| Anatomy of the ear | 1346 | ||
| Otitis media and its management | 1346 | ||
| Acute otitis media | 1346 | ||
| Characteristics, pathogenesis, and microbiology | 1346 | ||
| Diagnosis | 1346 | ||
| Standard treatment | 1347 | ||
| Treatment of antibiotic-resistant AOM | 1348 | ||
| Prevention | 1349 | ||
| Prevention and treatment of influenza. | 1349 | ||
| Vaccination against streptococcus pneumoniae. | 1349 | ||
| Recurrent otitis media | 1349 | ||
| Otitis media with effusion | 1350 | ||
| Otitis externa and its management | 1350 | ||
| Acute otitis externa | 1350 | ||
| Characteristics, pathogenesis, and microbiology | 1350 | ||
| Treatment | 1350 | ||
| Topical medications. | 1350 | ||
| Oral medications. | 1350 | ||
| Prevention | 1350 | ||
| Necrotizing otitis externa | 1351 | ||
| Fungal otitis externa (otomycosis) | 1351 | ||
| Key points | 1351 | ||
| 107 Miscellaneous noteworthy drugs | 1352 | ||
| Drugs for pulmonary arterial hypertension | 1352 | ||
| Prostacyclin analogs | 1352 | ||
| Epoprostenol | 1352 | ||
| Treprostinil | 1353 | ||
| Iloprost | 1353 | ||
| Endothelin-1 receptor antagonists | 1353 | ||
| Bosentan | 1353 | ||
| Actions and use. | 1353 | ||
| Pharmacokinetics. | 1354 | ||
| Adverse effects. | 1354 | ||
| Hepatotoxicity. | 1354 | ||
| Fetal injury. | 1354 | ||
| Anemia. | 1354 | ||
| Drug interactions. | 1354 | ||
| Phosphodiesterase type 5 inhibitors | 1354 | ||
| Sildenafil | 1354 | ||
| Drugs for neonatal respiratory distress syndrome | 1355 | ||
| Prenatal and postnatal glucocorticoids | 1355 | ||
| Lung surfactant | 1355 | ||
| Drugs for cystic fibrosis | 1356 | ||
| Pathophysiology of cystic fibrosis | 1356 | ||
| Drug therapy | 1356 | ||
| Nutritional drugs | 1356 | ||
| Pancreatic enzymes. | 1356 | ||
| Fat-soluble vitamins. | 1356 | ||
| Pulmonary drugs | 1356 | ||
| Inhaled antibiotics for chronic suppressive therapy. | 1356 | ||
| Oral and intravenous antibiotics for acute therapy. | 1356 | ||
| Inhaled dornase alfa. | 1356 | ||
| Oral ibuprofen. | 1357 | ||
| Inhaled beta2-adrenergic agonists. | 1357 | ||
| Drugs for sickle cell anemia | 1357 | ||
| Analgesics and glucocorticoids | 1357 | ||
| Hydroxyurea | 1357 | ||
| Drugs for hyperuricemia caused by cancer chemotherapy | 1358 | ||
| Phosphate binders for patients on dialysis | 1358 | ||
| Gamma-hydroxybutyrate for cataplexy in patients with narcolepsy | 1359 | ||
| Riluzole for amyotrophic lateral sclerosis | 1360 | ||
| Tetrabenazine for chorea of Huntington’s disease | 1360 | ||
| Drugs for fibromyalgia syndrome | 1361 | ||
| Antidepressants and related drugs | 1363 | ||
| Tricyclic antidepressants and cyclobenzaprine | 1363 | ||
| Selective serotonin reuptake inhibitors (SSRIs) | 1363 | ||
| Serotonin/norepinephrine reuptake inhibitors | 1363 | ||
| Duloxetine. | 1363 | ||
| Milnacipran. | 1363 | ||
| Anticonvulsants | 1364 | ||
| Analgesics | 1364 | ||
| Drugs for sleep disturbances | 1364 | ||
| Drugs for heriditary angioedema | 1364 | ||
| Old drugs for HAE | 1364 | ||
| New drugs for HAE | 1364 | ||
