CV III - Anti-anginal drugs

Question 1

What is angina?

Answer 1

Chest pain caused by coronary artery disease due to ischemia. The physical pain is from lack of oxygen at heart tissue.

Ischemia is reduced blood flow to the heart, usually because of atherosclerosis and myocardial infarction.

Vasospasms can also occur, leading to ischemia.

Question 2

List three broad treatment plans for angina

Answer 2

• Alter lifestyle
• Bypass surgery (angioplasty or stent)
• Drug therapy

Question 3

List the functions of drugs that treat angina

Answer 3

All of these aims to improve balance between oxygen supply and demand (especially decreasing oxygen demand)

Improving oxygen supply

• Dilate vessels
• Preventing vasospams

Reducing oxygen demand

• Reducing afterload (peripheral resistance)
• Reducing preload (venous return volume)
• Reduce contractility (force of contraction)
• Reduce heart rate

Question 4

List the types of drugs for angina (3)

Answer 4

• Organic nitrates
• β blockers
• Calcium channel blockers

Question 5

How do organic nitrates, such as nitroglycerin, treat angina (at a cellular level)?

Answer 5

Nitrates relax smooth muscle

• Denitrated in smooth muscle, forming NO
• NO activates guanylyl cyclase
• Guanylyl cyclase hydrolyzes GTP to cGMP

cGMP dephosphorylates contractile proteins called myosin light chains, which inhibits interaction with actin, causing relaxation.

Question 6

How can the action of nitrates on smooth muscles be amplified by viagra?

What can be the consequence of this?

Answer 6

Sildenafil inhibits a phosphodiesterase that converts cGMP (active) to GMP (inactive), therefore keeping NO’s muscle relaxing mechanism ON.

Sildenafil and nitrates can interact to dangerously lower blood pressure.

Question 7

What are the three reasons that make nitrates effective in the treatment of angina?

Answer 7

• Primary method: decreased preload through vasodilation. Pooling in veins decreases venous return and reduces oxygen demand at the heart.
• Redistributes blood flow to ischemic area through dilation of coronary arteries
• Prevents coronary spasms in coronary arteries to improve oxygen supply

Question 8

What two factors must be considered when dosing nitrates for angina?

Answer 8

Tolerance builds. Workers in factories get headaches on mondays because their tolerance dissapears over the weekend. Headaches are a consequence of vasodilation from nitrates.

A high dose must be given because of the very significant first pass effect. Sublingual (under tongue) administration is rapid and short lasting. Patches can give therapy for 8-10 hours.

Question 9

How can β blockers be used to treat angina?

Answer 9

They reduce oxygen demand by:

• Lowering heart rate
• Lowering force of contraction
• Lowering afterload

Question 10

Which receptors to the following drugs block?

Propranolol
Metoprolol

Answer 10

Propranolol: β1 and β2

Metoprolol: β1 (cardioselective)

Question 11

How do calcium channel blockers treat angina?

Name three

Answer 11

Act on heart cells AND vascular smooth muscle cells. Nifedipine only blocks VSMCs (hypertension)

Heart cell (lower oxygen demand):

• lowered force of contraction
• Lowered heart rate

VSMCs

• Lowered afterload (less oxygen demand)
• Lowered vasospasms (more oxygen supply)
• Verapamil
• Diltiazem
• Nifedipine (VSM only)