CPR 10.04 Anti-Anginal Pharm

Question 1

What are the 2 general ways we can aim to treat angina?

Answer 1

Increase Oxygen delivery or decrease oxygen demand.

Question 2

What are common B-blockers used to treat angina? What type are these?

Answer 2

B-1 selective Metoprolol, Atenolol

Question 3

Describe the MOA for B-blockers in the treatment of angina.

Answer 3

MOA: block cardiac β receptors and thereby reduce myocardial oxygen demand by decreasing HR, Inotropy, LV wall stress. Effectively reduce the frequency and severity of angina.

Question 4

Describe the indications and side effects of beta blockers.

These drugs are not helpful in what type of cardiac events?

Answer 4

3. Indications: First line agents for control of chronic stable angina. Prophylactic use only. All types of beta-blockers are effective, but β-1 selective agents used more commonly. Often used in combination with Nitrates and CCB’s.
4. Contraindications: Of no value in acute attack or vasospastic angina.
5. Side Effects: increase cell surface receptor numbers. Sudden withdrawal can cause supersensitivity to cathecholamines: can result in angina, MI, and death. ED is another side effect.

Question 5

What are 2 common examples of Organic nitrates used in the treatment of angina?

Answer 5

Nitroglycerine and Isosorbide dinnitrate

Question 6

Describe the MOA of organic nitrates in the treatment of angina.
Consider the two ways they can help.

Answer 6

(a) Release NO→ Venous dilation→ reduced preload→ Reduced oxygen demand.
(1) With higher doses, also decrease SVR and arterial pressure→ Decrease afterload and thus further reduce oxygen demand.
(b) Reverse/Inhibit coronary vasospasm→ improve Coronary blood flow (Increase oxygen supply). This is important for treatment of Printzmetal’s variant angina.

Question 7

What are the indications, contraindications, and side effects of Nitrates?

Answer 7

4. Indications: the variable preparations each have their own indication for treating types of angina. Effective in treating vasospastic angina due to direct effect on vascular smooth muscle.
5. Contraindications: ED drgus exacerbate effects of organic nitrates therefore contraindicated in pateints taking sildenafil, vardenafil, or tadalafil within 24 hours. (severe hypotension)
6. Side Effects: Reduced response with chronic use (espeiclaly with long acting formulations) involving reduced NO production, response, and compensatory mechanism. Taking a break from using Nitrates can reduce tolerance. Pentaerithrityl tetranitrate does not induce tolerance.

Question 8

Describe the bioavailability of Nitrates including their site of denitration and the variable onset and duration of administration methods.

Answer 8

7. Bioavailability: High first pass metabolism (90%) as they are rapidly denitrated in liver.
   (a) Sublingual or spray: 10-30 min. duration; relief of acute attacks.
   (b) Oral (higher concentration): slow onset, 2-4 hr duration; used as prophylactic.
   (c) Transdermal patch: slowest onset of effect, 10 hr. duration; as as prophylactic.

Question 9

What are some of the common examples of CCB’s used in the treatment of angina?

Answer 9

Dihydropiridines (Nifedipine, Amlodipine, Felodipine) Diltiazem, Verapamil.

Question 10

Describe the MOA of CCB’s in treating angina

Answer 10

1. MOA: Reduce O2 demand by systemic vasodilation→ reduced ventricular afterload. (Verapamil and Diltiazem also decrease inotropy and HR, thus further decreasing O2 demand). Also dilate coronary arteries and prevent coronary vasospasm.

Question 11

Describe the indications (when used, types of angina effective for) and side effects of CCB’s.

Answer 11

3. Indications: Prescribed when β-blckers or nitrates are innefective/can’t be used. Can also be added to β-Blcokers if monotherapy unsuccesful (be careful with verapamil and diltiazem). Effective as prophylactic in both effort and vaspspastic angina. Stable angina.
4. Side Effects: shart and rapid acting dihydropiridines (RR nifedipine) can increase mortality.

Question 12

Describe the MOA for Ranolazine as an anti-anginal drug

Answer 12

1. MOA: reduces late inward sodium currents (INa) that normally facilitates Ca++ entry via Na-Ca exchanger. This reduction in IC Ca++ reduces diastolic tension, inotropy, and work. (no efect on HR/BP)

Question 13

Describe the ADME, contraindications, and side effects of Ranolazine.

Answer 13

2. ADME: Orally active, 6-8 hour half-life.
3. Contraindications: patients taking CYP3A inhibitors.
4. Side Effects: Blocks outward potassium currents (IKR) and prolongs QT during phase 3 in dose-related manner.