Antianginal Pharmacology

Question 1

What is angina?

Answer 1

When oxygen supply to the myocardium is insufficient for its needs. Which causes retrosternal cardiac pain.
Difficult to distinguish between heart attack.

Question 2

What are the aims of treatments for angina?

Answer 2

Alleviate acute symptoms
Minimise frequency of symptoms
Decrease progression of atherosclerosis.

Question 3

Name some anti-anginal agents?

Answer 3

• Organic nitrates (acute attacks)
• CCB
• β-Adrenoreceptor antagonist (Slow heart rate so decrease metabolic demand)
• K channel activators (Vasodilators)

Question 4

What are organic nitrates?

Answer 4

Glyceryl trinitrate:
- Effective in angina
- Quick onset/short DOA
Isosorbide mononitrate:
- Longer DOA

Question 5

What is the MOA of nitrates?

Answer 5

• Nitric oxide (NO) released from organic nitrates.
• Relaxed all smooth muscle.
• Main effect on CV system.
• Lower doses : Marked dilation of large veins, Decrease in central pressure, decrease in cardiac output.
• Higher doses : Arteriolar dilation, Fall in BP, Decrease in CO, Headache.

Question 6

How does NO cause muscle relaxation?

Answer 6

• NO activates guanylyl cyclase
• This causes GTP to be converted to cGMP
• Which acts at cGMP dependent protein kinases which causes the activation of MLC phosphatase .
• This dephosphorylates Myosin-LC-PO4 to Myosin-LC which causes muscle relaxation

Question 7

What effect does β-Blockers have on angina?

Answer 7

• Decrease oxygen consumption
• Slow the heart (-ve chronotropy)
• Depress the myocardium (-ive inotropy)
  Indications :
• Angina prophylaxis
• Unstable angina.

Question 8

What CCB are used in angina?

Answer 8

3 main classes:
* Phenylalkylamines - Verapamil
* Dihydropyridines - Nifedipine, amlodipine
* Benzothiazepines - Diltiazem

Question 9

What is the MOA of β-Blockers?

Answer 9

Blocking Ca2+ entering cell through preventing opening of voltage gated L-type Ca channel
Bind to α-1 subunit of cardiac L-type Ca-Channel but at diff sites.

Question 10

What are the pharmacological effects of β-Blockers?

Answer 10

• Main effect on cardiac & vascular smooth muscle, –| Ca2+ entry caused by depolarisation in these tissue.
• Verapamil is relatively cardio selective
• Nifedipine is relatively smooth muscle selective
• Diltiazem is intermediate .