Factors
Myocardial oxygen demand
(governed by cardiac work)

- preload
- afterload
- myocardial contractility
- heart rate

Myocardial oxygen supply
(governed by blood supply to heart muscle)
- coronary artery narrowing / dilatation
- oxygen carrying capacity of blood, I.e., haemoglobin content

 

Angina Pectoris
Chest pain or discomfort due to transient myocardial ischaemia

Subsets
- Stable angina of effort
- Unstable angina pectoris
- Variant or Prinzmetal’s angina
- Mixed angina

Nitroglycerin

- Organic nitrate
- Vasodilator
- Useful in angina pectoris

 

Actions
Dilatation of arterial and venous circulation

Systemic Venodilation
- Decreases venous return, hence reduces preload
Arteriolar dilatation
- Systemic arteriolar dilatation, reduces peripheral resistance, hence reduces afterload- Coronary vasodilation, increases myocardial oxygen supply

 

Thus, nitroglycerin :

Reduces myocardial oxygen requirements
- Reduced preload
- Reduced afterload

Increases myocardial oxygen supply
- Coronary vasodilation of large epicardial vessels; does not affect autoregulation

 

Pharmacokinetics

- Readily absorbed from oral mucosa, but rapidly metabolised, hence only has fleeting durration of action
- Also absorbed from G.I.tract, but due to extensive first pass metabolism, higher doses ( > 6.5 mg) must be administered
- Absorbed through skin from ointment preparations
- Metabolised by hydrolysis into dinitrates and the mononitrate, which is the main urinary metabolite

 

Indications

Prophylaxis and management of all types of angina pectoris

 

Sublingual route

- Rapid onset and short duration of action, hence useful to relieve acute attacks
- Useful as a single form of treatment if attacks are infrequent
- Effective for immediate prophylaxis if frequency of attacks is predictable, e.g., may be administered prior to exercise

 

Buccal route

- Drug is placed under the upper lip
- Produces rapid action (in 2-5 minutes) but of short duration (up to 5 hours)

Skin ointment / patches

- Applied on skin, transdermal absorption
- Absorption may vary depending upon site of application
- Action lasts for about 6 hours

 

Oral route

- Needs to be administered in relatively higher doses to overcome hepatic first pass metabolism
- Suitable for the long term prophylaxis of angina pectoris

 

Adverse Effects

- Due to vasodilation
- flushing, dizziness, headache, tachycardia
- Drug tolerance (tachyphylaxis)

 

Salient Features

- Nitroglycerin has been the mainstay of angina treatment for years
- Decreases preload and afterload, hence reducing myocardial oxygen requirement
- Dilates large coronary vessels, redistributing blood to ischaemic myocardium
- Useful in all types of angina pectoris for prophylaxis or for managing acute attacks
- May be administered by sublingual, buccal, transdermal or oral route
- Compatible with other drugs, e.g., beta blockers and calcium antagonists