Several medications and classes of medications may interfere with lipid metabolism: thiazide diuretics, ciclosporin, glucocorticoids, beta blockers, retinoic acid, antipsychotics), certain anticonvulsants and medications for HIV as well as interferons. Genetics
Genetic contributions are usually due to the additive effects of multiple genes ("polygenic"), though occasionally may be due to a single gene defect such as in the case of familial hypercholesterolaemia. In familial hypercholesterolemia, mutations may be present in the APOB gene (autosomal dominant), the autosomal recessive LDLRAP1 gene, autosomal dominant familial hypercholesterolemia (HCHOLA3) variant of the PCSK9 gene, or the LDL receptor gene. Familial hypercholesterolemia affects about one in 250 individuals. Diagnosis
Cholesterol is measured in milligrams per deciliter (mg/dL) of blood in the United States and some other countries. In the United Kingdom, most European countries and Canada, millimoles per liter of blood (mmol/L) is the measure.For healthy adults, the UK National Health Service recommends upper limits of total cholesterol of 5 mmol/L, and low-density lipoprotein cholesterol (LDL) of 3 mmol/L.
Its chemical name is 3,4-dihydroxy-4-methyl-5-nitrobenzophenone. Synthesis
A synthesis of tolcapone proposed in 2008, begins with a Grignard reaction between a benzaldehyde derivative and p-tolyl magnesium bromide. The alcohol thus produced is then converted to a ketone using sodium t-butoxide. The benzyl protecting group is removed by palladium-catalyzed hydrogenation in the presence of ammonium formate. A nitro group is introduced at the 5-position adjacent to the hydroxyl group unmasked in the cleavage of the benzyl ether. The synthesis ends with cleavage of the methoxy group using aluminum chloride to yield the product alcohol. History
Tolcapone was introduced into the European market in August 1997, and subsequently into the United States market in March 1998. Liver toxicity was reported in four people who were administered tolcapone, three people died due to complications. Consequentially, the marketing authorization of tolcapone was suspended from December, 1998 until August, 2004 when it was lifted. In November 1998, the company that manufactured tolcapone voluntarily  removed the drug from the market. The authorization was then renewed in August 2009.As a result of reported complications, the U.S. Food and Drug Administration (FDA) issued a black box warning for tolcapone and label revisions that aimed to regulate the monitoring of those prescribed tolcapone for Parkinsons disease in November 1998. A number of other countries withdrew tolcapone from the market; Australia in February 1999, Bulgaria in April 1999, Iceland in November 1998, Lithuania in December 1998.