2. 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 RESULT FROM ABNORMALITIES IN LIPID METABOLISM OR PLASMA LIPID
TRANSPORT OR A DISORDER IN THE SYNTHESIS AND DEGRADATION OF PLASMA
LIPOPROTEINS .
3. INTRODUCTION
THESE ARE THE DRUG WHICH LOWER THE LEVEL OF LIPIDS AND LIPOPROTEIN IN BLOOD .
THESE DRUG HAVE THE POTENTIAL TO PREVENT CARDIOVASCULAR DISEASE BY
RETARDING THE ACCELERATED ATHEROSCLEROSIS IN HYPERLIPIDAEMIC INDIVIDUALS.
ATHEROMATOUS DISEASE IN THE MOST COMMON CAUSES OF DEATH (E.G. MYOCARDIAL
INFRACTION ) AND DISABILITY (E.G. STROKE ) IN INDUSTRIAL COUNTRIES .
4. DEFINITION
The Term Hyperlipidemia Or More Precisely Hyperlipoproteininamia Refer To
Conditions In Which The Concentration Of Cholesterol And /Or Triglyceride Rich
Lipoprotein Are Elevated Above Normal Levels . The Term Hyperlipemia Is Restricted
To Conditions That Involve Increased Level Of Triglycerides In Plama .
5. CAUSE OF HYPERLIPIDEMIA
Mostly Hyperlipidemia Is Caused By Lifestyle Habits Or Treatable
Medical Conditions. Obesity , Not Exercising And Smoking ,Diabetes
,Obstructive Jaundince, And Under Active Thyroid Gland Inherit
Hyperlipidemia .
6. Types of Hyperlipidemia
HYPERLIPIDEMIA OR HYPERLIPOPROTEIN MAY BE :-
1) PRIMARY …
They Are Generally Genetically Determined And Are Divided Into
Two Major Group . That Are Caused By An Inherited Single Gene Defect
,Called Monogenic Hyperlipoproteinemia. Those Caused By A Combination Of
Multiple Genetic Factors That Act A Long With The Environmental Causes
Such As Dietery And Physical Activity .These Are Called Multifactorial Or
Polygenic Hyperlipoproteinemias.
7. The Secondry
hyperlipoproteiemias
They Are Associated With A More Generalized Metabolic Disturbance
Such As Diabetes Mellitus Hyperthyrodisum Or Chronic Alcoholisum,
Some Drug Eg :-Thiazide, Beta Blocker , Estrogens, Retionoides May
Cause Hyperlipidemia .
8. Lipid Lowering Drugs
Acts Either By Reduce Production Of Lipoprotein Or By
Increasing Their Removal From Blood . Main Aim Is To
Decrease Plasma Cholesterol
9. What are lipoproteins
Since blood and other body fluids are watery ,so fats need a special transport system to travel
around the body .
They are carried from one place to another mixing with protein particles , called lipoprotein .
They are four or five types of lipoproteins each having very distinct job.
A Lipoprotein Contain Both Proteins And Lipids Bound To Another Protein Which Is Called
Apolipoproteins Which Allow Fats To Move Through The Water Inside And Outside Cells
Provide Structural Support And Stability Binds To Receptors
11. Classification of
antihyperlipidemic drugs
Several Different Classes Of Drug Are Used To Treat Hyperlipidemia .
These Class Differ Not Only In Their Mechanism Of Action But Also
In The Type Of Lipid Reduction And Magnitude Of The Reduction
14. HMG COA REDUCTASE INHIBITORS
Fungal Derived Product
Potent Competitive Inhibitor Of B-hydroxy B-methyl
Glutaryl Coa ( HMG- COA ) Reductase Enzyme .
Chemistry
Commonly Called Station Lactone Ring Of Stain Is Structurally Similar To Hmg-
coa
15. SAR OF HMG-REDUCTASE
INHIBITOR
Mevastatin And Lovastatin Are The Lead Compound In The Development Of Hmgris
Lactone Ring , Bicyclic Ring And Ethylene Bridge Are Very Important For Activity
Provastin Is The Ring Opened Dihydroxy acid With A 6 Hydroxyl Group Is More Hydrophilic Than
Lovastin . It Has The Low Penetration To The Peripheral Tissue And Less Side Effects
16. Ring A Subclass The Decalin Ring Is Essential For Anchoring The Compound To The Enzyme A
Ctive Site Replacement With A Cyclohexone Ring Resulted In 10,000 Fold Decrease In Activity
Stereochemistry Of The Ester Side Chain Is Important For Activity ,The Conversion Of His Ester To
An Ether Resulted In Decresse In Activity .
Methyl-substitution At The R2 Position Increase Enhance Hydrophilicity And May Provide Some
Celluler Specificity .
