Drugs

LIPID-LOWERING DRUGS

Dr. Arwa Mahmood Fuzi Alsarraf

Objectives

Describe the groups of lipid lowering drugs Describe the mode of action Their indication The clinical use

Indications

To prevent cardiovascular disease in all those at high risk of atherosclerosis,include Those who already have atherosclerotic disease Diabetics aged over 40 years. Abnormal lipid concentration Other risk factors (smoking, blood pressure, impaired glucose tolerance, male sex, age, premature menopause, ethnicity, obesity, triglyceride concentration, and a family history of premature cardiovascular disease). Those with a 10-year risk of cardiovascular disease of 20% or more stand to benefit from drug treatment.


Lowering the concentration of low-density lipoprotein (LDL) cholesterol and raising high-density lipoprotein (HDL) cholesterol slows the progression of atherosclerosis. Lipid-regulating drug treatment must be combined with Advice on diet and lifestyle measures, Lowering of raised blood pressure. Management of diabetes.

Classification

Statins Fibrates Ezetimibe Anion-exchange resins Nicotinic acid group Omega -3 fatty acid compounds

STATINS (HMG CoA) reductase inhibitors

(Atorvastatin, Fluvastatin, Pravastatin, Rosuvastatin, And Simvastatin) Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme a (HMG COA) reductase, an enzyme involved in cholesterol synthesis in the liver. More effective than other lipid-regulating drugs at lowering LDL-Cholesterol concentration but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration.

Indications

All patients with coronary heart disease (history of angina or acute myocardial infarction), occlusive arterial disease (peripheral vascular disease, non-haemorrhagic stroke, or transient ischaemic attacks). For all patients over 40 years with diabetes mellitus Prevention of cardiovascular disease in asymptomatic individuals at increased risk (10-year cardiovascular disease risk of 20% or more)

Caution

History of liver disease or with a high alcohol intake (should be avoided in active liver disease). Liver-function tests should be carried out before and within 1–3 months of starting treatment and thereafter at intervals of 6 months for 1 year Hypothyroidism should be managed adequately before starting treatment with a statin. Caution if there is risk for myopathy or rhabdomyolysisAvoided in porphyria

Contraindication

Active liver disease (or persistently abnormal liver function tests), In pregnancy (adequate contraception required during treatment and for 1 month afterwards) Breast-feeding

Side effects

Reversible myositis is a rare but significant side-effect. Headache Altered liver-function tests ( rarely, hepatitis) Paraesthesia Gastro-intestinal effects (abdominal pain, flatulence, constipation, diarrhoea, nausea and vomiting). Rash and hypersensitivity reactions (including angioedema and anaphylaxis) rarely

FLUVASTATINE (LESCOL(Hypercholesterolaemia or combined hyperlipidaemia, initially 20–40 mg daily in the evening, adjusted at intervals of at least 4 weeks; up to 80 mg daily Prevention of progression of coronary atherosclerosis, 40 mg daily in the eveningFollowing percutaneous coronary intervention, 80 mg daily

ROSUVASTATINE (CRESTOR( Initially 5–10 mg once daily increased if necessary at intervals of at least 4 weeks to 20 mg once daily, increased after further 4 weeks to 40 mg daily (only in severe hypercholesterolaemia with high cardiovascular risk and under specialist supervision) Elderly initially 5 mg once dailyPatient of asian origin, initially 5 mg once daily increased if necessary to max. 20 mg daily

SIMVASTATINE (ZOCOR( Primary hypercholesterolaemia, combined hyperlipidaemia, 10–20 mg daily at night, adjusted at intervals of at least 4 weeks; usual range 10–80 mg once daily at nightHomozygous familial hypercholesterolaemia, 40 mg daily at night or 80 mg daily in 3 divided doses (with largest dose at night)Prevention of cardiovascular events, initially 20–40 mg once daily at night, adjusted at intervals of at least 4 weeks; max. 80 mg once daily at night

FIBRATES

Caution
Fibrates can cause a myositis-like syndrome, especially if renal function is impaired. Combination of a fibrate with a statin increases the risk of muscle effects (especially rhabdomyolysis) -gemfibrozil and statins should not be used concomitantly. Monitoring of liver function and creatinine kinase should be considered

Contraindication

Severe hepatic impairment Renal impairment Hypoalbuminaemia Primary biliary cirrhosis Gall bladder disease Nephrotic syndrome Pregnancy Breast-feeding

Side effects

Gastro-intestinal disturbances Rash, pruritus less commonly headache, fatigue, dizziness, insomnia rarely Gallstones, hepatomegaly, cholestasis, hypoglycaemia, impotence, anaemia, leucopenia, thrombocytopenia, increased risk of bleeding, alopecia, photosensitivity reactions, raised serum creatinine (unrelated to renal impairment), and myotoxicity


Gemfibrazole (lopid(300 mg cap 600mg tab (0.9 – 1.2 gm/day) Indications Hyperlipidaemias of types IIa, II b, III, IV and V in patients who have not responded adequately to diet and other appropriate measures Side effects Gastro-intestinal disturbances Headache, fatigue, vertigo Eczema, rash less commonly Atrial fibrillation Rarely pancreatitis, appendicitis, disturbances in liver functin, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity

Anion-exchange resins

Cholestyramine , Colestipol Act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of cholesterol into bile acids; the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma Thus effectively reduce LDL-cholesterol but can aggravate hypertriglyceridaemia.

Caution

Interfere with the absorption of fat-soluble vitamins; supplements of vitamins A, D and K may be required when treatment is prolonged. Side effects Gastro-intestinal side-effects predominate. Constipation is common, diarrhoea, nausea, vomiting, and gastro-intestinal discomfort. Hypertriglyceridaemia may be aggravated. Increased bleeding tendency has been reported due to hypoprothrombinaemia associated with vitamin K deficiency.


Cholestyramine (4 g/sachet )Hyperlipidaemias, particularly type IIa, in patients who have not responded adequately to diet and other appropriate measures Pruritus associated with partial biliary obstruction and primary biliary cirrhosis Diarrhoeal disordersDose Lipid reduction 12–24 g daily in water, in single or up to 4 divided doses; up to 36 g daily

Ezetimibe

Caution
Hepatic impairment (avoid if moderate or severe( Pregnancy If ezetimibe is used in combination with a statin, there is an increased risk of rhabdomyolysis

Side effect

Gastro-intestinal disturbances Headache, fatigue, myalgia Rarely Arthralgia, hypersensitivity reactions including rash and angioedema, hepatitis Very rarely Pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis

NICOTINIC ACID(VIT B3)

Reduce perepherral fatty acid releaselowers both cholesterol and triglycerideincreases HDL-cholesterol.Indicated as adjunct to statin in dyslipidaemia or used alone if statin not tolerated Dose Initially 100–200 mg 3 times daily, gradually increased over 2–4 weeks to 1–2 g 3 times daily

Omega-3 fatty acid compounds

caution haemorrhagic disorders, anticoagulant treatment (bleeding time increased) hepatic impairment. pregnancy Side effects Gastro-intestinal disturbances Less commonly taste disturbances, dizziness, and hypersensitivity reactions Rarely hepatic disorders, headache, hyperglycaemia, acne, and rash