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ASSIGNMENT
ON
HYPOLIPIDIMCS DRUGS
SUBMITTED TO SUBMITTED BY
Ms RAJNEET KAUR SUMIT RANA
PHARM D
1450951011
INTRODUCTIONThese are drugs which lower the levels of lipidsand lipoproteins in blood
The hypolipidaemic drugs have attractedconsiderable attention because of their potentialto prevent cardiovascular disease by retardingthe accelerated atherosclerosis in hyperlipidaemicindividuals
CLASSIFICATION1 HMG-CoA reductase inhibitors (Statins)Lovastatin Simvastatin PravastatinAtorvastatin Rosuvastatin2 Bile acid sequestrants (Resins) Cholestyramine Colestipol 3 Activate lipoprotein lipase (Fibric acid derivatives)Clofibrate Gemfibrozil BezafibrateFenofibrate4 Inhibit lipolysis and triglyceride synthesisNicotinic acid5 Others Ezetimibe Gugulipid
HMG-CoA REDUCTASE INHIBITORS
(STATINS)this class of compounds are the most efficacious and best tolerated hypolipidaernic drugs They competitively inhibit conversion of 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) to mevalonate (rate limiting step in CH synthesis) by the enzyme HMG-CoA reductase Therapeutic doses reduce CH synthesis by 20-50 This results in compensatory increase in LDL receptor expression on liver cells 1048762 increased receptor mediated uptake and catabolism of IDL and LDL Over long term feedback induction of HMG-CoA reductase tends to increase CH synthesis but a steady-state is finally
attained with a dose dependent lowerings of LDL-CH levels
Lovastatin It is the first clinically used statin islipophilic and given orally in the precursor lactoneform Absorption is incomplete and first passmetabolism is extensive Metabolites are excretedmainly in bile The tlh is short (1-4 hours)Jose 10-40 mgday (max 80 mg)
ROVACOR AZTATN LOVAMEG 10 20 mg tabs
Atorvastatin This newer statin is more potent
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
INTRODUCTIONThese are drugs which lower the levels of lipidsand lipoproteins in blood
The hypolipidaemic drugs have attractedconsiderable attention because of their potentialto prevent cardiovascular disease by retardingthe accelerated atherosclerosis in hyperlipidaemicindividuals
CLASSIFICATION1 HMG-CoA reductase inhibitors (Statins)Lovastatin Simvastatin PravastatinAtorvastatin Rosuvastatin2 Bile acid sequestrants (Resins) Cholestyramine Colestipol 3 Activate lipoprotein lipase (Fibric acid derivatives)Clofibrate Gemfibrozil BezafibrateFenofibrate4 Inhibit lipolysis and triglyceride synthesisNicotinic acid5 Others Ezetimibe Gugulipid
HMG-CoA REDUCTASE INHIBITORS
(STATINS)this class of compounds are the most efficacious and best tolerated hypolipidaernic drugs They competitively inhibit conversion of 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) to mevalonate (rate limiting step in CH synthesis) by the enzyme HMG-CoA reductase Therapeutic doses reduce CH synthesis by 20-50 This results in compensatory increase in LDL receptor expression on liver cells 1048762 increased receptor mediated uptake and catabolism of IDL and LDL Over long term feedback induction of HMG-CoA reductase tends to increase CH synthesis but a steady-state is finally
attained with a dose dependent lowerings of LDL-CH levels
Lovastatin It is the first clinically used statin islipophilic and given orally in the precursor lactoneform Absorption is incomplete and first passmetabolism is extensive Metabolites are excretedmainly in bile The tlh is short (1-4 hours)Jose 10-40 mgday (max 80 mg)
ROVACOR AZTATN LOVAMEG 10 20 mg tabs
Atorvastatin This newer statin is more potent
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
CLASSIFICATION1 HMG-CoA reductase inhibitors (Statins)Lovastatin Simvastatin PravastatinAtorvastatin Rosuvastatin2 Bile acid sequestrants (Resins) Cholestyramine Colestipol 3 Activate lipoprotein lipase (Fibric acid derivatives)Clofibrate Gemfibrozil BezafibrateFenofibrate4 Inhibit lipolysis and triglyceride synthesisNicotinic acid5 Others Ezetimibe Gugulipid
HMG-CoA REDUCTASE INHIBITORS
(STATINS)this class of compounds are the most efficacious and best tolerated hypolipidaernic drugs They competitively inhibit conversion of 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) to mevalonate (rate limiting step in CH synthesis) by the enzyme HMG-CoA reductase Therapeutic doses reduce CH synthesis by 20-50 This results in compensatory increase in LDL receptor expression on liver cells 1048762 increased receptor mediated uptake and catabolism of IDL and LDL Over long term feedback induction of HMG-CoA reductase tends to increase CH synthesis but a steady-state is finally
attained with a dose dependent lowerings of LDL-CH levels
Lovastatin It is the first clinically used statin islipophilic and given orally in the precursor lactoneform Absorption is incomplete and first passmetabolism is extensive Metabolites are excretedmainly in bile The tlh is short (1-4 hours)Jose 10-40 mgday (max 80 mg)
ROVACOR AZTATN LOVAMEG 10 20 mg tabs
Atorvastatin This newer statin is more potent
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
HMG-CoA REDUCTASE INHIBITORS
(STATINS)this class of compounds are the most efficacious and best tolerated hypolipidaernic drugs They competitively inhibit conversion of 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) to mevalonate (rate limiting step in CH synthesis) by the enzyme HMG-CoA reductase Therapeutic doses reduce CH synthesis by 20-50 This results in compensatory increase in LDL receptor expression on liver cells 1048762 increased receptor mediated uptake and catabolism of IDL and LDL Over long term feedback induction of HMG-CoA reductase tends to increase CH synthesis but a steady-state is finally
