Cardiovascular Diseases

Y. Robert Li is Professor and Founding Chair of the Department of Pharmacology and Assistant Dean for Biomedical Research at Campbell University and holds Adjunct Professor appointments at Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia-Maryland Regional College of Veterinary Medicine, and University of North Carolina at Greensboro. He is an author of over 110 peer-reviewed publications, three monographs, and numerous book chapters and serves on the editorial boards of several leading journals. Dr. Li has over 20 years of teaching experience in the areas of biomedical sciences, free radical biology, toxicology, pharmacology, and therapeutics.

PREFACE xix

LIST OF ABBREVIATIONS xxii

UNIT I GENERAL INTRODUCTION 1

1 Introduction to Cardiovascular Diseases 3

1.1 Overview 3

1.2 Definition of Cardiovascular Diseases 3

1.3 Classification of Cardiovascular Diseases 3

1.4 Prevalence, Incidence, and Trend of Cardiovascular Diseases 5

1.5 Risk Factors of Cardiovascular Diseases 9

1.6 Prevention and Control of Cardiovascular Diseases 10

1.7 Cardiovascular Risk Prediction and Evidence?]Based Treatments 15

1.8 Summary of Chapter Key Points 18

1.9 Self-Assessment Questions 18

References 19

2 Introduction to Principles of Pharmacology 21

2.1 Overview 21

2.2 Definitions and History 21

2.3 Pharmacological Paradigm: the Central Dogma in Pharmacology 24

2.4 Principles of Drug Discovery, Development, and Regulation 31

2.5 Pharmacology Subspecialties 32

2.6 Introduction to Cardiovascular Pharmacology 32

2.7 Summary of Chapter Key Points 38

2.8 Self?]Assessment Questions 39

References 40

UNIT II DYSLIPIDEMIAS 43

3 Overview of Dyslipidemias and Drug Therapy 45

3.1 Introduction 45

3.2 Lipoprotein Metabolism 45

3.3 Dyslipidemias and Genetic Lipoprotein Disorders 51

3.4 Mechanistically Based Drug Therapy of Dyslipidemias 51

3.5 Summary of Chapter Key Points 53

3.6 Self?]Assessment Questions 54

References 54

4 Drugs for Dyslipidemias 56

4.1 Overview 56

4.2 Statins 56

4.3 Bile Acid Sequestrants 64

4.4 Cholesterol Absorption Inhibitors 69

4.5 Fibrates 72

4.6 Niacin 75

4.7 New Drugs for HoFH 80

4.8 Phytosterols and Phytostanols 83

4.9 Omega?]3 Fatty Acids 86

4.10 Emerging Therapeutic Modalities for Dyslipidemias 88

4.11 Summary of Chapter Key Points 93

4.12 Self-Assessment Questions 93

References 95

5 Management of Dyslipidemias: Principles and Guidelines 99

5.1 Overview 99

5.2 General Principles of the Management of Dyslipidemias 99

5.3 Current Evidence?]Based Guidelines on the Management of Dyslipidemias 102

5.4 Summary of Chapter Key Points 113

5.5 Self?]Assessment Questions 113

References 114

UNIT III HYPERTENSION AND MULTITASKING CARDIOVASCULAR DRUGS 117

6 Overview of Hypertension and Drug Therapy 119

6.1 Introduction 119

6.2 Definitions, Classifications, and Epidemiology of Hypertension 119

6.3 Pathophysiology of Hypertension 121

6.4 Mechanistically Based Drug Therapy of Hypertension: An Overview 123

6.5 Summary of Chapter Key Points 123

6.6 Self?]Assessment Questions 125

References 125

7 Diuretics 127

7.1 Overview 127

7.2 Volume Regulation and Drug Targeting 127

7.3 Thiazide and Thiazide?]Type Diuretics 129

7.4 Loop Diuretics 134

7.5 Potassium?]Sparing Diuretics 138

7.6 Other Diuretics 142

7.7 Summary of Chapter Key Points 143

7.8 Self?]Assessment Questions 143

References 144

8 Sympatholytics 147

8.1 Overview 147

8.2 Sympathetic Nervous System and Drug Targeting 147

8.3 alpha?]Adrenergic Receptor Antagonists 150

8.4 ß?]Adrenergic Receptor Antagonists 150

8.5 Centrally Acting Sympatholytics 157