17. Lovastine
Route Of Administration :- Mouth
Bioavailability :- <5 %
Protein Binding :- >98%
Metabolism :- Hepatic
Excretion :- Faeces (83%)
Uses :- The Primary Uses Of Lovastatin Is For The Treatment Of Dyslipidemia And The Prevention Of
Cardiovascular Disease It Is Recommended To Be Used Only After Other Measure Such As A Diet ,
Exercise , And Weight Reduction ,Have Not Improved Cholesterol Levels,
18. Mechanism OF action
Lovastatin Is An Inhibitor Of 3-hydroxy-3-methylglutaryl-coenzyme A Reductase (Hmg-coa Reductase),
An Enzyme That Catalyzes The Conversion Of Hmg-coa To Mevalonate.[15] Mevalonate Is A Required
Building Block For Cholesterol Biosynthesis And Lovastatin Interferes With Its Production By Acting As A
Reversible Competitive Inhibitor For Hmg-coa, Which Binds To The Hmg-coa Reductase. Lovastatin Is
A Prodrug, An Inactive Lactone In Its Native Form, The Gamma-lactone Closed Ring Form In Which It Is
Administered, Is Hydrolysed In Vivo To The Β-hydroxy Acid Open Ring Form; Which Is The Active Form.
Lovastatin And Other Statins Have Been Studied For
Their Chemopreventive And Chemotherapeutic Effects. No Such Effects Were Seen In The Early
Studies.[16] More Recent Investigations Revealed Some Chemopreventive And Therapeutic Effects, For
Certain Types Of Cancer, Especially In Combination Of Statins With Other Anticancer Drugs.[17] It Is
Likely That These Effect Are Mediated By The Properties Of Statins To Reduce Proteasome Activity,
Leading To An Accumulation Of Cyclin-dependent Kinase Inhibitors P21 And P27, And To Subsequent G1-
phase Arrest, As Seen In Cells Of Different Cancer Lines
19. SIMVASTATIN
Uses :- The Primary Uses Of Lovastatin Is For The Treatment Of Dyslipidemia And The Prevent
atherosclerosis related complication such as stroke and heart attack in those who are at high risk . It is
recommended to be used as an addition to a low – cholesterol diet .
Route Of Administration :- Mouth
Bioavailability :- <5 %
Protein Binding :- >98%
Metabolism :- liver
Excretion :- Faeces (60%) ,Kidney ( 13%)
20. ATORVASTATIN
Uses :- Atorvastine Is Used Together With Diet , Weight Loss , And Exercise To Reduce The Risk Of Heart
Attack And Stroke And To Decrease That Chance That Heart Surgery Will Be Needed I People Who Have
Heart Disease Or Who Have Heart Disease Or Who Are At Risk Of Developing Heart Disease .
Route Of Administration :- Mouth
Bioavailability :- 12%
Protein Binding :- >98%
Metabolism :- liver
Excretion :- Bile
21. PITAVASTATIN
Uses :- Pitavastatin Is Used Together With Diet , Weight Loss, and Excerise To Reduce The Amount Of Fatty
Substance Such As Low Density Lipoprotein (Ldl ) Cholesterol In The Blood And To Increase The Amount Of
High Density Lipoprotein In Adult .
Route Of Administration :- Mouth
Bioavailability :- 60%
Protein Binding :- 90%
Metabolism :- liver
Excretion :- Faeces
22. Rosuvastatin
Uses :- Rosuvastatin Belong To A Group Of Medicines Called Statins . It’s Used To Lower Cholesterol If
You Have Been Diagnosed With High Cholesterol . Its Also Taken To Prevent Heart And Blood Vessel
Disease , Heart Attack And Strokes .
Route Of Administration :- Mouth
Bioavailability :- 20%
Protein Binding :- 88%
Metabolism :- liver
Excretion :- Faeces( 90%)
24. SAR OF HMG-COA REDUCTASE
INHIBITORS
Mevastatin And Lovastatin Are The Lead Compound In The Development Of HMGRI S.
Lactone Ring, Bicyclic Ring And Ethylene Bridge Are Very Important For Activity .
Pravastatin Is The Ring Opened Dihydroxy acid With A 6 Hydroxyl group Is More
Hydrophilic Than Lovastin .So It Has The Low Penetration To The Peripheral Tissue And
Less Side Effects .
25. Fibric Acid Derivatives :-
Fibric Acid Derivatives ( Fibrates ) Are A Class Of Medication That Blood Triglyceride
Levels. Fibrate Lower Blood Triglyceride Levels By Reducing The Liver’s Production Of
VLDL ( The Triglyceride - Carrying Particle That Circulate In The Blood ) And By Speeding
Up The Removal Of Triglyceride From The Blood .
26. SAR OF FIBRATES
Isobutyric Acid Group Is A Essential For Activity .
Compound Containing On Ester, Such As Clofibfrate And Fenofibrate Are Prodrug And
Require In Vivo Hydrolysis .
Substitution At The Para Position Of The Aromatic Ring With A Chloro Group Or A
Chlorine Containing Isopropyl Ring Produce Compound With Significantly Longer Half
Life.
28. clofibrate
Uses :- Clofibrate Is A Lipid Lowering Agent Used For Controlling The High Cholesterol And Triacyl
Glyceride Level In The Blood . It Belongs To The Class Of Fibrates . It Increase Lipoprotein Lipase Activity
To Promote The Conversion Of Vldl To Ldl , And Hence Reduce The Level Of Vldl .
