Drugs for coronary (ischaemic) heart disease

Question 1

Examples of nitrates

Answer 1

1. GTN (glyceryl trinitrate)

2. Sodium nitroprusside (SNP)

Question 2

PK of GTN

Answer 2

Onset of action

1. Sublingual: 1-5min
2. Transdermal: 10-30min

Duration of action

1. Sublingual: 10-30min
2. Transdermal: 7-10h

Question 3

MOA of GTN

Answer 3

1. Nitric oxide (NO) through nitrate → activation of guanylyl cyclase → ↑ cyclic guanosine monophosphate (cGMP) → activation of protein kinase G

• Increases Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity → ↓ intracellular calcium → ↓ recruitment of contractile units → vasodilation
• Increases myosin light chain phosphatase activity → ↓ phosphorylated myosin → smooth muscle relaxation → vasodilation

2. Anginal pain relief: ↓ preload through venous pooling → ↓ heart size → ↓ oxygen demand → ↓ pain

Question 4

Side effects of GTN

Answer 4

1. Hypotension
2. Reflex tachycardia
3. Headache (meningeal artery vasodilation)
4. Tolerance (becomes less active if used chronically – hence not use in chronic setting)

Question 5

GTN can be combined with what drugs for synergistic effects in angina pectoris

Answer 5

beta-blockers or CCB