Agents Used in Dyslipidemia
Objective :
review of lipid metabolic pathway
Study of principle lipoprotein and their metabolism
Dyslipidemia , cause , complication of dyslipidemia
Target pharmacology
Pharmacotherapy
Avoid non pharmacotherapy
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Digestion and Absorption of Lipids
• short-chain of Free fatty acid can be absorbed.
• Droplets of lipid nutrition ( triglycerides /TG , phospholipid/ PL, ester of Cholesterol )
+ bile salts Micelle
monoglyceride(MG), fatty acid/AG, Lysophos-
LPase,CoLPaes,PLA,
pholipid,free Chol.
Chol esterase
bile salts
form mixed micelles (MG, AG, Lysophospholipid,free Chol. )
the intestinal epithelial cells
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Digestion and Absorption of Lipids
• resynthesize triglycerides and phospholipids within
the epithelial cells
• Triglycerides, phospholipids, and cholesterol are then
combined with protein inside the epithelial cells
(chylomicrons)
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Digestion and Absorption of Lipids
• Absorbed lipids thus pass through the lymphatic
system, eventually entering the venous blood by way
of the thoracic duct
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Free fatty
Transport of Lipids in the Blood
acid, energy
lipoprotein lipase source
chylomicrons
capillary endothelial cells, adipose tissue,cardiac
and skeletal muscles, mammary glands Chylomicrons
remnants
- VLDL : very-low-density
- LDL : low-density
- HDL : High-density lipoproteins
Liver (remnants R)
Ensure intake of fatty acid to all cells
Chol. and TG lipoprotein lipase
Liver VLDL LDL
apolipoproteins
HDL
Free Chol. Of Cells
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Transport of Lipids in the Blood
Lipoproteins Density Diameter Electrophoretic origin Principle
(g/ml) (nm) Mobility function
Chylomycrons < 0.95 500 Rest Intestinal Transport of
deposition exogenous TG
VLDL 0.96-1.006 43 Pre- liver Transport of
exogenous TG
IDL 1.007-1.019 27 Broad Catabolism of Precursor of
VLDL LDL
LDL 1.02-1.063 22 Catabolism of Transport of
VLDL,throught Chol
IDL
HDL 1.064-1.21 8 Liver, Transport of
intestinal reverse Chol
Catabolism of
CM,VLDL,
Lipides,Lipoprotéins et maladies cardiovasculaires(Biochimie medical,Wiliam .J. marshall, 2005
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Transport of Lipids in the Blood
The lipids are not soluble in water and therefore their transportation is provided by
lipoproteins. There are six classes of lipoproteins
Apoproteins (apolipoproteins): serve as structural components of the lipoproteiens
(ex: Apo AII and B48), ligands (ex: Apo B100 and E) for receivers of the lipoproteiens
in the membrane of the target (receiver B or E) cells, as well as activation of enzymes
(Apo AI and CII)
Lipides,Lipoprotéins et maladies cardiovasculaires(Biochimie medical,Wiliam .J. marshall, 2005
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
I. review of lipid metabolic pathway
Summery of lipid metabolic pathway
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
II. Principal function of lipid plasmatic
The major lipids of plasma are the fatty acid, TG, Chol., ester of Chol., PL
Chol. Formation of cell membrane, steroid
hormones, synthesis of bile salts, Vit. D
TG source AG, form of energy reserve
The two major clinical sequelae of hyperlipidemias are acute pancreatitis and
atherosclerosis. The former occurs in patients with marked hyperlipemia. Control of
triglycerides can prevent recurrent attacks of this life-threatening disease.
Lipoproteins that contain apolipoprotein (apo) B-100convey lipids into the artery
wall. These are low-density (LDL), intermediate-density (IDL), very-low-density
(VLDL),and lipoprotein(a) (Lp[a]).
