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Dyslipidemia Drug Therapy

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1

HMG-CoA Reductase Inhibitors (Statins)

MOA: inhibit HMG-CoA reductase (enzyme that catalyzed rate-limiting step in cholesterol synthesis), increase LDL receptor activity & increased clearance of LDL from blood

Adverse effects:

1. Myopathies

  • Myalgia - muscle aches or weakness w/o CK elevation
  • Myositis - muscle symptoms w/increased CK levels
  • Rhabdomyolysis - muscle symptoms w/marked CK elevation & creatinine elevation

2. Elevated hepatic transaminases

  • Irreversible liver damage is RARE
  • 0.5-2% of pts; usually transient
  • Increased risk w/hepatotoxic agents (fibrates, niacin, acetaminophen, ETOH)
  • Removal of ROUTINE monitoring of liver function tests
  • Check liver enzymes prior to statin initiation, then if symptomatic

3. Cognitive impairment

  • Post-marketing reports of memory loss or cognitive impairment - uncommon
  • Age >50
  • Reversible upon discontinuation of statin
  • Variable time

Most Effective LDL Lowering Drugs, improve endothelial functions, plaque stabiliztion, first line agents for LDL lowering

2

Bile Acid Sequestrants (BAS)

Colesevelam (Welchol), Colestipol (Colestid), Cholestyramine (Questran)

MOA: binds bile acid in GI tract (not systemically absorbed)

Adverse effects: GI distress, constipation, decreased absorption of other drugs

  • Add-on therapy to statins
  • Used in pregnancy
  • Contraindicated in Hx of bowel obstruction, TG concentrations >500mg/dl, do not used in pts w/history of hypertriglyceridemia-induced pancreastitis
  • Mix w/water, juice, or noncarbonated beverage; can be refrigerated; take other meds 1 hr prior or 4 hrs after; frequently causes constipation (add fluid or fiber to diet)
3

Nicotinic Acid (Niacin)

MOA: reduces hepatic synthesis or TG & secretion of VLDL; inhibit conversion of VLDL into LDL - increased HDL; inhibit mobilization of free fatty acids from peripheral tissues

Adverse effects: FLUSHING, hypergylcemia, hyperuricemia (gout), hepatoxicity (more common w/sustained release), GI upset, peptic ulcer disease

  • Used as additional therapy to statin or as alternative to statin
  • Used in combined hyperlipidemia (increased TG, HDL, LDL) as seen in DM
  • Contraindicated in chronic liver disease, severe gout, if relative has hyperuricemia, PUD, diabetes
  • To reduce flushing, take w/meal, take aspirin 30 mins before, avoid hot drinks, ETOH, or hot showers near dose
  • Usually administered 2 or 3 times per day, except Niaspan which is given once daily at bedtime
4

Fibric Acid Derivatives

MOA: increased functional activity of lipoprotein lipase

Adverse effects: dyspepsia, nausea/vomiting, skin rash, gallstones, myopathy (increases if statin & fibrate used together

  • First line for increased TG
  • Used as additional therapy to statin
  • Primarily used to decrease TG & increase HDL (needed in DM)
  • Gemfibrozil has been shown to decrease morbidity & mortality in pts w/CHD
  • Contraindicated in pts w/severe renal or hepatic disease
  • Monitor LFT every 3 months for first year then periodically
  • Monitor CPK if myopathies occur
5

Cholesterol Absorption Inhibitor

Ezetimibe (Zetia)

MOA: inhibits absorption of dietary & biliary cholesterol by blocking transport at brush border of small intestine

Adverse effects: flatulence, diarrhea, myalgia (in combo w/statins), liver transaminase elevations (in combo w/statins)

  • Additive LDL lowering in addition to statin
  • Not recommended in moderate or severe hepatic impairment

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