THERAPEUTIC ACTIONS ㅡ 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.

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).

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

CNS: Headache, blurred vision, dizziness, insomnia, fatigue, muscle cramps, cataracts.
GI: Flatulence, abdominal pain, cramps, constipation, nausea, vomiting, heartburn, elevations of CK, alkaline phosphatase, and transaminases.
Musculoskeletal: Rhabdomyolysis with possible 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 drug at bedtime; highest rates of cholesterol synthesis are between midnight and 5 AM. Consult with dietitian about low-cholesterol diets. Arrange for diet and exercise consultation. Provide comfort measures to deal with headache, muscle cramps, nausea. Arrange for periodic ophthalmologic examination to check for cataract development. Offer support and encouragement to deal with disease, diet, drug therapy, and follow-up.

TEACHING POINTS

Take these drugs at bedtime.
Institute appropriate diet changes.
Use contraceptive measures to avoid pregnancy while using these drugs.
Avoid grapefruit juice while taking these drugs.
Report severe GI upset, changes in vision, unusual bleeding or bruising, dark urine or light-colored stools; muscle pain, weakness.

MEDICATIONS

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

REFERENCES

Lexicomp, www.lexicomp.com
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
UpToDate, www.uptodate.com

Pharmacology of HMG-CoA inhibitors (Statins)