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Drugs for Angina Pectoris Drugs for Angina Pectoris Angina pectoris Sudden pain beneath the sternum, often radiating to left shoulder and arm Oxygen supply to the heart is insufficient to meet oxygen demand Two goals of angina drug therapy Prevention of myocardial infarction and death Prevention of myocardial ischemia and anginal pain Drugs for Angina Pectoris Three families of antianginal agents Organic nitrates • Nitroglycerin Beta blockers • Example: propranolol Calcium channel blockers • Example: verapamil Ranolazine A newer drug with limited indications Can be combined with other drugs Determinants of Cardiac Oxygen Demand and Supply Oxygen demand Heart rate Myocardial contractility Intramyocardial wall tension (preload/afterload) Oxygen supply Myocardial blood flow Myocardial perfusion only in diastole Angina Pectoris: Pathophysiology and Treatment Three forms of angina pectoris Chronic stable angina (exertional angina) Variant angina (Prinzmetal’s or vasospastic angina) Unstable angina Chronic Stable Angina (Exertional) Pathophysiology Emotional excitement Large meals Cold exposure Coronary artery disease (CAD) Treatment strategy Increase cardiac oxygen supply Decrease oxygen demand Chronic Stable Angina (Exertional) Therapeutic agents (provide symptomatic relief) Organic nitrates Beta blockers Calcium channel blockers Ranolazine Nondrug therapy Avoid factors that can precipitate angina Decrease risk factors Fig. 51–1. Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD. Variant Angina (Prinzmetal’s: Vasospastic) Pathophysiology Treatment strategy Coronary artery spasm Increasing cardiac oxygen supply Therapeutic agents Calcium channel blockers Organic nitrates Unstable Angina: Medical Emergency Severe CAD complicated by vasospasm Pathophysiology Symptoms of angina at rest New-onset exertional angina Intensification of existing angina Treatment strategy Maintain oxygen supply Decrease oxygen demand Unstable Angina: Medical Emergency Therapeutic agents for acute management Anti-ischemic therapy Antiplatelet therapy Anticoagulant therapy Anti-ischemic Therapy Nitroglycerin Beta blocker Supplemental O2 IV morphine ACE inhibitor Antiplatelet/Anticoagulant Therapy Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin) Anticoagulant therapy Subcutaneous LMW heparin or IV unfractionated heparin LMW = low-molecular-weight. Organic Nitrates Nitroglycerin Stable and variant angina Vasodilator Adverse effects Headache Orthostatic hypotension Reflex tachycardia Organic Nitrates: Nitroglycerin Vasodilator actions Mechanism of antianginal effects Stable angina Variant angina Pharmacokinetics Adverse effects Organic Nitrates: Nitroglycerin Drug interactions Hypotensive drugs Phophodiesterase type 5 inhibitors Beta blockers, verapamil, and diltiazem Organic Nitrates: Nitroglycerin Tolerance Can develop rapidly Cross-tolerance to all other nitrates To minimize, use the lowest effective dose Long-acting formulas: 8 drug-free hours per day Organic Nitrates: Nitroglycerin Preparations and routes of administration Sublingual tablets Sustained-release oral capsules Transdermal delivery systems Translingual spray Topical ointment Intravenous infusion Organic Nitrates: Nitroglycerin Long-acting preparations Discontinue slowly Therapeutic uses summarized Acute anginal therapy Sustained anginal therapy IV for perioperative control of blood pressure and treatment of heart failure with MI, unstable angina, and uncontrolled exacerbations of chronic angina Organic Nitrates: Other Isosorbide mononitrate and isosorbide dinitrate Actions identical to those of nitroglycerin Used for angina, taken orally, produce headache, hypotension, and reflex tachycardia Amyl nitrite Ultrashort-acting agent used to treat acute episodes of angina pectoris Beta Blockers Decrease cardiac oxygen demand Propranolol, metoprolol • Adverse effects Bradycardia Decreased atrioventricular (AV) conduction Reduction of contractility Asthmatic effects Use with caution in patients with diabetes Insomnia Depression Bizarre dreams Sexual dysfunction Calcium Channel Blockers Verapamil, diltiazem, nifedipine Block calcium channels in vascular smooth muscle (VSM) Used for stable and variant angina Adverse effects • Dilation of peripheral arterioles • Reflex tachycardia • Hypotension • Beta blockers • Bradycardia • Heart failure • AV block Ranolazine Belongs to first new class of antianginal agents approved in more than 25 years Benefits modest and greater in men than in women Does not reduce heart rate, blood pressure, or vascular resistance Can prolong QT; multiple drug interactions Exact mechanism unknown Not a first-line therapy; combine with first-line agents for inadequate response to other firstline medications Revascularization Therapy Coronary artery bypass graft (CABG) surgery Percutaneous transluminal coronary angioplasty (PTCA) Comparison of CABG surgery with percutaneous coronary intervention (PCI) Drugs Used to Prevent Myocardial Infarction and Death Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE) inhibitors Antianginal agents Reduction of Risk Factors Smoking High cholesterol Hypertension Diabetes Physical inactivity Management of Variant Angina Treatment of vasospastic angina Initial therapy • Calcium channel blocker or long-acting nitrate If either of these alone is inadequate, add a nitrate If combination fails, CABG may be indicated Beta blockers are not effective with vasospastic angina
