21- Atherosclerosis Drugs Flashcards
clofibrate (Atromid-S)
fibric acid
-serve as ligand for PPARa leading to upregulation of lipoprotein lipase, apo A-I, and apo A-II
++apo A-I and A-II are major components of HDL and promote cholesterol efflux
-clears chylomicrons and VLDL quickly
-lowers triglycerides, and LDL and raises HDL cholesterol
**primarily useful for treating hypertriglyceridemias (VLDL)
-Toxicities: 1. rashes, GI symptoms, arrhythmias, low K, elevated LFTs
2. risk of myopathy when used with statins
3. inc. risk of gallstones
fenofibrate (Tricor)
fibric acid
-serve as ligand for PPARa leading to upregulation of lipoprotein lipase, apo A-I, and apo A-II
++apo A-I and A-II are major components of HDL and promote cholesterol efflux
-clears chylomicrons and VLDL quickly
-lowers triglycerides, and LDL and raises HDL cholesterol
**primarily useful for treating hypertriglyceridemias (VLDL)
-Toxicities: 1. rashes, GI symptoms, arrhythmias, low K, elevated LFTs
2. inc. risk of gallstones
-does not cause inc. blood statin levels like other fibrates
gemfibrozil (Lopid)
fibric acid
-serve as ligand for PPARa leading to upregulation of lipoprotein lipase, apo A-I, and apo A-II
++apo A-I and A-II are major components of HDL and promote cholesterol efflux
-clears chylomicrons and VLDL quickly
-lowers triglycerides, and LDL and raises HDL cholesterol
**primarily useful for treating hypertriglyceridemias (VLDL)
-Toxicities: 1. rashes, GI symptoms, arrhythmias, low K, elevated LFTs
2. risk of myopathy when used with statins
++inc. blood statin levels by inhibiting their metabolism
3. inc. risk of gallstones
ezetimibe (Zetia)
- inhibitor of intestinal sterol absorption
- prevents absorption of cholesterol (inhibits NPC1L1)
- absorbed and glucuronidated
- excreted into bile and feces
- is not a CYP450 substrate
nicotinic acid (niacin)
-water soluble vitamin incorporated into nicotinamide adenine dinucleotide
-inhibits VLDL secretion therefore ultimately decreases production of LDL
-decreases triglycerides > cholesterol
-no effect on bile production
Toxicities:
1. prostaglandin mediated cutaneous vasodilation (blunted with ASA/NSAID 30 before use)
2. Can cause elevated LFTs labels that are reversible but severe dysfunction noted with sustained-release preps
3. Long-term niacin treatment may inc. insulin resistance
4. Hyperuricemia d/t competition with uric acid for excretion in kidneys
cholestyramine
bile acid sequestrant
large polymeric cationic exchange resins- insoluble in water
-have to be taken with meals, not appetizing
-bind bile acids through ionic and hydrophobic interactions to prevent reabsorption
-increased uptake of LDL from upregulation of LDL receptors
-increased hepatic production of VLDL-increase triglycerides by 15-20%
-side effects: dyspepsia, constipation, bloating, diarrhea, malabsorption of vitmain K
-impaired absorption of other drugs: digoxin, thyroxine, warfarin, thiazides, iron salts, pravastatin, fluvastatin, exetimide, folic acid, aspirin, ascorbic acid
colesevelam HCL
bile acid sequestrant (2nd gen)- more selective for bile acid with fewer s/fx
large polymeric cationic exchange resins- insoluble in water
-have to be taken with meals, not appetizing
-bind bile acids through ionic and hydrophobic interactions to prevent reabsorption
-increased uptake of LDL from upregulation of LDL receptors
-increased hepatic production of VLDL-increase triglycerides by 15-20%
-reduced hyperglycemia
-side effects: dyspepsia, constipation, bloating, diarrhea(reduced), malabsorption of vitmain K (reduced)
-impaired absorption of other drugs: thyroxine, thiazides, iron salts, exetimide, folic acid, aspirin, ascorbic acid
atorvastatin
HMG CoA reductase inhbitor (competitively) prodrug
