CPR 9.16 Pharmacologic Control of Dyslipidemias

Question 1

What are some common examples (5) of Statins?

Answer 1

Atorvastatin (Lipitor®), Simvastatin (Zocor®), Lovastatin (Mevacor®), Fluvastatin (Lescol®), Rosuvastatin (Crestor®)

Question 2

Describe the MOA, ADME, Side Effects, and Indications for Statins

Answer 2

B. MOA: Inhibit the enzyme HMG-CoA Reductase
C. ADME: All are PO. Lo-, ator- sim-vastatins all CYP3A4 metabolized. Fluva-, rusuva-statins are CYP2C9 metabolized.
D. Adverse Effects/Contraindications:
1. Muscle Toxicities: myopathy, rhabdomyolysis.
2. Liver toxicities: elevated liver enzymes (AST, ALT can be >3x)
3. Diabetes: 9% increased risk of Type II DM
4. Avoid in Pregnancy! (X-rating)
E. Indication: High LDL’s in patients with CHD or at high risk. Large LDL decrease.

Question 3

What are some common examples (2) of Fibrates?

Answer 3

Gemfibrazole (Lopid®), Fenofibrate (Tricor®)

Question 4

Describe the MOA, ADME, Side Effects, and Indications for Fibrates.

Answer 4

B. MOA: act as ligands for the transciption factor peroxisome proliferator-activated receptor alpha (PPAR-α)
1. Up-regulates: LPL, ApoA-1, ApoA-2
2. Down-regulates: ApoC-III
3. ↑ FA Oxidation in liver and skeletal muscle→ ↓ Triglyceride synthesis and ↑ Peripheral triglyceride utilization → ↓ Triglyceride levels!
C. ADME; PO, binds plasma porteins tightly, eliminated mostly unchanged through kidney.
D. Side Effects: GI effects. Increased risk for myopathies and rhabdomyolisis when used with Statins. Caution for use in pts. With hepatic or renal dysfunction or biliary tract disease. Also potentiates effects of Warfarin.
E. Indications: Hypertriglyceridemias.

Question 5

What is the drug name for Nicotinic Acid?

Answer 5

Niacin

Question 6

Describe the MOA, ADME, Side effects, and Indications for Niacin.

Answer 6

B. MOA: inhibits VLDL secretion that causes decreased LDL. Also increases HDL.
C. ADME: PO, some is converted to niacinamide and incorporated into NAD. Excreted by the kidneys unchanged or modified.
D. Side Effects: Vasodilation with hot/warm flush (this is prostaglandin mediated so NSAID’s can attenuate this). Pruritis, rashes, dry skin, acanthosis nigricans, hyperuricemia, macular edema.
E. Indications: Low HDL or high VLDL.

Question 7

What are some common examples (2) of bile-acid binding resins?

Answer 7

Colestipol (Colestid®), Cholestyramine (Questran®)

Question 8

Describe the MOA, ADME, Side effects, and Indications for Bile-acid binding resins.

Answer 8

B. MOA: large cationic resins bind bile acids and prevent their reabsoprtion in the intestines. This causes increased hepatic LDL receptors and thus increased LDL uptake by the liver.
C. ADME: PO, non-absorbed.
D. Side Effects: Constipation, bloating, may see Vitamin K malabsoprtion so get aPTT or PT on patients on anticoagulants. Potential mechanical drug-drug interactions.
E. Indications: Mild to moderate LDL or in combination.

Question 9

What is the name of a commonly used sterol absorption inhibitor?

Answer 9

Ezetimibe (Zetia®)

Question 10

Describe the MOA, ADME, Side effects, and Indications for Ezetimibe.

Answer 10

B. MOA: blocks transport of cholesterol through NPC1L1 transporter (typically involved in bulk uptake of lipids).
C. ADME: PO. Converted to active form by phase II metabolism (glucouronidation). Some systemic absoprtion, but most excreted in feces.
D. Side Effects: very few. Myositis rarely.
E. Indications: possibly in patients that don’t tolerate statins.