Atorvastatin cholesterol-lowering effects

In an isolated case, phenytoin reduced the cholesterol-lowering effect of simvastatin, fluvastatin and atorvastatin. The concurrent use of phenytoin and fluvastatin modestly raises the levels of both drugs. 

Thus, atorvastatin may have effects on inflammatory endpoints independent of cholesterol lowering. Activity on serum amyloid P could result in the lowering of plaque formation and inhibition of complement activation. 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

The answer is d. (Hardman, pp 885-886. Katzung, pp 591-592.) Atorvastatin is a structural analogue of an intermediate formed from the action of HMG-CoA reductase. This could result in a modest decrease in plasma cholesterol. Hepatic cholesterol synthesis may decrease significantly however, nonhepatic tissues increase their rate of synthesis as a compensatory mechanism. The other and perhaps more important effect of the HMG-CoA inhibitors is to increase high-affinity LDL receptors. The plasma LDL is lowered by this action because of an increase in the catabolic rate of LDL and hepatic extraction of LDL precursors. 

The adverse effects of statins have been reviewed in the light of the ever increasing dosages that are being used to lower LDL cholesterol to a minimum (2). In another review high doses of atorvastatin and simvastatin were specially emphasized (3). 

Other statins include simvastatin (also a lactone prodrug), pravastatin, atorvastatin, and cerivastatin (active form with open ring). The statins are the most important therapeutics for lowering cholesterol levels. Their notable cardiovascular protective effect, however, appears to involve additional actions. 

The ability of statins to lower hsCRP was first described for pravastatin using data accumulated in the Cholesterol and Recurrent Events (CARE) trial. These data were initially highly controversial because they suggested that statins have both hpid-lowering and antiinflammatory effects. However, confirmatory work rapidly showed the effect of statins on hsCRP to be a consistent and important class effect. Studies of atorvastatin, cerivastatin, lovastatin, pravastatin, and simvastatin have shown that, on average, median hsCRP concentrations decline 15% to 25% as early as 6 weeks after initiation of therapy. Importantly the magnitude of LDL cholesterol reduction caused by statin therapy is minimally correlated with the magnitude of hsCRP reduction. ... 

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