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Chapter 51

Drugs for Angina Pectoris

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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

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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

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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

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Angina Pectoris: Pathophysiology and Treatment

Three forms of angina pectoris Chronic stable angina (exertional angina) Variant angina (Prinzmetal’s or vasospastic

angina) Unstable angina

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Chronic Stable Angina (Exertional)

Pathophysiology Emotional excitement Large meals Cold exposure Coronary artery disease (CAD)

Treatment strategy Increase cardiac oxygen supply Decrease oxygen demand

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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

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

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Variant Angina (Prinzmetal’s: Vasospastic)

Pathophysiology Coronary artery spasm

Treatment strategy Increasing cardiac oxygen supply

Therapeutic agents Calcium channel blockers Organic nitrates

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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

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Unstable Angina: Medical Emergency

Therapeutic agents for acute management Anti-ischemic therapy Antiplatelet therapy Anticoagulant therapy

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Anti-ischemic Therapy

Nitroglycerin Beta blocker Supplemental O2

IV morphine ACE inhibitor

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Antiplatelet/Anticoagulant Therapy

Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin)

Anticoagulant therapy Subcutaneous LMW heparin or IV

unfractionated heparin

LMW = low-molecular-weight.

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Organic Nitrates

Nitroglycerin Stable and variant angina Vasodilator

Adverse effects Headache Orthostatic hypotension Reflex tachycardia

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Organic Nitrates: Nitroglycerin

Vasodilator actions Mechanism of antianginal effects Stable angina Variant angina Pharmacokinetics Adverse effects

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Organic Nitrates: Nitroglycerin

Drug interactions Hypotensive drugs Phophodiesterase type 5 inhibitors Beta blockers, verapamil, and diltiazem

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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

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Organic Nitrates: Nitroglycerin

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

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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

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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

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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

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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

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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

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Revascularization Therapy

Coronary artery bypass graft (CABG) surgery Percutaneous transluminal coronary

angioplasty (PTCA) Comparison of CABG surgery with

percutaneous coronary intervention (PCI)

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Drugs Used to Prevent Myocardial Infarction and Death

Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE)

inhibitors Antianginal agents

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Reduction of Risk Factors

Smoking High cholesterol Hypertension Diabetes Physical inactivity

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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