-decreases cholesterol synthesis and up-regulates LDL receptors and decreases LDL
-marked 1st pass metabolism, more important than high bioavailability to achieve the statin effect
-metabolized by CYP3A4
-recommended to be taken in the evening and absorption enhanced by food
-toxicities: increased LFTs, increased CK, myopathy, rhabdomyoylsis– worse with concurrent cyclosporin, clofibrate, niacin, erythromycin
Drug-drug interactions: increased drug levels in the presence of CYP3A4 inhibitors– macrolids, cyclosporine, ketaconazole, fibrates, tacrolimus, paroxetine
decreased drug levels in the presence of CYP3A4 inducers– phenytoin, barbiturates, rifampin
-plasma levels can be elevated with grapefruit juice
-undergo glycosylation– interaction with gemfibrozil
fluvastatin
HMG CoA reductase inhbitor (competitively) active form
-decreases cholesterol synthesis and up-regulates LDL receptors and decreases LDL
-marked 1st pass metabolism, more important than high bioavailability to achieve the statin effect
-metabolized by CYP2C9
-recommended to be taken in the evening and absorption enhanced by food
-toxicities: increased LFTs, increased CK, myopathy, rhabdomyoylsis– worse with concurrent cyclosporin, clofibrate, niacin, erythromycin
Drug-drug interactions: increased drug levels in the presence of CYP2C9 inhibitors– ketoconazole, metronidazole, amiodarone
-undergo glycosylation– interaction with gemfibrozil
lovastatin
HMG CoA reductase inhbitor (competitively) prodrug
-decreases cholesterol synthesis and up-regulates LDL receptors and decreases LDL
-marked 1st pass metabolism, more important than high bioavailability to achieve the statin effect
-metabolized by CYP3A4
-recommended to be taken in the evening and absorption enhanced by food
-toxicities: increased LFTs, increased CK, myopathy, rhabdomyoylsis– worse with concurrent cyclosporin, clofibrate, niacin, erythromycin
Drug-drug interactions: increased drug levels in the presence of CYP3A4 inhibitors– macrolids, cyclosporine, ketaconazole, fibrates, tacrolimus, paroxetine
decreased drug levels in the presence of CYP3A4 inducers– phenytoin, barbiturates, rifampin
-plasma levels can be elevated with grapefruit juice
-undergo glycosylation– interaction with gemfibrozil
simvastatin
HMG CoA reductase inhbitor (competitively) prodrug
-decreases cholesterol synthesis and up-regulates LDL receptors and decreases LDL
-marked 1st pass metabolism, more important than high bioavailability to achieve the statin effect
-metabolized by CYP3A4
-recommended to be taken in the evening and absorption enhanced by food
-toxicities: increased LFTs, increased CK, myopathy, rhabdomyoylsis– worse with concurrent cyclosporin, clofibrate, niacin, erythromycin
Drug-drug interactions: increased drug levels in the presence of CYP3A4 inhibitors– macrolids, cyclosporine, ketaconazole, fibrates, tacrolimus, paroxetine
decreased drug levels in the presence of CYP3A4 inducers– phenytoin, barbiturates, rifampin
-plasma levels can be elevated with grapefruit juice
-undergo glycosylation– interaction with gemfibrozil
pravastatin
HMG CoA reductase inhbitor (competitively) active form
-decreases cholesterol synthesis and up-regulates LDL receptors and decreases LDL
-marked 1st pass metabolism, more important than high bioavailability to achieve the statin effect
-metabolized by CYP2C9
-recommended to be taken in the evening and absorption enhanced by food
-toxicities: increased LFTs, increased CK, myopathy, rhabdomyoylsis– worse with concurrent cyclosporin, clofibrate, niacin, erythromycin
Drug-drug interactions: increased drug levels in the presence of CYP2C9 inhibitors– ketoconazole, metronidazole, amiodarone
-undergo glycosylation– interaction with gemfibrozil
