Cholesterol Absorption Inhibitors, Fish Oils and Orlistat

Cholesterol Absorption Inhibitors

Exetimibe

It interferes with absorption of cholesterol and phytosterols in small intestine by interfering with a transport protein NPC1L1.

Decreases absorption of cholesterol
Decrease delivery of cholesterol to liver
In turn, decrease production of lipids
Decrease LDL by 17-18%
Decrease TG by 6%
Increase HDL by 1-2%

Potency

Not very potent drug. Given only when patient is not responding to other drugs.

Pharmacokinetics

a. Absorption –Exetimibe is readily absorbed

b. Metabolized by glucuronidation

c. PPC achieved in 12 hours

d. Half life –undergoes enterohepatic circulation so half life is increased up to 22 hours.

e. Elimination -80% in faeces

f. When co-administered with fibrates, there is increased plasma concentration of this drug.

g. When co-administered with bile acid binding resins, concentration decreases.

Uses

Primary hypercholesterolemia

Phytosterolemia

Adverse effects

1. GIT –can interfere with absorption of lipids -steatorrhea

Flatulence

2. Can produce liver injury

3. Rarely myositis

4. Does not interfere with absorption of fat soluble vitamins

Fish oils

Precursors of TGs
Decrease levels of VLDL, TG, and LDL.
Dose -5 g/day.

Orlistat

Weight reducing agent that decreases plasma lipid levels.
Decreases absorption of fatty acids and increases excretion, so plasma levels of lipids are decreased
Inhibits lipases in stomach, pancreas and intestines and decreases plasma lipid levels.
Loss of dietary lipids is about 30%
Loss of weight is about 5-10%

Adverse effects

GIT upsets

Interfere with absorption of fat soluble vitamins

Interfere with absorption of lipids

Dose

Given in a dose of 120 mg, thrice a day. Effect is very slow, and takes about 1-2 months. If there is decrease in weight in those 1-2 months, then continued for 2 years.