Drugs Used in Chronic IHD

Question 1

Classic angina

Answer 1

Occlusion of coronary aa. resulting from atherosclerotic plaque

Question 2

Variant (Prinzmetal) angina

Answer 2

Episodes of vasoconstriction of coronary aa.

Question 3

Angina def:

Answer 3

Imbalance between oxygen demand of the heart and oxygen supply via the coronary aa.

Question 4

Why does angina occur during exercise or stress?

Answer 4

Oxygen demand of the heart increases significantly, which is greater than the supply of oxygen through the partially blocked coronary a.

Question 5

3 approaches to treating angina pectoris

Answer 5

1. Decrease cardiac work
2. Increase blood flow through coronary aa.
3. Reduce myocardial oxygen demand

Question 6

What is the best way to treat vasospastic (Prinzmetal) angina?

Is it helpful in classic angina?

Answer 6

Increase coronary blood flow using vasodilators.

No.

Question 7

What is the “coronary steal” phenomenon?

Answer 7

The redistribution of blood to non-ischemic areas associated w/ dilation of small arterioles. This is the reason vasodilators don’t work well in classic angina.

Question 8

3 phases of phasic coronary flow

Answer 8

1. Isovolumetric contraction
2. Ejection
3. Diastole

Question 9

3 drug classes used in chronic IHD

Answer 9

Nitrates
Ca++ channel blockers
Beta-blockers

Question 10

How do organic nitrates work?

Answer 10

Once ingested, the nitrates are activated and lead to SM relaxation and vasodilation.

Question 11

3 Nitrovasodilators (nitrates)

Answer 11

Nitroglycerin
Isosorbide dinitrate
Isosorbide mononitrate

Question 12

What is the first-pass metabolism of nitrates?

Answer 12

It is significant, meaning the oral bioavailability is low. Other routes that avoid the GI tract are used mostly.

Question 13

What nitrate is a poor substrate of nitrate reductase and has a greater bioavailability?

Answer 13

Isosorbide mononitrate

Question 14

What is needed to release NO from nitrates?

Answer 14

Thiols

Question 15

What does NO dilate?

Answer 15

Veins and large arteries (higher conc. needed for aa.)

Question 16

NO dilates veins and arteries. What is the effect of dilating them?

Answer 16

Veins:

• increased venous capacitance
• reduced ventricular preload

Arteries:
-reduce afterload

*there is no substantial increase in coronary blood flow into the ischemic area in classic angina.

Question 17

MOA of nitrates to treat variant angina

Answer 17

Vascular SM relaxation -> coronary a. dilation -> coronary spasm relief

Question 18

MOA of nitrates to treat classic angina

Answer 18

Venous dilation -> reduced preload -> decrease oxygen demand

Question 19

4 ways to develop tolerance to nitrates

Answer 19

Depletion of thiol components

Increased generation of superoxide radicals (leads to depletion of NO)

Reflex activation of SNS

Salt and water retention

Question 20

What is the use of short-acting nitrates vs. long-acting nitrates?

Answer 20

Short-acting: relieve angina attack

Long-acting: prevent future attacks

Question 21

S/E of nitrates

Answer 21

HA

Orthostatic hypoTN

Tachy/inotropy

Increased Na+ and water reabsorption

Question 22

3 Non-cardioactive (Dihydropines) Ca++ channel blockers

Answer 22

Amlodipine (long-acting)
Nifedipine (short-acting)
Nicardipine (short-acting)

Question 23

2 Cardioactive Ca++ channel blockers

Answer 23

Diltiazem

Verapamil

Question 24

Ca++ channel blockers MOA

Answer 24

Ca++ enters via voltage-dependent Ca++ channels to cause SM contraction, so by blocking it, it is inhibited.

Question 25

What are some anti-anginal mechanisms of Ca++ channel blockers for classic angina?

Answer 25

Decrease myocardial oxygen demand. - dilation of peripheral aa. -> dec. PVR and afterload, decreased BP. - arterioles are more affected than vein.s All of this leads to decreased cardiac contractility and HR.

Question 26

What are some anti-anginal mechanisms of Ca++ channel blockers for variant angina?

Answer 26

Increased blood supply by dilating coronary aa. to relieve local spasm.

Question 27

Major S/E of Ca++ channel blockers? Minor?

Answer 27

Cardiac depression/arrest Acute HF (cardioactives) Bradyarrhythmias, AV block Flushing, HA, anorexia, dizziness, edema, constipation.

Question 28

What's a unique S/E of NIfedipine (immediate-release)?

Answer 28

Increases risk of MI in pts. w/ HTN

Question 29

4 beta-blockers indicated in angina

Answer 29

Propranolol Nadolol Metoprolol Atenolol

Question 30

MOA of beta-blockers for treating angina

Answer 30

Decreased myocardial oxygen demand. - decreased HR -> improved myocardial perfusion. - decrease contractility - decrease in BP leads to reduced afterload

Question 31

S/E of beta-blockers

Answer 31

``` Reduced CO Bronchoconstriction Poor Glc metabolism Bad LDL/HDL profile Sedation SNS hyperresponsiveness ```

Question 32

Contraindications for use of beta-blockers

Answer 32

``` Asthma Peripheral vascular DZ T1DM Bradyarrhythmias Low cardiac function ```

Question 33

Using nitrates alone, what are 2 major undesirable effects?

Answer 33

Increased HR Increased contractility

Question 34

Using either beta-blockers or Ca++ channel blockers, what are 2 major undesirable effects?

Answer 34

Increased end-diastolic vol. Increased ejection time

Question 35

Overall, what is the approach to a pt. w/ variant angina?

Answer 35

Prevention is the choice, but: | Ca++ channel blockers are first choice. If they are contraindicated, long-acting nitrates are used.

Question 36

Overall, what is the approach to a pt. w/ classic angina?

Answer 36

Lifestyle mods/prevention/diet, etc are first choice, but: 1. Beta-blocker (or CCB or LA nitrate) 2. Add CCB or BB (if not used first) 3. Consider triple therapy 4. CABG surgery