Drugs for Lipid Disorders Flashcards
Bile acid sequestrants (resins)
- effect on LDL
- effect on HDL
- effect on TGs
- big decrease LDL
- slight increase HDL
- minimal effect on TG
most effective drug for increasing HDL
niacin
what patients should avoid niacin
those with:
- hepatic dz
- active peptic ulcer
- DM patients
adverse rxn for statins on muscle
- creatinine kinase activity may increase
- rhabdomyolosis
- myopathy
why should you avoid administration of ezetimibe and bile acid sequestrants (resins)
due to impaired ezetimibe absorption
MOA of PCSK9
antibodies bind to PCSK9 and inhibit LDL receptor metabolism
what do resins treat
pts with primary hypercholesteremia
what would you give a patient with hypertriglyceridemia, dysbetalipoproteinemia, and hypertriglyceridemia that results from treatment with viral protease inhibitors (saquinavir, indinavir, or nelfinavir)
fibrates
MOA of Lomitapide
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
what is the effect of niacin on fibrinogen and tissue plasminogen
- fibrinogen levels are reduced
- tissue plasminogen activator levels are increased
adverse rxn with Lomitapide
- inhibits CYP3A4 –> interactions with a number of drugs
- GI symptoms
- increase liver aminotransferase levels
- hepatic fat accumulation
what are the two statins NOT metabolized by CYP450
Pitavastatin
Pravastatin
adverse rxn to Mipomersen
- injection site reactions
- flu like sx
- HA
- elevation of liver enzymes
MOA of ezetimibe
selectively inhibits intestinal absorption of cholesterol and phytosterols
- lowers LDL by 18%
- lowers TG by 6%
- raising HDL by 1.3%
adverse rxn for statins on liver
elevation of serum aminotransferase activity
MOA of niacin
inhibits lipolysis of triglycerides in adipose tissue which reduces circulating free fatty acids
- less VLDL and LDL
- catabolism of HDL decreased
MOA of statins
inhibit HMG-CoA reductase, the rate limiting enzyme in cholesterol synthesis, increases surface LDL receptors which reduces circulating LDL levels
liver adverse rxn from fibrates
increased serum transaminases
most effective drug for lowering LDL
statins
therapeutic uses of ezetimibe
- various causes of elevated cholesterol
- mixed hyperlipidemia
MOA of bile acid sequestrants (resins)
positively charged compounds bind to negatively charged bile acids (cholesterol) and increase bile acid excretion up to tenfold
- enhances LDL clearance and lowers levels
major effect of fibrates
- 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
pharmacokinetics of niacin
niacin –> nicotinamide –> nicotinamide adenine dinucleutide (NAD)
what dz does Mipomersen treat
familial hypercholestermia
adverse rxn to resins
- constipation, nausea, flatulence
- impaired absorption of vitamins D, E, A, K
- impaired absorption of tetracycline, phenobarbitol, digoxin, warfarin, parvastatin, fluvastatin, aspirin, and thiazide diuretics
MOA of Mipomersen
targets apolipoprotein B-100 mRNA, resulting in decrease in the levels of apolipoprotein B (apo B), LDL, and total cholesterol
weakest statin mentioned in this lecture
fluvastatin
pitavastatin is metabolized by
undergoes limited CYP450 biotransformation
fluvastatin and rosuvastatin are metabolized primary by
CYP2C9
statins are NOT recommended for what patients
- pregnant women
- lactating women
- children with homozygous familial hypercholesteremia
adverse rxn to ezetimibe
none have been reported
MOA of fibrates (gemfibrozil and fenofibrate)
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
how does alcohol affect VLDL
causes hypertriglyceridemia by increasing hepatic secretions of VLDL
Fibrates
- effect on LDL
- effect on HDL
- effect on TGs
- slight decrease LDL
- bigger increase HDL
- great decrease TG
what patients should avoid taking fibrates
- pts with biliary tree dz
- hepatic or renal dysfunction
- pregnant and lactating women
most potent statins mentioned in this lecture
atorvastatin and rosuvastatin
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)
statins still improve coronary endothelial function, inhibit platelet thrombus formation, and have anti-inflammatory effects
what dz does Lomitapide treat
familial hypercholesteremia
Statins
- effect on LDL
- effect on HDL
- effect on TGs
- greatly decrease LDL
- increase HDL
- decrease TG
why is it a good idea to pair resins with statins?
resins enhance LDL clearance but also upregulate HMG-CoA, so by combining with a statin you block the HMG-CoA and just decrease LDL
adverse rxn to niacin
- intense cutaneous flush with uncomfortable feeling of warmth
- pruritus
- rashes
- dry skin or mucous membranes
- acanthosis nigricans
risk of prescribe fibrates to a pt on anticoagulants
fibrates may potentiate the effects of anticoagulants
GI adverse rxn from fibrates
- mild GI disturbances
- increased risk of cholelithiasis
muscle adverse rxn from fibrates
- myositis can occur (muscle weakness and tenderness)
- myopathy
- rhabdomyolysis
what dz does PCSK9 treat
familial hypercholesteremia
most effective drug for decrease TG
fibrates
Niacin
- effect on LDL
- effect on HDL
- effect on TGs
- decrease LDL
- great increase HDL
- big decrease TGs
what pts should not take resins
those with:
- diverticulitis
- preexisting bowel dz
- cholestasis
Cholesterol absorption inhibitor
- effect on LDL
- effect on HDL
- effect on TGs
- slight decrease LDL
- slight increase HDL
- slight decrease TG
adverse rxn for statins on pts taking warfarin
statins increase warfarin levels
how does fat, sucrose, and fructose affect VLDL
increase it
best tolerated drug for treating hyperlipidemia
statins
lovastatin, simvastatin, atorvastatin are metabolized primarily by
CYP3A4
