ANTILIPEMIC DRUGS(ANTIHYPERLIPIDEMIC AGENTS)

By: MJJH

ANTILIPEMIC DRUGS(ANTIHYPERLIPIDEMIC AGENTS)

Used for patients/clients with elevated blood lipids, such as cholesterol, triglycerides, and phospholipids.

Drugs are used in combination with lifestyle changes (such as proper diet, weight loss, and exercise) to decrease

the risk of CAD.

THE CLASSES OF ANTILIPEMIC DRUGS

INCLUDE:

BILE-SEQUESTERING DRUGS- The bile-sequestering drugs are cholestyramine, colestipol, and

colesevelam.

Bile Sequestering drug bind with bile acids, leading to their

excretion in the feces.

Pharmacokinetics-Bile-sequestering drugs aren’t

absorbed from the GI tract. Instead, they remain in the

intestine, where they combine with bile acids for about 5 hours.

Eventually, they’re excreted in stool.

Pharmacodynamics-The bile-sequestering drugs lower blood levels of low-density lipoproteins

(LDLs). These drugs combine with bile acids in the intestines to form an insoluble compound

that’s then excreted in stool. The decreasing level of bile acid in

the gallbladder triggers the liver to synthesize more bile acids.

Pharmacotherapeutics- Bile-sequestering drugs are the drugs

of choice for treating type ii hyperlipoproteinemia (familial

hypercholesterolemia) when the patient can’t lower his LDL levels

through diet alone.

Drug interactions- They may bind with acidic drugs in the GI

tract, decreasing their absorption and effectiveness. Bile-

sequestering drugs may reduce absorption of lipid-soluble

vitamins, such as vitamins A, D, E and K. Poor absorption of vitamin K can affect prothrombin times

significantly, increasing the risk of bleeding.

ADVERSE REACTIONS TO BILE-SEQUESTERING DRUGS

Short-term adverse reactions to these drugs are relatively mild.

More severe reactions can result from long-term use. Adverse GI effects with long-term therapy include severe fecal impaction,

vomiting, diarrhea, and hemorrhoid irritation.

FIBRIC ACID DERIVATIVES

Fibric acid is produced by several fungi. Two derivatives of this acid are Fenofibrate and gemfibrozil.

These drugs are used to reduce high triglyceride levels, and to a lesser extent, high LDL levels.

Pharmacokinetics- Fenofibrate and gemfibrozil are

absorbed readily from the GI tract and are highly protein-

bound. Fenofibrate is hydrolyzed while gemfibrozil

undergoes extensive metabolism in the liver. Both

drugs are excreted in the urine.

Pharmacodynamics- Although the exact mechanism of action for these

drugs isn’t known, researchers believe that fibric acid derivatives may:

•Reduce cholesterol production early in its formation

•Mobilize cholesterol from the tissues•Increase cholesterol excretion

•Decrease synthesis and secretion of lipoproteins

•Decrease synthesis of triglycerides.

Pharmacotherapeutics- Fibric acid drugs are used primarily to

reduce triglyceride levels, especially very-low-density

triglycerides, and secondarily to reduce blood cholesterol levels. They’re typically used to treat

patients with types ii, iii, iv, and mild type v hyperlipoproteinemia.

Drug interactions- Fibric acid drugs may displace acidic drugs, such as barbiturates, phenytoin, thyroid derivatives, and cardiac glycosides. The risk of bleeding

increases when fibric acid derivatives are taken with oral

anticoagulants.

HMG-COA REDUCTASE (OR 3-HYDROXY-3-METHYL-GLUTARYL-

COA REDUCTASE OR HMGCR)is the rate-controlling enzyme of the mevalonate pathway, the metabolic

pathway that produces cholesterol and other

isoprenoids.If these enzyme is blocked, serum

cholesterol and LDL levels decrease, because more LDLs are absorbed by

the cells for processing into cholesterol. HDL levels increase slightly with this alteration in fat

metabolism.

Therapeutic Action and Indications- HMG-coA Reductase inhibitors block the formation of cellular cholesterol, leading to

decrease in serum LDLs, with a slight increase or no change in the levels of HDLs. Because these drugs undergo a

marked first-pass effect in the liver, most of their effects on the process that generates atheromas in vessel

walls. That exact mechanism of action is not understood.

These drugs are indicated as adjuncts with diet and exercise for the treatment of increased cholesterol and LDL levels that

are unresponsive to dietary restrictions alone; to slow the progression of CAD in patients with documented CAD; and to prevent first MI in patient who

are at risk for MI.

Pharmacokinetics-the statins are all absorbed from the GI tract

and undergo the first- pass metabolism in the liver. They are excreted in the feces and urine. The peak effect of this drug is usually seen within 2-4 weeks. These drugs cross the placenta and have been associated with skeletal malformations of he

fetus.

Contraindications and action- These drugs are contraindicated in the presence of allergy to any

of the statins or to fungal byproducts or compounds. They

are also contraindicated with active liver disease or a history of alcoholic liver disease, w/c could exacerbate, leading to

severe liver failure.

Adverse Effect- The most common adverse effects

associated with these drugs reflect their effects on the GI system: flatulence, abdominal pain, nausea, vomiting, and

constipation. CNS effects can include headache, dizziness, blurred vision, fatigue, and

cataract development and may effect changes in the cell

membrane and synthesis of cholesterol.

Cholesterol Absorption Inhibitors- are a class of

compounds that prevents the uptake of cholesterol from the small

intestine into the circulatory system.

Lower the amount of cholesterol that your body absorbs. So your blood has lower total cholesterol and lower LDL (bad) cholesterol

Therapeutic action and indications- Ezetimibe works in the brush border of the small intestine

to decrease the absorption of dietary cholesterol, leading to drop in serum cholesterol levels. It is indicated as an adjunct to diet and exercise to

lower cholesterol levels as monotherapy or as part of

combination therapy with an HMG-CoA inhibitors or a bile acid

sequesterant.

Pharmacokinetics- Ezetimibe is absorbed well after oral

administration, reaching peak levels in 4-6 hours. It is

metabolized in the liver and the small intestine, with a 22 hours half- life. Excretion in the feces

and urine.

Contraindications and Cautions- Ezetimibe is

contraindicated with allergy to any component of the drug. If it

is used in combination with a statin, it should not be used

during pregnancy or lactation or with severe liver disease

because of the known effects of statins, including possible liver

problems and renal failure.

Adverse Effect- The most common adverse effect associated with

ezetimibe are mild abdominal pain and diarrhea. It is not associated with the bloating and flatulence

that occurs with the bile acid sequestrants and fibrates, other

adverse effect have been reported include headache, dizziness,

fatigue, URI, back pain, muscle aches and pain.

NICOTINIC ACID- Lowers total cholesterol, LDL-cholesterol, and triglyceride levels, while raising

HDL-cholesterol levels.Vitamin B (Niacin) or Nicotinic Acid, inhibits release of free fatty acids in

the adipose tissue, increases the rate of triglyceride removal form

plasma, and generally reduces LDL and triglycerides level and increases

HDL levels.

The initial effect on lipid levels is usually seen within 5 to 7 days,

with the maximum effect occurring 3 to 5 weeks. Niacin is

associated with intense cutaneous flushing, nausea, and abdominal pain, making its use

somewhat limited.

It also increases serum levels of uric acid and may predispose patients to the development of gout. Niacin is often combined with bile acid sequestrants fro increased effect. It is given at

bedtime to make maximum use of nighttime cholesterol synthesis, and it must be given 4 to 6 hours after bile sequestrant to ensure

absorption.