Drugs for Lipid Disorders

Question 1

Bile acid sequestrants (resins)

• effect on LDL
• effect on HDL
• effect on TGs

Answer 1

• big decrease LDL
• slight increase HDL
• minimal effect on TG

Question 2

most effective drug for increasing HDL

Answer 2

niacin

Question 3

what patients should avoid niacin

Answer 3

those with:

• hepatic dz
• active peptic ulcer
• DM patients

Question 4

adverse rxn for statins on muscle

Answer 4

• creatinine kinase activity may increase
• rhabdomyolosis
• myopathy

Question 5

why should you avoid administration of ezetimibe and bile acid sequestrants (resins)

Answer 5

due to impaired ezetimibe absorption

Question 6

MOA of PCSK9

Answer 6

antibodies bind to PCSK9 and inhibit LDL receptor metabolism

Question 7

what do resins treat

Answer 7

pts with primary hypercholesteremia

Question 8

what would you give a patient with hypertriglyceridemia, dysbetalipoproteinemia, and hypertriglyceridemia that results from treatment with viral protease inhibitors (saquinavir, indinavir, or nelfinavir)

Answer 8

fibrates

Question 9

MOA of Lomitapide

Answer 9

directly binds to and inhibits microsomal triglyceride transfer protein (MTP) which will prevent the assembly of apo-B containing lipoproteins –> reduction in chylomicrons and VLDL and LDL

Question 10

what is the effect of niacin on fibrinogen and tissue plasminogen

Answer 10

• fibrinogen levels are reduced

- tissue plasminogen activator levels are increased

Question 11

adverse rxn with Lomitapide

Answer 11

• inhibits CYP3A4 –> interactions with a number of drugs
• GI symptoms
• increase liver aminotransferase levels
• hepatic fat accumulation

Question 12

what are the two statins NOT metabolized by CYP450

Answer 12

Pitavastatin

Pravastatin

Question 13

adverse rxn to Mipomersen

Answer 13

• injection site reactions
• flu like sx
• HA
• elevation of liver enzymes

Question 14

MOA of ezetimibe

Answer 14

selectively inhibits intestinal absorption of cholesterol and phytosterols

• lowers LDL by 18%
• lowers TG by 6%
• raising HDL by 1.3%

Question 15

adverse rxn for statins on liver

Answer 15

elevation of serum aminotransferase activity

Question 16

MOA of niacin

Answer 16

inhibits lipolysis of triglycerides in adipose tissue which reduces circulating free fatty acids

• less VLDL and LDL
• catabolism of HDL decreased

Question 17

MOA of statins

Answer 17

inhibit HMG-CoA reductase, the rate limiting enzyme in cholesterol synthesis, increases surface LDL receptors which reduces circulating LDL levels

Question 18

liver adverse rxn from fibrates

Answer 18

increased serum transaminases

Question 19

most effective drug for lowering LDL

Answer 19

statins

Question 20

therapeutic uses of ezetimibe

Answer 20

• various causes of elevated cholesterol

- mixed hyperlipidemia

Question 21

MOA of bile acid sequestrants (resins)

Answer 21

positively charged compounds bind to negatively charged bile acids (cholesterol) and increase bile acid excretion up to tenfold
- enhances LDL clearance and lowers levels

Question 22

major effect of fibrates

Answer 22

• increased oxidation of fatty acids
• increased lipolysis of TG via lipoprotein lipase
• intracellular lipolysis in adipose tissue is decreased
• VLDL decreased
• LDL decreased
• HDL increased

Question 23

pharmacokinetics of niacin

Answer 23

niacin –> nicotinamide –> nicotinamide adenine dinucleutide (NAD)

Question 24

what dz does Mipomersen treat

Answer 24

familial hypercholestermia

Question 25

adverse rxn to resins

Answer 25

- constipation, nausea, flatulence - impaired absorption of vitamins D, E, A, K - impaired absorption of tetracycline, phenobarbitol, digoxin, warfarin, parvastatin, fluvastatin, aspirin, and thiazide diuretics