8.6 Summary of Chapter Key Points 158

8.7 Self?]Assessment Questions 159

References 159

9 Inhibitors of the Renin-Angiotensin-Aldosterone System 161

9.1 Overview 161

9.2 The RAAS and Drug Targeting 161

9.3 Direct Renin Inhibitors 162

9.4 ACE Inhibitors 166

9.5 ARBs 174

9.6 Comparative Pharmacology of Direct Renin Inhibitors, ACE Inhibitors, and ARBs 179

9.7 Summary of Chapter Key Points 181

9.8 Self-Assessment Questions 181

References 182

10 Calcium Channel Blockers 185

10.1 Overview 185

10.2 Calcium Channels and Drug Targeting 185

10.3 L-TYPE CCBs 186

10.4 Summary of Chapter Key Points 192

10.5 Self-Assessment Questions 192

References 193

11 Nitrates and Other Vasodilators 194

11.1 Overview 194

11.2 Drug Class and Drug Targeting 194

11.3 Organic Nitrates and Sodium Nitroprusside (Nitric Oxide?]Releasing Vasodilators) 196

11.4 ET Receptor Antagonists 201

11.5 Phosphodiesterase 5 Inhibitors 204

11.6 sGC Stimulators 207

11.7 K+ATP Channel Openers 209

11.8 Other Vasodilators 210

11.9 Summary of Chapter Key Points 212

11.10 Self-Assessment Questions 212

References 213

12 Management of Hypertension: Principles and Guidelines 215

12.1 Overview 215

12.2 Introduction to Current Guidelines for the Management of Systemic Hypertension 215

12.3 Key Recommendations of Major Guidelines for the Management of Systemic Hypertension 217

12.4 Lifestyle Modifications for the Management of Systemic Hypertension 221

12.5 Drug Therapy of Systemic Hypertension 223

12.6 Drug Therapy of Prehypertension 234

12.7 Drug Therapy of Pulmonary Hypertension 235

12.8 Summary of Chapter Key Points 237

12.9 Self-Assessment Questions 238

References 239

UNIT IV ISCHEMIC HEART DISEASE: STABLE ISCHEMIC HEART DISEASE 243

13 Overview of Ischemic Heart Disease, Stable Angina, and Drug Therapy 245

13.1 Introduction 245

13.2 Classification, Epidemiology, and Pathophysiology 245

13.3 Stable Angina and Drug Targeting 250

13.4 Summary of Chapter Key Points 252

13.5 Self-Assessment Questions 252

References 253

14 Drugs for Stable Angina 254

14.1 Overview 254

14.2 ß-Blockers for Treating Stable Angina 254

14.3 CCBs for Treating Stable Angina 255

14.4 Organic Nitrate for Treating Stable Angina 255

14.5 New Antianginal Drugs: Ranolazine 255

14.6 Other New and Emerging Drugs 258

14.7 Summary of Chapter Key Points 259

14.8 Self-Assessment Questions 259

References 260

15 Management of Stable Angina/Stable Ischemic Heart Disease: Principles and Guidelines 262

15.1 Overview 262

15.2 Introduction to Current Guidelines on Management of Stable Angina/SIHD 262

15.3 General Principles of Management of Stable Angina/SIHD 265

15.4 Current Guideline Recommendations on Stable Angina/SIHD Management 266

15.5 Management of Special Types of Stable Angina 271

15.6 Summary of Chapter Key Points 273

15.7 Self-Assessment Questions 273

References 273

UNIT V ISCHEMIC HEART DISEASE: ACUTE CORONARY SYNDROMES 275

16 Overview of Acute Coronary Syndromes and Drug Therapy 277

16.1 Introduction 277

16.2 Definitions and General Considerations 277

16.3 Pathophysiology and Drug Targeting 278

16.4 Summary of Chapter Key Points 280

16.5 Self-Assessment Questions 281

References 281

17 Anticoagulants, Platelet Inhibitors, and Thrombolytic Agents 283

17.1 Overview 283

17.2 Hemostasis 283

17.3 Anticoagulants 285

17.4 Platelet Inhibitors 295

17.5 Thrombolytic Agents 304

17.6 Summary of Chapter Key Points 307

17.7 Self-Assessment Questions 307

References 308

18 Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction: Principles and Guidelines 310

