1. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.1 Drugs for Angina Pectoris

2. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 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

3. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Drugs for Angina Pectoris  Three families of antianginal agents  Organic nitrates Nitroglycerin  Beta blockers Example: propranolol  Calcium channel blockers Example: verapamil

4. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 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

5. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.5 Chronic Stable Angina (Exertional)  Pathophysiology Emotional excitement Large meals Cold exposure Coronary artery disease (CAD)  Treatment strategy Increase cardiac oxygen supply Decrease oxygen demand

6. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.6 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

7. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.7 Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD.

8. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.8 Variant Angina (Prinzmetal’s – Vasospastic)  Pathophysiology Coronary artery spasm  Treatment strategy Increasing cardiac oxygen supply  Therapeutic agents Calcium channel blockers Organic nitrates

9. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.9 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

10. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.10 Unstable Angina – Medical Emergency  Therapeutic agents for acute management Anti-ischemic therapy Antiplatelet therapy Anticoagulant therapy

11. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.11 Anti-Ischemic Therapy  Nitroglycerin – VSM relaxation  Beta blocker  Supplemental O 2  IV morphine  ACE inhibitor

12. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.12 Antiplatelet/Anticoagulant Therapy  Aspirin (indefinitely) Clopidogrel (Plavix) Abciximab (ReoPro) Eptifibatide (Integrilin)  Anticoagulant therapy Subcutaneous LMW heparin or IV unfractionated heparin

13. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.13 Organic Nitrates  Nitroglycerin Stable and variant angina Vasodilator  Adverse effects Headache Orthostatic hypotension Reflex tachycardia

14. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.14 Biochemistry of nitrate-induced vasodilation.

15. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.15 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

16. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.16 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

17. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.17 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

18. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.18 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

19. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.19 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

20. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.20 Revascularization Therapy  Coronary artery bypass graft (CABG) surgery  Percutaneous transluminal coronary angioplasty (PTCA)

21. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.21 Drugs Used to Prevent Myocardial Infarction and Death Antiplatelet drugs Cholesterol-lowering drugs Angiotensin-converting enzyme (ACE) inhibitors Antianginal agents

22. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.22 Reduction of Risk Factors Smoking High cholesterol Hypertension Diabetes Obesity Physical inactivity

23. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.23 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

24. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.24 Questions W2