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
III. Cause of atherosclerosis and their complication
multifactorial
Hyperlipemia ( LDL,VLDL,IDL,Lp(a)) - Cigarette smokingHDL
- Diabetes
- oxidative stress
When LDL is oxidized during their plasma transport, they can no longer be
recognized by the apoB/apoE receptor
They are then taken by a depolyanions receptor expressed on the surface of
macrophages, This title called 'scavenger receptor' (scavenger).
the early stages of the formation of atherosclerotic plaques (Foam cell)/ fatty
streaks foam cell formation and macrophage necrosis
Platelet activation PLAQUE RUPTURE
Thrombus and inflammation
- Coronary Artery Disease, ischemia , Myocardial infarction , AVC
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
IV. Classification of Dyslipoproteinemias
Dyslipoproteinemias may occur in isolation or as a Mixed Dyslipidemia.
a secondary cause
a secondary cause
a primary (genetic)
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
a secondary cause
Agents Used in Dyslipidemia
V. Target pharmacology
Chol.
TG
Apo B
Apo AI
Statine
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
V.Target pharmacology
COMPETITIVE INHIBITORS OF HMG-COA REDUCTASE (REDUCTASE INHIBITORS; “STATINS”)
• Inhibit of the mevalonate, a key step in the
endogenous synthesis of Chol.
• increases hepatic LDL receptors IDL and VLDL
• a significant reduction of LDL, a moderate decrease
in triglycerides, and a slight increase in HDL
• direct effect on the rate of circulating
lipoproteins/pleiotropic” effects of statins involve
improving endothelial function, enhancing the
stability of atherosclerotic plaques, decreasing
oxidative stress and inflammation, and inhibiting
the thrombogenic response.
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
V. Target pharmacology
FIBRIC ACID DERIVATIVES (FIBRATES)
up-regulate LPL Catabolism of TG
/VLDL,LDL,
ligands for the nuclear transcription receptor, PPAR-α
up-regulate apo A-I HDL
down-regulate apo B
decrease of Chol biosynthesis by modulating the activity of HMG-CoA reductase
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
V. Target pharmacology
BILE ACID-BINDING RESINS
enterohepatic cycle of bile acids
Ammoniums quaternary Sequestrate the Bile acid
increasing their fecal elimination of bile acids
increased the hepatic uptake of circulating LDL
and decreased their serum level. The resulting
effect is a significant decrease in LDL
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
V. Target pharmacology
NIACIN (NICOTINIC ACID)
not completely understood of mechanistic action
Nicotinic Acid decreases the release of free fatty acids by adipose tissue
decreased serum levels of apolipoprotein B
Increase concentrations of apolipoprotein AI
BENFLUOREX
decrease the intestinal absorption of triglycerides
promote mobilization of peripheral fat
EZETIMIBE
selectively inhibits the absorption of cholesterol and plant sterols to the intestine via
the carrier of sterols NPC1L1
TIADENOL
inhibiting the synthesis of cholesterol at a step before mevalonate .
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
V. Target pharmacology
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Agents Used in Dyslipidemia
VI. non pharmacologic treatment
first line intervention
The modification of lifestyle by the diet low in saturated fat and cholesterol, exercise,
stopping smoking
Dietary therapy is designed to decrease saturated fatty acids, total cholesterol and
promote the loss of weight in obese patients by decreasing the excess calories and
increasing physical activity
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
VII. Strategy of therapeutic dyslipidemias
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
References
- Pharmacology : des cibles vers l’ indication thérapeutique,Yves LANDRY, Jeanperre
GIES, Jean Edouard GAIRIN,Jean CROS
- Basic & Clinical Pharmacology , Bertram G.Katzung,Susan B.Masters, Anthony J.Trevor
- Pharmacie clinique et thérapeutique, CALOP, LIMAT,FERNANDEZ
- Anatomie et physiologie humaines, MARIEB
- Atlas de poche de parmacologie ,Lüllmann
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
Ph.Tan chantrea, Pharmacy lectuer, University of Puthisastra
