Nitroglycerin forms the free radical nitric oxide which has many beneficial properties in the presence of myocardial ischemia and is used in the treatment of angina.
Venodilation (predominant mechanism) results in decreased preload in turn reducing left ventricular pressure and left ventricular volume (decreases radius). Some arterial vasodilation from smooth muscle relaxation occurs as well increasing oxygen supply and reducing vasospasm. It is important to note that nitrates have never been proven in clinical trials improve survival or reduce the risk acute coronary syndromes.
Nitroglycerine is available as a sublingual tablet or spray for acute angina attacks on an as-needed basis. When an anginal spell occurs, one tablet/spray is used and relief should be noted within 1-3 minutes. If no relief is seen, a second tablet/spray can be taken and at this point (according to ACC/AHA guidelines) that patient should dial 911 as an acute coronary syndrome may be present. Long-acting nitrates are available in a pill form (isosorbide mononitrate and isosorbide dinitrate) and as a patch as well to prevent angina from occurring.
Significant headaches can occur and limit higher doses of nitrates. Hypotension is common, especially in patients who are “preload dependant” such as during right ventricular infarction. This hypotension can cause a reflex tachycardia which is not ideal since increased heart rate will increase oxygen demand. Tachyphylaxis occurs with nitrates (tolerance resulting in decreased efficacy) requiring drug free intervals for best results. For example, nitroglycerine patches must be applied in the morning and removed in the evening. When left on all day, tolerance quickly develops and the clinic benefits decrease significantly.
Phosphodiesterase inhibitors (sildenafil, vardenafil, tadalafil) used to treat erectile dysfunction enhance nitric oxide production and can cause potentially fatal hypotension when used in combination of nitrates. These two drugs should not be used together within 24 hours (sildenafil) or 48 hours (vardenafil, tadalafil) due to this interaction. Interestingly, phosphodiesterase inhibitors were initially being investigated for the treatment of stable angina when researchers noted the improvement of erectile dysfunction and thus redirected their efforts.