Statins- pharmacology in detail

1. 1
PHARMACOLOGY
ANTIHYPERCHOLESTERAEMIC AGENTS
Merlin Dinesh
M.Sc. CREM
FAHS, CARE

2. 2
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

3. 3
✓ 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

4. 4
ANTIHYPERCHOLESTRAEMIC /
ANTIHYPERLIPIDIMIC / HYPOLIPIDAEMIC AGENTS
Agents which lower the level of
lipids and lipoproteins in the blood
are called antihypercholestraemic
agents

5. 5
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.

6. 6
• 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

7. 7

8. 8
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

9. 9
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:

10. 10
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

11. 11
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

12. 12
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

13. 13
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

14. 14