Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.
In many aspects, the present data agree with results of studies from other countries addressing the cooperation between GPs and OPs and/or other specialists. Many suggestions obtained in this study are practical and could be implemented into daily routine. Future quantitative research is required to better assess the relative weight of the suggestions presented here.
The decision whether to keep giving a drug or to discontinue it must always be made individually on the basis of current treatment goals; drug lists and a pertinent general practitioners' guideline can be useful aids in decision-making. Efforts to pay more attention to multimorbidity and polypharmacy in future studies and guidelines are deserving of support.
The data show potential interest of both physicians groups to develop cooperation. As the ratings often differed significantly, particularly in regard to statements presented, answers influenced by social desirability are generally unlikely.
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