Statins

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Statins

Drugs in class

• simvastatin

• pravastatin

• atorvastatin

Mechanism of Action

• Competitive HMG-CoA reductase inhibitors

• lead to reduced cytoplasmic levels of cholesterol in hepatocytes

• hepatocytes increase expression of LDL receptors

• increased uptake LDL → reduced plasma LDL levels

• little effect of triglycerides, HDL

Side effects

• nausea

• flatulence

• fatigue

• insomnia

• rash

• reversible myositis / rhabdomyolysis

• hepatitis

• angioedema

Contra-indications

• alcoholics

• Chronic Liver Disease

• Pregnancy

Interactions

• efficacy increased by pairing with anion exchange resin

Lipid lowering drugs – the statins

The statins (simvastain, pravastatin, and antorvastatin) act to lower low density lipoprotein (LDL) levels. Their use is indicated in cases were plasma cholesterol exceeds 5 mmol/l.

Action

They act by inhibiting HMGCoA reductase, the rate limiting step in cholesterol biosynthesis. The subsequent reduction in hepatocyte cholesterol content results in the increased expression of LDL receptors on the cell membrane. This results in increased uptake of cholesterol and hence leads to a reduction in plasma cholesterol.

Side effects

Mild side effects include: nausea, constipation, diarrhoea, flatulence, fatigue, insomnia, and rash. More severe side effects include: rhabdomyolysis (the potential for this is increased if used concurrently with a fibrate), hepatitis, and angioedema. Due to the potential for hepatic effects it is necessary to do LFTs prior to commencing treatment, and at intervals throughout the treatment. Contraindications include alcoholics, patients with active liver disease, and pregnant women.

Pharmacokinetics

The statins are well absorbed from the intestine and are then extracted by the liver. Simvastatin is a prodrug which is metabolised to b-hydroxy fatty acid, the active form, in the liver.

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