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25 Cards in this Set

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  • Back
Dietary Mgmt of hyperlipidemia
recommended before using drugs except for familial hyperlipidemia/cholesterolimia.

Recomm: low fat (<30% total cal intake), low saturated fat (<7%), low cholesterol (<200 mg/day).

This diet can reduce cholesterol by 10-20%
Bile Acid-Binding Resins: Cholestyramine, Colestipol
They bind bile acids in the intestine, preventing their reabsorption. Therefore, denovo synth. of bile acid kics in which uses cholesterol as the precursor. This intrahepatic decrease of cholesterol causes UPREGULATION of apoB and apo E (LDL receptors), causing extraction of LDL from blood to the liver >>> low BLOOD cholesterol.

Decrease LDL cholesterol by 15-30%. Often used in combo with HMG-CoA reductase.
Adverse effects of cholestyramine and colestipol
reduction of intra-hepatic cholesterol stimulates secondary production of cholesterol.

constipation, bloating, and rerely gallstones and steatorrhea.
Cholestyramine and Colestipol: drug interractions
These guys interfere with abosorption of other drugs: digitalis, beta blockers, thiazides, coumadin, Vit K.

Take with or just before meals. Take other drugs 2 hours before cholestyramine and colestipol or 4 hours after.
The Statins: HMG-CoA reducatase inhibitors
includes lovastatin, simvastatin, fluvastatin, rosuvastatin.

competitively Inhibit cholesterol synthesis in liver > increase apoB and apoE receptors > lower blood LDL level.

Increase HDL, lower Triglycerides.

Indications: familial hypercholesterolimia, combined hyperlipidemia

Used in the evening (diurnal chol. synthesis)
The Statins: HMG-CoA reductase SIDE EFFECTS
mild hepatotoxicity (increased aminotransferase), myopathy esp. pts on cyclosporin, RHABDOMYOLYSIS.

NEVER give to pregnant women.
HMG-CoA reductase: clinical efficacy
LDL: reduced by 20-40%

TG reduction: 10-25%

HDL increased: 5-15%
Statins and healthy people?
Yes, evidence of 30% decrease in heart attacks and stroke.
Statins: drug interraction
Grapefruit Juice, Verapamil increase the serum concentration of:

lovastatin, simvastatin, atorvastain (A.L.S.)

Done via inhibition of CYP3A4. Pravastatin and fluvastatin not affected by it.
Lovastatin (Mevacor)
first statin, pro-drug, activated into beta hydroxyl dervitive in GI tract. Low reabosption (30%) from GI, high first pass elimination.

only 5% of oral dose reaches circulation.
Simvastatin (Zocor)
similar to lovastatin but better absoprtion (85%) than lovastatin and 2x more potent.
Atorvastatin (lipitor)
ACTIVE drug (not a pro drug unlike lovastatin and simvastatin). Good absorption and 2x potent.

Highest LDL reduction: 50-60%
TG: 20-30%

Rosuvastatin (Crestor)
similar to atorvastatin, but higher incidence of RHABDOMYOLYSIS and renal failure.

in ASIANS, levels tend to be twice as high due to metabolism differences.
Estrogen replacement Therapy
increases HDL upto 15% and LDL decreased by 15%.

Counter-intuitive b/c of the whole postmenopausal heart dz deal.
Dietary Cholesterol Absorption Inhibitor: Ezetimibe (Zetia)
works at the brush border. If combined with statin drug, it will lower LDL an ADDITIONAL 25%.
Niacin (Nicotinic Acid): directly decreases VLDL synth in liver
directly decrease in VLDL synthesis in the liver, which then causes IDL and LDL decreases.

gives the HIGHEST HDL INCREASE: 15-35%

Indicated for: hetero fam. hyperchol., mixed lipidemia, combined hyperlipoproteinimia, familial dysbetalipoproteinemia, Lp(a) hyperlipoproteinemia.

side effects: FLUSHING, pruritis, rashes, reversible carb. tolerance impairnment, hyperuricema, rarely heptotoxicity.
Fibric-Acid Derivatives: fenofibrate
indicated for moderate and severe Familial hypertriglycridemia, Familial disbetalipoproteinima

binds PPAR-alpha in liver and brown fat, and activatin of PPARalpha receptor regulates gene transcription resulting in:

VLDL catabolism (via increase lipoprotein lipase activity)

decrease VLDL synthesis and excretion.

Increase HDL (due to increase in sytnh of apoA-I and apoA-II.
Fenofibrate: clinical efficacy
decrease TG by 20-50%, increase HDL 10-15%.

LDL may decrease or increase.

side effects: myopathy-rhabdomyolysis can occur when combined with statin.

Drug interraction: potentiates action of Coumadin and indanedione anticoagulants by displacing them from albumin.
Fish Oil Omega 3 FA
decrease TG levels by reducing vldl prodcution and increasing HDL cholesterol.

may also have antiplatelet activity.
antimicrobila, used in combo with niacin where it excerts highly complementary effect for lowering cholesterol.

Used in pts with familial hyperchol. or familial combined hyperlipidemia.
Combo therapy for: Chylomicronemia
high chylomicrons and VLDL.

Use Niacin and Fibrate
Fmailial hypertriglyceridemia
high vldl and chylomicrons

use Niacin and fibrate
familial combined hyperlipoproteinemia
high vldl and ldl

use niacin and resin or statin
Familial hypercholesterolemia
hetero: some LDL icrease

use: niacin, statin pm resin.

Homozygous: LDL very high

use: niacin and atorvastatin
Lp(a) hyperlipoproteinemia
elevated Lp (a)

use: niacin and neomycin.