Drug

Pharmacodynamics

Pharmacokinetics

Unwanted effects

Clinical Use

Bile acid-binding resins:

·        Cholestyramine

·        Colestipol

·        Bind to bile acids, preventing their reabsorption & increasing their excretion by 10-fold.

·        Large polymeric basic cation exchange resins, insoluble & not absorbed.

·        Constipation

·        Nausea & vomiting

·        Steatorrhoea

·        Bloating sensation

Impair absorption of:

·        Digoxin

·        Warfarin

·        Thiazides

·        Tetracyclines

·        Pravastatin

·        Fluvastatin

·        The resins are the only drugs that eliminate cholesterol from the body.

·        Cholesterol lowering effect can be enhanced if they are used in combination with an HMG-CoA reductase inhibitor.

Nicotinic acid

·        Inhibit hepatic production of VLDL, resulting in reduced plasma levels of VLDL & LDL.

·        Increasing VLDL clearance by the LPL pathway.

·        These actions lower plasma triglycerides by 20-80% depending on the dose.

·         

·        Intense cutaneous flush & pruritus involving face & upper part of body.

·        Gastrointestinal disturbances: vomiting, diarrhea, dyspepsia.

·        Jaundice

·        Hyperglycaemia & abnormal glucose tolerance

·        Hyperuricaemia

·        Cardiac arrhymia & toxic ambiyopia with blurring of distant vision (rare)

Contraindicated in patients with:

·        Hepatic disease

·        Diabetes mellitus

·        Gout

·         

Fibric acid drugs:

·        Gemfibrozil

·        Fenofibrate

·        Bezafibrate

·        Stimulate activity of lipoprotein lipase.

·        Activate receptor-mediated pathway for LDL uptake so that more cholesterol is cleared from plasma.

·        Lower plasma triglycerides & cholesterol.

·         

·        Flu-like symptoms of myalgia

·        Increased incidence of gallstones & cancer deaths.

Drug interaction:

·        Oral hypoglycaemics

·        Coumarin anti-coagulants

·         

HMG CoA reductase inhibitors:

·        Simvastatin

·        Pravastatin

·        Lovastatin

·        Fluvastatin

(arranged in decreasing order of potency)

·        Inhibits HMG CoA reductase, the enzyme mediating the first committed step in cholesterol synthesis.

·        Cause up-regulation of LDL receptors, leading to increased catabolism of LDL & liver extraction of LDL.

·        High-first pass extraction by liver.

·        Absorbed drug is excreted in bile, with 5-20% excreted in the urine.

·        Increase in plasma creatine kinase activity.

·        Lenticular opacities.

Contraindicated in:

·        Pregnant mothers

·        Children

·        Patients with liver disease

·        Useful when taken alone or with bile acid-binding resins or nicotinic acid to treat elevated levels of LDL.

·        Should be preferably given in the evening so that their effects coincide with the pattern of cholesterol biosynthesis.

Probucol

·        Inhibition of cholesterol synthesis

·        Enhancement of cholesterol transport from periphery to liver.

·        A lipophilic drug which distributes into adipose tissue & persists for a long time.

·        Cardiac abnormalities: QT prolongation.

·        Thrombocytopenia

·        Myopathies

·        Neuropathy

·        Hyperuricaemia

·        Hyperglycaemia

·        Effective in reducing atherogenesis in patients with homozygous familial hypercholestrolaemia.

·        Avoided in patients who are on drugs that cause QT prolongation: digitalis, quinidine, sotalol & erythromycin.