1. Drugs for Angina Pectoris1

2. Drugs for 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 2

3. 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 3

4. Determinants of Cardiac Oxygen Demand and Supply
Heart rate
Myocardial contractility
Intramyocardial wall tension (preload/afterload)
Oxygen supply
Myocardial blood flow
Myocardial perfusion only in diastole 4

5. 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. 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

7. 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 7

8. Fig. 51–1. Effect of exertion on the balance between oxygen supply and oxygen demand in the healthy heart and the heart with CAD. 8

9. Variant Angina (Prinzmetal’s: Vasospastic)
Pathophysiology
Coronary artery spasm
Treatment strategy
Increasing cardiac oxygen supply
Therapeutic agents
Calcium channel blockers
Organic nitrates 9

10. 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

11. Unstable Angina: Medical Emergency
Therapeutic agents for acute management
Anti-ischemic therapy
Antiplatelet therapy
Anticoagulant therapy 11

12. Anti-ischemic Therapy
Nitroglycerin
Beta blocker
Supplemental O2
IV morphine
ACE inhibitor 12

13. Antiplatelet/Anticoagulant Therapy
Aspirin (indefinitely)
Clopidogrel (Plavix)
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Anticoagulant therapy
Subcutaneous LMW heparin or IV unfractionated heparin
LMW = low-molecular-weight. 13

14. Organic Nitrates Nitroglycerin Adverse effects
Stable and variant angina
Vasodilator
Adverse effects
Headache
Orthostatic hypotension
Reflex tachycardia 14

15. Organic Nitrates: Nitroglycerin
Vasodilator actions
Mechanism of antianginal effects
Stable angina
Variant angina
Pharmacokinetics
Adverse effects

16. Organic Nitrates: Nitroglycerin
Drug interactions
Hypotensive drugs
Phophodiesterase type 5 inhibitors
Beta blockers, verapamil, and diltiazem 16

17. 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 17

18. Organic Nitrates: Nitroglycerin
Preparations and routes of administration
Sublingual tablets
Sustained-release oral capsules
Transdermal delivery systems
Translingual spray
Topical ointment
Intravenous infusion 18

19. 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 19

20. 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 20

21. 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 21

22. 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 22

23. 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 23

24. Revascularization Therapy
Coronary artery bypass graft (CABG) surgery
Percutaneous transluminal coronary angioplasty (PTCA)
Comparison of CABG surgery with percutaneous coronary intervention (PCI) 24

25. Drugs Used to Prevent Myocardial Infarction and Death
Antiplatelet drugs
Cholesterol-lowering drugs
Angiotensin-converting enzyme (ACE) inhibitors
Antianginal agents 25

26. Reduction of Risk Factors
Smoking
High cholesterol
Hypertension
Diabetes
Physical inactivity 26

27. 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 27