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Chapter 16: Drug Therapy of Myocardial Ischemia

INTRODUCTION

This chapter will be most useful after having a basic understanding of the material related to angina at the beginning of Chapter 27, Treatment of Myocardial Ischemia and Hypertension in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, the 12th Edition contains:

  • Table 27-1 Organic Nitrates Available for Clinical Use, which provides information about the preparations, usual doses, and routes of administration of organic nitrates

  • The molecular structures of drugs used to treat myocardial ischemia

LEARNING OBJECTIVES

  • Understand the mechanisms of action of drugs used to treat myocardial ischemia and relieve symptoms of angina.

  • Understand the goals of treatment based on a knowledge of the underlying cause(s) of angina.

  • Know which drugs are most effective in treating different types of angina.

  • Know which drugs are used in combination to treat angina.

  • Know the untoward effects and contraindications of the major classes of drugs used to treat angina.

  • Know the role of drug-eluting stents to treat patients with acute coronary syndromes.

DRUGS INCLUDED IN THIS CHAPTER

  • Antithrombin agents (see Chapter 19)

  • Antiplatelet drugs (see Chapter 19)

  • β Adrenergic receptor antagonists (see Chapter 7)

  • Numerous dihydropyridines (nifedipine [ADALAT, PROCARDIA, others], amlodipine [NORVASC, others], felodipine [PLENDIL, others], isradipine [DYNACIRC, others], nicardipine [CARDENE, others], nisoldipine, nimodipine, clevidipine, others)

  • Diltiazem (CARDIZEM, DILACOR-XR, others)

  • Isosorbide dinitrate (ISDN; ISORDIL, SORBITRATE, DILATRATE-SR, others)

  • Isosorbide-5-mononitrate (ISMN; IMDUR, ISMO, others)

  • Nitroglycerin (glyceryl trinitrate; NITRO-BID, NITROSTAT, NITROL, NITRO-DUR, others)

  • Paclitaxel drug-eluting stents

  • Ranolazine (RANEXA)

  • Sildenafil (VIAGRA, REVATIO)

  • Sirolimus drug-eluting stents

  • Tadalafil (CIALIS, ADCIRCA)

  • Thrombolytic agents (see Chapter 19)

  • Vardenafil (LEVITRA)

  • Verapamil (CALAN, ISOPTIN, others)

MECHANISMS OF ACTION OF DRUGS USED TO TREAT MYOCARDIAL ISCHEMIA
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MECHANISMS OF ACTION OF DRUGS USED TO TREAT MYOCARDIAL ISCHEMIA
DRUG CLASS DRUG MECHANISM OF ACTION
Organic Nitrates (Nitrovasodilators, NO Donors)

Nitroglycerin (glyceryl trinitrate)

Isosorbide dinitrate (ISDN)

Isosorbide-5-mononitrate (ISMN)

 Prodrugs that are the source of NO that increase intracellular cGMP and cause relaxation of large veins (reduced preload reduces myocardial O2 demand), relaxation of arteriolar resistance vessels (reduced afterload reduces myocardial O2 demand), and relaxation of coronary vessels (improved myocardial O2 supply)
β Adrenergic Receptor Antagonists see Chapter 7 Block myocardial β adrenergic receptors to slow heart rate (improved myocardial O2 supply and reduced O2 demand) and reduce ventricular contractility (reduced O2 demand)
Ca2+ Channel Antagonists (Ca2+ Entry Blockers)

Verapamil

Diltiazem

Numerous dihydropyridines (nifedipine, amlodipine, felodipine, isradipine, nicardipine, nisoldipine, nimodipine, clevidipine, others)

 Blocking voltage-sensitive L-type Ca2+ channels relaxes coronary arteries (improved myocardial O2 supply) and relaxes peripheral arteriole resistance vessels (reduced afterload reduces myocardial O2 demand)
Antiplatelet Drugs see chapter 19 Inhibiting platelet aggregation at site of ruptured coronary atherosclerotic plaque prevents occlusion of coronary blood flow
Statins see chapter 20 Correct dyslipidemias that lead to coronary atherosclerosis and stabilize ...

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