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Drugs for Angina Pectoris Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 1 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 2 Drugs for Angina Pectoris Three families of antianginal agents Organic nitrates Nitroglycerin Beta blockers Example: propranolol Calcium channel blockers Example: verapamil Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 3 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 4 Chronic Stable Angina (Exertional) Pathophysiology • Emotional excitement • Large meals • Cold exposure • Coronary artery disease (CAD) Treatment strategy • Increase cardiac oxygen supply • Decrease oxygen demand Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 5 Chronic Stable Angina (Exertional) Therapeutic agents (provide symptomatic relief) • Organic nitrates • Beta blockers • Calcium channel blockers Nondrug therapy • Avoid factors that can precipitate angina • Decrease risk factors Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 6 Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 7 Variant Angina (Prinzmetal’s – Vasospastic) Pathophysiology • Coronary artery spasm Treatment strategy • Increasing cardiac oxygen supply Therapeutic agents • Calcium channel blockers • Organic nitrates Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 8 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 9 Unstable Angina – Medical Emergency Therapeutic agents for acute management • Anti-ischemic therapy • Antiplatelet therapy • Anticoagulant therapy Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 10 Anti-Ischemic Therapy Nitroglycerin – VSM relaxation Beta blocker Supplemental O2 IV morphine ACE inhibitor Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 11 Antiplatelet/Anticoagulant Therapy Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin) Anticoagulant therapy Subcutaneous LMW heparin or IV unfractionated heparin Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 12 Organic Nitrates Nitroglycerin • Stable and variant angina • Vasodilator Adverse effects • Headache • Orthostatic hypotension • Reflex tachycardia Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 13 Biochemistry of nitrate-induced vasodilation. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 14 Organic Nitrates Tolerance • Can develop rapidly • Cross-tolerance to all other nitrates • To minimize, use the lowest effective dose • Long-acting formulas: 8 drug-free hours/day Drug interactions • Hypotensive drugs • Phosphodiesterase type 5 inhibitors • Beta blockers, verapamil, and diltiazem Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 15 Organic Nitrates Preparations and routes of administration • Sublingual tablets • Sustained-release oral capsules • Transdermal delivery systems • Translingual spray • Transmucosal (buccal) tablets • Topical ointment • Intravenous infusion Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 16 Organic Nitrates Long-acting preparations • Discontinue slowly – rebound vasospasm 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 17 Beta Blockers Decrease cardiac oxygen demand Propranolol, metoprolol Adverse effects Bradycardia Decreased AV conduction Reduction of contractility Asthmatic effects Use with caution in patients with diabetes Insomnia Depression Bizarre dreams Sexual dysfunction Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 18 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 19 Revascularization Therapy Coronary artery bypass graft (CABG) surgery Percutaneous transluminal coronary angioplasty (PTCA) Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 20 Drugs Used to Prevent Myocardial Infarction and Death • • • • Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE) inhibitors Antianginal agents Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 21 Reduction of Risk Factors • • • • • • Smoking High cholesterol Hypertension Diabetes Obesity Physical inactivity Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 22 Management of Variant Angina Treatment of vasospastic angina • Initial therapy Either a 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 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 23 Questions W2 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 24