HYPOLIPIDEMIC DRUGS

NIKITA SHAKYA
Roll No: 11
Batch: 12th
 These drugs decrease the level of lipid and lipoprotein in the
blood and can prevent cardiovascular disease by retarding
atherosclerosis process.
LIPID ABSORPTION
 Lipid reaches blood stream in the form of lipoprotein after
associating itself with apoprotein.
STRUCTURE OF LIPOPROTEIN
 Core of lipoprotein
consist of trigycerides
(TGs) or cholesteryl
esters (CHEs)
 Outer surface has
phospholipids, free
cholesterol (CH) and
apoproteins.
MECHANISM OF LIPID TRANSPORT
 Dietary fat including cholesterol and triglycerides are absorbed in the intestine
and released in the blood stream as chylomicrons.
 Lipoprotein lipase (LPL) acts on these particles to release some free fatty acids
that deposit in adipose tissues.
 The remnants of chylomicrons are picked up by the liver and secrets them as
VLDL.
 LPL works on these VLDL particles changing the content of the particles to
IDL and LDL.
 LDL receptors on the cell membranes of the extrahepatic cells pick up the LDL
particles. Thus cholesterol reaches the interior of normal cells.
 Within cells, LDL particles are repackaged called HDL. Excess cholesterol is
esterified and stored. Excess cholesterol suppresses the biosynthesis of LDL-
receptors so that intake of cholesterol decreases. It also suppresses cholesterol
biosynthesis.
 HDL particles are then released into the blood stream. These particles are
sensed by the liver through the HDL-receptors. Thus the liver gets constant
information as to how much LDL and HDL are present in the blood.
DYSLIPIDEMIA
 Abnormal amount of lipid in the blood. In developed
countries it mostly refers to hyperlipidemia.
LIPID MODULATING DRUGS
Classification
 HMG-CoA reductase inhibitors (statins) eg: Pravastatin
 Bile acid sequestrants (resins) eg: Colestipol and
Cholestyramine
 Activate lipoprotein lipase (Fibric acid derivatives) eg:
Gemifibrozil, Fenofibrate
 Nicotinic acid
HMG-COA REDUCTASE INHIBITORS
(STATIN)
Pharmacological Action
 limits CH synthesis
 increases LDL receptor expression which increases LDL
uptake
Pharmacokinetics
 All statins are administered orally at bedtime as HMG-CoA
activity is maximum at mid night.
Adverse reactions
 Headache, nausea, bowel upset
 Sleep disturbance

 Muscle tenderness and rise in CPK level

 Myopathy is the only serious reaction

Uses
 First choice drug for primary ( increased LDL and CH level)
and secondary (diabetes, nephrotic syndrome)
hypercholesterolemia.
BILE ACID SEQUESTRANTS
 Bind bile acids in the intestine and interrupt
enterohepatic circulation
 Feacal excretion of bile salts and CH is increased
FIBRIC ACID DERIVATIVES
 Activates lipoprotein lipase which is a key enzyme is
degradation of VLDL resulting lower TG
 However fibrates are never used alone. They are used in
combination with bile acid sequestrants.
GEMIFIBROZIL

 Completely orally absorbed

 Excreted in urine and has plasma half life of 1-2 hr

 Myopathy is rare but incidence increases when used with

statins
FENOFIBRATE

 2nd gen fibric acid derivative which has greater LDL-CH

lowering action than other fibrates
 Has plasma half life of 20 hrs.
NICOTINIC ACID
 It can decrease plasma lipid when used in high dose.
 It is more effective to raise HDL-CH.

 TGs and VLDLs decrease rapidly.

 Decrease in LDL is greater if used with Resins.

Adverse reaction
 It can cause cutaneous vasodilation, dyspepsia, liver
dysfunction and jaundice
 It is contraindicated during pregnancy.
ANTI-ATHEROSCLEROTIC
AGENTS
DEVELOPMENT OF ATHEROSCLEROSIS
 LDL in plasma are absorbed by the wall of blood vessel,
these LDLs are treated as foreign body in the cell and
engulfed by macrophages. These macrophages become
foam cell, accumulate and form fatty streaks.
 Fatty streaks develop into fibrous plaque which ruptures
and activates platelet aggregation leading to thrombus
formation.
ANTI-ATHEROSCLEROTIC AGENTS

 HMG-CoA reductase inhibitor (statin): inhibit CH

synthesis and decrease LDL in blood.
 Anti-platelet drugs. Eg: Aspirin, Clopidogrel,
Ticlopidine
ASPIRIN
 Aspirin irreversibly inhibits cyclooxygenase activity in
platelets. Consequently the platelet is unable to produce
thromboxane A 2 , the platelet-specific prostaglandin
that induces platelet aggregation.
 Gastrointestinal side effects increase with increasing
dosage.
CLOPIDOGREL AND TICLOPIDINE
 inhibit adenosine diphosphate-mediated platelet
activation.
 more rapid onset of action

 lower incidence of serious adverse events

THANK YOU