rosuvastatin

Mechanism: Rosuvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. This upregulates LDL receptor expression on hepatocytes, increasing LDL clearance from the blood and lowering LDL-C by up to 55% (high-intensity statin). It also modestly raises HDL and lowers triglycerides.

Pharmacokinetics: Hydrophilic statin (compared to lipophilic atorvastatin/simvastatin), minimally metabolized by CYP450 (primarily CYP2C9, minor CYP3A4), giving it fewer drug interactions than atorvastatin/simvastatin. Long half-life (~19 hours) allows once-daily dosing at any time.

Clinical uses: Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), hyperlipidemia, familial hypercholesterolemia. Classified as a high-intensity statin at doses of 20-40 mg (along with atorvastatin 40-80 mg).

Adverse effects: Myopathy/myalgia, rare rhabdomyolysis (risk increased with fibrates, especially gemfibrozil), hepatotoxicity (transaminase elevation), increased risk of new-onset diabetes mellitus, teratogenic (avoid in pregnancy). Statins are contraindicated in active liver disease and pregnancy.

Monitoring: Baseline and periodic LFTs (though routine monitoring is now less emphasized), lipid panel to assess efficacy, CK levels if muscle symptoms occur.

Board relevance: Know statin mechanism, high-intensity vs moderate-intensity dosing, statin-associated myopathy pathophysiology (possibly related to CoQ10 depletion and altered muscle cell membrane), and the importance of LDL receptor upregulation in mechanism of action. Also tested: statins reduce mortality in ASCVD, are first-line for LDL lowering, and rosuvastatin's renal excretion (partial) vs primarily hepatic metabolism of other statins.