antihyperlipidemic agents. hyperlipidemia hyperlipidemia is the most prevalent indicator for...
DESCRIPTION
Lipoproteins MetabolismTRANSCRIPT
Hyperlipidemia
Hyperlipidemia is the most prevalent indicator for susceptibility to atherosclerotic heart disease.
it is a term used to describe elevated plasma levels of lipids that are usually in the form of lipoproteins.
Lipoproteins Metabolism Dietary
Fat Intestines Chylomicrones Lipoprotein Remnants
FFA Receptor
Liver
Liver
VLDL LipoproteinLipase
Lipase
FFA
IDL LDL
LDL receptorLiver
LDL receptorExtrahepatic tissue
HDL
LCAT
Exogenous Pathway
Endogenous Pathway
Exogenous and endogenous Pathways of lipoprotein metabolism
Lipid-lowering drugs can be classified into:
Sequestering agents (Bile acids sequestrants) Inhibitor of de novo cholesterol biosynthesis. (HMG-
CoA Reductase inhibitors) Alteration of cholesterol metabolism Inhibition of lipoprotein synthesis. Miscellaneous.
Cholestyramine Resin (Questran)
It is a styrene copolymer with divinylbenzene with quaternary ammonium functional groups.
HC
H2C
HC
H2C
CH2N(CH3)3CH2H2C
n
Cl
Colestipol HCl (Colestid)
It is a high-molecular-weight, insoluble, granular copolymer.
It reduces cholesterol levels without affecting triglycerides.
N N
NH2
N
R
OHR
HOCl
Colesevelam (Welchol)
It does not possess Cl- ion (as in Cholestyramine and colestipol) and is not an anion-exchange resin.
H2N HN HN HN
H2N HN HN HN
(CH2)6 (CH2)9CH3
(CH2)6 (CH2)9CH3
N(CH3)3
N(CH3)3
n
OH
H3C C
O
SCoA
Acetyl CoA
3
C
SCoA
CH2COOH
O
HO
H3C
HMG-CoA
HMG-CoAReductase
C
OH
CH2COOHHO
H3C
Mevalonic acid
HOCholesterol
Lovastatin (Mevacor)
It is a potent inhibitor of HMG-CoA reductase.
For inhibitory effect on HMG-CoA reductase, the lactone ring must be hydrolyzed to the open-ring heptanoic acid
CH3
O
CH3
O
HO
O
O
H3C
Simevastatin (Zocor)
It is an analogue of Lovastatin.
CH3
O
O
HO
O
O
H3C
H3C CH3
Dextrothyroxine sodium (Choloxin)
O-(4-Hydroxy-3,5-diiodsophenyl)-3,5-diiodo-D-tyrosine monosodium hydrate.
HO
I
I
O
I
I
H2C C
NH2
H
COONa H2O
Clofibrate (Atromid-S)
Ethyl 2-(p-chlorophenoxy)-2-methylpropionate
Cl O C COOC2H5
CH3
CH3
Clofibrate is prepared by Williamson synthesis.
OH
Cl
+H3C
H3CC O
NaOH- H2O
O
Cl
C
CH3
O
CH3
Na
CHCl3
O
Cl
C
CH3
C
CH3
Cl
ClCl
+3NaOH
-3NaCl
O
Cl
C
CH3
COONa
CH3
O
Cl
C
CH3
COOC2H5
CH3 C2H5OHH2SO4
Gemfibrozil (Lopid)
5-(2,5-Dimethylphenoxy)-2,2-dimethyl pentanoic acid
It is structurally similar to clofibrate. Its mechanism of action and use are similar
to those of clofibrate.
CH3
H3C
O (CH2)3 C COOH
CH3
CH3
Finofibrate (Tricor)
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid 1-methylethyl ester.
It has structural features represented in clofibrate.
CCl O OC CHCH3
CH3
C
OCH3
CH3
O
Structure-activity relationship of fibrates
Aromatic ring O Spacer group C
CH3
CH3
C
O
OH
Probucol (Lorelco)
4,4-[(1-Methylethyliden)-bis thio-[2,6-bis(1,1-dimethyethyl)] phenol.
Probucol has high lipophilic characters with strong antioxidant properties.
HO
(H3C)3C
(H3C)3C
S C S
CH3
CH3
OH
C(CH3)3
C(CH3)3
Nicotinic acid, Niacin
3-Pyridine carboxylic acid.
It has the ability to inhibit lipolysis (i.e. prevent the release of free fatty acids and glycerol from fatty tissues).
N
OHC
O
Pentaerthritol tetranicotinate
Pentaerthritol tetranicotinate is an example of molecular association in which a tetra-replicate of nicotinic acid was developed (Molecular replication).
COO
OO
N
N N
N
OO
O O
β-Sitosterol
Sitosterol is a plant sterol, whose structure is identical with that of cholesterol, except for the substituted ethyl group on C-24 of its side chain.
The drug inhibits the absorption of dietary cholesterol from the gastrointestinal tact.
H3C
H3C
HO
H2C
CH2
CH3H3C
H2CCH3
CH3