Hyperlipidemia Agents

Hyperlipidemia

• elevation in plasma concentrations of lipids (cholesterol) or any of the lipoproteins

• High LDL, Low HDL

• increases risk of atherosclerosis → stroke/Myocardial Infarction chance

Other Terms:

• Dyslipiedmia

• Hypercholesterolemmia

• Hyperlipoproteinemia

• Lipid Disorder

Remember: mevalonoic acid pathway origin of cholesterol and others

Lipoproteins

• lipid + apolipoprotein

• APolipoprotein (aka, Apo) is transport protein of lipids

Types:

• d

LDL & HDL

Low Density Lipoprotein:

• LDL

• the bad cholesterol

• primarily

High Density Lipoprotein:

• the smallest, most protein rich (55%) lipoprotein

• transport excess cholesterol from cells to liver for bile disposal

• “good” lipoprotein, has anti-atherogenic effects

Drug Therapy

• after short trial (3 months or less) of lifestyle modifications

• Decision to treat hyperlipidemia with drug therapy is based on LDL levels

LDL Level Chart and Risk Factors

<2 Risk Factors:

• <160 mg/dL LDL Goal

• Initiate Dietary Therapy >= 160

• Initiate Drug Therapy >= 190

>2= Risk

Risk Factors:

• Age: 

  • Men => 45 yo; Women => yo

• family history

• current cigarette smoking

• hypertension

  • BP of > 140/90 mmHg on several occasions

  • or taking anti-HPN meds

• Diabetes mellitus

• Low HDL cholesterol

Drug Classes

1. HMG-CoA Reductase Inhibitors (ex: Statins)

2. Bile Acid Resins

3. Nicotinic Acid

4. Fibric Acid Derivatives

5. Ezetimibe

6. Estrogen Replacement Therapy

HMG-CoA Reductase Inhibitors

Statins:

• Pravastatin

• Lovastatin

• Simvastatin

• Fluvastatin

• Atorvastatin

• Rosuvastatin

Should be taken once daily in evening

• inhibition of HMG-CoA Reductase, prevents formation of mevalonic acid

• which is a precursor to cholesterol

• most effective in reducing LDL

• also increases LDL receptors in liver

  • increases LDL liver uptake; decreases LDL cholesterol in bloodstream

Useful alone, or with resins, niacin, or ezetimibe in reducing LDL

Rosuvastatin: most efficacious agent for severe hypercholoseroemia 

Contraindications:

• pregnant, lactating, those likely to become pregnant

• active liver disease, elevated aminotransferase levels

• liver disease history, high alcohol consumption

• lifestyle can deactivate statin effect

Side Effects:

• Dyspepsia (indigestion)

• Headache

• Myopathy

• Asymptomatic Elevations in Liver Function Tests (except for Atorvastatin, Pravastatin, Simvastatin)

  • discontinue if 2 consecutive results = 2-3x above normal limits

Bile Acid-Binding Resins

• also called bile acid sequestrant resins

• MOA: bind bile acids (synthesized from cholesterol) within intestines/secreted in feces → effect is lowered LDL (bound acids are easy to excrete)

  • excreted so do not contribute to LDL (fats don’t get absorbed)

• discolors feces sometimes

• useful only for isolated increases in LDL

• Indications:

  • Primary Hypercholesterolemia

  • Other (check ppt)

• Resins should be taken in two/three doses, with meals

  • lack effect when taken between meals

  • because bile acids are secreted during digestion

Ex:

• Cholestyramine (Questran)

• D

Adverse Effects:

• flatulence, bloating, abdominal pain

• heartburn, constipation, GI discomfort

Interactions:

• may bind to other medications and decrease bioavailablity

  • actually quite useful for drug overdoses

• decrease intestinal absorption of ADEK vitamins

Contraindications:

• special populations (pregnant, lactating)

  • decrease vitamins in milk = vitamin deficiency in infant

Administration:

• mix with water, juice, soup, NOT soda, (etc)

• should not be taken dry (causes esophageal distress)

• Do not take with carbonated beverages

• Should be taken with meals to maximize effectiveness

Cholestyramine

• Powder (4g/sachet)

• 4-8 grams once/twice a day

• Max dose, 24 grams a day

• Powder hould be mixed with

Colestipol