A 62-year-old woman on atorvastatin 80 mg daily for 6 months presents with progressive myalgias and proximal muscle weakness. Vital signs: BP 138/82, HR 88, RR 16, Temp 37°C, SpO2 98%. Serum creatine kinase is markedly elevated at 2,500 U/L; urinalysis shows no myoglobinuria. LDL cholesterol decreased appropriately to 65 mg/dL. She denies recent alcohol use or concurrent medications. Which mechanism best explains statin-induced myotoxicity?
- A)Enhanced muscle protein degradation through upregulation of ubiquitin-proteasome pathway
- B)Accumulation of oxidized LDL in the muscle membrane
- C)Depletion of mevalonate-derived products essential for protein prenylation and mitochondrial functionGABARITO
- D)Increased circulating triglycerides causing lipotoxicity in muscle
- E)Direct inhibition of myosin heavy chain synthesis
Explicação
Statins inhibit HMG-CoA reductase, blocking mevalonate synthesis. Mevalonate is not only a precursor for cholesterol but also for prenylation of small GTPases (Ras, Rac, Rho) and ubiquinone synthesis. Deficiency of these prenylated proteins and CoQ10 impairs m... Ver explicação completa e trilha adaptativa →