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Statins

The most popular and loved Anti hyperlipidemics world wide are the Statins.

Mechanism of Action: 

They act by inhibiting HMG CoA Reductase enzyme. The results of Statin use over lipid profile may be listed as below-

  • Decreased Liver Cholesterol levels.
  • Decreased LDL.
  • Decreased VLDL synthesis and Decreased Triglycerides.
  • Increased HDL cholesterol to some extent.
  • Increased LDL receptor expression.
Since HMG CoA Reductase activity is at its peak at midnight, Statins are given at bed time. But Atorvastatin and Rosuvastatins have long half lives (t1/2), therefore they need not be timed at bed time specifically. Statins are most potent LDL lowering agents.  They are the number 1 drug of choice in case of Metabolic Syndrome (along with Metformin).

Longest acting Statin is Rosuvastatin (14 hrs half life). The Statins also have anti-inflammatory and anti-oxidant properties (especially Atorvastatin), thereby making them good drugs to prevent atherosclerosis and giving stability to atherosclerotic lesions if they had already formed.

Another interesting area where Statins can be used is in Alzheimer's Disease. Statins reduce prenylation of proteins. Prenylated Rho activates Rho kinase causing Vascular pathology. Prenylated Rab increases accumulation of A Beta proteins in neurons. Statins can be helpful here.

Side-Effects:

  • Hepatotoxic- Bad for Liver. Need to monitor Liver Function Tests (LFT) while starting a patient on Statins.
  • Myopathy and Myalgia- Monitor Creatine Kinase. Genetic variation in an Anion transporter (OTP1B1) is involved in sever myopathy and Rhabdomyolysis. Myopathy of Statins is increased by drugs such as- Nicotinic Acid, Gemfibrozil,Clofibrate, Erythromycin, Ketaconazole, Cyclosporine and HIV Protease Inhibitors.
  • Rhabdomyolysis. Gemfibrozil potentiates this side effect.
  • Lovastatin additionally causes lens opacities.
  • Pravastatin reduces plasma fibrinogen levels.
Clinical Situation (Question):

I got this question from a colleague on a doctors' networking site:

"64 yr old pt is on medication for Hypertension & dyslipedemia ( Enarapril 10 mg, Amlodipine Besilate 25, Rosuvastatin10 mg & Aspirin 75 mg). Pt BP is well controlled & is asymptomatic. Current biochemical profile is as follows:- Blood Sugar F-86, PP- 110 ,Blood Urea-24, Creatinine-0.8,Cholesterol-116 (Triglyceride-96,LDL-54,HDL-35),Uric acid-4.0,SGOT-38,SGPT-21- Is stopping Tab Rosuvastatin for Dyslpiedmia indicated? If not when & why indicated?"

Best Answer that I could find was:

"Dear Doctor, Evaluale the cardiovascular risk factor assesment and continue statin only if moderately-high to high risk profile patients. Recent guidelines have disreputed the LDL values to a great degree and have recomended the treatment on basis of cardiovascular risk status of the patient."

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