| C1-inhibitor | 1364 | ||
| Ecallantide | 1365 | ||
| Icatibant | 1366 | ||
| Belimumab for systemic lupus erythematosus | 1366 | ||
| Key points | 1367 | ||
| 108 Dietary supplements | 1369 | ||
| Regulation of dietary supplements | 1370 | ||
| Dietary supplement health and education ACT of 1994 | 1370 | ||
| Core provisions | 1370 | ||
| Package labeling | 1370 | ||
| Adverse effects | 1370 | ||
| Impurities, adulterants, and variability | 1370 | ||
| Other provisions | 1371 | ||
| Current good manufacturing practices ruling | 1371 | ||
| Dietary supplement and nonprescription drug consumer protection ACT | 1371 | ||
| A comment on the regulatory status of dietary supplements | 1371 | ||
| Private quality certification programs | 1371 | ||
| Standardization of herbal products | 1371 | ||
| Adverse interactions with conventional drugs | 1372 | ||
| Some commonly used dietary supplements | 1372 | ||
| Black cohosh | 1372 | ||
| Coenzyme Q-10 | 1373 | ||
| Cranberry juice | 1373 | ||
| Echinacea | 1373 | ||
| Feverfew | 1374 | ||
| Flaxseed | 1374 | ||
| Garlic | 1374 | ||
| Ginger root | 1375 | ||
| Ginkgo biloba | 1375 | ||
| Glucosamine | 1376 | ||
| Green tea | 1376 | ||
| Probiotics | 1376 | ||
| Resveratrol | 1377 | ||
| Saw palmetto | 1377 | ||
| Soy | 1378 | ||
| St. John’s wort | 1378 | ||
| Valerian | 1379 | ||
| Harmful supplements to avoid | 1379 | ||
| Comfrey | 1379 | ||
| Kava | 1379 | ||
| Ma huang (ephedra) | 1380 | ||
| Key points | 1380 | ||
| 109 Management of poisoning | 1381 | ||
| Fundamentals of treatment | 1381 | ||
| Drugs and procedures used to minimize poison absorption | 1382 | ||
| Reducing absorption of ingested poisons | 1382 | ||
| Activated charcoal | 1382 | ||
| Surface decontamination | 1382 | ||
| Drugs and procedures used for poison removal | 1382 | ||
| Drugs that enhance renal excretion | 1382 | ||
| Nondrug methods of poison removal | 1382 | ||
| Specific antidotes | 1383 | ||
| Heavy metal antagonists | 1383 | ||
| Other important antidotes | 1385 | ||
| Poison control centers | 1385 | ||
| Key points | 1386 | ||
| 110 Potential weapons of biologic, radiologic, and chemical terrorism | 1387 | ||
| Bacteria and viruses | 1387 | ||
| Bacillus anthracis (anthrax) | 1387 | ||
| Microbiology | 1387 | ||
| Clinical manifestations | 1387 | ||
| Appendix A Adult immunization, United States, 2011 | 1397 | ||
| Immunization schedule notes | 1397 | ||
| 1. Influenza vaccination | 1397 | ||
| 2. Tetanus, diphtheria, and acellular pertussis (Td/Tdap) vaccination | 1397 | ||
| 3. Varicella vaccination (“shingles”) | 1397 | ||
| 4. Human papillomavirus (HPV) vaccination | 1399 | ||
| 5. Herpes zoster vaccination | 1399 | ||
| 6. Measles, mumps, rubella (MMR) vaccination | 1399 | ||
| Measles component. | 1399 | ||
| Mumps component. | 1399 | ||
| Rubella component. | 1399 | ||
| Healthcare personnel born before 1957. | 1399 | ||
| 7. Pneumococcal polysaccharide (PPSV) vaccination | 1399 | ||
| Medical indications. | 1399 | ||
| Other indications. | 1399 | ||
| 8. Revaccination with PPSV | 1399 | ||
