View
214
Download
1
Category
Preview:
Citation preview
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 51
Drugs for Angina Pectoris
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
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Angina Pectoris: Pathophysiology and Treatment
Three forms of angina pectoris Chronic stable angina (exertional angina) Variant angina (Prinzmetal’s or vasospastic
angina) Unstable angina
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chronic Stable Angina (Exertional)
Pathophysiology Emotional excitement Large meals Cold exposure Coronary artery disease (CAD)
Treatment strategy Increase cardiac oxygen supply Decrease oxygen demand
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fig. 51–1. Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD.
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Variant Angina (Prinzmetal’s: Vasospastic)
Pathophysiology Coronary artery spasm
Treatment strategy Increasing cardiac oxygen supply
Therapeutic agents Calcium channel blockers Organic nitrates
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Unstable Angina: Medical Emergency
Therapeutic agents for acute management Anti-ischemic therapy Antiplatelet therapy Anticoagulant therapy
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Anti-ischemic Therapy
Nitroglycerin Beta blocker Supplemental O2
IV morphine ACE inhibitor
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antiplatelet/Anticoagulant Therapy
Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin)
Anticoagulant therapy Subcutaneous LMW heparin or IV
unfractionated heparin
LMW = low-molecular-weight.
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Organic Nitrates
Nitroglycerin Stable and variant angina Vasodilator
Adverse effects Headache Orthostatic hypotension Reflex tachycardia
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Organic Nitrates: Nitroglycerin
Vasodilator actions Mechanism of antianginal effects Stable angina Variant angina Pharmacokinetics Adverse effects
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Organic Nitrates: Nitroglycerin
Drug interactions Hypotensive drugs Phophodiesterase type 5 inhibitors Beta blockers, verapamil, and diltiazem
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Organic Nitrates: Nitroglycerin
Preparations and routes of administration Sublingual tablets Sustained-release oral capsules Transdermal delivery systems Translingual spray Topical ointment Intravenous infusion
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Revascularization Therapy
Coronary artery bypass graft (CABG) surgery Percutaneous transluminal coronary
angioplasty (PTCA) Comparison of CABG surgery with
percutaneous coronary intervention (PCI)
25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs Used to Prevent Myocardial Infarction and Death
Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE)
inhibitors Antianginal agents
26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Reduction of Risk Factors
Smoking High cholesterol Hypertension Diabetes Physical inactivity
27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
Recommended