Lipid lowering agentsBy: Dr Israa Omar

MBBS, MRCP, MSc pharmacology

Reduces plasma concentration of LDL-Cholestrol by more than 30%.

Also cause a small reduction on plasma TGA and a small increase in plasma HDL

(statins)include simvastatin, pravastatin, atorvastatin.

REDUCE THE RISK OF CORONARY RTERY DISEASE BY 42%

HMG-CoA reductase inhibitors

Suppress HMG-COA reductase in the liver and therefore depress the production of cholesterol, which leads to increase synthesis of LDL receptors .

As a result, the clearance of LDL is enhanced

MOA

To treat patient with hyperlipidemia

Clinical uses

GIT disturbance Insomnia Rash More serious adverse effects (myositis,

hepatitis, angio-oedema )

Adverse effects

Include clofibrate, gemofibrate, fenofibrate. Mainly reduce VLDL and hence triglyceride . Also reduce LDL and increase HDL Gemofibrozil has been shown to reduce

coronary heart disease by one third compared to the placebo in male patients with primary hyperlipidaemia

fibrates

Stimulate the lipoprotien lipase in the peripheral tissues, and hence, increase hydrolysis of TGA in chylomicron and VLDL particles.

Also probably reduce hepatic VLDL production and increase LDL uptake

MOA

To treat patients with mixed hyperlipidemia (raised TGA and raised cholestrol)

Clinical uses

Myositis which can cause myoglobinuria and acute renal failure

Clofibrate can cause gallstone so its use is limited to patients who have had cholcystomy

Adverse effects

Cholestyramine and Colestipol They reduce the plasma concentration of

LDL-cholestrol by more than 10%

Bile acid-binding resins

They sequester the bile in the intestine and prevent their reabsorption and entero-hepatic recirculation.

This lead to increase expression of LDL receptors in the liver and hence removal of LDL from the blood

MOA

Used in addition to statins to treat hyperlipidemia

Clinical uses

N/V, abdominal pain , bloating, constipation or diarrhea are the commonest adverse effects

They interfere with absorption of fat- soluble vitamins and drugs like Digoxin and Warfarin

Adverse effect

Mechanism of action is poorly understood It is a water soluble vitamin Inhibit the production of hepatic triglyceride

and VLDL secretion with reduction of in TGA and LDL and increase HDL

It increase the blood sugar and causes flushing of the face an effect that can be reduced by taking Aspirin

Modified release prepartion are well tolerated

Nicotinic acid derivatives

Specifically inhibits absorption of cholesterol by blocking NPC1L1 in the brush border without affecting the absorption of bile salts or fat soluble vitamins

Combined with statins to treat patients with severe dyslipidemia

Generally well tolerated but can cause diarrhea, headache, rash and angioedema also reported

Ezetimibe

Thank you

RANGE AND DALE ,PHARMACOLOGY

Reference