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ANTI-HYPERLIPIDEMIC DRUGS
HMG-COA INHIBITORS
Lovastatin; Atarvostatin
 Analogs of HMG (3-hydroxy-3 methylglutaryl-CoA)
 HMG-CoA reductase catalyzes synthesis of
mevalonic acid from HMG-CoA and is the rate
limiting step in cholesterol biosynthesis
 Leads to up-regulation of LDL receptors in liver
 ACTIONS


Decrease LDL by 20 – 55%
 Decrease TG by 10 – 35%
 Slight increase in HDL

HMG-COA INHIBITORS


Adverse
Hepatotoxicity (check ALT and AST, if >3x normal...stop drug)
 Myopathy (w/ rhabodmyolysis) and may cause
myoglobinuria which may lead to urine obstruction
(measure CPK levels)







Increased chances when mixed with fibric acid derivatives
(gemfibrizol), niacin, or P450 3A4 inhibitors

CATEGORY X in pregnancy

Therapeutic Uses
Great for all hyperlipidemias involving increased levels of LDL
or cholesterol
 Atherosclerosis; stroke prevention
 Primary prevention of CAD

BILE ACID RESIN
Cholestyramine
 Anion-exchange resin – binds bile acids in intestinal
lumen preventing enterohepatic circulation (this
increases excretion of bile which is made from
cholesterol)  this causes an up-regulation of
hepatic LDL receptors and increased production of
cholesterol
 Action: decreases LDL by 10 – 35%
 Not absorbed at all

BILE ACID RESIN


Adverse








Constipation, flatulence, dyspepsia
Hypertriglyceridemia
Hyperchloremic acidosis (since they exchange Cl)
Bind many things (drugs, vitamins, toxins, anything
fat soluble) which limits their absorption
Prexisting coagulopathy is a contraindication since
they prevent absorption of vit K

Uses
Hyperlipidemias involving ISOLATED INCREASES
OF LDL
 Diarrhea from excess fecal bile resins

VLDL SECRETION INHIBITORS
NIACIN (vit B3)
 MoA: inhibition of VLDL production by hepatocyte
 decreases TG synthesis in liver; inhibition of
Hormone sensitive lipase in adipose; stimulation of
LPL which causes hydrolysis of VLDL
 Actions


Decreases LDL by 15-25%
 Decreases VLDL by 40%
 Decreases TG by 30 – 50%
 Increases HDL by 15-30% (niacin is MOST EFFECTIVE
in increasing HDL levels!!)

VLDL SECRETION INHIBITORS


Adverse











Cutaneous flush (prevented with NSAID)
Stimulates histamine release  pruritis, rash, nausea, etc
Decreased glucose tolerance (contra in DM pts)
Hyperuricemia (inhibits tubular secretion of uric acid)
Lowers fibrinogen (good for AS; bad for coag disorders)
Hepatotoxicity (check AST, ALT levels)
Rhabdomyolysis (especially when given with Statins)

Uses
Hyperlipidemias with very high VLDL and LDL
 Pts with very low HDL (despite risk factors you should give
niacin)

FIBRIC ACID DERIVATIVES
Gemfibrozil
 MoA: activation of nuclear transcription receptor to
increase LPL synthesis (removes TGs from
lipoproteins); enhanced removal of VLDL from
plasma
 Actions


Decreases TG by 30-60%
 Decreases VLDL by 30%
 Increases HDL by 5 – 10%

FIBRIC ACID DERIVATIVES


Adverse
Myopathy (rhabdomyolysis) when combined with
statins
 Cholesterol levels may actually increase
 Cholethiasis due to increased biliary excretion of
cholesterol




Therapeutic Uses
DOC fro type III lipoproteinemia (familial
dysbetalipoproteinemia)
 Hypertriglyceridemias

INTESTINAL STEROL ABSORPTION INHIBITOR
Ezetimibe
 Localizes at the brush border, selectively inhibits
intestinal absorption of cholesterol and related
sterols (only blocks exogenous sterol intake)
 Actions


Decreases LDL by 15-20%
 Decreases TG by 5-8%
 THIS DRUG IS WEAK ALONE

INTESTINAL STEROL ABSORPTION INHIBITOR


Adverse
Hypersensitivity reactions
 Severe hepatic disease prolongs drug life




Uses


Combined with statins for hyperlipidemias
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Pharmacology: Anti hyperlipidemic drugs flashcards

