<unk>  also known as glyceryl trinitrate (GTN), is a medication used for heart failure, high blood pressure, anal fissures, painful periods, and to treat and prevent chest pain caused by decreased blood flow to the heart (angina) or due to the recreational use of cocaine. This includes chest pain from a heart attack. It is taken by mouth, under the tongue, applied to the skin, or by injection into a vein. Common side effects include headache and low blood pressure. The low blood pressure can be severe. It is unclear if use in pregnancy is safe for the baby. It should not be used together with medications within the sildenafil (PDE5 inhibitor) family due to the risk of low blood pressure.<unk> is in the nitrate family of medications. While it is not entirely clear how it works, it is believed to function by dilating blood vessels.<unk> was written about as early as 1846 and came into medical use in 1878. It is on the World Health Organization's List of Essential Medicines. The drug<unk> (GTN) is a dilute form of the same chemical used as the explosive,<unk>  Dilution makes it non-explosive. In 2019, it was the 184th most commonly prescribed medication in the United States, with more than 3million prescriptions. Medical uses Three different forms of<unk>  intravenous, sublingual spray, and the<unk> patch.<unk> is used for the treatment of angina, acute myocardial infarction, severe hypertension, and acute coronary artery spasms. It may be administered intravenously, as a sublingual spray, or as a patch applied to the skin. Angina GTN is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of glyceryl trinitrate, providing 24-hour release. However, the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus, glyceryl trinitrate works best when used only in short-term, pulse dosing. Glyceryl trinitrate is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose. It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack. Other uses Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair. GTN is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment. GTN has been used to decrease pain associated with dysmenorrhea. GTN was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada. Tolerance After long-term use for chronic conditions, nitrate tolerance—tolerance to agents such as GTN— may develop in a patient, reducing its effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of GTN and/or the need for higher doses of the drug to achieve the same effects, and was first described soon after the introduction of GTN in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis. These include endothelial and autonomic dysfunction. The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including: # plasma volume expansion # impaired transformation of GTN into NO or related species # counteraction of GTN vasodilation by neurohormonal activation # oxidative stress Recent evidence suggests that deleterious GTN-induced production of oxygen free radicals might induce a number of abnormalities, include those described above, so that the oxidative stress hypothesis might represent a unifying principle.
Nitroglycerin 
Sodium nitroprusside
Amrinone
Papaverine
Nitroxinil
Adenosine
Nadolol
Atenolol