DLD moa Flashcards
Statins/HMG CoA reductase inhibitors
moa
inhibit HMG CoA reductase which dec synthesis of cholesterol in the liver; inhibits rate limiting step (HMG CoA→ mevalonate)
Hepatic cholesterol is dec so LDL receptors are upregulated causing inc clearance of LDL from the blood
myositis
inflammation of muscle
statins pregnancy
x
antilipid effects of statins
Mostly dec LDL
Also inc HDL and dec TG
statins dose response?
NONLINEAR DOSE RESPONSE- doubling each dose only dec LDL by 6%; more meds not always = better
which statins have a shorter half life
Simvastatin, Pravastatin, lovastatin, fluvastatin
take at night
which statin uses CYP3A4?
simvastatin and lovastatin
which statin uses no cyp?
pravastatin
Over 1 quart of grapefruit juice a day is a problem with theses statins
atorvastatin, lovastatin, and simvastatin
moa fibrates
Stimulates PPAR alpha in the liver which leads to inc TG removal
PPAR alpha is a transcription factor that upregulates LDL which breaks down FFA
fibrates antilipid effects
Mostly TG dec
HDL inc and LDL dec
moa zetia
MOA: binds to NPC1L1 (Niemann Pick C1 like 1) in brush border of jejunum which inhibits cholesterol absorption and enhances LDL clearance
normally NPc1L1 does this
absorbes cholesterol in jejunum
zetia antilipid effects
Mainly dec LDL
Also inc HDL and dec TG
statins se
SE= liver effects, myopathy (myalgia, myositis, rhabdomyolysis), elevated glucose and A1C
statins caution
Caution: inc blood glucose/A1C, caution with fibrates bc they have inc risk for myopathy too
fibrates SE
SE: cholelithiasis, myopathy (inc risk when combined with statin)
fibrates caution
Caution: risk of myopathy and rhabdo inc with statins
zetia SE
SE: diarrhea, fatigue, nausea (overall very positive)
Niacin/Nicotinic acid
moa
inhibits lipase from binding to adipose tissue
Reduction in TG synthesis dec LDL
Raises HDL as well
Niacin/Nicotinic acid
effects on lipid profile
Affects all lipoproteins
DOSE INDEPENDENT
Best with at least 1.5 g daily
LINEAR dose response relationship for dec LDL
Niacin/Nicotinic acid
se
SE: cutaneous flushing (take at bedtime, take ASA ½ hr before)
moa omega 3 FA
inhibiting diglyceride acyltransferase which is involved in the biosynthesis of TG in the liver… so no TG are made
Omega 3 fatty acids
lipid effects
Dec TG and inc LDL
Only omega 3 acid ethyl esters inc LDL bc it has DHA
Also inc HDL
Omega 3 fatty acids
se
SE: burping, indigestion, fishy aftertaste
Omega 3 fatty acids
caution
Caution: may inc LDL (can switch to Ethyl eicosapentaenoic acid)
Bile acid sequestrants (BAS)
moa
MOA: bind bile acids in the SI; bind bile acid salts and prevent enterohepatic reutilization of bile salts. They also repair dietary cholesterol. Lower LDL
Bile acid sequestrants (BAS)
antilipid effects
Dec LDL
Inc HDL
Bile acid sequestrants (BAS)
se
none bc its not absorbed in the circulation; may have some GI complaints
Safest drug to treat hypercholesterolemia
Bile acid sequestrants (BAS)
drug interactions
Drug interactions: inhibit GI absorption of other drugs so take other drugs 1-2 hours before or 4-6 hrs after
Safest drug to treat hypercholesterolemia
bas
PCSK9 inhibitors
moa
Monoclonal Ab that binds to PCSK9
PCSK9 is a serine protease that binds to LDL receptors and destroys them. This causes dec LDL receptors and dec LDL clearance and inc plasma LDL levels
PCSK9 inhibitors dec LDL receptors and improve LDL clearance
PCSK9 inhibitors
lipid lowering effects
Dec LDL
Dec risk of heart attack
Dec risk of stroke
Add a statin to get optimal effects
Nexletol prodrug
Bempedoic acid
Nexletol moa
MOA: inhibits ATP citrate lyase which is involved in livers biosynthesis of cholesterol upstream of HMG CoA reductase
Nexletol se
SE: hyperuricemia, muscle pain with simvastatin and pravastatin (he found muscle pain interesting)
