Drugs for Angina Pectoris 1

Drugs for 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 2

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 3

Determinants of Cardiac Oxygen Demand and Supply Heart rate Myocardial contractility Intramyocardial wall tension (preload/afterload) Oxygen supply Myocardial blood flow Myocardial perfusion only in diastole 4

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 6

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 7

Fig. 51–1. Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD. 8

Variant Angina (Prinzmetal’s: Vasospastic) Pathophysiology Coronary artery spasm Treatment strategy Increasing cardiac oxygen supply Therapeutic agents Calcium channel blockers Organic nitrates 9

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 10

Unstable Angina: Medical Emergency Therapeutic agents for acute management Anti-ischemic therapy Antiplatelet therapy Anticoagulant therapy 11

Anti-ischemic Therapy Nitroglycerin Beta blocker Supplemental O2 IV morphine ACE inhibitor 12

Antiplatelet/Anticoagulant Therapy Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin) Anticoagulant therapy Subcutaneous LMW heparin or IV unfractionated heparin LMW = low-molecular-weight. 13

Organic Nitrates Nitroglycerin Adverse effects Stable and variant angina Vasodilator Adverse effects Headache Orthostatic hypotension Reflex tachycardia 14

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 16

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 17

Organic Nitrates: Nitroglycerin Preparations and routes of administration Sublingual tablets Sustained-release oral capsules Transdermal delivery systems Translingual spray Topical ointment Intravenous infusion 18

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 19

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 20

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 21

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 22

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 first-line medications 23

Revascularization Therapy Coronary artery bypass graft (CABG) surgery Percutaneous transluminal coronary angioplasty (PTCA) Comparison of CABG surgery with percutaneous coronary intervention (PCI) 24

Drugs Used to Prevent Myocardial Infarction and Death Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE) inhibitors Antianginal agents 25

Reduction of Risk Factors Smoking High cholesterol Hypertension Diabetes Physical inactivity 26

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 27