| 9. Meningococcal vaccination | 1400 | ||
| Appendix B Guide to gender-related drugs | 1401 | ||
| Drugs used in pregnancy | 1401 | ||
| Drugs related to labor and delivery | 1401 | ||
| Drugs used in perinatal therapy | 1401 | ||
| Drugs and breast-feeding | 1401 | ||
| Drugs for women’s health disorders | 1401 | ||
| Drugs used to prevent or terminate pregnancy | 1401 | ||
| Drugs for male health disorders | 1401 | ||
| Drugs for sexually transmitted diseases (STDs) | 1401 | ||
| Appendix C Commonly used abbreviations | 1402 | ||
| Appendix D Canadian drug information | 1404 | ||
| International system of units | 1404 | ||
| Drug serum concentrations | 1404 | ||
| Canadian drug legislation | 1404 | ||
| Prescription drugs (schedule F) | 1404 | ||
| Nonprescription medications | 1406 | ||
| National drug schedules | 1406 | ||
| New drug development in Canada | 1406 | ||
| Patent laws | 1406 | ||
| References | 1407 | ||
| Appendix E Prototype drugs and their major uses | 1408 | ||
| Peripheral nervous system drugs | 1408 | ||
| Muscarinic agonists | 1408 | ||
| Muscarinic antagonists | 1408 | ||
| Cholinesterase inhibitors | 1408 | ||
| Neuromuscular blockers | 1408 | ||
| Adrenergic agonists | 1408 | ||
| Alpha-adrenergic blockers | 1408 | ||
| Beta-adrenergic blockers | 1408 | ||
| Indirect-acting antiadrenergics | 1408 | ||
| Central nervous system drugs | 1408 | ||
| Drugs for Parkinson’s disease | 1408 | ||
| Drugs for Alzheimer’s disease | 1408 | ||
| Drugs for multiple sclerosis | 1408 | ||
| Drugs for epilepsy | 1408 | ||
| Drugs for migraine | 1408 | ||
| Local anesthetics | 1408 | ||
| General anesthetics | 1409 | ||
| Opioid (narcotic) analgesics and antagonists | 1409 | ||
| Antipsychotic agents | 1409 | ||
| Antidepressants | 1409 | ||
| Drugs for bipolar disorder (manic-depressive illness) | 1409 | ||
| Drugs for anxiety and insomnia | 1409 | ||
| Central nervous system stimulants | 1409 | ||
| Drugs for attention-deficit/hyperactivity disorder | 1409 | ||
| Pharmacologic aids to smoking cessation | 1409 | ||
| Diuretics | 1409 | ||
| Drugs that affect the heart, blood vessels, and blood | 1409 | ||
| Drugs that affect the Renin-Angiotensin-Aldosterone system | 1409 | ||
| Calcium channel blockers | 1409 | ||
| Drugs for hypertension | 1409 | ||
| Drugs for angina pectoris | 1410 | ||
| Drugs for heart failure | 1410 | ||
| Antidysrhythmic drugs | 1410 | ||
| Drugs used to lower blood cholesterol | 1410 | ||
| Anticoagulants | 1410 | ||
| Antiplatelet and thrombolytic drugs | 1410 | ||
| Hematopoietic and thrombopoietic growth factors | 1410 | ||
| Drugs for hemophilia | 1410 | ||
| Drugs for endocrine disorders | 1410 | ||
| Drugs for diabetes | 1410 | ||
| Drugs for thyroid disorders | 1411 | ||
| Drugs for adrenal insufficiency | 1411 | ||
| Women’s health | 1411 | ||
| Estrogens | 1411 | ||
| Progestins | 1411 | ||
| Contraceptive agents | 1411 | ||
| Drugs for infertility | 1411 | ||
| Drugs that affect uterine function | 1411 | ||
| Men’s health | 1411 | ||
