by mallika.b.n m.sc mbhg 060149006

8/14/2019 By Mallika.b.n m.sc Mbhg 060149006

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INTRODUCTION

"Statins" are a class of drugs that lowerthe level ofcholesterol in the blood by

reducing the production of cholesterol bythe liver

Scientifically, statins are referred to asHMG-CoA reductase inhibitors.

They also lower the concentrations ofplasma LDL and VLDL levels
http://www.medicinenet.com/script/main/art.asp?articlekey=320http://www.medicinenet.com/script/main/art.asp?articlekey=320


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BACK


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HISTORY

And the credit goes toAKIRA ENDO &MASAO KURODA

Started a project in 1971 to search for microbialmetabolites that inhibit HMG-CoAreductase

Implying plasma cholesterol reductions in humans

Led to the discovery of MEVASTATIN from

P.citrinum 1st statin approved for use in humans

LOVASTATIN (merck) from A.terreus


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BACK


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MECHANISM OF ACTION

Inhibit hepatic cholesterol synthesis

Increased expression of LDL receptor gene

Increased uptake of LDL from blood


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ABSORPTION,

METABOLISM &

EXCRETION Administered orally & at bedtime

Intestinal absorption:- 30% - 85%

Administration:

1) Most of the statins- active form

2) simvastatin & lovastatin-inactive prodrugs Uptake by the liver:

1) Mediated by organic anion transporter 2 (OATP)

2) Simple diffusion

Liver biotransforms all statins & >70% statin metabolites are

excreted by the liver with subsequent elimination in the feces.


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PLIEOTROPIC EFFECTS

OF STATIN

Statin therapy enhances endothelial production of

the vasodilator nitric oxide, leading to improved

endothelial function after a month of therapy Statins decreased the risk of CHD and levels of C-

reactive protein

). Statins reduce the susceptibility of lipoproteins

to oxidation both in vitro and ex vivo

STATINS & coagulation


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Doug Peterson developed slurred speech,balance problems and severe fatigue afterthree years on Lipitor--for two and a halfyears, he had no side effects at all. Itbegan with restless sleep patterns--twitching and flailing his arms. Loss of

balance followed and the beginning ofwhat Doug calls the "statin shuffle"--aslow, wobbly walk across the room. Finemotor skills suffered next. It took himfive minutes to write four words, much ofwhich was illegible. Cognitive functionalso declined. It was hard to convince hisdoctors that Lipitor could be the culprit,but when he finally stopped taking it, his

coordination and memory improved.

My Husband had a cholesterol level of7. He was prescribed simvastatin 18months ago 40mg. Previously he hadmanaged to reduce his cholesterol toaround 6 by diet but it kept creeping upagain. Heart disease was a hereditary

factor in his family.Firstly after takingsimvastain, he suffered constipationand had slight pain in the groin and hiparea. He went to the Doctor who couldfind nothing wrong and eventuallyreduced his statin to 20mg. All theseailments disappeared but unfortunatelyhe has now been diagnosed with

prostate cancer. I believe thatsimvastatin is responsible for thisdiagnosis


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ADVERSE EFFECTS

MILD UNWANTEDEFFECTS:

Gastrointestinal

disturbance Insomnia

Rashes

Increased plasmaconcentrations of liverenzymes

SERIOUS EFFECTS:

Rhabdomyolysis

Hepatotoxicity


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CONCLUSION


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STATIN IS ADVISABLE

Provided that the patients metabolic

response to statin is under surveillance


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REFERENCES

Chapter 35: . drug therapy for hypercholesterolemiaand dyslipidemia -Robert W. Mahley and Thomas P.

Bersot

Essentials of medical pharmacology:K.D.Tripathi

Brodys human pharmacology- molecular toclinical- 4th ed- by minneman & wecker

medical pharmacology at a glace- 4thed;m.j neal

World wide web


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NOT OVER YET

by mallika.b.n m.sc mbhg 060149006

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