4. Lipid drugs Flashcards
What cholesterol lowering meds can be used in pregnancy?
resins
In what way do resins interfere with the action of other drugs?
interfering with absorption
What is the MOA of statins?
competitive HMG CoA reductase inhibitor
increases number of LDL receptors in liver
Which statins can be used to decrease triglycerides in addition to cholesterol?
How do they do this?
atorvastatin, rosuvastatin
larger half life, higher increase in LDL receptors, ability to clear IDLs
What are the adverse effects of statins?
Which statins are least likely to cause these?
increased AST/ALT, increased CPK (myalgias)
fluvastatin, pravistatin
Which drugs cannot be concurrently used with statins?
CYP3A4 inhibitors: gemfibrozil, ketoconazole, erythromycin, nicotinic acid
For which patient groups are statins contraindicated?
nursing and pregnant mothers
How long does the maximal effect of statins take?
2 weeks
Which statins need to be taken at night?
simvastatin, lovastatin, fluvastatin
Which drug has increased muscle pain due to SNPs?
simvastatin
What drug has a therapeutic advantage when combined with statins?
What risk does this combo carry?
ezetimibe
risk of increased transaminase levels
What is the MOA of ezetimibe?
inhibiting cholesterol uptake at brush border of enterocytes
by inhibiting NPC1L1 transporter protein
What drug cannot be combined with resins?
Why not?
ezetimibe
undergoes enterohepatic recirculation
Which drugs are PCSK9 inhibitors?
What is their net result?
alirocumab and evolocumab
increased LDL receptors
What is the MOA of fibrates?
activating PPAR alpha and increasing FA oxidation, reducing FFA
reducing ApoCIII,, increasing endothelial LPL
increasing ApoCII and CIII
Which fibrate increases gallstone risk?
clofibrate
Which fibrate has the worst CPK risk when given with statins?
Why?
gemfibrozil
OATP2 inhibitor
What is the difference between nicotinic acid and fibrates?
nicotinic acid: hormone sensitive lipase on fat cells, doesn’t inhibit PPAR alpha
fibrates: inhibits endothelial cell LPL, inhibits PPAR alpha
What are the side effects of nicotinic acid?
itching and flushing
elevate AST/ALT levels (titrate and monitor CPK)
What is he defect in familial hypercholesterolemia type I?
How is it treated?
ApoCII or LPL
gemfibrozil and nicotinic acid
What is the worst familial hypercholesterolemia?
IIa (defective LDL clearance)
statins, ezetimibe, resins
How is hyperlipoproteinemia IIb treated?
How does it manifest?
statins, nicotinic acid
elevated LDL and VLDL
What is the defect in familial dysbetalipoproteinemia?
What drugs work the best?
ApoE2 results in faulty VLDL clearance, buildup of IDL
fibrates
What is the MOA of resins?
removing feedback inhibition on 7 alpha hydroxylase
due to increased fecal excretion of bile acids
What are the main side effects of resins?
bloating, constipation, abdominal pain
Which statins are prodrugs?
lovastatin, simvastatin
Which statins are metabolized by CYP3A4?
simvastatin, atorvastain, lovastatin
Which statins are metabolized by CYP2C9?
fluvastatin and rosuvastatin
Which statin is metabolized by CYP2D6?
simvastatin
Which statins need to be taken at night?
fluvastatin, lovastatin, simvastatin
