Antianginal drugs

Question 1

Nitrates and their mechanism

Answer 1

• Nitroglycerin, Isosorbide dinitrate, Amyl nitrite
• Denitration within smooth muscles release nitric oxide
• NO increase intracellular cGMP –> dephosphorylate myosin light chain phosphate –> smooth muscle relaxation
• Adverse effects; reflex tachycardia, orthostatic hypotension, throbbing headache

Question 2

Nitrates; cardiac effect

Answer 2

• Venous dilation decreases preload –> decreases cardiac work load
• Dilates coronary vasculature, providing increased blood supply to the heart muscle

Question 3

Nitrates; indications

Answer 3

• Effective in stable and unstable angia, as well as in varian angina pectoris
• Treatment of acute anginal pain; sublingual tablet, duration of 10-20 min
• Antidote for cyanide poisoning by causing methemoglobin

Question 4

Ca-channel blockers and their mechanism

Answer 4

• Verapamil, Diltiazem, Nifedipine
• Block voltage-gated “L-type” Ca-channels in cardiac and smooth muscle cells
• Cause decreased cardiac contractility and arteriolar vasodilation
• Adverse effects; constipation, pretibial edema, nausea, flushing, and dizziness. HF, AV block, sinus node depression

Question 5

Verapamil and Diltiazem

Answer 5

• Ca-channel blockers
• Reduce rate and contractility of the heart
• Decrease blood pressure and oxygen demand
• Used to treat AV nodal arrhythmias
• Verapamil –> greater negative inotropic effect, weaker vasodilator
• Diltiazem –> have similar activities on vasodilation and negative inotropic effect

Question 6

Nifedipine

Answer 6

• Great arteriolar vasodilator
• Minimal effect on cardiac cells
• Useful in treatment of angina caused by spontaneous coronary spasm

Question 7

Ca-channel blockers; indications

Answer 7

• Angina, hypertension and supraventricular arrhythmias
• Prophylactic therapy in both effort and vasospastic angina
• Nifedipine - abort acute anginal attacks
• Combined with nitrates - atherosclerotic angina
• Used in migraine, preterm labor, stroke, and Raynaud’s syndrome

Question 8

β-blockers

Answer 8

• Propranolol, Metoprolol, Aneolol, Acebutolol
• Drug of choice to treat effort-induced angina
• Reduce cardiac work by decreasing heart rate, contractility, CO, and blood pressure
• Reduce oxygen demand
• Reduce the severity and frequency of angina attacks
• Ineffective and should not be used in vasospastic angina
• Contraindicated in patients with asthma, diabetes, severe bradycardia, COPD