This document discusses antihyperlipidemic agents, which are drugs used to lower lipid levels in the blood. It focuses on statins, describing their mechanism of action as inhibiting HMG-CoA reductase to reduce cholesterol synthesis and increase LDL receptors. This decreases LDL and IDL and increases HDL levels. The document also classifies primary and secondary hyperlipidemias, describes other antihyperlipidemic drugs like ezetimibe, fibrates, and niacin, and recommends lifestyle changes and drug therapy to manage hyperlipidemia.

1. Antihyperlipidemic

2. Q.
 Discuss the SAR and MOA of Statins as Antihyperlipidemic
agents.
 Write note on Antihyperlipidemic agents

3. Introduction
 Antihyperlipidemic agents promote reduction of lipid levels in the blood.
 Some antihyperlipidemic agents aim to lower the levels of low-density
lipoprotein (LDL) cholesterol, some reduce triglyceride levels, and some
help raise the high-density lipoprotein (HDL) cholesterol.
 By reducing the LDL cholesterol, they can prevent both the primary and
secondary symptoms of coronary heart disease
 cholesterol does not occur alone in plasma. It is always associated with
lipoproteins. Lipoproteins are proteins carrying lipids.
 There are several forms of lipoproteins, very low density lipoproteins
(VLDL), intermediate density lipoproteins (IDL), low density lipoproteins
(LDL), and high density lipoproteins (HDL), depending on the density of
their packing or alternatively their size.
 The term hyperlipidemia refers to the excessive lipid content in the
blood plasma.
 A lipid profile of patient's blood plasma is the distribution in
concentration of various forms lipoproteins.

4. What is Hyperlipidemia?
Hyperlipidemia a broad term, also called hyperlipo-
proteinemia, is a common disorder in developed countries and
is the major cause of coronary heart disease.
It results from abnormalities in lipid metabolism or plasma lipid
transport or a disorder in the synthesis and degradation of
plasma lipoproteins
Causes of hyperlipidemia
•Mostly hyperlipidemia is caused by lifestyle habits or treatable medical
conditions.
•Obesity, not exercising, and smoking
•diabetes, kidney disease, pregnancy, and an under active thyroid gland

5. The chemistry and biochemistry of Plasma lipids
What are lipids?
Lipids are the fats that are present in the body.
The major lipids in the bloodstream are cholesterol and it’s esters,
triglycerides and phospholipids.
Hyperlipidemia ; Increases concentrations of lipids
Hyperlipoproteinemia ; Increases concentrations of lipoproteins
Hypercholesterolemia; high concentration of cholesterol
Atherosclerosis and coronary artery disease
Hypertriglyceridemia; high concentration of triglyceride
Pancreatitis & Development of atherosclerosis and heart disease

6. Classification of lipoproteins? By density
Classification Composition Primary function
Chylomicrons Triglyceride TGs Transport dietary TGs to adepose
tissue & muscle
VLDL newly synthesized TGs Transport endogenous TGs to
adepose tissue & muscle
IDL intermediate between
VLDL and LDL
They are not usually detectable in
the blood.
LDL Mainly cholesterol
(bad cholesterol
lipoprotein)
Transport endogenous cholesterol
HDL Mainly cholesterol
(good cholesterol
lipoprotein)
Collect cholesterol from the body's
tissues, and take it back to the liver

7. What are the "bad" and the "good" types of
cholesterol?
LDL cholesterol, the cholesterol carried in LDL particles, is the
"bad" cholesterol because.
When elevated, LDL cholesterol can promote coronary artery
disease.
HDL cholesterol, the cholesterol carried in HDL particles, is the
"good" cholesterol.
It protects against coronary artery disease.

8. GROUPS OF HYPERLIPIDEMIA:
Primary or familial hyperlipoproteinaemia
Secondary hyperlipoproteinaemia
The current classification of hyperlipidemias is based on the
pattern of lipid abnormality in the blood.

