Drug Breakdown: Atorvastatin

Dr Sharon Rees @reesprescribe

Day 1, #atorvastatin: In the 1970s, a Japanese scientist, Akira Endo reviewed thousands of fungal ‘broths’, ultimately discovering Penicillium citrinum, which causes the blue-green mould on citrus fruit. An active metabolite ‘compactin’ was found. ‘Compactin’ was found to be structurally similar to HMG-CoA reductase, one of the enzymes needed for liver cholesterol synthesis. Compactin was discovered to be a competitive inhibitor of this enzyme, which controls the rate of cholesterol synthesis #prescribing

Dr Sharon Rees @reesprescribe

Day 2: Lovastatin was the first commercial statin licensed c.1987 (FDA), followed by simvastatin (semi-synthetic) and synthetic versions, such as #atorvastatin. Indications are primary and secondary prevention of cardiovascular events and primary and familial hypercholesterolaemia. All statins reduce triglycerides. #atorvastatin is 1st line for primary (20mg) and secondary (80mg) hypercholesterolaemia, despite primary dose unlicensed & secondary prev being an unlicensed indication. Nonetheless, there is grade A evidence for each #prescribing

Dr Sharon Rees @reesprescribe

Day 3: Mechanism of action: Cholesterol is made in the liver for use in bile salts, fat soluble vitamins, transport to cells etc. A key step is the conversion of HMG CoA to mevalonate by HMG CoA reductase. Statins such as #atorvastatin all inhibit this enzyme, halting cholesterol production. Sensing the reduced cholesterol level, liver cells up-regulate their cell surface low-density lipoprotein (LDL) receptors, extracting more LDL from blood. This lowers circulating cholesterol, ultimately helping to decrease atheroma formation and lower risk of heart attack and stroke #prescribing