Cholesterol Flashcards

1
Q
A

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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2
Q
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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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3
Q
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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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4
Q
A

Cervistatin sodium

HMG - CoA reductase inhibitor

withdrawn from market

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5
Q
A

Fluvastatin

HMG - CoA reductase inhibitor

higher than normal bioavailability

high PPB

CYP 2C9

30% LDL reduction

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6
Q
A

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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7
Q
A

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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8
Q
A

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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9
Q
A

Cholic Acid

bile acid sequestrant (cholestyramine, colestipol, and colesevelam)

lipid soluble

dec LDL, inc HDL, may inc TG

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10
Q
A

Clofibrate

ester prodrug —> converted to active CPIB

enhances LPL activity

rapid hydrolysis occurs, parent drug not detected in plasma

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11
Q
A

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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12
Q
A

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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13
Q
A

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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14
Q
A

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

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