Simvastatin is a methyl analogue of lovastatin and acts as an HMG-CoA reductase inhibitor effective in the treatment of hypercholesterolaemia. Like lovastatin, it is an inactive hydrophobic lactone prodrug which is metabolised in vivo to several more polar, pharmacologically active compounds, most notably the corresponding hydroxy acid form, simvastatin acid. HPLC techniques have been developed to assay simvastatin and its metabolites. In addition, a pharmacodynamic assay has been developed that measures HMG-CoA reductase inhibitory activity. This latter assay may be more applicable to clinical situations since simvastatin is not active, while its metabolites are. Simvastatin is well absorbed from the gastrointestinal tract but is highly extracted by the liver and only 7% of the dose reaches the general circulation intact. The peak inhibition of HMG-CoA reductase activity occurs within 2 to 4 hours. Increasing the dose of simvastatin from 5 to 120 mg increases the pharmacological activity in a linear fashion. The several metabolites tend to remain within the liver and the intestines (via biliary excretion). Some gastrointestinal reabsorption of metabolites may occur. Simvastatin is eliminated mainly in the faeces due to biliary excretion but only a small percentage of the dose is found in the stool in the form of the parent compound or simvastatin acid. Since simvastatin is metabolised by the cytochrome P450 system, a potential for drug interactions exists. Elevated HMG-CoA reductase inhibitory activity has been observed when simvastatin was administered concurrently with cyclosporin, possibly increasing the risk of myopathy and subsequent rhabdomyolysis which are associated with simvastatin use. Simvastatin has also been shown to potentiate the effects of warfarin [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)

Based on the data currently available, it appears that ezetimibe has a potential role in the treatment of primary hypercholesterolemia; however further data are needed to determine its long-term tolerability and efficacy. The potential roles for ezetimibe include its concurrent use with a statin to further enhance the lowering of LDL-C. Other possible roles for ezetimibe include its concurrent use with a statin to permit a lowering of statin dosage to avoid statin-related complications or its use as monotherapy to treat hypercholesterolemia when statin use cannot be tolerated or is contraindicated. Outcome data demonstrating that cardiovascular morbidity and/or mortality are reduced by ezetimibe therapy have yet to be generated.

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Syncope is a common disorder with many different etiologies. The patient's history and physical examination are extremely important in making the diagnosis. The recent availability of head-upright tilt testing and electrophysiologic studies of the myocardium have helped define the etiology in many patients in whom an etiology would not have been found in the past. When the cause of syncope has been diagnosed, the appropriate therapy to prevent future attacks will be defined in many instances. One form of syncope, known as neurocardiogenic syncope, can be difficult to treat. Recent trials have suggests the use of beta-blockers, fludrocortisone, disopyramide, or selective serotonin reuptake inhibitors may be helpful in some patients.