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DRUGS WHICH LOWER SERUM CHOLESTEROL

A variety of agents to choose from for the hypercholesterolaemic ~ati~nt . Diet is the treatment of choice for hypercholesterolaemia and drugs are an adjunct for those m v.:hlc~ diet do~s not work. The essence of drug intervention is a lowering of serum cholesterol reflecting a lowering oflow density hpoprotel~ (LDL). ~.Sitosterollowers cholesterol apparently by competitive inhibition of cholesterol absorption and may provide a 10·15 %

cholesterol (and LDL) drop. Side effects are usually limited to gastrointestinal disorders. .., Nicotinic acid probably limits the availability of free fatty acids used in hepatic synthesis of very low density h~protel~ (VLDL) the immediate precursor of LDL. In the Coronary Drug Project nicotinic acid reduced cholesterol by 10% ~d tnglycend~ by 26 %. Non-fatal infarctions were reduced but overall mortality was unaffected. Side effects are usually flushmg, .para~thesla or pruritus; but may be gastrointestinaLintolerance, arrhythmias, liver dysfunction, glucose intolerance or hyperuncaemla.

D-thyroxine (with 10% of the metabolic effect of L-thyroxine) increases cholesterol synthesis and its conversion to bile acids with a consequent drop in LDL without significant effect on VLDL. Cholesterol and LDL can be reduced by 20 % but an increase in total mortality in those at high risk stopped the use of this drug in the Coronary Drug Project. Clofibrate has been used extensively for over 10 years. Its action is probably to inhibit hepatic synthesis of triglycerides and/ or VLDL (though there may be some inhibition of cholesterol synthesis too). In fact clofibrate may cause cholesterol levels to rise in some with hypertriglyceridaemia. There have been several primary and secondary prevention trials of ischaemic heart disease using clofibrate, but the effect on cardiac morbidity and mortality have not been conclusive and there has not always been a correlation between cholesterol reduction and cardiovascular benefit. In the Coronary Drug Project cholesterol levels were reduced by 6 % While triglyceride levels fell 21 %. There was an increase in cardiovascular morbidity ~nd a 2-fold increase in the incidence of gallstones. Cholestyramine is an anion exchange resin which binds bile acids and prevents cholesterol reabsorption. It may lower cholesterol levels by 50 % and LDL by 27-40 %. No effect on triglycerides is seen. Cholesterol is removed from tissue stores (as seen by reduction of xanthomas) and substantial regression of atheromatous vascular lesions has been seen in animals. A 7 -year, multicentre trial is in progress. Colestipol is also a cholesterol binding resin. which can produce a 2 I % drop in cholesterol. In I controlled trial mortality due to heart disease was reduced but total mortality was affected only in men under SO, not in women. The adverse effects of both resins is usually gastrointestinal, especially constipation. Probucol is a recent addition which may reduce cholesterol levels by 12 % beyond that produced by diet alone (total drop 26 %). Again gastrointestinal disorders are the main side effect. In the treatment of hyper cholesterolaemia, laboratory measurements must be reliable. An optimal serum cholesterol range to aim for might be I 70-240mg/ dl, if any effect is to be seen in the retardation of atherosclerosis. The role of high density lipoprotein (HDL) should also be taken into account since it appears inversely related to atherosclerosis, and may in fact be the body's scavenger removing cholesterol from the periphery and returning it to the liver.

'The degree of uncertainty in this area of therapeutics, on critical reflection, is not really much greater than in many other areas of drug use. For the high risk patient there are currently available a variety of agents approved for lowering cholesterol which are reasonably effective and safe for long-term use;'

Martz. S.L.: American Heart Journal 97: 389 (Mar 1979)

16 INPHARMA 10 Mar 1979 0156-2703/79/0310-0016 $00.50/0 CADIS Press