Lipid lowering drugs Flashcards
What are the classes of lipid lowering drugs
Niacin Fibrates Resins HMG-CoA reductase inhibitors Ezetimibe
What is niacin
Is nicotinic acid/Vit B3
Niacin MOA
main action: increase HDL cholesterol levels –> reduce plasma cholesterol
minor:
- inhibit lipolysis in adipose tissue –> decrease plasma TGs in VLDL, decrease plasma cholesterol in VLDL and LDL
- decrease circulating fibrinogen and increase tPA –> reverse thrombosis associated with hypercholesterolemia and atherosclerosis
Niacin PK
oral administration
converted in body to nicotinamide
Niacin clinical uses
widely used to lower TG, esp type 2b and 4
NOT useful for 2a as niacin does not have direct effect on cholesterol
Niacin adverse effects
- intense cutaneous flush and pruritus
2. hyperuricemia and gout
Name 3 fibrates
gemfibrozil, fenofibrate, clofibrate
Fibrates MOA
- are ligands for PPAR-a protein (peroxisome proliferators-activated receptor)
- -> interaction increases activity of LPL
- -> increased hydrolysis of TG into FFA for storage or use
- -> decrease plasma TG levels + reduce VLDL (secretion by liver reduced as TGs depleted)
- HDL levels rise moderately
Fibrates clinical uses
hypertriglyceridemias with VLDL elevation
- 2b, 3, 4, 5 (esp 3)
Fibrates adverse effects
- GI effects
- skin rashes
- gall stones
- myositis
Name 2 bile acid binding resins
colestipol, cholestyramine
resins MOA
- bind negatively charged bile acids and bile salts in small intestine
- -> reduce reabsorption of bile acids/salts
- -> reduces bile acid concentration –> hepatocytes increase conversion of cholesterol to bile acid to compensate
- -> reduce intracellular cholesterol concentration
- -> hepatocytes increase expression of LDLR–> increase hepatic uptake of cholesterol containing LDL –> decrease plasma LDL
- may increase VLDL
- little effect on HDL
resins clinical uses
- treatment for 2a
2. treat LDL elevations in 2b when used together with niacin
resins adverse effects
- GI effects
2. impaired absorption of fat soluble vitamins ADEK (absorbed at terminal ileum with bile acid)
Name HMG-CoA reductase inhibitors (statins)
atorvastatin, lovastatin, simvastatin, pravastatin, fluvastatin
HMG = 3-hydroxy-3-methylglutarate
Statins MOA
- HMG CoA reductase is enzyme in rate limiting step in cholesterol synthesis –> statins inhibit cholesterol synthesis
- depletion of intracellular cholesterol –> hepatocytes increase expression of LDLR –> more uptake of LDL from circulation –> decrease plasma LDL
Statins PK
oral, given in evening
- HMG CoA reductase activity is highest in evening when there is synthesis of basal amounts of cholesterol (no dietary intake here) –> most effective inhibition at this time
Statins clinical uses
for all hyperlipoproteinemias (statins reduce cholesterol levels)
reduces risk of coronary events and mortality in IHD
Statins adverse effects
- Liver: biomedical abnormalities in function (some enzymes get upregulated)
- Muscle: myopathy, rhabdomyolysis - muscle weakness, tea coloured urine
Statins contraindications
pregnancy, nursing mothers, teenagers/children
- cholesterol vital for brain development
Ezetimibe MOA
selective inhibitor of cholesterol transport protein NPC1L1 (inhibit dietary uptake)
Is ezetimibe effective in absence of dietary cholesterol
Yes - inhibit enterohepatic recycling of cholesterol (recycling of bile salts which are subsequently converted to cholesterol in liver)
Ezetimibe PK
oral, readily absorbed
conjugated in intestinal wall to active glucuronide
Ezetimibe clinical uses
reduce LDL
- alone: 18% reduction
- Vytorin (ezetimibe + simvastatin) more effective
