Lipid Pharmacology

Question 1

Statin MOA

Answer 1

inhibits hepatic HMG-CoA reductase –> dec IC chol –> inc LDL-R expression
–> Inc hepatic uptake of LDL-C –> Dec LDL-C

Also, dec IC chol–> dec VLDL –> dec TGs

Question 2

Statin Lipid effects

Answer 2

Dec LDL-C (30%-63%)
Dec TGs (35-45%)
Inc HDL-C (5-15%)

Question 3

Statin AE

Answer 3

AEs:
Hepatotoxicity
Skeletal muscle toxicity
 myalgia (muscle discomfort)
 myopathy (muscle weakness)
 myositis (muscle inflammation)
 rhabdomyolysis -->myoglobinuria --> renal tox

Question 4

Factors that inc SKM Tox

Answer 4

Inc statin dose
DDI that dec hep uptake, metab
Low Thyroid hormone levels
Low Vit D

Question 5

Cholesterol Absorption Inhibitors MOA

Answer 5

Inhibit intestinal NPC1L1 transporter –> dec absorp of chol–> dec incorporation of chol into CM –> dec chol delivery to liver –> dec IC chol –> Inc LDL-R expression –> Inc hep uptake of LDL-C –> Dec LDL-C

Question 6

Lipid effects of cholesterol absorption inhibitors

Answer 6

Dec LDL-C (18-22%)
Dec TGs (<2%)
Inc HDL-C (<2%)

Question 7

Cholesterol Absorption inhibitors AE

Answer 7

Minimal

Question 8

BA Sequestrants MOA

Answer 8

Binds BAs i the intestine –> Inc fecal excretion of BAs –> Dec IC BAs –> Inc BA synth –> Dec IC chol –> Inc LDL-R expression –> Inc hepatic uptake of LDL-C –> Dec LDL-C

Question 9

BA Sequestrant Lipid Effects

Answer 9

Dec LDL-C (15-25%)
Inc TGs (3-10%)
Inc HDL-C (<5%)

Question 10

BA Sequestrant AE

Answer 10

GI:
bloating
constipation
nausea
flatulence
Can affect absorption of other drugs and fat soluble vitamins

Question 11

PCSK-9 Inhib MOA

Answer 11

monoclonal antibody to PCSK-9 –> Inc hepatic LDL-R expression –> INc hepatic uptake of LDL-C –> Dec LDL-C

Question 12

PCSK-9 Inhib lipid effects

Answer 12

Dec LDL-C (up to 70%)

Question 13

PCSK-9 AE

Answer 13

injection site rxn

allergic rxn

Question 14

Nicotinic Acid MOA

Answer 14

Activates niacin receptors (Gi-coupled) on fat cells –> Dec HSL –> Dec lipolysis –> Dec release of fatty acids –> Dec hepatic TG synth –> Dec VLDL -> LDL-C

Also, niacin is taken up by the liver –> inhib TG synth

Question 15

Niacin lipid effects

Answer 15

Dec LDL-C (20-30%)
Dec TGs (35-40%)
Inc HDL-C (30-40%)

Question 16

Niacin AE

Answer 16

Flushing, itching, dyspepsia, headache (maybe due to
increased prostaglandins)
Hepatotoxicity
Hyperglycemia
Hyperuricemia

Inc Risk of SKM tox if combined w statins

Question 17

Fibrates MOA

Answer 17

Activate PPARalpha -R –> Inc LPL –> Inc clearance of TG rich VLDL and CM –> Dec VLDL –> May inc LDL-C

Also, has complex effects on various apoproteins and Inc FA ox –> dec hep VLDL secretion

Question 18

Fibrate Lipid Effects

Answer 18

LDL-C (variable, may inc)
Dec TGs (Up to 50%)
Inc HDL-C (up to 15%)

Question 19

Fibrate AE

Answer 19

GI:
dyspepsia
Abd pain
Diarrhea
Constipation

Inc gallstone formation
Inc risk of SKM tox if combo w statins (esp. gemfibrozil)

Question 20

Highest LDL-C lowering

Answer 20

Statins

PCSK9 inhib

Question 21

Highest TG lowering

Answer 21

fibrates
niacin
statins

Question 22

Highest HDL-C raising

Answer 22

niacin

Question 23

With statins, get baseline _____ values

Answer 23

AST
ALT
CK

Question 24

Other benefits of statins

Answer 24

plaque stabilization

reversal of endothelial dysfunction

Question 25

PCSK-9 administered via ___

Answer 25

SQ injection

Question 26

What attenuating action is seen with cholesterol absorbing inhibitors and BA sequestrants?

Answer 26

Dec IC chol–> Inc HMB CoA reductase –> attenuates LDL-C lowering action

Question 27

Which drugs have their LDL-C lowering action attenuated?

Answer 27

Chol absorbing inhibitors

BA sequestrants

Question 28

Which drug is very safe because it is not systemically absorbed?

Answer 28

BA sequestrants

Question 29

Which drugs are hepatotoxic?

Answer 29

Niacin

Statins