Route Of Administration :- Mouth
Bioavailability :- 20%
Protein Binding :- 88%
Metabolism :- liver
Excretion :- Renal ( 95-99%)
30. Fenofibrate
Uses:- Fenofibrate Is Used With A Low – Fat Diet Exercise And Sometimes With Other Medication To
Reduce The Amount Of Fatty Substance Such As Cholesterol And Trigly Cerides In The Blood And To
Increase The Amount Of Hdl (High –Density Lipoprotein : A Type Of Fatty Substance That Decrease The
Risk Of Heart Disease .
Route Of Administration :- Mouth
Bioavailability :- 70%
Protein Binding :- 99%
Metabolism :- glucuronidation
Excretion :- Renal ( 95-99%)
31. Gemfibrozil
USES :- Gemfibrozil Is Used With Diet Changes ( Restriction Of Cholesterol And Fat Intake ) To Reduce
The Amount Of Cholesterol And Triglycerides In The Blood In Certain People With Very High
Triglycerides Who Are At Risk Of Pancreatic Disease Affecting The Pancreas A Gland That Produce .
Route Of Administration :- Mouth
Bioavailability :- 100%
Protein Binding :- 95%
Metabolism :- Hepatic
Excretion :- Renal ( 94%)
32. FLUVASTATIN
Uses :- Fluvastatin Is Used Together With Diet , Weight Loss, And Exercise To Reduce The Risk Of Heart
Attack And Stroke And To Decrease The Chance That Heart Surgery Will Be Needed In People Who
Have Heart Disease Or Who Have Heart Disease Or Who Are At Risk Of Developing Heart Disease .
Route Of Administration :- Mouth
Bioavailability :- 24-30%
Protein Binding :-98%
Metabolism :- Hepatic
Excretion :-95%
33. Bile Acid sequesterant :-
The Bile Acid Sequesterant Are A Group Of Resins Used To Bind Certain Compounds Of
Bile In The Gastrointestinal Tract . They Disturb The Enterohepatic Circulation Of Bile
Acids By Combining With Bile Constituents And Preventing
Their Reabsorption From The Gut.
34. Sar Of Bile Acid SEQUESTRANTS
Cholestyramine Is A Copolymer Consisting Primarily Of Polystyrene With Small Amount Of Divinyl
Benzene As A Crosslinking Agent .
In Addition It Contain Some Fixed Quaternary Ammonium Groups .
This Positively Charged Group . Function As Binding Site For Anions .
The Adsorption Capacity Of Cholestyramine For Bile Salts Is More Than The Colestipol .
36. Colestyramine
Uses:- Cholestyramine Is Used Along With A Proper Diet To Lower Cholesterol In The Blood . Lowering
Cholesterol Helps Decrease The Risk For Strokes And Heart Attacks .
Route Of Administration :- Mouth
Bioavailability :- low
Protein Binding :-Unknown
Metabolism :- Bile Acid
Excretion :-Faceal
37. COLESTIPOL
USES:- Colestipol Is Used Along With Diet Changes To Decrease The Amount Of Fatty Substance Such
As Low –Density Lipoprotein (LDL ) In Certain People With High Cholesterol . Colestipol Is In A Class
Of Medication Called Bile Acid Sequestrants .
Route Of Administration :- Oral
Bioavailability :- None
Protein Binding :-Unknown
Metabolism :- Bile Acid
Excretion :-Faeces
38. LDL Oxidation Inhibiters
Low Density Lipoprotein Consist Of About 3000 Fatty Acids (50 % Polyunsaturated ) And A
Single Molecule Apolipoprotein B (500 KDA) .The Endogenous Antioxidants Of LDL Consist
Mainly Of Tocopherols And Few Carotenoids , Which Protect The Pufas Against Oxidation .
39. Probucol
USES:- Probucol Is A Powerful Antioxidant Drug Normally Used To Prevent Vascular Disease Caused
By The Free Redicals In The Body . Probucol Lowers Serum Cholesterol By Increasing The Fractional
Rate Of Low – Density Lipoprotein Catabolism In The Final Metabolic Pathway For Cholesterol
Elimination From The Body .
41. Pyridine derivatives :-
Pyridine is A Basic Heterocyclic Organic Compound Pyridine Is A Colourless But
Older Or Impure Samples Can Appear Yellow . The Pyridine Ring Occurs In Many
Important Compound Including Agrochmemicals ,Pharmacuticls And Vitamins .
Historically Pyridine Was Produced From Coal Tar .
42. Nicotinamide
USES :- Nicotinamide Is A Form Of Vitamin B3 ( Niacin ) And Is Used To Prevent And Treat Deficiency
(Pellagra) . Niacin Deficiency Can Causes Diarrhea , Confusion Tongue , Redness, Swelling And Peeling
Red Skin .
Route Of Administration :- Mouth
Bioavailability :- None
Protein Binding :-Unknown
Metabolism :- Bile Acid
Excretion :-Faeces
