Antianginal agents

Question 1

treatment strategies

Answer 1

1. decrease O2 demand

2. increase O2 delivery

Question 2

nitrates MOA

Answer 2

releases NO when metabolized → binds to and activates guanylyl cyclase, leading to ↑ cGMP

Question 3

antiischemic effect of nitrates

Answer 3

decrease myocardial O2 demand by producing systemic vasodilation.

Question 4

How do nitrates decrease platelet aggregation?

Answer 4

NO stimulation of guanylate cyclase in platelets results in increased platelet cGMP

Question 5

nitrate tolerance

Answer 5

• Effectiveness diminishes significantly with continuous use
• A nitrate-free period of at least 8 hours between doses is required to prevent tolerance
o Generally not a problem with sublingual nitroglycerin

Question 6

nitrate drug/drug interaction

Answer 6

• Synergistic hypotension wth phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) because they both act by increasing GMP

Question 7

First line therapy to reduce frequency of angina and improve exercise tolerance

Answer 7

Propanolol

Question 8

Why are beta blockers not effective in variant angina

Answer 8

Variant angina is due to vasospasm which is mediated by alpha 1. Beta blockers work on beta receptors

beta blockers could precipitate the problem!

Question 9

beta blocker contraindications

Answer 9

• Asthma/COPD
o Blockade of β2 receptors in bronchial smooth muscle may lead to increase in airway resistance
• Diabetes
o Glycogenolysis is partially inhibited after β2 blockade
o May mask signs of hypoglycemia

Question 10

clinical use of beta blockers

Answer 10

ischemic heart diseae

stabilizes heart rate and prolongs survival after MI
timolol, propanolol, metropolol

Question 11

propanolol drug/drug interaction

Answer 11

Can cause heart block if combined with a CCB (verapamil or diltiazem) → will slow conduction

Question 12

DHP pharmocodynamics

Answer 12

• Arterioles more sensitive than veins
• Orthostatic hypotension is not a problem.
• Relaxation of arteriolar smooth muscle leads to decreased afterload and decreased O2 demand
• Little effect on preload
• Also increases O2 supply due to dilation of coronaries

Question 13

Adverse effects of verapamil

Answer 13

constipation

peripheral edema

Question 14

Contraindications for CCBs

Answer 14

• Use of verapamil/dilitiazem with a β-blocker is contraindicated because of the potential for AV block
• Should not be used in pts with ventricular dysfunction, SA or AV nodal conduction defects
• Short-acting DHPs can cause reflex tachycardia

Question 15

MOA of ranolazine

Answer 15

ate Na channel blocker that facilitates Ca entry; resultant reduction in intracellular calcium reduces cardiac contractility and work

Question 16

When is ranolazine used?

Answer 16

o Typically reserved for angina that is refractory to treatment with beta blockers, CCBs, and nitrates
o Used either in combination with beta blocker or as a substitute in pts who cannot receive beta blockers