Pharm 101: Glycerol trinitrate (GTN)

Class

Vasodilator

Pharmacodynamics

• Causes release of NO in vascular smooth muscle, which increases cGMP causing smooth muscle relaxation and vasodilation
• Affects arteries and veins, veins first / at lower concentrations
  • At lower doses, venodilation leads to decreased preload and stroke volume
  • At higher doses, arterial dilation leads to reduced blood pressure, which reduces CO and myocardial oxygen demand. Also causes dilation of coronary arteries
• Decreases LV volume, therefore decreases LV wall tension and subsequent myocardial oxygen demand
• Also decreases platelet aggregation (clinically insignificant)

Pharmacokinetics

• Bioavailability 10-20%
• Half life 2-8 mins
• Liver metabolism to 1,2-dinitro derivative (significant vasodilator), excreted by kidney
• Sublingual route, onset in 1-3 minutes, duration of action 15-30 mins
• Tachyphlaxis occurs with continuous use due to a decrease in tissue sulfhydryl groups:
  • Smooth muscle develops tolerance to effects, especially with continuous IV infusion or long acting preparation
  • “Drug-free” interval of 8 hours between doses may reduce this

Clinical uses

• Angina
• Acute coronary syndrome
• Hypertensive emergencies
• APO
• Aortic dissection (with beta-blockade)

Adverse effects

• Headache
• Postural hypotension
• Tachycardia
• Salt and water retention with longer acting nitrates

Precautions/contraindications

• Hypotension
• Inferior and posterior MI / RV infarct
• Fixed cardiac output e.g. aortic stenosis, tamponade
• Significant tachycardia or bradycardia

Further Reading

• Nickson C. Severe heart failure management