Cholesterol Flashcards
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Simvastatin
HMG - CoA reductase inhibitor
prodrug
lactone is hydrolyzed
has reversible reaction once its undergone glucuronidation
ionized at phys. pH
once gluc, eliminiated in the feces
low bioavailability
high PPB
CYP 3A4
dec LDL by 47%
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lovastatin
HMG - CoA reductase inhibitor
prodrug
ionized at phys pH
lactone is hydrolyzed forming active compound
undergoes gluc and is elim in feces
once gluc, can undergo reverse reaction
low bioavailability
high PPB
high fecal excretion
CYP 3A4
42% LDL reduction
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Atorvastatin
high intensity HMG - CoA reductase inhibitor
low bioavailability
high PPB
high fecal excretion
CYP 3A4
60% LDL reduction
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Cervistatin sodium
HMG - CoA reductase inhibitor
withdrawn from market
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Fluvastatin
HMG - CoA reductase inhibitor
higher than normal bioavailability
high PPB
CYP 2C9
30% LDL reduction
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Rosuvastatin
HMG - CoA reductase inhibitor
sulfonamide inc polarity which dec metabolism and dec DDI
similar to atorvastatin
Can dec cholesterol levels significantly (63%)
high PPB
fecal excretion
CYP 2C9/2C19
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Pitvastatin
HMG - CoA reductase inhibitor
Admin at low dose (2 mg or 4 mg)
increase potency and decreased metabolism
high bioavailability
high PPB
high fecal excretion
minimal CYP
43% LDL reduction
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Ezetimibe
inihbits cholesterol absorption in small intestines
Prodrug
beta lactam ring
when glucuronidated, it is active then undergoes biliary excretion and subsequent entero-hepatic recycling
primarily excreted in bile
half life 22 hrs
ADR: HA, diarrhea
Less common ADR: myopathy, myalgia, HSR, pancreatitis, and thrombocytopenia
Preg category C
DDI: cholestyramine (dec ezetimibe abs)
LDL dec 18%
TG dec 8%
HDL inc 0%
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Cholic Acid
bile acid sequestrant (cholestyramine, colestipol, and colesevelam)
lipid soluble
dec LDL, inc HDL, may inc TG
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Clofibrate
ester prodrug —> converted to active CPIB
enhances LPL activity
rapid hydrolysis occurs, parent drug not detected in plasma
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Gemfibrozil
Enhances LPL activity
not a prodrug
more potent, lipophilic
high PPB
caution with co - admin with acidic drugs (warfarin)
it is an inhibitor of OATP1B1. Statins use this transporter to gain access to liver
it increases concentration of insulin
it is inactivated by ring methyl group oxiation to the alcohol or completely to the acid
metabolites excreted via T.S. in urine as glucuronides (as gluc it is a potent 2C8 inhibitor)
parent drug may be enterohepatically recycled
parent drug is potent 2C9 inhibitor
ADR: GI, dyspepsia, HA, drowsy, blurry vision, gallstones, myositis, muscle pain, myalgia, rhabdomylosis - seen with co-admin of statin
Pregnancy category C
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Fenofibrate
prodrug
not ransported by OATP1B1 b/c it is not an anion
active fenofibric acid is also available as a formulation
active compound is glucuronidated and then eliminated in the urine
20 hr half life
inhibits 2C9
preg category C
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Niacin
treats dyslipidemia and is also a cofactor
MOA: inhibits lipolysis and therefore releases free FA from adipose tissue, increases VLDL clearance and decrease TG levels. ApoA - I clearance is inhibited and so HDL levels increase.
well absorbed and elim unmetabolized in urine
in liver there is amidation and conjugation with glycine that occurs. Amidated metabolite has low capacity and high affinity and is more likely to form. It is also hepatotoxic. Glycine conjugated metabolite has high capacity and low affinity. It causes release of prostaglandins which causes flushing.
ADR: flushing, itching, HA, GI disturbance, elevated liver transaminases
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Lomitapide
orphan drug
inhibitor of microsomal TG tranfer protein (MTP) which is necessary for VLDL secretion from liver.
use: HoFH
Result: reduction in VLDL, chylomicron, LDL, total cholesterol, and TG.
Used with low fat diet and other lipid lowering meds
high PPB, 34 hour half life
first pass effect mediated by CYP 3A4 —> inactive OND metabolite
ADR: bad GI disturbances, increased risk of influenza, elevated liver enzymes
can increase the AUC of other statins and warfarin