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Drugs for
Angina Pectoris
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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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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.
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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.
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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.
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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
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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.
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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.
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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.
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Organic Nitrates
Nitroglycerin
• Stable and variant angina
• Vasodilator
Adverse effects
• Headache
• Orthostatic hypotension
• Reflex tachycardia
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Biochemistry of nitrate-induced vasodilation.
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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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.
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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.
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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.
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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.
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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
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Dilation of peripheral arterioles
Reflex tachycardia
Hypotension
Beta blockers
Bradycardia
Heart failure
AV block
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Revascularization Therapy
Coronary artery bypass graft (CABG) surgery
Percutaneous transluminal coronary angioplasty
(PTCA)
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Drugs Used to Prevent Myocardial Infarction
and Death
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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.
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Reduction of Risk Factors
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Smoking
High cholesterol
Hypertension
Diabetes
Obesity
Physical inactivity
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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
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Questions
W2
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