5 - HMG-CoA Reductase Inhibitors

What are the HMG-CoA reductase inhibitors?

• atrovastatin

• fluvastatin

• lovastatin

• pitavastatin

• pravastatin

• rosuvastatin

• simvastatin

What is the MOA of Statins?

competitively inhibits HMG-CoA reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol synthesis.

What is the effect of statins on LDL?

reduces LDL ~30% by decreasing it’s production and increasing expression of LDL receptors of liver cell membranes

What is the effect of statins on HDL & TG?

increases HDL by 5-10%, decreases TG by 10-30%

What is the rule for dose-dependent LDL reduction?

the rule of 6: for every doubling of a dose, there is 6% more of a reduction of LDL

When are the maximal effects on serum lipids seen?

4 weeks

What is the exception for statin efficacy?

not effective for homozygous familial hypercholesterolemia (HoFH)

Which ingredients are high-intensity statins and what is their effect?

• atorvastatin 40-80mg

• rosuvastatin 20-40mg

daily dose lowers LDL by ~50% on average

Which ingredients have a long t_1/2?

atorvastatin, pitavastatin, and rosuvastatin

Atorvastatin, lovastatin, and simvastatin are metabolized by what enzyme?

CY3A4

Fluvastatin is metabolized by what enzyme?

CYP2C9

How is pravastatin eliminated?

unchanged in the urine

What is rosuvastatin eliminated?

unchanged in the feces; ~10% CYP2C9

What drugs should be avoided with statins?

• CYP3A4 inhibitors

• gemfibrozil - nearly doubles plasma concentration

What are the two mechanisms for gemfibrozil interaction with statins?

1. inhibits transport of statins into hepatocytes for metabolism and into bile/feces for elimination

2. inhibits hepatic glucuronidation of statins

What are the musculoskeletal ADE of statins?

• myalgia

• myopathy (CK elevated 10x upper limit of normal)

• rhabdomyolysis (CK elevated 40x ULN)

What are the risk factors for musculoskeletal ADE of statins?

concentration-dependent effect:

• higher doses

• drug interactions

• advanced age (>80 years)

• hepatic dysfunction

• renal dysfunction

untreated hypothyroidism, strenuous exercise

What are the ADE of statins?

• hepatotoxicity

• hyperglycemia & diabetes

• renal

What are the patient care considerations of statins?

• timing of dose - evening/bedtime

• pregnancy - should be discontinued

• intolerance

What should be monitored when on a statin?

• fasting lipid profile at baseline and 4-6 weeks after initiation/dose change

• liver enzymes at basline

• CK only when muscle symptoms develop