Nitroglycerin (medication)

Nitroglycerin can cause severe hypotension, reflex tachycardia, and severe headaches that necessitate analgesic intervention for pain relief, the painful nature of which can have a marked negative effect on patient compliance. Nitroglycerin also can cause severe hypotension, circulatory collapse, and death if used together with vasodilator drugs that are used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil. Nitroglycerin transdermal patches should be removed before defibrillation due to the risk of explosion or burns, but investigations have concluded that nitroglycerin patch explosions during defibrillation were due to the breakdown voltage of the metal mesh in some patches. ==Mechanism of action==

Nitroglycerin is a prodrug which must be denitrated, with the nitrite anion or a related species further reduced to produce the active metabolite nitric oxide (NO). Organic nitrates that undergo these two steps within the body are called nitrovasodilators, and the denitration and reduction occur via a variety of mechanisms. The mechanism by which such nitrates produce NO is widely disputed. It has been postulated that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of nitroglycerin bioactivation. The NO produced by this process is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Among other roles, cGMP serves as a substrate for a cGMP-dependent protein kinase that activates myosin light chain phosphatase. Thus, production of NO from exogenous sources such as nitroglycerin increases the level of cGMP within the cell, and stimulates dephosphorylation of myosin, which initiates relaxation of smooth muscle cells in blood vessels. ==History==

It was known almost from the time of the first synthesis of nitroglycerin by Ascanio Sobrero in 1846 that handling and tasting of nitroglycerin could cause sudden intense headaches, which suggested a vasodilation effect. Constantine Hering developed a form of nitroglycerin in 1847 and advocated for its dosing as a treatment of a number of diseases; however, its use as a specific treatment for blood pressure and chest pain was not among these. This is primarily due to his deep rooted focus in homeopathy. Following Thomas Brunton's discovery that amyl nitrite could be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to alleviate angina and reduce blood pressure, and showed that the accompanying headaches occurred as a result of overdose. Murrell began treating patients with small doses of nitroglycerin in 1878, and the substance was widely adopted after he published his results in The Lancet in 1879. The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive. Overdoses may generate methemoglobinemia. == Society and culture ==

Brand names In the United States, the tablet form of nitroglycerin is marketed (brand name Nitrostat) by Viatris after Upjohn was spun off from Pfizer. Nitroglycerin used for treatment of angina has multiple brand names depending on the mode of administration, such as Minitran, Nitro-Dur, Nitrolingual, Nitromist, and Nitro-Bid. The brand name Nitro-bid is an ointment form of Nitroglycerin that is applied twice daily to the skin, hence the name, where "BID" indicates "twice daily" (B.I.D). == References ==