9. Primary familial hyperlipoproteinaemia
• Sub classified into six phenotypes
I , IIa , IIb, III, IV, and V based on lipoproteins and lipids were
elevated.
•current literature, however, favors the more descriptive
classifications and sub classification

10. Hyperlipoprotein
emia
Synonyms Increased
lipoprotein
Treatment
Type I (rare) '''Primary hyperlipoproteinaemia'', or
''Familial hyperchylomicronemia''
Chylomicrons Diet control
Type IIa ''Polygenic hypercholesterolemia'' or
''Familial hypercholesterolemia
LDL statins, niacin
Type IIb ''Combined hyperlipidemia'' LDL and VLDL Statins, niacin,
fibrate
Type III (rare) ''Familial Dysbetalipoproteinemia'' IDL Fibrates,
statins
Type IV ''Familial hyperlipidemia'' VLDL Fibrate,
niacin], statins
Type V (rare) ''Endogenous hypertriglyceridemia VLDL and
Chylomicrons
Niacin, fibrate

11. Secondary hyperlipidaemias results from:
 Liver disease
 Obesity
 Hypothyroidism
 Diabetes,
 Diet
 Alcohol excess
 Renal disease (nephrotic syndrome)
 Drugs,, thiazide diuretics, oral contraceptive steroids
 The most severe hyperlipidaemias usually occur In patients with
concurrent conditions, e.g. Diabetes Mellitus with one of the primary
hyperlipidaemias

12. Drug therapy: the primary goal of therapy is to:
 Decrease levels of LDL
 Increase in HDL
 Management:
 Lipid lowering therapies have a key role in the secondary and
primary prevention of CVS disease.
 Assessment of absolute risk, treatment of all modifiable risk factors
and optimization of lifestyle factors especially diet and exercise are
control to the management.

13. Non pharmacological treatment
 1- Reduce intake of saturated fat to less than 7-10% of total energy.
 2- Reduce intake of cholesterol to less than 250mg/day.
 3- Reduce sources of saturated fat and cholesterol by low fat
dietary products and low glycemic index carbohydrates.
 4- Consumption of vegetable, fruits,.
 5- Supplementary intake of fish oil (contain n3 FA) & dietary fibers.
 6- Achieve ideal body weight and increase activity and exercise.
 7- Reduce or stop alcohol intake, also stop smoking.

14. Pharmacological treatment:
 Predominant hypercholesterolemia:
 1) Statins (HMG CoA reductase inhibitors).
 2) Nicotinic acid (vit.B3) Niacin.
 3) Cholesterol absorption inhibitors (Ezetimibe)
 4) Bile acid sequestrating resins.
 *start with statin (Ezetimibe if intolerant)
 So: statin ± Ezetimbe ± Resin or Niacin

15.  What is Statin ?
 Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels
by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of
cholesterol in the liver, which produces about 70 percent of total cholesterol in the body.
CH3
H
O
O
HO O
HH3C
O
MEVASTATIN
CH3
H
O
O
HO O
HH3C
H3C
O
LOVASTATIN (MEVACOR)
CH3
H
O
O
HO O
CH3H3C
O
SIMVASTATIN (ZOCOR)
CH3
H
O
COOH
HO
HH3C
O
HO
OH
PRAVASTATIN (PRAVACHOL)

17. Ezetimibe (Zetia)
N
OH
O
F
OH
F
EZETIMIBE
is a drug that lowers plasma cholesterol levels.
It acts by decreasing cholesterol absorption in the intestine

18. FIBRIC ACID DERIVATIVES
CH3
H3C
O (CH2)3 C
CH3
CH3
COOH
GEMFIBROSIL (LOPID)
Cl O C
CH3
CH3
COOEt
CLOFIBRATE(ATROMID-S)
Cl
OC
CH3
CH3
iPrO2C
O
FENOFIBRATE (TRICOR)

19. Mechanism of action:
 These drugs inhibit cholesterol synthesis by competing effectively to
inhibit the HMG CoA reductase the rate limiting step in the cholesterol
synthesis thus depleting the intracellular supply of cholesterol.
 This depletion leads to increased activity and number of LDL receptors
which increase the clearance of LDL and it‘ precursor IDL and causing
secondary reduction in LDL synthesis.
 As a result Statins reduce LDL by up to 60% reduce TG up to 30%and
↑HDL up to 10%.
 The therapeutic benefits also include plaque stabilization.
 Improvement of coronary endothelial function, inhibition of platelet
thrombus formation , and anti inflammatory activity.
 Adverse effects:
 These drugs are well tolerated & safe.
 Side effects are rare.