Lipid lowering agents Flashcards
What is a example of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors?
Alirocumab, evolocumab
Name the drugs that mainly target LDL & total cholesterol
statins cholesterol absorption inhibitors bile acid-binding (anion exchange) resins PCSK9 inhibitors bempedoic acid
Name the drugs that mainly target triglycerides
fibrates
Ω-3 fatty acids / fish oils
What drugs are used to reduce LDL?
statins
What drugs are used to reduce triglycerides?
fibrates
What are the drugs of choice in raising HDL?
niacin
Name six examples of statins
lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin
What are Anti-PCSK9 monoclonal antibodies
responsible for?
Inhibit action of liver-produced enzyme PCSK9, responsible for promoting metabolism and subsequent degradation of LDL-R on liver cells
PCSK9 inhibitors _______ hepatic LDL-R expression and LDL clearance
______ HDL (modest)
______ LDL, VLDL & triglycerides
Increase
Raise HDL
Lower LDL
What are statins main effect?
To block the rate-limiting step represented by the formation of mevalonate from HMG CoA in the liver.
What are statins secondary effects?
Reduce hepatic cholesterol synthesis
Increase hepatic LDL-R expression, LDL clearance & reduce VLDL production
Raise HDL
Lower LDL, VLDL & triglycerides
How do statins manage cardiovascular risk?
via LDL lowering but also possibly through pleiotropic effects such as anti-thrombotic and anti-inflammatory actions
What are Bile acid-binding (anion exchange) resins secondary effects?
Increase bile acid synthesis-activation by activation of hepatic 7-α-hydroxylase, more cholesterol needed to replace lost bile acids, reduces hepatic store of cholesterol.
Increase hepatic LDL-R expression & LDL clearance
May raise HDL
Lower LDL
Name three examples of Bile acid-binding (anion exchange) resins?
colestipol, cholestyramine, colesevelam
What are Bile acid-binding (anion exchange) resins main effects?
Reduce bile acid reabsorption,
interrupts enterohepatic bile acid circulation,
reduces (bile acid) cholesterol reabsorption
What are Bile acid-binding (anion exchange) resins secondary effects?
Increase bile acid synthesis-activation of hepatic 7-α-hydroxylase, more cholesterol needed for de novo bile acid synthesis reduces hepatic store of cholesterol.
Increase hepatic LDL-R expression & LDL clearance
May raise HDL
Lower LDL
How is PCSK9 Administered?
Administered by subcutaneous injection
Give three examples of Fibrates
Gemfibrozil, fenofibrate, bezafibrate, ciprofibrate, clofibrate
Fibrates _____ lipoprotein lipase (LPL) activity & increase triglyceride clearance
Induce
Fibrates ______hepatic FFA uptake Increase mitochondrial FFA oxidation (ß-oxidation)
Increase
Fibrates ________ hepatic VLDL & triglyceride production
Raise HDL
_______ VLDL, LDL & triglycerides.
Reduce
Lower
Which drugs do Bile acid-binding (anion exchange) resins reduce the absorption of?
digoxin, warfarin, thyroxine, cholorothiazide
What are Bile acid-binding (anion exchange) resins side effects?
reduced absorption of fat soluble vitamins (A, D, E, K),
susceptibility to bleeding (reduced vitamin K),
bloating, dyspepsia, flatulence
Which drug is an example of cholesterol absorption inhibitors?
ezetimibe
What are cholesterol absorption inhibitors main effects?
prevents the absorption of both dietary and bile (free) cholesterol; but does not affect the absorption of e.g. dietary TG, fat soluble vitamins or bile acids.
What are cholesterol absorption inhibitors secondary effects?
Inhibit cholesterol uptake receptor
Reduce hepatic VLDL production
Increase hepatic LDL-R expression & LDL clearance
Reduce LDL
What are ezetimibe side effects?
myopathy, rhabdomyolysis, dyspepsia, diarrhoea, abdominal pain, arthralgia, myalgia, headache, elevated liver function tests, angioedaema
Fibrates can displace ____
Wafarin
Give an example of Ω-3 fatty acids (fish oils)
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
Ω-3 fatty acids are responsible for?
Regulate nuclear transcription factors
eg. PPARα & SREBP-1c
Ω-3 fatty acids ______ triglyceride biosynthesis & _______ fatty acid oxidation in liver
Reduce triglyceride
increase fatty acid
Ω-3 fatty acids _____ VLDL & triglycerides
_____ HDL
Reduce VLDL
Raise HDL
Niacin (nicotinic acid/vitamin B3) are responsible for?
Inhibits hormone-sensitive lipase
reduces FFA release from adipose (lipolysis)
Naicin ____ hepatic VLDL production & triglyceride synthesis
______ hepatic HDL uptake
Lowers Hepatic VLDL
Reduces hepatic HDL
