He began treating his patients with small diluted doses of nitroglycerin in 1878, and this treatment was soon adopted into widespread use after Murrell published his results in the journal The Lancet in 1879. A few months before his death in 1896, Alfred Nobel was prescribed nitroglycerin for this heart condition, writing to a friend: "Isnt it the irony of fate that I have been prescribed nitro-glycerin, to be taken internally! They call it Trinitrin, so as not to scare the chemist and the public." The medical establishment also used the name "glyceryl trinitrate" for the same reason. Wartime production rates
Large quantities of nitroglycerin were manufactured during World War I and World War II for use as military propellants and in military engineering work. During World War I, HM Factory, Gretna, the largest propellant factory in the United Kingdom, produced about 800 tonnes of cordite RDB per week. This amount required at least 336 tonnes of nitroglycerin per week (assuming no losses in production). The Royal Navy had its own factory at the Royal Navy Cordite Factory, Holton Heath, in Dorset, England. A large cordite factory was also built in Canada during World War I. The Canadian Explosives Limited cordite factory at Nobel, Ontario, was designed to produce 1,500,000 lb (680 t) of cordite per month, requiring about 286 tonnes of nitroglycerin per month. Instability and desensitization
In its undiluted form, nitroglycerin is a contact explosive, with physical shock causing it to explode.
Inclisiran, sold under the brand name Leqvio, is a medication for the treatment of people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk-equivalents, and heterozygous familial hypercholesterolemia (HeFH). It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.Inclisiran was approved for use in the European Union in December 2020. In August 2021, it received NICE approval for use by the National Health Service in the UK. In December 2021, it was approved for medical use in the United States. Medical uses
In the European Union, inclisiran is indicated in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in people unable to reach LDL-C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in people who are statin-intolerant, or for whom a statin is contraindicated.In the United States, it is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low- density lipoprotein cholesterol (LDL-C). Discovery and mechanism of action
Inclisiran is a small interfering RNA that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein termed proprotein convertase subtilisin/kexin type 9 (PCSK9).