Statins are a class of drugs that lower blood cholesterol levels by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. They work by reducing cholesterol production in the liver and increasing uptake of LDL cholesterol from the bloodstream. Common statins include atorvastatin, simvastatin, and rosuvastatin, which can lower LDL cholesterol by 40-60% and are first-line treatments for high cholesterol. Statins are well absorbed orally and metabolized in the liver, with some variations in pharmacokinetics between different statins. They are effective for treating familial hypercholesterolemia and secondary causes of high cholesterol like diabetes. Adverse effects can include muscle

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PHARMACOLOGY
ANTIHYPERCHOLESTERAEMIC AGENTS
Merlin Dinesh
M.Sc. CREM
FAHS, CARE

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Lipids and proteins form complexes called
lipoproteins and circulate in the blood vessels.
LIPID TRANSPORT
Types of lipoproteins:
✓ Chylomicron
✓ Chylomicron remnant
✓ Very Low Density Lipoproteins (VLDL)
✓ Intermediate density lipoprotein (IDL)
✓ Low density lipoprotein (LDL)- Bad CH
✓ High density lipoprotein (HDL)- Good CH
Lipids can be
• Triglycerides
• Cholesterol
• Cholesterol esters
• Phospholipid

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✓ Hypercholesterolemia refers to increased
levels of cholesterol in the blood.
✓ It is also called high cholesterol.
✓ Our body needs some cholesterol to make
hormones and digest fatty foods.
✓ But too much raises the risk of heart
disease and other cardiovascular problems.
HYPERCHOLESTRAEMIA

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ANTIHYPERCHOLESTRAEMIC /
ANTIHYPERLIPIDIMIC / HYPOLIPIDAEMIC AGENTS
Agents which lower the level of
lipids and lipoproteins in the blood
are called antihypercholestraemic
agents

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STATINS (HMG Co A Reductase inhibitors)
• Statins are drugs that lower the Blood cholesterol by inhibiting the
enzyme HMG Co A Reductase
• Therapeutic doses of statins reduce Cholesterol synthesis by 20-50%.
• Different statins differ in their potency and maximal efficacy in
reducing the LDL-CH.

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• 3-Hydroxy3-methylglutaryl-CoA reductase (HMG-CoA) is the
rate-controlling enzyme in the biosynthesis of cholesterol.
• Statins competitively inhibit conversion of HMG-CoA to
mevalonate by the enzyme HMG-CoA reductase.
• This results in reduced synthesis of Cholesterol and
compensatory increase in LDL receptor expression on liver cells
and causes increased receptor mediated catabolism
STATINS-
MECHANISM OFACTION

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PHARMACOKINETICS
➢ Good oral absorption
➢ Extensive FPM
➢ Should be administered at bedtime to obtain
maximum effectiveness because HMG Co A
reductase activity is maximum at midnight.
• Exception: Atorvastatin and rosuvastatin has
long plasma half life.
➢ All statins are metabolized by CYP3A4
• exception: Rosuvastatin

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CLINICAL USES:
• first-line drugs for familial hyperlipidemia with raised LDL CH and total CH
• First choice for secondary hyperlipidaemia as in diabetes mellitus.
• lower morbidity and mortality in patients with coronary heart disease. (used in MI, angina, stroke and transient
ischemic attacks to lower cholesterol levels.
PLEOTROPIC USES:

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ADVERSE EFFECTS CONTRAINDICATION
Statins are contra indicated in
• pregnancy
• Lactation
• Diabetes (chance of 10% increase in diabetes)
H- Hepatotoxicity
M- Myositis, myopathy
G- GI disturbance
Co- ↑ Creatin kinase
A Allergic reaction, Angioedema
R Rashes, Rhabdomylosis
I Insomnia

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DRUG INTERACTIONS
• Enzyme inhibitors: grapefruit juice and drugs that inhibit
microsomal enzymes (erythromycin, amiodarone,
metronidazole, ketoconazole) can raise the plasma levels of
statins.
Statins are metabolized by the CYP450 enzyme system
• Enzyme inducers: Drugs that induce microsomal enzymes like rifampicin, barbiturates,
phenytoin, can speed up the metabolism and lower plasma levels of statins.
• Statins + fibrates = myositis & rhabdomyolysis

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LOVASTATIN
• Lipophilic
• Given as lactone precursor form
• Incomplete oral absorption
• Extensive FPM
• Metabolites are excreted in bile
SIMVASTATIN
• Lipophilic
• Given as lactone precursor form
• Better oral absorption
• Extensive FPM
• t Τ
1
2 = 2- 3 hr
ATORVASTATIN
• Most common statin
• Lower LDL CH by 55-60%
• t Τ
1
2 = 14 - 18 hrs
• Reduces TG
DRUGS

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DRUGS
PITAVASTATIN
• Latest
• Lower LDL CH by 40%
• t Τ
1
2 = 12 hr
ROSUVASTATIN
• Most common statin
• High potency; high efficacy
• Lower LDL CH
• Raises HDL CH
• t Τ
1
2 = 18 - 24 hrs
• Reduces TG
PRAVASTATIN
• Hydrophilic
• Given as active form
• Potency & efficacy = lovastatin
• t Τ
1
2 = 1- 3 hr

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