1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 51 Drugs for Angina Pectoris

2. 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

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drugs for Angina Pectoris  Three families of antianginal agents  Organic nitrates Nitroglycerin Nitroglycerin  Beta blockers Example: propranolol Example: propranolol  Calcium channel blockers Example: verapamil Example: verapamil  Ranolazine  A newer drug with limited indications  Can be combined with other drugs

4. 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

5. 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

6. 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

7. 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

8. 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.

9. 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

10. 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

11. 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

12. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anti-ischemic Therapy  Nitroglycerin  Beta blocker  Supplemental O 2  IV morphine  ACE inhibitor

13. 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.

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta Blockers  Decrease cardiac oxygen demand  Propranolol, metoprolol Adverse effects 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

22. 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 Dilation of peripheral arterioles Reflex tachycardia Reflex tachycardia Hypotension Hypotension Beta blockers Beta blockers Bradycardia Bradycardia Heart failure Heart failure AV block AV block

23. 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

24. 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)

25. 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

26. 26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Reduction of Risk Factors  Smoking  High cholesterol  Hypertension  Diabetes  Physical inactivity

27. 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 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