Treatment of Hyperlipidemia

Study Notes

Certain drugs should be avoided in pregnant and lactating women, and those likely to become pregnant.
All drugs that alter plasma lipoprotein concentrations may require adjustment of warfarin doses.

Children with heterozygous familial hypercholesterolemia may be treated with resins or statins after 7 or 8 years of age, when myelination of the CNS is complete.
The decision to treat a child should be based on the level of LDL, other risk factors, the family history, and the child's age.
Drugs are rarely indicated before age 16.

Mechanism of action: Inhibit the synthesis/activity of HMG-CoA reductase, leading to increased LDL receptors and decreased secretion of VLDL.
Clinical effects:
- Decrease LDL cholesterol by 30-40%.
- Decrease plasma triglycerides by 10-30%.
- Increase HDL cholesterol by 5-15%.
Therapeutic uses:
- Familial and non-familial hypercholesterolemias.
- May reduce the incidence of some cancers.
- May reduce osteoporosis.
- May have weak anti-inflammatory activity.
Adverse effects:
- Nausea, epigastric fullness, distension, constipation, and headache.
- Mild increase in transaminases.
- Myositis (0.1-0.2%).
- Rarely, rhabdomyolysis.
- Hypotension.
Combination regimens: Statins/bile acid sequestrants combination exerts an additive effect on LDL cholesterol.

Mechanism of action: Bind bile acids, preventing enterohepatic recycling of bile acids, leading to increased synthesis of bile acids from endogenous cholesterol.
Clinical effects:
- Decrease LDL cholesterol by 10-30% in patients with normal LDL receptors.
- Do not affect HDL cholesterol levels.
Dosage and administration: Powder taken with water or fruit juice, starting with one sachet daily and increasing as needed.
Adverse effects:
- Constipation, heartburn, abdominal pain, bloating, and nausea.
- Impair absorption of fat-soluble vitamins and other substances.
- Bind other acidic drugs.

Mechanism of action: Stimulate the activity of peroxisome proliferating activating receptors alpha (PPARα), altering transcription of genes involved in triglyceride metabolism.
Clinical effects:
- Decrease total serum cholesterol and LDL-C levels by about 10-20%.
- No change in triglyceride levels.
- Increase serum HDL-cholesterol concentrations by 15-20%.
Adverse effects:
- Diarrhea, bloating, indigestion, and heartburn.
- Headache, arthralgia.
- Increase the QT interval on the electrocardiogram.

Mechanism of action: Reduces VLDL synthesis in the liver, hence LDL, by inhibiting the synthesis and esterification of fatty acids in the liver and reducing lipolysis in adipose tissue.
Clinical effects:
- At high doses, affects all plasma lipid subtypes.
- Lowers plasma total and LDL cholesterol by 10-25%.
- Decreases triglycerides by 5-30%.
- Increases plasma HDL cholesterol by 10-20%.
Adverse effects:
- Flushing, tingling, and headache.
- Nausea, flatulence, and diarrhea.
- May exacerbate peptic ulceration and gout.
- Relatively contraindicated in gout and in diabetics.

Mechanism of action: Acts within the intestine to reduce cholesterol absorption by blocking one or more of cholesterol transporters.
Examples: Ezetimibe (Zetia).
Used alone or combined with a statin.
Adverse effects: Fatigue, abdominal pain, and diarrhea.