18.1 Overview 310

18.2 Introduction to Evidence-Based Guidelines 310

18.3 General Principles of Management of UA/NSTEMI 311

18.4 Guideline-Based Recommendations on the Management of UA/NSTEMI 311

18.5 Summary of Chapter Key Points 324

18.6 Self-Assessment Questions 325

References 325

19 Management of ST-Elevation Myocardial Infarction: Principles and Guidelines 327

19.1 Overview 327

19.2 Definition and Epidemiology 327

19.3 Introduction to Recent Guidelines on the Management of STEMI 328

19.4 Principles and Guideline Recommendations for the Management of STEMI 329

19.5 Summary of Chapter Key Points 339

19.6 Self-Assessment Questions 340

References 340

UNIT VI HEART FAILURE 343

20 Overview of Heart Failure and Drug Therapy 345

20.1 Introduction 345

20.2 Definition, Classification, and Epidemiology 345

20.3 Pathophysiology and Drug Targeting 348

20.4 Summary of Chapter Key Points 349

20.5 Self-Assessment Questions 350

References 350

21 Drugs for Heart Failure 352

21.1 Overview 352

21.2 Diuretics for Heart Failure 352

21.3 ß-Blockers for HF 352

21.4 Inhibitors of the RAAS for HF 353

21.5 Vasodilators for HF 354

21.6 Positive Inotropic Agents for HF 354

21.7 Emerging Drugs for HF 359

21.8 Summary of Chapter Key Points 360

21.9 Self-Assessment Questions 360

References 361

22 Management of Heart Failure: Principles and Guidelines 364

22.1 Overview 364

22.2 Management of Hf-REF 364

22.3 Management of HF-PEF 367

22.4 Management of Acute Heart Failure Syndromes 368

22.5 Summary of Chapter Key Points 372

22.6 Self-Assessment Questions 373

References 374

UNIT Vii CARDIAC ARRHYTHMIAS 375

23 Overview of Cardiac Arrhythmias and Drug Therapy 377

23.1 Introduction 377

23.2 Definition, Classification, and Epidemiology 377

23.3 Pathophysiology and Drug Targeting 380

23.4 Summary of Chapter Key Points 388

23.5 Self-Assessment Questions 389

References 390

24 Drugs for Cardiac Arrhythmias 391

24.1 Overview 391

24.2 Classification of Antiarrhythmic Drugs 391

24.3 Class I Antiarrhythmic Drugs 392

24.4 Class II Antiarrhythmic Drugs 398

24.5 Class III Antiarrhythmic Drugs 399

24.6 Class IV Antiarrhythmic Drugs 404

24.7 Other Antiarrhythmic Drugs 406

24.8 Summary of Chapter Key Points 408

24.9 Self-Assessment Questions 409

References 410

25 Management of Cardiac Arrhythmias: Principles and Guidelines 411

25.1 Overview 411

25.2 General Principles of Management 411

25.3 Management of Supraventricular Arrhythmias 411

25.4 Management of Ventricular Arrhythmias 414

25.5 Summary of Chapter Key Points 421

25.6 Self-Assessment Questions 423

References 424

UNIT Viii ISCHEMIC STROKE 427

26 Overview of Ischemic Stroke and Drug Therapy 429

26.1 Introduction 429

26.2 Definition and Classification of Cerebrovascular Diseases 429

26.3 Definition and Classification of Stroke 429

26.4 Epidemiology of Stroke 430

26.5 Risk Factors of Stroke 432

26.6 Pathophysiology of Ischemic Stroke and Drug Targeting 432

26.7 Summary of Chapter Key Points 434

26.8 Self?]Assessment Questions 434

References 435

27 Drugs for Ischemic Stroke 436

27.1 Overview 436

27.2 Drugs for Primary Prevention of Ischemic Stroke 436

27.3 Drugs for Early Treatment of Acute Ischemic Stroke 438

27.4 Drugs for Neuroprotection 439

27.5 Drugs for Secondary Prevention of Ischemic Stroke 441

27.6 Stem Cell Therapy for Neurorepair 442

27.7 Summary of Chapter Key Points 442

27.8 Self-Assessment Questions 443

References 444

28 Management of Ischemic Stroke: Principles and Guidelines 447

28.1 Overview 447

28.2 Introduction to Stroke Systems of Care 447

28.3 Current AHA/ASA Guidelines on Early Management of Acute Ischemic Stroke 449

28.4 Summary of Chapter Key Points 450

28.5 Self-Assessment Questions 455

References 456

INDEX 457