Question 26

MOA of Mipomersen

Answer 26

targets apolipoprotein B-100 mRNA, resulting in decrease in the levels of apolipoprotein B (apo B), LDL, and total cholesterol

Question 27

weakest statin mentioned in this lecture

Answer 27

fluvastatin

Question 28

pitavastatin is metabolized by

Answer 28

undergoes limited CYP450 biotransformation

Question 29

fluvastatin and rosuvastatin are metabolized primary by

Answer 29

CYP2C9

Question 30

statins are NOT recommended for what patients

Answer 30

- pregnant women - lactating women - children with homozygous familial hypercholesteremia

Question 31

adverse rxn to ezetimibe

Answer 31

none have been reported

Question 32

MOA of fibrates (gemfibrozil and fenofibrate)

Answer 32

agonist for peroxisome proliferator-activated receptor alpha (PPARa) which binds to DNA --> regulates the expression of genes encoding proteins involved in lipoprotein structure and function

Question 33

how does alcohol affect VLDL

Answer 33

causes hypertriglyceridemia by increasing hepatic secretions of VLDL

Question 34

Fibrates - effect on LDL - effect on HDL - effect on TGs

Answer 34

- slight decrease LDL - bigger increase HDL - great decrease TG

Question 35

what patients should avoid taking fibrates

Answer 35

- pts with biliary tree dz - hepatic or renal dysfunction - pregnant and lactating women

Question 36

most potent statins mentioned in this lecture

Answer 36

atorvastatin and rosuvastatin

Question 37

why are statins included in the management of familial hypercholesteremia when they rely on function LDL receptors to work? (FH doesn't have functional LDL receptors)

Answer 37

statins still improve coronary endothelial function, inhibit platelet thrombus formation, and have anti-inflammatory effects

Question 38

what dz does Lomitapide treat

Answer 38

familial hypercholesteremia

Question 39

Statins - effect on LDL - effect on HDL - effect on TGs

Answer 39

- greatly decrease LDL - increase HDL - decrease TG

Question 40

why is it a good idea to pair resins with statins?

Answer 40

resins enhance LDL clearance but also upregulate HMG-CoA, so by combining with a statin you block the HMG-CoA and just decrease LDL

Question 41

adverse rxn to niacin

Answer 41

- intense cutaneous flush with uncomfortable feeling of warmth - pruritus - rashes - dry skin or mucous membranes - acanthosis nigricans

Question 42

risk of prescribe fibrates to a pt on anticoagulants

Answer 42

fibrates may potentiate the effects of anticoagulants

Question 43

GI adverse rxn from fibrates

Answer 43

- mild GI disturbances | - increased risk of cholelithiasis

Question 44

muscle adverse rxn from fibrates

Answer 44

- myositis can occur (muscle weakness and tenderness) - myopathy - rhabdomyolysis

Question 45

what dz does PCSK9 treat

Answer 45

familial hypercholesteremia

Question 46

most effective drug for decrease TG

Answer 46

fibrates

Question 47

Niacin - effect on LDL - effect on HDL - effect on TGs

Answer 47

- decrease LDL - great increase HDL - big decrease TGs

Question 48

what pts should not take resins

Answer 48

those with: - diverticulitis - preexisting bowel dz - cholestasis

Question 49

Cholesterol absorption inhibitor - effect on LDL - effect on HDL - effect on TGs

Answer 49

- slight decrease LDL - slight increase HDL - slight decrease TG

Question 50

adverse rxn for statins on pts taking warfarin

Answer 50

statins increase warfarin levels

Question 51

how does fat, sucrose, and fructose affect VLDL

Answer 51

increase it

Question 52

best tolerated drug for treating hyperlipidemia

Answer 52

statins

Question 53

lovastatin, simvastatin, atorvastatin are metabolized primarily by

Answer 53

CYP3A4