hypolipidemic drugs Flashcards
LDL
low density lipoproteins
- transports cholesterol from liver to the blood stream
- aka “bad cholesterol”
- high levels in the blood are associated with an increased risk of atherosclerosis and coronary artery disease
- normal 100 start treatment
HDL
High density lipoprotein
- “good cholesterol”
- HDLs acquire cholesterol from peripheral tissue i.e. arterial walls
- low HDL levels = risk factor for cardiovascular disease
-
LP(a) Lipoprotein
formed from a LDL-like moiety and LP(a) protein
- highly homologous to plasminogen but lacks the ability to be activated by tPA
- repair of vessels
competitive inhibition
has same Vmax different Km
noncompetitive inhibition
has same Km different Vmax (squashed graph)
Cholesterol metabolism
?
statins
simvastatin fluvastatin atorvastatin pravastatin lovastatin
statins use and MOA
- lower LDL levels (by almost 60% ; TG down 40%)
MOA: competitive inhibitors of HMC-CoA reductase - leads to an induction of high affinity LDL receptors–> thus lowering serum LDL levels
- increasing LDL receptors is the important part of the mechanism!!
clinically all statins have the same efficacy
statin side effects
- elevations of serum aminotransferase and hepatotoxicity (increase in liver enzymes ALT/AST)
- myositis (muscle pain), marked by elevated creatine kinase activity
- if drug is not discontinued, rhabdomyolysis may occur–> producing myoglobinemia –> may lead to acute renal failure
*always monitor liver enzymes and creatine kinase when giving statins!
statin drug interactions
- drugs that may inhibit CYP enzymes (erythromycin, ketoconazole) will increase the plasma concentrations of statins
- concomitant use of amiodarone (class 3) or verapamil (class 4) or fibrates causes an increased risk of myopathy
- statin + BABR/ezetimibe (which works better in conjunction with statins)
- never use statins + fibrate bc toxicity! (myositis)
- never combine statins + niacin bc toxicity! (myositis)
niacin
aka nicotinic acid
when used in high doses
Niacin MOA and use
- water soluble VB3 which is converted in the body into nicotinamide adenine dinucleotide (NAD) but in high [ ]
- decreases plasma LDL levels and VLDL **
- markledly decreases plasma TG levels
mechanism primarily involves the inhibition of VLDL synthesis and esterification of Fatty Acids in the liver
Niacin Side Effects
- flushing (PGE2–> vasodilation–> flushing…..treated by aspirin or other NSAIDS)
- diarrhea
- hyperuricemia (can precipitate gout)
- hyperglycemia (so statins are preferred in diabetics)
Fabric Acid Derivatives and use
Gemfibrozil
Fenofibrate
Use: Increases the activity of LPL and Reduces VLDL levels, especially TG!!!
Fenofibrate MOA and use and A/E and drug interactions
MOA: agonist at peroxisome proliferator-activated receptor alpha (PPARalpha) which is a nuclear receptor
- PPARalpha affects genes necessary for carb and fat metabolism –> activation –> increase plasma HDL and decrease plasma TG
- increases the activity of lipoprotein lipase!!
- reduces VLDL levels esp lowers triglycerides
Use: typically used to treat hypertriglyceridemias
(preferred over statins)
A/E:
- GI symptoms
- myopathy (increased with given with statins)
- risk of cholesterol gallstones
Major Drug Interactions:
- fabric acid derivatives can displace other albumin bound drugs like warfarin–> thereby increase the anticoagulant effect of warfarin and sulfonyl ureas
Bile Acid Binding Resins and use
Colestipol
Cholestyramine
Colesevelam
Use: DECREASE LDL levels and INCREASE HDL
drugs that may inhibit CYP enzymes
erythromycin (macrolide antibiotics) ketoconazole cimetidine SSRIs fluoroquinolones HIV protease inhibitors grapefruit juice
CYP450 enzyme INDUCERS
rifampicin barbiturates phenytoin carbamazepine glucocorticoids chronic alcohol administration
Gemfibrozil MOA and use and A/E and drug interactions
MOA: agonist at peroxisome proliferator-activated receptor alpha (PPARalpha) which is a nuclear receptor
- PPARalpha affects genes necessary for carb and fat metabolism –> activation –> increase plasma HDL and decrease plasma TG
- increases the activity of lipoprotein lipase!!
- reduces VLDL levels esp lowers triglycerides
Use: typically used to treat hypertriglyceridemias
(preferred over statins)
A/E:
- GI symptoms
- myopathy (increased with given with statins)
- risk of cholesterol gallstones
Major Drug Interactions:
- fabric acid derivatives can displace other albumin bound drugs like warfarin–> thereby increase the anticoagulant effect of warfarin and sulfonyl ureas
Colestipol: use, MOA, A/E and drug interactions
**Decreases LDL levels and increases HDL
MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors –> thereby decreasing serum LDL levels
Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)
- side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*
Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin
Side Effects vs Toxicities
- side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*
patient has flushing. what drug did you give the patient and how do you treat it
the patient was given Niacin to lower LDL and VLDL
you treat this with aspirin or other NSAIDs
cholestyramine: use, MOA, A/E and drug interactions
**Decreases LDL levels and increases HDL
MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors –> thereby decreasing serum LDL levels
Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)
- side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*
Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin
Ezetimibe: use & toxicity
(zetia*)
- Prodrug
- lowers serum LDL and TG*
- decreases GI absorption of cholesterol
- used alone reduces LDL by 18% but MUCH more effective when given with statins (72%)
Toxicity: well-tolerated, MC side effect = diarrhea, abdominal pain
MOA = decrease synthesis of VLDL
name that drug!
Niacin
MOA = decrease cholesterol synthesis and increase LDL receptors
name that drug!
statins
MOA = interrupts enterohepatic circulation of bile acids and increases synthesis of bile acids and LDL receptors
name that drug!
Bile acid binding resins
Colestipol
Cholestyramine
colesevelam
colesevelam: use, MOA, A/E and drug interactions
**Decreases LDL levels and increases HDL
MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors –> thereby decreasing serum LDL levels
Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)
- side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*
Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin
MOA = increase LPL and TG hydrolysis
name that drug!
Fibrates
gemfibrozil
fenofibrate
MOA = decrease intestinal absorption of cholesterol
name that drug!
Ezetimibe
drug causes flushing, diarrhea, hepatic dysfunction, nausea, pruritus and gout
name that drug!
niacin
drug causes hepatotoxicity and myopathy
name that drug!
statins
drug causes hepatotoxicity, nausea and myositis
name that drug!
Fibrates
gemfibrozil
fenofibrate
drug causes GI disturbances
name that drug!
exetimibe
drug causes constipation, bloating, nausea and fat soluble vitamin deficiency
name that drug!
Bile acid binding resins
Colestipol
Cholestyramine
colesevelam
during drug treatment with atorvastatin it is important to routinely monitor serum concentrations of
alanine and aspartate transaminases and creatine kinase
two primary adverse effects HMG CoA inhibitors
hepatotoxicity and myopathy
dyslipidemia
general term associated with high cholesterol and/or high triglyceride (TG) levels in plasma.
CYP450 enzyme inducers
- rifampicin
- barbiturates
- phenytoin
- carbamazepine
- glucocorticoids
- chronic alcohol use
CYP450 enzyme inhibitors
- cimetidine
- SSRIs
- ketoconazole
- macrolide antibiotics
- fluoroquinolones
- HIV protease inhibitors
- grapefruitjuice
