Pharmacology of HMG-CoA inhibitors (Statins)
Therapeutic actions
HMG-CoA inhibitors are antihyperlipidemic. They are a fungal metabolite that inhibits the enzyme that catalyzes the first step in the cholesterol synthesis pathway in humans, resulting in a decrease in serum cholesterol and serum LDLs (associated with increased risk of CAD); either an increase or no change in serum HDLs (associated with decreased risk of CAD); and a decrease in triglycerides.
Clinical pharmacology
Indications
Adjunct to diet in the treatment of elevated total and LDL cholesterol in patients with primary hypercholesterolemia (types IIa and IIb) whose response to dietary restriction of saturated fat and cholesterol and other nonpharmacologic measures has not been adequate. Primary prevention of coronary events (lovastatin, pravastatin). Secondary prevention of CV events (fluvastatin, lovastatin, pravastatin, simvastatin). Pregnancy category X (contraindicated).
| Table (1). High-, Moderate-, and Low-Intensity Statin Therapy Recommended by the ACC/AHA Guideline | ||
|---|---|---|
| High-intensity statin therapy | Moderate-intensity statin therapy | Low-intensity statin therapy |
| Atorvastatin (Lipitor), 40 to 80 mg | Atorvastatin, 10 mg | Lovastatin, 20 mg |
| Rosuvastatin (Crestor), 20 mg | Fluvastatin, 40 mg twice daily | Pravastatin, 10 to 20 mg |
| Lovastatin, 40 mg | ||
| Pravastatin (Pravachol), 40 mg | ||
| Rosuvastatin, 10 mg | ||
| Simvastatin (Zocor), 20 to 40 mg | ||
Contraindications
Contraindicated with allergy to HMG-CoA inhibitors, fungal byproducts, pregnancy, or lactation, concurrent gemfibrozil therapy. Use cautiously with impaired hepatic function, cataracts.
Adverse effects
Statins can cause various adverse effects across different systems in the body. CNS effects include headache, blurred vision, dizziness, insomnia, fatigue, muscle cramps, and cataracts. Gastrointestinal side effects include flatulence, abdominal pain, cramps, constipation, nausea, vomiting, heartburn, and elevations in creatine kinase (CK), alkaline phosphatase, and transaminases. In the musculoskeletal system, statins can potentially cause rhabdomyolysis, which may lead to renal failure.
Interactions
Monitor patients receiving HMG-CoA inhibitors for possible severe myopathy or rhabdomyolysis if taken with cyclosporine, erythromycin, gemfibrozil, niacin, azole antifungals. Risk of increased serum levels if combined with grapefruit juice.
Clinical considerations
Administer the drug at bedtime, as the highest rates of cholesterol synthesis occur between midnight and 5 AM. Consult with a dietitian about low-cholesterol diets and arrange for diet and exercise consultations. Provide comfort measures to manage headache, muscle cramps, and nausea. Arrange for periodic ophthalmologic examinations to check for cataract development. Offer support and encouragement to help patients cope with the disease, diet, drug therapy, and follow-up.
Teaching points
Take these drugs at bedtime. Institute appropriate diet changes and use contraceptive measures to avoid pregnancy while using these drugs. Avoid grapefruit juice while taking these medications. Report any severe gastrointestinal upset, changes in vision, unusual bleeding or bruising, dark urine or light-colored stools, and muscle pain or weakness.
References
- Rosenson RS. Statins: Actions, side effects, and administration. UpToDate. https://www.uptodate.com/contents/statins-actions-side-effects-and-administration.
- Sizar, O., Khare, S., Jamil, R.T. and Talati, R. (2020). Statin Medications. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK430940.
