Pharmacology-II (B.Ph- V semester)

1. Anti-Hyperlipidemic Agents
By:- Dr. Manish Pal Singh,
Associate Professor
1AGRA PUBLIC PHARMACY COLLEGE, ARTONI, AGRA, UP, INDIA

2. ➢ A lipoprotein is a biochemical assembly whose primary purpose is to transport
hydrophobic lipid (also known as fat) molecules in water, as in blood plasma
or other extracellular fluids.
➢ Examples include plasma lipoprotein particles (HDL, LDL, IDL, VLDL and
chylomicrons).
➢ Lipid originate from two sources:-
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ARTONI, AGRA, UP, INDIA
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Endogenous lipids : synthesized in the
liver
Exogenous lipids: ingested and processed in
the intestine

3. ➢ Dietary cholesterol & triglycerides : packaged into chylomicrons in the
intestine into bloodstream via lymphatic's.
➢ Liver synthesizes TG and cholesterol packages them as VLDLs before
releasing them into the blood.
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Chylomicrons
• Carry triglycerides from the intestines to liver to skeletal muscle to adipose tissue.
VLDL
• Very low density lipoprotein
• VLDLs become progressively more dense & and turn into LDLs
LDL
• Most LDLs taken up by Liver for disposal
• some circulate and distribute cholesterol to the rest of the body tissue
HDL
• HDLs, which are also secreted from the liver and intestine, have the task of preventing lipid
accumulation.
• They remove surplus cholesterol from tissues and transfer it to LDLs that return it to the liver.

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ARTONI, AGRA, UP, INDIA
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6. Hyperlipoproteinaemias
❑ Secondary:
➢ Associated with some other conditions like:- diabetes, use of drugs (oral contraceptives)
etc.
➢ Alcoholism,
➢ Nepherotic syndrome.
❑ Primary:
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Monogenic or genetic (A Single gene defect)
Polygenic or Multifactorial (Multiple gene)

7. Management of Dyslipidaemia
❑ Drug therapy to lower plasma lipids is only one approach to treatment.
❑ Used in addition to dietary management.
❑ Correction of other modifiable cardiovascular risk factors.
❑ Several drugs are used to decrease plasma LDL-CHO.
❑ On the whole, LDL is the primary carrier of plasma CHE & VLDL that of
TGs.
❑ The purpose of treating lipid disorders is to prevent the development of
other diseases, particularly cardiovascular disease. Use following link-
❑ For complete coverage of all related areas to visit following link
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WWW.ENDOTEXT.ORG.

8. Classifications
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*Newer Drugs:- CETP Inhibitors- Ex; Torcetrapib, Anacetrapib

9. HMG-COA reducate inhibitors (Statins):
✓ Introduced in the 1980, they used as anti-hyperlipidemic drugs because
competitively inhibit conversion of ‘3-Hydroxyl-3-methyl glutaryl
coenzyme A’ (HMG-COA) to mevalonate (rate limiting step in CH
syntehsis).
✓ This results in compensatory increase in LDL-receptor expression on liver
cells- increase receptor mediated uptake & catabolism of IDL & LDL.
✓ Because of MHG-COA reductase activity is maximum at night , all statins
are administered at bed time to better result obtaining.
✓ BRAND:-
✓ LOVASTATIN (ROVACOR); SIMAVASTATIN (SIMCARD)
✓ ATROVASTATIN ( AZTOR, ATROVA)
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How to satins work (MAO):-

11. ❑ ADR’s:
▪ Sleep disturbance (lipophilic drug)
▪ Bowel upset
▪ Muscle tenderness
▪ Hepatotoxicity
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Therapeutic
Actions
(Uses)

12. Fibric Acid Derivatives:
❑ These are the isobutyric acid derivatives & primarily activate lipoprotein lipase- which
is a key enzyme in the degradation of VLDL resulting in lowering of circulating TGs.
❑ It binds with PPAR α (proliferator-activated receptor)- gene transcription regulating
receptor expressed in liver , fat & muscle.
❑ Activating it stimulate Lipase synthesis & fatty acid oxidation.
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ARTONI, AGRA, UP, INDIA
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13. ❑ ADR’s:
• GI upset (dyspepsia)
• Epigastric distress, loose motion
• Skin rashes, blurred vision
• It contraindicated in pregnancy; Preexisting gall bladder disease; Patients with impaired
renal functions
• Hepatitis Rare
❑ Interactions:
• Increased risk of myopathy when combined with statins.(fenofibrate)
• Displace drugs from plasma proteins( e.g. oral anticoagulants and oral hypoglycemic drugs)
❑ Brands:
❖ GEMFIBROZIL (GEMPAR; NORMOLIP)
❖ BEZAFIBRATE (BEZALIP)
❖ FENOFIBRATE (LIPICARD)
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14. Nicotinic Acid (Niacin):
❑ It is a B-Vitamin group, higher dose can be reduced plasma lipids.
❑ This is unrelated to its vitamin activity and not present in nicotinamide.
❑ Nicotinic acid is the most effective drug to raise HDL-CH.
❑ Nicotinic acid reduces production of VLDL in liver by inhibiting TG-
synthesis.
❑ No direct effect on CH& bile acid metabolism has been found.
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ADR’s:
•Skin flushing,
•paresthesias,
•pruritus,
•GI upset,
•↑LFTs,
•hyperglycemia,
•Hyperuricemia
Brands:
NIALIP

16. Bile acid resins:
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❑MAO: Bind intestinal bile acids → ↓bile
acid stores & ↑ catabolism of LDL from
plasma.
❑ADR’s:
•Constipation,
•↑ Gallstone formation,
•GI upset,
•LFT abnormalities,
•Myalgias.
•↓ Absorption of drugs ADEK vitamins
from the small intestine.
❑Contraindications:
•Complete biliary obstruction( because bile
is not secreted into the intestine).
• Chronic constipation.
•Severe hypertriglyceridemia(TG >400
mg/dL)

17. Cholesterol absorption inhibitors (EZETIMIBE):
❑ It’s a new drug with its own kind of effect by cholesterol & phytosterols
absorption inhibition.
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NPC1L1-Specific
CH transport protein in
intestinal mucosa