U01.07.062 Nitrates

Mechanism of Action

Nitrates work by inducing vasodilation through the following mechanism:

Nitric Oxide (NO) Release: They increase the availability of nitric oxide (NO) in vascular smooth muscle.
cGMP Pathway: Nitric oxide stimulates the production of cyclic guanosine monophosphate (cGMP), which leads to smooth muscle relaxation.
Effect on Vascular System: Nitrates dilate veins more than arteries, leading to a decrease in venous return (preload).

Nitrates are commonly used in the management of the following conditions:

Angina: They reduce myocardial oxygen demand by decreasing preload.
Acute Coronary Syndrome: They help alleviate chest pain and improve coronary blood flow.
Pulmonary Edema: They reduce pulmonary congestion by decreasing preload.

While nitrates are effective, they can cause the following adverse effects:

Reflex Tachycardia: A compensatory increase in heart rate due to reduced preload. This can be mitigated by using β-blockers.
Hypotension: Caused by the vasodilation effect.
Flushing and Headache: Common side effects due to vasodilation.
“Monday Disease”: Seen in industrial exposure where tolerance to vasodilatory effects develops during the work week, and upon reexposure after the weekend, symptoms like tachycardia, dizziness, and headache may occur.

Nitrates are contraindicated in the following conditions:

Right Ventricular Infarction: Nitrates may worsen hypotension.
Hypertrophic Cardiomyopathy: Nitrates can exacerbate left ventricular outflow obstruction.
Concurrent PDE-5 Inhibitor Use: Combining nitrates with drugs like sildenafil (used for erectile dysfunction) can lead to severe hypotension.

Drug	Mechanism	Clinical Use	Adverse Effects	Contraindications
Nitroglycerin	Releases NO, increases cGMP, causes vasodilation	Angina, acute coronary syndrome, pulmonary edema	Reflex tachycardia, hypotension, flushing, headache, “Monday disease”	Right ventricular infarction, hypertrophic cardiomyopathy, PDE-5 inhibitors
Isosorbide Dinitrate	Same as nitroglycerin	Same as nitroglycerin	Same as nitroglycerin	Same as nitroglycerin
Isosorbide Mononitrate	Same as nitroglycerin	Same as nitroglycerin	Same as nitroglycerin	Same as nitroglycerin

Mechanism: Nitrates increase NO in vascular smooth muscle, increasing cGMP and causing smooth muscle relaxation.
Primary Effect: Dilate veins more than arteries, decreasing preload.
Clinical Use: Primarily used in angina, acute coronary syndrome, and pulmonary edema.
Adverse Effects: Include reflex tachycardia, hypotension, and headaches. “Monday disease” is specific to industrial exposure.
Contraindications: Avoid use in right ventricular infarction, hypertrophic cardiomyopathy, and with PDE-5 inhibitors.