Question

Q7. NV is a 45-year-old Caucasian female with a history of hypertension and type 2 diabetes, and elevated LDL. She is started on atorvastatin in an attempt to control her condition. She returns to her physician complaining of muscle weakness and pain. Her creatine kinase levels are tested and found to be high. a. What is the likely cause of her symptoms? b. What genetic test might be undertaken that could explain this reaction? c. Can the prescription continue to be safely taken or should it be modified? d. What other drug might be prescribed that acts independently of the affected genetic pathway in this individual?

Answer 1

A. Creatine kinase is an indicator of muscle damage. The observed phenomenon is termed as myositis. This is an inflammatory reaction caused by muscle injury, in this case it is drug induced (statin) induced myopathy. Statins are HMG-CoA reductase inhibitors, which is key enzyme in mevalonic access d synthesis. Mevalonic acid is precursor for cholesterol , but also important player in isoprenoid synthesis which are structural elements of vitamins like K, ubiquinone involved in oxidative phosphorylation calcium assimilation etc. while statins lower overall cholesterol production, it has to be noted cholesterol is an essential membrane component whose depletion result in suboptimal membrane strength which reflects in abnormal membrane excitation, especially in muscles cells

B. Statinsmart genetic test Can be undertaken to explain the reason for the symptoms seen. A gene SLCO1B1 codes for transporter protein that carries statins ( compounds) from blood to liver for their clearance. Mutation in this gene is reported to be responsible for statin induced myotoxicity.

C. Withdrawal of statin is imminent to decrease the myopathy symptoms, it should be modified

D.paravstatin seems to be lowest risk statin, and hence can be suggested as an alternative if statin mediated control is indispensable.