lipid lowering drugs Flashcards
What is HMG-CoA reductase?
rate-limiting step in cholesterol synthesis
found in endoplasmic reticulum cells especially in the liver
Name 3 HMG-CoA reductase inhibitors
ALL THE STATINS
1. atorvastatin
2. pravastatin
3. simvastatin
HMG-CoA reductase inhibitors MOA
- inhibit HMG-CoA reductase, inhibit biosynthesis of cholesterol
- upregulates LDL receptors on cell surface: depletion of intracellular cholesterol causes cell to increase LDLr to bind and internalise LDL-Cs
HMG-CoA reductase inhibitor clinical use
- lower plasma cholesterol LDL-C in ALL types of hyperlipidaemia
- reduce risk of coronary events and mortality
HMG CoA reductase inhibitor adverse effects
- liver dysfunction
- myopathy and rhabdomyolysis
- contraindicated in pregnant women, children or teenagers
Name 2 PCSK9 inhibitor
- evolocumab
- alirocumab
MONOCLONAL AB
PCSK9 inhibitor MOA
- inhibition of hepatic proprotein convertase subtilisin-kexin (PCSK9) which targets LDL receptors for degradation in lysosomes
- decrease LDLr degradation, increase in LDL receptors on cell surface that can bind and internalise circulation LDL-C
PCSK9 inhibitors clinical uses
- used for intolerance to statins (HMG CoA reductase inhibitors)
- indication for lowering plasma LDL-C levels
- used for familial hypercholesterolaemias
- used on top of statins and diet control for patients with significant atherosclerotic CVD
PCSK9 inhibitors adverse effects
- hypersensitivity
- inflammatory reactions at site of injection
- increased incidence of nasopharyngitis and sinusitis
Name 2 fibrates derivatives
- gemfibrozil
- fenofibrate
fibrates derivatives MOA
- fibrates derivatives are ligands for PPAR-alpha protein
- binding results in increased activity of lipoprotein lipase
- decrease in plasma triacylglycerol levels
- decreased secretion by liver
- levels of VLDL decrease
HDL levels rise moderately
fibrates derivatives clinical uses
treatment of hypertriacylglycerol with VLDL elevation
especially for dysbetalipoproteinemia
fibrates derivatives adverse effect
- GI disturbance
- skin rashes
- gall stones
- myositis (inflammation of the muscle)
What are omega-3 acid ethyl esters?
omacor
- eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ethyl esters
people eat it from fish oil supplements too
omega-3 acid ethyl esters clinical uses
- hypertriglyceridemia type 4
- familial combined hyperlipidemia in combination with statins
- NOT indicated for hyperchylamicronaemia
omega-3 acid ethyl esters MOA
- reduces triglyceride production and increases TG clearance from VLDL
- inhibit diglyceride acyltransferase responsible for TG biosynthesis
- increase free fatty acid breakdown via beta ox
- increase lipoprotein lipase activity
omega 3 acid ethyl esters adverse effects
- contraindicated to people allergic to fish
- gi disturbance
- LDL-C levels increased due to DHA in some patients
- decreases production of TXA2, inhibit platelet aggregation, increased bleeding time
Name a bile acid binding resin
cholestyramine
Cholestyramine MOA
- resins bind to bile acids and salts in small intestine
- bile acid concentration decreased
- hepatocytes increase conversion to bile acids
- intracellular cholesterol concentration decreases - increase hepatic uptake of cholesterol containing LDL, decreasing plasma LDL
cholestyramine effects on VLDL and HDL
may inc VLDL but not effect on HDL
cholestyramine clinical uses
treat primary hypercholesterolemia
used with niacin to treat LDL elevation in combination with hyperlipidaemia
cholestyramine adverse effects
- gi disturbances
- imparied absorptions of vitamins ADEK
Name a drug that inhibits intestinal sterol absorption
ezetimibe
ezetimibe MOA
reduces cholesterol absorption at small intestines by inhibiting sterol transporter NPC1L1
clinical uses of ezetimbe
reduction of LDL
vytorin: ezetimibe+ simvastatin
ezetimibe adverse effects
- GI disturbances
- rhabdomyolysis
