Statine

The statines (or inhibiting of HMG-CoA réductase ) form a class of Hypolipidémiant S, used as Médicament S to lower the Cholestérol emy of people who risk a Cardiovascular disease because of their Hypercholestérolémie.

Members

The statines include/understand:

the Atorvastatine
the Fluvastatine
the oldest Lovastatine, more hardly used
the Pravastatine
the most recent Rosuvastatine,
the Simvastatine
withdrawn of the market:

the Cérivastatine, withdrawn from the market in 2001 because of its serious side effects, in particular in partnership with Fibrate S.

Use

These molecules are effective in:

reduction in the cholesterol level in blood
reduction in the risk of occurred (primary Prevention) or of repetition (secondary prevention) of diseases resulting from the contracting or the occlusion of arteries (Myocardial infarction, Angina pectoris, Artériopathie obliterating of the lower extremities, Cerebral vascular accident).

There exist many studies concerning the effectiveness of one or the other of the statines on one or more parameters. It is currently not completely clearly if the reduction in the vascular risk is an effect of “class” (all the statines are equivalent), or if it is about a specific effect to each molecule which can thus differ in their effectiveness. In the same way, the connection between the fall of cholesterol in blood and the reduction in cardiovascular morbidity are not clearly established since the latter is observable, at the takers of statines, even at those which have a normal cholesterol.

A preventive effect is also suspecté in many other diseases but remains to be been formally shown. This effect is called pléiotrope . It is the case in particular of the Cardiac failure, in the prevention of the Cancer S (of which those of the colon or those of the lung, of the reduction of the frequencies of the fractures at the time of the Ostéoporose, of the reduction of the progression of the diabetes, in the prevention of the major venous thromboses (phlebites), in the prevention of the Démence. The multiplicity of these effects, usually called effects pleiotropes , do not have, a priori, relationship with the action on cholesterol. They could be due to properties anti-inflammatory drugs or anti-oxydative. They all were noted at the time of observational studies and little in randomized tests. The assumption of a skew of recruitment (the statines would be prescribed more readily among patients overall in better health condition or with better conditions of follow-up) was raised. The interest and the utility of the statines are currently constestés by a certain number of researchers and clinicians, the first of which Michel de Lorgeril, cardiologist and researcher at the CNRS, which is based precisely on the caused clinical studies and controlled tests, by underlining silences and contradictions raised in the majority of the articles published in the great international reviews. Michel de Lorgeril notes that these articles all are almost subsidized by the drug company and denounces what it calls the " cholesterol delirium" , by deploring that the war carried out against cholesterol occults the other risk factors (in particular the lifestyle, the food of the Western type, sedentariness…).

Pharmacology

Its metabolism is hepatic. A certain number are métabolysé by the means of the Cytochrome p450 (Lovostatine, Simvastatine, Atorvastatine, with a less fluvastatine degree), which make them sensitive with certain medicamentous interactions.

Groups

Mode of action

The statines act by decreasing LDL-cholesterol, by reducing the progression of the athéromateuse plate and the vascular markers of the ignition and by improving the dysfonction endothéliale.

Actions related to other factors that cholesterol

Safety

The principal side effects are of a hepatic and muscular nature.

The muscular attack is defined by a Myopathie (associating muscular pains, a weakness as well as a rise in the muscular enzymes (CPK) being able to go, in cases extrèmes, to a table of Rhabdomyolyse with a massive destruction of the muscles which can lead to the Impaired renal function. This risk increases with the prescribed amount of statines as at the time of certain interactions with other drugs (role of the Cytochrome P450) insulate in 1973 the mévastatine, first inhibiting of HMG-CoA réductase, the goal being to find new a Antibiotique, the inhibition of this enzyme which can cause the death of certain germs. The beneficial role of this molecule for the reduction of the rate of Cholestérol was evoked by Brown at the end of the Seventies.

The Lovostatine was commercialiée the first in 1987, was followed by the Simvastatine (1988), the Pravastatine (1991), the Fluvastatine (1994), the atorvastatine (1997) and the Rosuvastatine (2003). the Cérivastatine was introduced in 1998 but was withdrawn from the market three years later because of serious scondaires effects.

References

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