Hypolipidemic Drugs

Maj Kulsoom Farhat

Hypolipidemic Drugs
Lower lipid & lipoproteins
First measure
Attracted attention- prevent
cardiovascular diseases

Lipid transport
Lipoproteins
Function
Classified as
Chylomicrons, VLDL, IDL, LDL,
HDL
Lipoprotein metabolism
2 Pathways
Endogenous
Exogenous

Exogenous Pathway
Nutritive substances
Assembled with apolioprotein B-48chylomicrons
Blood-HDL apolipoprotein C-II & E- mature
chylomicrons
Lipoprotein lipase
Absorbed in peripheral tissues
Chylomicron remnants
Chylomicron remnant receptor-Endocytosishydrolysis
Glycerol & fatty acids

Endogenous Pathway
Liver
Assembled with apolioprotein B-100- VLDL
Blood-HDL apolipoprotein C-II & E- mature
VLDL
Lipoprotein lipase
Absorbed in peripheral tissues
Hydrolysed -VLDL remnants/IDL
VLDL remnant/IDL receptor-Hepatic lipases
IDL remnant/LDL
IDL remnant/LDL receptor -Liver & peripheral
cells- releasing lipids

Excess lipoproteins
CH deposition
Raised levels of VLDL, IDL, LDL
Raised levels of HDL

Risk factors for

hyperlipidemias

Genetics
Over weight
Sedentary life style
Smoking
Unhealthy diets
Hormonal Disease
Medications

Types of Hyperlipidemias
Type 1 (Familial Hyperchylomicronemias)
Type 11A (Familial Hypercholesterolemia)
Type 11B (Familial Combined
Hyperlipidemias)
Type 111 (Familial Dysbetalipoproteinemias)
Type IV (Familial Hypertriglyceridemia)
Type V (Familial Mixed Hypertriglyceridemia)

HMG CoA Reductase Inhibitors

Lovastatin
Mevastatin
Pravastatin
Simvastatin
Rosuvastatin
Atorvastatin
Fluvastatin
Cerivastatin

Fibric Acids Derivatives

Clofibrate
Fenofibrate
Bezafibrate
Ciprofibrate
Gemfibrozil

 Bile Acid Binding Resins

Cholestyramine
Colestipol
Colesevelam

Butylated Hydroxytoluene
Probucol

Nicotinamides
Nicotinic acid
Nicfuranose
Acipimox

Cholesterol Absorption inhibitors

Ezetimibe
Fish Oils
Omega-3 marine triglycerides
Orlistat

HMG Co A Reductase
Inhibitors

Source
Chemistry
Site of action
Structural analogues
Competitive Inhibition
Up regulation of LDL receptors
Catabolism
Raised HDL
Effect on LDL, TGs, HDL

Pharmacokinetics

Administration
Absorption
Extensive first pass metabolism
PPC
PPB
Excretion
T1/2

Adverse effects
CYP3A4, CYP2C9

Contraindication
Dose
Uses

Fibric acid Derivatives

Clofibrate
Stimulate lipoprotein lipase
PPAR a
LDL receptor expression
TGs synthesis
Up & down regulation of genes
HDL
Decrease TGs
Decrease LDL
Raised HDL
Uses

Pharmacokinetics
Absorption
PPC
PPB
Excretion
T1/2

Adverse effects
Contraindications
Dose

Bile Acid binding resins

Ion exchange resins

Bind BA in intestine
Fecal excretion of Bile salts
metabolism of CH to bile acids
LDL receptors in liver
Clearance of IDL, LDL & VLDL raised

 Adverse effects
Uses
Contraindications
Dose

Probucol
CH, LDL
Absorption
Effect 3 months
Deposition
Contraindication
Adverse effects
Uses

Nicotinamide

Used in v high doses

TGs
LDL
HDL
In combination
Peak effectMOA
LiverAdipose tissuesClearance of VLDL
HDL--apo A-1
Fibrinogen & TPA

 Uses
Hypercholesterolemia
Hypertriglyceridemia
Dose
Toxicity
Cutaneous flushing
Abdominal discomfort
Pruritis
Liver enzyme deranged
Hyperuricemia
Carbohydrate tolerance
Hyperpigmentation
Blurring of vision

 Nicfuranose
Acipimox
Niaspan

Cholesterol Absorption Inhibitors

Exetimibe
Absorption of cholesterol
Cholesterol-liver
Lipids
LDL
TG
HDL
Potency
Pharmacokinetics
Adverse effects

Fish oils
Omega 3 fatty acids
TGs
Other uses
Adverse effects
Dose

Orlistat
Inhibits lipase
Loss -Dietary lipids
Loss-Weight
Adverse effects
Fat soluble vitamins
Lipid absorption
GIT
Dose