chapter 51
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Chapter 51. Drugs for Angina Pectoris. 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 - PowerPoint PPT PresentationTRANSCRIPT
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 51
Drugs for Angina Pectoris
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2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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