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In this essay we will discuss about the drugs used for lowering LDL cholesterol and triglycerides.
1. Statins (HMG-CoA Reductase Inhibitors):
Lovastatin, pravastatin, simvastatin, fluvastatin, atrovastatin and rosuvastatin are the statins having similar mechanism of action and side effects. Statins act by inhibiting cellular cholesterol production, depleting the intracellular pool of cholesterol, and in consequence increasing the expression of LDL receptors. The increased number of receptors promotes LDL uptake from the bloodstream, which can result in drop of LDL cholesterol levels by 20-60%, depending on the drug and dosage.
Statins are the drugs of choice for lowering LDL cholesterol and are generally used in combination with a fibrate or niacin, which lowers triglycerides and raises HDL cholesterol. They are given at night because cholesterol synthesis is greatest at that time. Side effects occur infrequently (approximately 5% of patients) and most commonly include gastrointestinal discomfort and myalgia’s. Liver function tests should be carried out for the first year of the treatment and substitution of another statin may be better tolerated in presence of liver disturbances.
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Myopathy is an infrequent side effect but has been reported more often when statins are combined with cycloserine, fibrate, niacin or erythromycin. Statins are contraindicated in active liver disease, pregnancy and breast-feeding.
2. Bile Acid Binding Resins:
Cholestyramine and colestipol are anion exchange resins, which combine with bile acids and cholesterol in the gut and prevent their absorption and increase their fecal excretion. This drain on the bile acid stimulates hepatic synthesis of bile acid from cholesterol. The depletion of hepatic pool of cholesterol results in the production of more LDL receptors on the hepatocytes which increases LDL cholesterol uptake from the circulation with an effective reduction in plasma LDL cholesterol.
Resins can cause rise of triglycerides and therefore they should not be used as mono-therapy in patients with triglycerides above 250 mg/dl (normal triglycerides are less than 150 mg/dl). Resins can be combined with niacin or statins in patients with severe elevations of LDL cholesterol when greater reductions of LDL are required.
Colesevelam is another bile acid-binding drug, which causes less gastrointestinal side effects and interactions with other drugs. Resins interfere with the absorption of fat-soluble vitamins. Side effects are mainly GIT disorders (bloating, hard stools, and constipation) and increased bleeding tendency due to hypo-prothrombinaemia associated with vitamin K deficiency.
3. Cholesterol Absorption Inhibitor:
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Ezetimibe blocks the absorption of cholesterol at the level of enterocyte. LDL cholesterol levels can decrease by approximately 20%. It can be used alone or in combination with statins. Side effects include diarrhea. Liver function tests are required because of the additional use of statins.
4. Nicotinic Acid (Niacin):
Niacin can lower triglycerides, raise HDL, and lower LDL in higher doses. It is particularly useful in combined hyperlipidemia with low levels of HDL. The use of nicotinic acid is limited by its side effects, especially vasodilatation. Nausea and fatigue are early signs of toxicity. It may rarely cause severe liver toxicity, angioedema, bronchospasm and anaphylaxis. Diabetic patients should monitor blood sugar closely.
Niacin should be avoided in patients with a history of gout, active peptic ulcer and liver disease. Acipimox is a synthetic analogue of nicotinic acid and is less liable to produce flushing and glucose intolerance, but is also less effective as a lipid lowering drugs.
5. Fibrates:
Gemfibrozil and fenofibrate are broad spectrum lipid lowering fibrates. Their main action is to decrease serum triglycerides but they also tend to reduce LDL cholesterol and raise HDL cholesterol in patients with hypertriglyceridemia. Side effects are mainly gastrointestinal disorders. A myositis syndrome (muscle pain) has been reported in patients with poor renal function. They are contraindicated in alcoholism, hepatic and renal impairment, biliary disease, pregnancy and breastfeeding.