  • 2. HMG-COA INHIBITORS Lovastatin; Atarvostatin  Analogs of HMG (3-hydroxy-3 methylglutaryl-CoA)  HMG-CoA reductase catalyzes synthesis of mevalonic acid from HMG-CoA and is the rate limiting step in cholesterol biosynthesis  Leads to up-regulation of LDL receptors in liver  ACTIONS  Decrease LDL by 20 – 55%  Decrease TG by 10 – 35%  Slight increase in HDL 
  • 3. HMG-COA INHIBITORS  Adverse Hepatotoxicity (check ALT and AST, if >3x normal...stop drug)  Myopathy (w/ rhabodmyolysis) and may cause myoglobinuria which may lead to urine obstruction (measure CPK levels)     Increased chances when mixed with fibric acid derivatives (gemfibrizol), niacin, or P450 3A4 inhibitors CATEGORY X in pregnancy Therapeutic Uses Great for all hyperlipidemias involving increased levels of LDL or cholesterol  Atherosclerosis; stroke prevention  Primary prevention of CAD 
  • 4. BILE ACID RESIN Cholestyramine  Anion-exchange resin – binds bile acids in intestinal lumen preventing enterohepatic circulation (this increases excretion of bile which is made from cholesterol)  this causes an up-regulation of hepatic LDL receptors and increased production of cholesterol  Action: decreases LDL by 10 – 35%  Not absorbed at all 
  • 5. BILE ACID RESIN  Adverse       Constipation, flatulence, dyspepsia Hypertriglyceridemia Hyperchloremic acidosis (since they exchange Cl) Bind many things (drugs, vitamins, toxins, anything fat soluble) which limits their absorption Prexisting coagulopathy is a contraindication since they prevent absorption of vit K Uses Hyperlipidemias involving ISOLATED INCREASES OF LDL  Diarrhea from excess fecal bile resins 
  • 6. VLDL SECRETION INHIBITORS NIACIN (vit B3)  MoA: inhibition of VLDL production by hepatocyte  decreases TG synthesis in liver; inhibition of Hormone sensitive lipase in adipose; stimulation of LPL which causes hydrolysis of VLDL  Actions  Decreases LDL by 15-25%  Decreases VLDL by 40%  Decreases TG by 30 – 50%  Increases HDL by 15-30% (niacin is MOST EFFECTIVE in increasing HDL levels!!) 
  • 7. VLDL SECRETION INHIBITORS  Adverse         Cutaneous flush (prevented with NSAID) Stimulates histamine release  pruritis, rash, nausea, etc Decreased glucose tolerance (contra in DM pts) Hyperuricemia (inhibits tubular secretion of uric acid) Lowers fibrinogen (good for AS; bad for coag disorders) Hepatotoxicity (check AST, ALT levels) Rhabdomyolysis (especially when given with Statins) Uses Hyperlipidemias with very high VLDL and LDL  Pts with very low HDL (despite risk factors you should give niacin) 
  • 8. FIBRIC ACID DERIVATIVES Gemfibrozil  MoA: activation of nuclear transcription receptor to increase LPL synthesis (removes TGs from lipoproteins); enhanced removal of VLDL from plasma  Actions  Decreases TG by 30-60%  Decreases VLDL by 30%  Increases HDL by 5 – 10% 
  • 9. FIBRIC ACID DERIVATIVES  Adverse Myopathy (rhabdomyolysis) when combined with statins  Cholesterol levels may actually increase  Cholethiasis due to increased biliary excretion of cholesterol   Therapeutic Uses DOC fro type III lipoproteinemia (familial dysbetalipoproteinemia)  Hypertriglyceridemias 
  • 10. INTESTINAL STEROL ABSORPTION INHIBITOR Ezetimibe  Localizes at the brush border, selectively inhibits intestinal absorption of cholesterol and related sterols (only blocks exogenous sterol intake)  Actions  Decreases LDL by 15-20%  Decreases TG by 5-8%  THIS DRUG IS WEAK ALONE 
  • 11. INTESTINAL STEROL ABSORPTION INHIBITOR  Adverse Hypersensitivity reactions  Severe hepatic disease prolongs drug life   Uses  Combined with statins for hyperlipidemias
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