| Androgens | 1411 | ||
| Drugs for erectile dysfunction | 1411 | ||
| Drugs for benign prostatic hyperplasia | 1411 | ||
| Anti-inflammatory, antiallergic, and immunologic drugs | 1411 | ||
| Immunosuppressants | 1411 | ||
| Antihistamines (h1 antagonists) | 1411 | ||
| COX inhibitors (aspirin-like drugs) | 1411 | ||
| Glucocorticoids | 1411 | ||
| Drugs for bone and joint disorders | 1411 | ||
| Drugs for rheumatoid arthritis | 1411 | ||
| Drugs for hyperuricemia of gout | 1411 | ||
| Drugs for osteoporosis | 1412 | ||
| Respiratory tract drugs | 1412 | ||
| Drugs for asthma | 1412 | ||
| Drugs for allergic rhinitis | 1412 | ||
| Drugs for cough | 1412 | ||
| Gastrointestinal drugs | 1412 | ||
| Drugs for peptic ulcer disease | 1412 | ||
| Laxatives | 1412 | ||
| Antiemetics | 1412 | ||
| Drugs for irritable bowel syndrome (IBS) | 1412 | ||
| Drugs for inflammatory bowel disease | 1412 | ||
| Drugs for weight loss | 1412 | ||
| Drugs for bacterial infections | 1412 | ||
| Penicillins, cephalosporins, and other drugs that weaken the bacterial cell wall | 1412 | ||
| Bacteriostatic inhibitors of protein synthesis | 1413 | ||
| Aminoglycosides (bactericidal inhibitors of protein synthesis) | 1413 | ||
| Fluoroquinolones | 1413 | ||
| Cyclic lipopeptides | 1413 | ||
| Sulfonamides and trimethoprim | 1413 | ||
| Drugs for tuberculosis | 1413 | ||
| Drugs for fungal infections | 1413 | ||
| Drugs for viral infections | 1413 | ||
| Drugs for cytomegalovirus infection | 1413 | ||
| Drugs for herpes simplex virus infection | 1413 | ||
| Drugs for hepatitis | 1413 | ||
| Drugs for influenza | 1413 | ||
| Drugs for respiratory syncytial virus infection | 1413 | ||
| Drugs for HIV infection | 1413 | ||
| Drugs for parasitic diseases | 1413 | ||
| Drugs for malaria | 1413 | ||
| Drugs for ectoparasitic infestation | 1413 | ||
| Anticancer drugs: Cytoxic agents | 1413 | ||
| Anticancer drugs: Hormonal agents, targeted drugs, and other noncytotoxic anticancer drugs | 1414 | ||
| Drugs for breast cancer | 1414 | ||
| Drugs for prostate cancer | 1414 | ||
| Glucocorticoids | 1414 | ||
| Biologic response modifiers: Immunostimulants | 1414 | ||
| Targeted drugs | 1414 | ||
| Other important drugs | 1414 | ||
| Drugs for acne | 1414 | ||
| Drugs for open-angle glaucoma | 1414 | ||
| Drugs for age-related macular degeneration | 1414 | ||
| Drugs for pulmonary arterial hypertension | 1414 | ||
| Drugs for neonatal respiratory distress syndrome | 1414 | ||
| Drugs for fibromyalgia syndrome | 1414 | ||
| Drugs for hereditary angioedema | 1414 | ||
| Index | 1415 | ||
| 0-9, and symbols | 1415 | ||
| A | 1415 | ||
| B | 1422 | ||
| C | 1424 | ||
| D | 1430 | ||
| E | 1433 | ||
| F | 1435 | ||
| G | 1437 | ||
| H | 1438 | ||
| I | 1441 | ||
| J | 1443 | ||
| K | 1443 | ||
| L | 1444 | ||
| M | 1445 | ||
| N | 1449 | ||
| O | 1451 | ||
| P | 1452 | ||
| Q | 1457 | ||
| R | 1457 | ||
| S | 1459 | ||
| T | 1462 | ||
| U | 1465 | ||
| V | 1465 | ||
| W | 1467 | ||
| X | 1467 | ||
| Y | 1467 | ||
| Z | 1467 | ||
| Special interest topics | ibc |