Antihyperlipidemic Flashcards
Statins
CLASS: HMG-Coa reductase inhibitor
Rosuvastatin most potent
Fluvastatin least
Lovastatin & Simvastatin prodrugs activated by B-hydroxyl derivatives
MOA:Competitively inhibit HMG-CoA reductase (RLE
for de novo cholesterol synthesis) !↓ intracellular cholesterol!↑HMG-CoA reductase & ↑LDL receptors!↑LDL clearance
Best when used in combo with resins, niacin or
ezetimibe
USES:DOC for ↓LDL
↓cardiovascular mortality
AE:↑aminotransferases (must be monitored)
Myopathy and rhabdomyolysis (measure CK)
!myoglobinuria!renal injury
Patients who are homozygous for familial hypercholesterolemia benefit less from this TXT
d/t lack of fxnal LDL-r
Contraindicated in women who are pregnant/lactating/want to be pregnant!
Category X
Niacin
CLASS:Niacin
MOA: Activate Gi !↓adenylyl cyclase! ↓cAMP &
↓PKA!inhibit HSL!↓FA transport!↓TAG synthesis!↓VLDL production/release
↑LPL activity!↑chylomicron & VLDL clearance
↓HDL catabolism!↑HDL
↓fibrinogen, ↑t-PA!reverse endothelial dysfxn
USES: DOC for ↑HDL
Useful in patients with combined hyperlipidemia and
↓HDL levels Adjunct therapy with statins
AE:Intense cutaneous flush after each dose (PG mediated so it can be blocked by aspirin)
Pruritus, rashes, dry skin, and acanthosis nigricans
Nausea and abdominal discomfort
Hepatotoxicity!↑transaminases
Insulin resistance!hyperglycemia
(Caution in pts with diabetes)
↑uric acid!gout
Gemgibrozil
CLASS:Fibrates
MOA:Activate PPAR-α (peroxisome proliferator
activated receptor α) expressed in liver and
brown adipose tissue
↓TAG d/t ↑LPL, ↓apoC-III & ↑hepatic oxidation
of FA
Gemfibrozil inhibits uptake of
statins!↑concentration of both
drugs!↑rhabdomyolysis
USES:DOC for severe hypertriglyceridemia
AE:Mild GI disturbances Myositis Rhabdomyolysis Cholelithiasis d/t ↑cholesterol excretion Avoid in pts with hepatic/renal dysfxn
Fenofibrate
CLASS:Fibrates
MOA:Activate PPAR-α (peroxisome proliferator
activated receptor α) expressed in liver and
brown adipose tissue
↓TAG d/t ↑LPL, ↓apoC-III & ↑hepatic oxidation
of FA
USES:DOC for severe hypertriglyceridemia
AE:Mild GI disturbances Myositis Rhabdomyolysis Cholelithiasis d/t ↑cholesterol excretion Avoid in pts with hepatic/renal dysfxn
Cholestyramine
CLASS:Bile Acid-Binding Resins
MOA:Binds to anionic bile acids in
intestine!prevents
reabsorption!↑production in liver!↓ intracellular cholesterol!upreg LDL-r!↓LDL (partially offset by ↑cholesterol synthesis)
Modest ↑HDL
USES:Useful only in
hyperlipoproteinemias with ↑LDL
Used with statins/niacin
to ↑LDL reduction
DOC for children and
pregnant
AE:Little effect on pts with dysfxn LDL-r
Bloating, cramping & constipation (Colesevelam is better tolerated than others)
Contraindicated in pts. w/ very high LDL
Cholestyramine & Colestipol interfere with absorption of other drugs and Vit. ADEK
Colestipol
CLASS:Bile Acid-Binding Resins
MOA:Binds to anionic bile acids in
intestine!prevents
reabsorption!↑production in liver!↓ intracellular cholesterol!upreg LDL-r!↓LDL (partially offset by ↑cholesterol synthesis)
Modest ↑HDL
USES:Useful only in
hyperlipoproteinemias with ↑LDL
Used with statins/niacin
to ↑LDL reduction
DOC for children and
pregnant
AE:Little effect on pts with dysfxn LDL-r
Bloating, cramping & constipation (Colesevelam is better tolerated than others)
Contraindicated in pts. w/ very high LDL
Cholestyramine & Colestipol interfere with absorption of other drugs and Vit. ADEK
Colesevelam
CLASS:Bile Acid-Binding Resins
MOA:Binds to anionic bile acids in
intestine!prevents
reabsorption!↑production in liver!↓ intracellular cholesterol!upreg LDL-r!↓LDL (partially offset by ↑cholesterol synthesis)
Modest ↑HDL
USES:Useful only in
hyperlipoproteinemias with ↑LDL
Used with statins/niacin
to ↑LDL reduction
DOC for children and
pregnant
AE:Little effect on pts with dysfxn LDL-r
Bloating, cramping & constipation (Colesevelam is better tolerated than others)
Contraindicated in pts. w/ very high LDL
Cholestyramine & Colestipol interfere with absorption of other drugs and Vit. ADEK
Ezetimibe
CLASS:Cholesterol absorption inhibitors
MOA: H20 insoluble, Selectively inhibit NPC1L1 in jejunal enterocytes!↓ cholesterol!↑cholesterol synthesis & upreg of LDL-r! ↓LDL
Effective even in absence of cholesterol b/c it inhibits reabsorption of cholesterol excreted in bile
USES:Combo with statin in pts.
who can’t reach their LDL goal
AE:Reversible impaired hepatic fxn
Myositis
Absorption inhibited by bile acid sequestrants
EPA
CLASS:ω-3 Fatty Acids,Fish oils that ↓TAG in a dose
dependent way
MOA:↓TAG synthesis and ↑FA oxidation in the liver
impact on HDL varies
USES:↑LDL-C
AE:May ↑ total LDL as they ↓TAG
DHA
CLASS:ω-3 Fatty Acids,Fish oils that ↓TAG in a dose
dependent way
MOA:↓TAG synthesis and ↑FA oxidation in the liver
impact on HDL varies
USES:↑LDL-C
AE:May ↑ total LDL as they ↓TAG
Lovaza
CLASS:ω-3 Fatty Acids, Contain both EPA & DHA
MOA:↓TAG synthesis and ↑FA oxidation in the liver
impact on HDL varies
USES:↑LDL-C
AE:May ↑ total LDL as they ↓TAG
Vascepa
CLASS:ω-3 Fatty Acids, Ethyl ester of EPA
MOA:↓TAG synthesis and ↑FA oxidation in the liver
impact on HDL varies
USES:↓TAG without ↑LDL
AE:May ↑ total LDL as they ↓TAG