attained with a dose dependent lowerings of LDL-CH levels
Lovastatin It is the first clinically used statin islipophilic and given orally in the precursor lactoneform Absorption is incomplete and first passmetabolism is extensive Metabolites are excretedmainly in bile The tlh is short (1-4 hours)Jose 10-40 mgday (max 80 mg)
ROVACOR AZTATN LOVAMEG 10 20 mg tabs
Atorvastatin This newer statin is more potent
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
attained with a dose dependent lowerings of LDL-CH levels
Lovastatin It is the first clinically used statin islipophilic and given orally in the precursor lactoneform Absorption is incomplete and first passmetabolism is extensive Metabolites are excretedmainly in bile The tlh is short (1-4 hours)Jose 10-40 mgday (max 80 mg)
ROVACOR AZTATN LOVAMEG 10 20 mg tabs
Atorvastatin This newer statin is more potent
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
and appears to have the highest LDL-CHlowering efficacy at maximal daily dose of 80 mgAt this dose a greater reduction in TGs is noted ifthe same was raised at baseline Atorvastatin hasa much longer plasma tlh of 18-24 hr than otherstatins and has additional antioxidant propertyDose 10-40 mg day (max 80 mg)
AZTOR ATORVA ATORUP 10 20 mg tabs
Adverse effects All statins are remarkably welltolerated overall incidence of side effects notdiffering from placebo Notable side effects arebull Headache nausea bowel upset rashesbull Sleep disturbances (probably more withlipophilic drugs)
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
bull Rise in serum transaminase can occur but liverdamage is rarebull Muscle tenderness and rise in CPK levelsoccurs infrequently Myopathy is the onlyserious reaction but is rare ( lt 1 per 1000) Few
fatalities due to rhabdomyolysis are on record
Use Statins are the first choice drugs for primaryhyperlipidaemias with raised LDL and total CHlevels with or without raised TG levels (Type Ilalib V) as well as for secondary (diabetesnephrotic syndrome) hypercholesterolaemiaEfficacy of statins in reducing raised LDL-CHassociated mortality and morbidity is now wellestablished
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
BILE ACID SEQUESTRANTS
(RESINS)
Cholestyramine and Colestipol These are basic ion exchange resins supplied in the chloride form
They are neither digested nor absorbed in the gut bind bile acids in the intestine interrupting their enterohepatic circulationFaecal excretion of bile salts and CH (which is absorbed with the help of bile salts) is increased This indirectly leads to enhanced hepatic metabolism of CH to bile acidsMore LDL receptors are expressed on liver cells clearance of plasma IDL LDL and indirectly that of VLDL is increasedResins have been shown to retard atherosclerosis but are not popular clinically because they are unpalatable inconvenient have to be taken in large doses caLL-lt flatulence and other gi symptoms interfere
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
wilT absorption of many drugs and have poor patienc acceptability
NICOTINIC ACID (NIACIN)
It is a B group vitamin which in muchhigher doses reduces plasma lipids This actionis unrelated to its vitamin activity and not presentin nicotinamide When nicotinic acid is givenTGs and VLDL decrease rapidly followed by amodest fall in LDL-CH and total CH A 20-50reduction in plasma TGs and 15-25 reductionin CH levels has been recorded Nicotinic acidis the most effective drug to raise HDL-CH a20--35 increase is generally obtained Relativelylower dose suffices to raise HDL-CHNicotinic acid reduces production of VLDLin liver by inhibiting TG synthesis Indirectly theVLDL degradation products IDL and LDL are also
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
reduced No direct effect on CH and bile acidmetabolism has been found It inhibits intracellularlipolysis in adipose tissue and increases
the activity of lipoprotein lipase that clears TGs
OTHER HYPOLIPIDAEMICS
1 Ezetimibe It is a new drug of its own kindthat acts by inhibiting intestinal absorption ofcholesterol and phytosterols It interferes with aspecific CH transport protein NPC1C1 in theintestinal mucosa and reduces absorption of bothdietary and biliary CH There is compensatoryincrease in hepatic CH synthesis but LDL-CHlevel is lowered by 15--20 The enhanced CH
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
synthesis can be blocked by statins and the two
drugs have synergistic LDL-CH lowering effect
FIBRIC ACID DERIVATIVESFIBRIC ACID DERIVATIVES
The fibrates (isobutyric acid derivatives primarily activate lipoprotein lipase which is akey enzyme in the degradation of VLDL resultingin lowering of circulating TGs This effect i5exerted through paroxisome proliferator-activated
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
receptor a (PP ARa) that is a gene trancriptionregulating receptor expressed in liver faand muscles Activation of PP ARa enhance5lipoprotein lipase synthesis and fatty acidoxidation PP ARa may also mediate enhancedLDL receptor expression in liver seen particularlywith second generation fibrates Fibrates decrease hepatic TG synthesis as well
