Pharmacology Lipid Disorders

Question 1

Niacin mechanism

Answer 1

in adipose, inhibits FFA mobilization (GPR109A)

in liver, decreases VLDL-TG synth

inhibits uptake of HDL-apoA1

(main effect is to decrease TG)

Question 1

adverse effects gemfibrozil, fenofibrate

Answer 1

increased creatine kinase is coadmin with statin > renal failure

gemfibrozil may block statin transport in liver (icnreased concentrations)

Question 1

greatest LDL impact

Answer 1

HMG Coa reductase inhibitors

Atorvastatin

Lovastatin

Simvastatin

Question 1

mechanism omega3 FA

Answer 1

unique TG lowering properties

results in very low density VLDL TG

Question 1

pharmacokinetics MTP inhibitors

Answer 1

extensive CYP#A4 to inactive metabolites M1 and M3

Question 2

contraindications to statins

Answer 2

pregnant, lactating, could become pregnant

hypersensitivty

active liver disease

Question 2

pharmocokinetics cholestyramien

Answer 2

not absorbed

Question 2

mechanism ezetimibe

Answer 2

acts at NPC1L1 to decrease absorption of cholesteryl ester incorporation into chylomicrons (reduced cholesterol flux from intestine to liver)

Question 3

Dominant mechanism for controlling LDL plasma concentrations

Answer 3

Regulation of hepaatic LDL receptor pathway

Question 4

associated polymorphism with statin myopathy

Answer 4

SLCO1B1

(lead to reduced hepatic uptake and increased plasma concentration)

Question 5

___ and ___ are admined as inactive lactones, which are transformed to active forms in liver

Answer 5

Simvastatin and lovastatin

Question 5

niacin mechanism - decrease synthesis of VLDL-TG

Answer 5

inhibit DGAT2 that catlayzes final TG synthesis

increases ApoB degradation (major protein of VLDL/LDL)

Question 6

pharmacokinetics niacin

Answer 6

oral admin, multiple formulations

Question 6

Greatest HDL impact

Answer 6

Niacin

Question 7

Ezetimibe lipoprotein pofile

Answer 7

TG decrease by 5%

LDL decrease by 15-20%

HDL increase by 1-2%

Question 8

only mechanism of cholesterol excretion

Answer 8

conversion to bile salts via 7a Hydroxylase

Question 9

Statin lipid profile

Answer 9

TG decrease by 20-55%

LDL decrease by 5-10%

HDL increase by 5-10%

Question 11

adverse effecs cholestyramiune

Answer 11

constipation, bloating

interferes with other drug absorption

modest increase in TG (but normalizes)

gritty consistency

Question 12

lipoprotein profile gemfibrozil, fenofibrate

Answer 12

TG decrease 30-50%

LDL - decrease 15-20%

HDL - increase 5-15%

Question 13

Niacin mechanism - inhibit FFA mobilization from adipose

Answer 13

Niacin receptor 1 > decrease in cAMP

> PKA doesn’t phos perilipin and HSL

>TG not broken down into FFA and glycerol

Question 14

mechanism of action, statins

Answer 14

competitive inhibition of active site on HMG CoA reductase > rate limiting step of cholesterol biosynth

reduction leads to increased numbers of LFL-receptors and thus more uptake

Question 16

pharmokinetics of statins

(uptake via)

Answer 16

extensive first pass

uptake via OAT1B1

extensive plasma protein binding

Question 18

other beneficial effects of omega 3

Answer 18

reduced risk for fatal arrhythmias

enhanced plaque stability

reduced HR

improved endothelial function

Question 19

metabolism of statins primarily via

Answer 19

P450 CYP3A4

Question 20

specific HTP inhibitor indication

Answer 20

homozygous FH

Question 22

meechanism PCSK9 inhibitors

Answer 22

blocks PCSK9 targeting of LDR to lysosome for recyling \> increase LDLR

Question 23

primary impact of Fibrates

Answer 23

lover levels of TG rich lipoproteins

Question 24

mechanism of statin induced myopathy

Answer 24

blockade of HMG CoA reductase also supprsses formation of isoprenoids required for normal muscle function

Question 25

pharmacokinetics fenofibrate, gemfibrozil

Answer 25

oral plasma protein binding fenofibraate metabolized to active gemfibrozil metabolized to inactive

Question 26

pharmacokinetics ezetimibe

Answer 26

oral admin metabolized to active form half life 22

Question 27

niacin lipid profile

Answer 27

TG decrease 35-50% LDL decrease by 25% HDL - increase by 15-30% Lpa reduced by 40%

Question 28

mechanism gemfibrozil, fenofibrate

Answer 28

bind as heterodimers to PPAR-a receptor in liver, adipose \> regulates gene transcription, chief among those increase LPL that breaks down TG lowers levels of TG rich lipoproteins

Question 29

first choice hyperchholesterolemia drugs

Answer 29

HMG Coa reductase inhibitors

Question 30

apoB 100 inhibitors adverse effects

Answer 30

injxn site flu-like elevation of liver enzyems (rsk hepatotoxicity)

Question 31

mechanism Cholestyramine

Answer 31

highly postive binds highly negative bile acids \> large resins not absorbed and thus excreted (excretion depletes bile acids, which are synthesized from cholesterol) (reduced chol \> activates SREBP \> increase LDL receptor gene transcription

Question 33

drug of choice for hypertriglyceridemia

Answer 33

Gemfibrozil/fenofibrate | (then niacin, then Omega3)

Question 34

greatest TG impact

Answer 34

Fenofibrate, Gemfibrozil

Question 36

Class Atrovastatin Lovastatin Simvastatin

Answer 36

HMG CoA reductase inhibitors

Question 37

MTP inhibitors adverse effects

Answer 37

significant GI hepatotoxicity

Question 38

ApoN-100 inhibtion mechanism

Answer 38

antisense oglionucleotide inhibit synthesis of apoB-100 in liver (apo B binds LDL to receptor, crucial for transport)

Question 40

adverse effects niacin

Answer 40

**intense cutaneous flsuh/pruritis (via PGD2 from macrophages)** **.**GI effects hyperuricemia (gout concern) Increase fasting glucose, insulin resistance

Question 41

cholestyramine liporotein profile

Answer 41

TG - transient increase (larger if higher baseline) LDL - decrease by 12-25% HDL - increase by 4-5%

Question 42

rarer, serious side effects statins

Answer 42

myositis or liver enzyme elevations myopathy rhabdomyolysis

Question 43

MTP inhibitors mechanism

Answer 43

prevent assembly of apo-B containing lipoproteins in entoerocytes and hepatocytes \> reduced chylomicrons and VLDL \> reduced plasma LAL-C concetration

Question 44

(statin use) when cholesterol decreases, ___ and ____ no longer bind, so SREBP-SCAP is transpoted to golgi and cleaved at ___ and \_\_\_ this leads to transcriptionally active SREBP \> activates target genes

Answer 44

(statin use) when cholesterol decreases, **SCAP **and **INSIG** no longer bind, so SREBP-SCAP is transpoted to golgi and cleaved at **S1P** and **S2P** this leads to transcriptionally active SREBP \> activates target genes