Drugs to treat Angina

Question 1

Organic nitrates (nitroglycerin)

specific mechanism of action, 3 ways how it works, way to take it

Answer 1

They relax smooth muscle – inhibit phosphodiesterase, get a lot of cGMP, get profound relaxation of VSM (lower BP)
Work in 3 ways: decrease preload (decreased O2 demand), redistribute blood flow to ischemic area, and prevent coronary spasms (last 2 improve O2 supply)
Get tolerance to it quickly – can’t take them all the time
Almost all is metabolized in the first pass effect
Can take them under the tongue (rapid acting, doesn’t last long) or in a patch (slow delivery, longer lasting)

Question 2

Beta-Adrenergic Blockers

Answer 2

Block beta receptors in the SNS
Reduce O2 demand because they decrease HR, decrease FVC, and decrease afterload (decrease BP) = decrease work of the heart
Block the increase in HR that is a result of the big drop in BP when using nitrates – can use these two together

Question 3

Calcium channel blockers (2)

Answer 3

Nifedipine (act on VSM only)
i. It blocks Ca influx into VSM cells – has no effect on heart cells – causes vasodilation, decrease vasospasms (increase O2 supply) and decrease afterload (decrease O2 demand)
Verapamil, diltiazem
i. Acts on heart and VSM cells – block Ca influx into heart and smooth muscle cells – same way as nifedipine

Question 4

Newer agents

Answer 4

Can shift the way the heart is using energy – inhibit FA oxidation in ischemic heart and shift to glucose oxidation for metabolism – less oxygen is needed for glucose oxidation so function can be maintained in ischemia

Also selective cardiac rate inhibitors – work on specific channels

Question 5

4 ways to treat myocardial infarction

Answer 5

1. Aspirin
2. Statins
3. Beta-blockers
4. ACE inhibitors

Question 6

2 ways to improve O2 supply

Answer 6

1. Dilate vessels (like the coronary blood vessels)
2. Prevent vasospasms
   Both of these increase coronary blood flow

Question 7

4 ways to reduce O2 demand

Answer 7

1. Reduce afterload
2. Reduce preload (dilate veins)
3. Reduce contractility (decrease FVC so it has to use less oxygen)
4. Reduce HR

Question 8

How do nitrates work?

Answer 8

Nitrates –> NO –> activated guanylyl cyclase, which catalyzes GTP to cGMP. cGMP causes the dephosphorylation of MLC and then the relaxing of vascular smooth muscle