Mechanism of Action
The antianginal effect of nitroglycerin (Nitroglycerinum) is due to a complex set of hemodynamic alterations. The drug induces systemic vasodilation, leading to the following physiological changes:
- Decreased preload: Venous dilation reduces venous return (preload) to the heart.
- Decreased afterload: Arterial dilation decreases total peripheral resistance (afterload).
- Improved coronary blood flow: Blood is redistributed in favor of ischemic subendocardial layers. Furthermore, by decreasing ventricular wall tension, extravascular compression of subendocardial vessels is reduced.
Clinical note: The drug does not slow the heart rate (it does not cause bradycardia) to reduce oxygen demand; on the contrary, it may provoke reflex tachycardia.
Pharmacokinetics and Routes of Administration
Chemically glyceryl trinitrate (nitroglycerol), it is a colorless, oily liquid with high lipophilicity (readily soluble in alcohol, ether, and chloroform). This property dictates its various routes of administration:
- Sublingual: Rapidly absorbed through the oral mucosa, bypassing the portal circulation. The latency period is 1–2 minutes, duration of action is about 30 minutes, and the half-life ($t_{1/2}$) is very short (1–4 minutes).
- Oral: Subject to a marked first-pass effect. After intestinal absorption, the drug enters the liver via the portal vein, where over 90% is eliminated. Therefore, oral (per os) doses must be significantly higher than sublingual doses (e.g., 6.4 mg vs. 0.5 mg).
- Transdermal: Ointments and transdermal patches provide systemic resorption. The lipophilic compound penetrates the skin directly into systemic circulation, avoiding presystemic metabolism. Patches maintain a constant plasma concentration for up to 12 hours.
Indications
Nitroglycerin is versatile, used for both acute termination and prophylaxis of ischemic events.
- Angina pectoris: Immediate pain relief (short-acting formulations) and prevention of attacks. Pearl: Due to circadian rhythms, sublingual nitroglycerin is often more effective at relieving angina in the morning compared to the afternoon.
- Myocardial infarction: Administered via continuous intravenous infusion.
- Acute heart failure: Used as a potent vasodilator to reduce cardiac filling pressures.
Adverse Effects and Tolerance
Adverse reactions directly stem from the drug's primary vasodilatory properties:
- Central nervous system: Severe throbbing headache due to meningeal vessel dilation, and dizziness.
- Cardiovascular system: Orthostatic hypotension (sharp drop in blood pressure with postural changes) and reflex tachycardia mediated by baroreceptors in response to hypotension.
Tolerance phenomenon (Tachyphylaxis): The risk of tolerance is low with short-acting forms, but high with sustained-release formulations. To overcome tolerance and restore receptor sensitivity, patients must maintain a daily nitrate-free interval (10–12 hours).
Formulations
For immediate attack termination, sublingual forms are used: tablets (0.5 mg), capsules with a 1% oil solution (0.5 mg and 1 mg), aerosols/sprays (0.4 mg per actuation), or a 1% alcoholic solution (1–2 drops on a sugar cube). For continuous intravenous infusion in acute settings, a 1% ampoule concentrate is used.