Topic: Antihypertensive, Antidiuretics, General and cardiac vasodilators
Question: Describe the mechanism of action, therapeutic uses and adverse effects of Nitrates. Add a note on Prinzmetal Angina.
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Mechanism of Action:
– Nitrates are converted to nitric oxide (NO) which causes vascular smooth muscle relaxation and vasodilation.
– NO activates guanylyl cyclase which converts GTP to cGMP. cGMP causes dephosphorylation of myosin light chains which results in smooth muscle relaxation.
– Vasodilation decreases preload and afterload, reducing cardiac workload and oxygen demand.
Therapeutic Uses:
– Angina Pectoris – Used to prevent and relieve angina attacks by decreasing myocardial oxygen demand. e.g. nitroglycerin, isosorbide mononitrate.
– Heart Failure – Used along with other medications to improve exercise tolerance by reducing preload and afterload. e.g. isosorbide dinitrate.
– Acute Myocardial Infarction – IV nitroglycerin used to reduce preload and ventricular filling pressures. Decreases ischemia and improves outcomes.
– Hypertension – Used as add-on therapy for persistent hypertension unresponsive to first line agents.
Adverse Effects:
– Headache – Due to vasodilation of cerebral vessels. Tolerance develops over time.
– Hypotension – Due to excessive vasodilation and reduced preload. Risk of syncope.
– Tachycardia – Reflex sympathetic response to vasodilation.
– Flushing – Vasodilation of skin vessels causes cutaneous flushing.
– Tolerance – Tolerance develops after 24-48 hrs of continuous use requiring dose adjustments.
Prinzmetal Angina:
– Caused by coronary vasospasm leading to reduced blood flow rather than atherosclerotic plaque obstruction.
– Chest pain occurs at rest rather than on exertion. Diurnal pattern observed.
– ST segment elevation seen on ECG during attacks rather than ST depression.
– Nitrates are used for both prevention and relief of attacks. They dilate coronary vessels and prevent vasospasm.
