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10:53 AM | Posted by Unknown

Lipid lowering agents : rapid review

Preface

Triglycerides:

* main constituent of vegetable oil & animal fat .

* High triglycerides (normal range 150mg/dl ) lead to atherogenesis .

* It's used by the body as energy store except for the brain

Cholesterol:

* Used as building block of biological membrane & precursor for most steroid hormones .

* Rate limiting enzyme in cholesterol synthesis in the liver is HMGCA reductase enzyme .

* Liver use cholesterol in the synthesis of bile acids & VLDL .

* 85% of the blood cholesterol is produced in the body .

Lipid lowering agents

1- Statins (atorvastatin, fluvastatin, rosuvastatin, simvastatin) .

* Mechanism of action : statins are inhibitors of HMGcoA reductase (hydroxyl methyl glutaryl co A enzyme) so they inhibit cholesterol synthesis .in addition to that, they increase expression of LDL receptor .

* statins may occur naturally in some foods like mushroom & red yeast rice .

* Cholesterol synthesis appears to occur mostly at night so short acting statin e.g.simvastatin ( zocor) must be taken at night to maximize its effect but long acting statin e.g.atorvastatin (lipitor) may be taken at any time .

* The most potent statin [atorvastatin , rosuvastatin (crestor)]

* The least potent statin {fluvastatin (lescol) }

* The result of statin therapy appears rapidly may be after one week

* Side Effects : rarely [skeletal musculature damage , liver enzymes become high ]

2-fibrates (bezofibrate, etofibrate, gemfibrozil, fenofibrate)

* Used as accessory therapy in many forms of hypercholesterolemia usually in combination with statins specially fenofibrate (tricor) and gemfibrozil (lopid600) because using of them with statin will increase muscle toxicity by decreasing statin metabolisms .

* It's indicated solely for patient no tolerant to statin .

* Mechanism of action :- activate PPAR (peroxisome proliferators activated receptor) which induce transcription of number of genes that facilitate lipid metabolism, also it decrease VLDL and increase HDL .

* When triglycerides increase more than 1000mg/dl lead to pancreatitis with abdominal pain &
as fibrates decrease triglycerides they decrease pancreatitis .

* Side effects : high risk of gallstones (use over several years) myopathy, myalgia and rhabdomyolysis .

* Usage of statins with fibrates may increase the likelihood of rhabdomyolysis & liver
failure .

3-nicotinic acid [niacin or vit b3 & its derivatives ]

* Mechanism of action : stimulate endolthelial lipoprotein lipase so decease triglycerides .

* At the first of the therapy PG mediated vasodilatation occur leading to 2 side effects {flushing and hypotension} .

* To overcome these 2 side effects 325mg of ASA can be taken 30 min prior to nicotinic acid (niaspan) . also the extended release dosage decrease flushing

* Flushing which occur as side effect of nicotinic acid may make nicotinic acid to be used for male impotence .

* Deficiency of vit b3 may lead to pellagra disease (3 diseases : diarrhea, dementia & dermatitis)

4-cholesteramine & colestipol :

* They are bile acid sequestrants which bind bile acid in the GIT & prevent its reabsorbtion . As bile acid decrease , liver convert cholesterol into bile acid so cholesterol decrease .
* Side effects of cholesteran (questran) & colestipol (colestid) :

a- diverse GIT disturbance (constipation , diarrhea) .

b- decrease the absorption of lipid soluble vitamins (A,D,E,K) .

c- decrease absorption of vit K antagonist , digitoxin , diuretics .

* If used with any other drug (statin or other) must be taken 1hour after the

drug or the other drug taken 4 hour after it as they bind statin in the intestine

& decrease its absorption .

5- omega-3 (polyunsaturated fatty acid [eicosapentanoate-docosahexapentaneoate]

* Decrease each of (trigycerides, synsises of VLDL lipoprotein B , remnant particles) .

* Although it doesn't decrease LDL or total cholesterol, with increasing some dietary supplements as fish-leafy green vegetables-nuts-hummus-eggs- linseed-flaxseed this decrease Congestive heart disease .

6-probucol :
decrease HDL more than LDL nonetheless decrease atherogenesis and that may be due to decreasing LDL oxidation .

*references: color atlas of pharmacology, drugs.com, wikepedia, medicine.net, master of Egypt's drugs, master of Sadie's drugs .

*prepared by : Dr. Mostafa Abd eltawab .
*all rights are reserved for pharmacist development group .

====================================================================================

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