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Chapter 51
Drugs for Angina Pectoris
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for Angina Pectoris
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Angina pectoris
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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
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Prevention of myocardial infarction and death
Prevention of myocardial ischemia and anginal
pain
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Drugs for Angina Pectoris
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Three families of antianginal agents
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Organic nitrates
• Nitroglycerin
 Beta blockers
• Example: propranolol
 Calcium channel blockers
• Example: verapamil
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Ranolazine
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A newer drug with limited indications
 Can be combined with other drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Determinants of Cardiac Oxygen
Demand and Supply
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Oxygen demand
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Heart rate
Myocardial contractility
Intramyocardial wall tension (preload/afterload)
Oxygen supply
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Myocardial blood flow
Myocardial perfusion only in diastole
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Angina Pectoris:
Pathophysiology and Treatment
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Three forms of angina pectoris
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Chronic stable angina (exertional angina)
Variant angina (Prinzmetal’s or vasospastic
angina)
Unstable angina
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Chronic Stable Angina (Exertional)
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Pathophysiology
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Emotional excitement
Large meals
Cold exposure
Coronary artery disease (CAD)
Treatment strategy
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Increase cardiac oxygen supply
Decrease oxygen demand
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Chronic Stable Angina (Exertional)
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Therapeutic agents (provide symptomatic
relief)
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Organic nitrates
Beta blockers
Calcium channel blockers
Ranolazine
Nondrug therapy
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Avoid factors that can precipitate angina
Decrease risk factors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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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.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Variant Angina
(Prinzmetal’s: Vasospastic)
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Pathophysiology
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Treatment strategy
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Coronary artery spasm
Increasing cardiac oxygen supply
Therapeutic agents
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Calcium channel blockers
Organic nitrates
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Unstable Angina:
Medical Emergency
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Severe CAD complicated by vasospasm
Pathophysiology
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Symptoms of angina at rest
New-onset exertional angina
Intensification of existing angina
Treatment strategy
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Maintain oxygen supply
Decrease oxygen demand
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Unstable Angina:
Medical Emergency
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Therapeutic agents for acute management
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Anti-ischemic therapy
Antiplatelet therapy
Anticoagulant therapy
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Anti-ischemic Therapy
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Nitroglycerin
Beta blocker
Supplemental O2
IV morphine
ACE inhibitor
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Antiplatelet/Anticoagulant Therapy
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Aspirin (indefinitely)
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Clopidogrel (Plavix)
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Anticoagulant therapy
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Subcutaneous LMW heparin or IV
unfractionated heparin
LMW = low-molecular-weight.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Organic Nitrates
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Nitroglycerin
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Stable and variant angina
Vasodilator
Adverse effects
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Headache
Orthostatic hypotension
Reflex tachycardia
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Organic Nitrates: Nitroglycerin
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Vasodilator actions
Mechanism of antianginal effects
Stable angina
Variant angina
Pharmacokinetics
Adverse effects
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Organic Nitrates: Nitroglycerin
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Drug interactions
Hypotensive drugs
Phophodiesterase type 5 inhibitors
Beta blockers, verapamil, and diltiazem
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Organic Nitrates: Nitroglycerin
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Tolerance
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Organic Nitrates: Nitroglycerin
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Preparations and routes of administration
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Sublingual tablets
Sustained-release oral capsules
Transdermal delivery systems
Translingual spray
Topical ointment
Intravenous infusion
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Organic Nitrates: Nitroglycerin
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Long-acting preparations
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Discontinue slowly
Therapeutic uses summarized
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Organic Nitrates: Other
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Isosorbide mononitrate and isosorbide
dinitrate
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Actions identical to those of nitroglycerin
Used for angina, taken orally, produce headache,
hypotension, and reflex tachycardia
Amyl nitrite
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Ultrashort-acting agent used to treat acute
episodes of angina pectoris
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta Blockers
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Decrease cardiac oxygen demand
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Propranolol, metoprolol
• Adverse effects
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Bradycardia
Decreased atrioventricular (AV) conduction
Reduction of contractility
Asthmatic effects
Use with caution in patients with diabetes
Insomnia
Depression
Bizarre dreams
Sexual dysfunction
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Calcium Channel Blockers
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Verapamil, diltiazem, nifedipine
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Ranolazine
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Belongs to first new class of antianginal
agents approved in more than 25 years
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Revascularization Therapy
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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
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Antiplatelet drugs
Cholesterol-lowering drugs
Angiotensin-converting enzyme (ACE)
inhibitors
Antianginal agents
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Reduction of Risk Factors
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Smoking
High cholesterol
Hypertension
Diabetes
Physical inactivity
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Management of Variant Angina
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Treatment of vasospastic angina
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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
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