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Nolotil - Metazmizol

Nolotil - Generic name Metzmizol and also known as Analgin, Dipyrone, Novalgin.

Nolotil, Metamizol is a pyrazolone derivative with a strong analgesic, antipyretic and spasmolytic activity. Its antiphlogistic properties are less manifested. Compared to the narcotic analgesics, it does not suppress the respiratory center even in high doses, has no effect on intestinal peristalsis, does not induce constipation and does not lead to habit-forming and addiction. The mechanism of its analgesic action is associated with the inhibition of the formation of allgogenic substances, stimulation of non-piate antinociceptive system and inhibition of prostaglandin synthesis.

It is quickly and completely absorbed in the digestive tract, metabolized in the liver to various metabolites, and only 3% of the administered dose is excreted unchanged through the kidneys. Its half-time in the blood is about 2.7 h.

Acute and chronic pain accompanying the following diseases: rheumatoid arthritis, headache, toothache,traumas, dysmenorrhea and surgical intervention, strong pain associated with smooth muscles spasms of the gastrointestinal tract, biliary ducts and urogenical system, and for reducing the body temperature in febrile states.

The main side effects are due to the development of hypersensitivity to the drug, the most important being shock and changes in the blood count (agranulocytosis, leukopenia and thrombocytopenia). Transitory disfunctions accompanied by oliguria, polyuria, proteinuria and intestinal nephritis can originate in patients suffering from renal diseases or after the administration of high doses. Urticarial rashes and itching on the skin, mucosa and conjuctiva can rarely be observed. Asthmatic paroxysms can be provoked in patients suffering from asthma.

Metamizole sodium ( [(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl) methylamino] methanesulfonate ) is a non-steroidal anti-inflammatory drug ( NSAID ), commonly used in the past as a powerful painkiller and fever reducer. It is better known under the names Dipyrone, Analgin, and Novalgin.

Metamizole was first synthesized by the German company Hoechst AG in 1920, and its mass production started in 1922. It remained freely available worldwide until 1970s, when it was discovered that the drug carries a small risk of causing agranulocytosis - very dangerous and potentially fatal condition. Recent studies estimate that the incidence rate of metamizole-induced agranulocytosis is between 0.2 and 2 cases per million person days of use, with approximately 7% of all cases fatal ( provided that all patients have access to urgent medical care ). In other words, one should expect 50 to 500 deaths annually due to metamizole in a country of 300 million, assuming that every citizen takes the drug once a month. This is not a very high rate, especially compared to other drugs - for example, prescription drug clozapine is known to be at least 50 times more likely to trigger agranulocytosis.

However, at the time the risk was assumed to be much greater [1] and, as such, excessive for an over-the-counter analgesic, especially considering the existence of safer alternatives ( aspirin, paracetamol, and ibuprofen ). Metamizole was banned in Sweden in 1974, in United States in 1979; more than 30 countries, including Japan, Australia, and most of European Union, have followed suit. In these countries, metamizole is still occasionally used as a veterinary drug. Some Western pharmaceutical countries, notably Hoechst and Merck, continue to develop metamizole-containing drugs and market them in third-world countries, despite the fact that they can't sell them at home.

In the rest of the world ( esp. in Third World countries, Mexico, India, Brazil, Russia ) metamizole is still freely available over-the-counter and remains one of the most popular analgesics. For example, metamizole and metamizole-containing drugs account for 80% of OTC analgesic market in Russia, whereas ibuprofen (Advil), although much safer and more familiar to Westerners, only accounts for 2.5%.

Metamizole received brief period of attention by American media in 2001[2], when a Latino immigrant boy was admitted into Salt Lake City clinic with symtoms of agranulocytosis. It was discovered that the drug remained freely available in Latino shops and highly popular among Mexican immigrants, despite the ban.