Drugs for hyperlipidemia Flashcards
What are the primary drugs in the bile acid resin binding agents?
Cholestyramine (Questran)
Colestipol (Colestid)
Colesevelam (WelChol)
What population will bile acid resin not have effect in?
Familial Hyperlipidemia (no LDL receptor)
What is the hallmark side effect of bile acid resins?
Constipation and bloating
What is the MOA of bile acid-binding resins?
Bind bile acids and prevent their intestinal absorption
What overall effect will a decrease in bile acids have on LDL receptors? In whom is this effect not seen?
An increase in expression of LDL receptors leads to more LDL uptake to create bile acids; familial hypercholesterolemia
What is the primary indication for bile acid-binding resins?
Whenever LDL is elevated
When should bile acid-binding resins be taken?
With meals. Not absorbed (obviously) which makes them the safest
What are two rare side effects of bile acid-binding resins?
Gallstone formation in obese patients, hypoprothrombinemia due to Vit K malabsorption
Absorption of these drugs may be impaired by use of bile acid binding resins
digitalis, thiazides, STATINS, tetracyclines, aspirin, thyroxine
What is the MOA for Niacin?
lowers plasma VLDL and LDL by inhibiting VLDL secretion by the liver.
What is the primary indication for Niacin use?
to increase levels of HDL
What are the hallmark adverse effects of niacin?
Cutaneous vasodilation (“niacin flush”), elevated aminotransferases or alkaline phosphatases will decrease glucose tolerance
What drugs are in the HMG-CoA reductase inhibitors?
Statins: Atorvastatin, fluvastatin, pravastatin, rosuvastatin
What is the MOA of HMG-CoA reductase inhibitors?
structural analogs of HMG-CoA reductase intermediate in mevalonate synthesis
How do statins reduce plasma LDL?
By inhibiting the reductase to increase high-affinity LDL receptors (still effective in LDL receptor deficiency because they have another MOA)
What are the indications and therapeutic effects of statins?
DECREASE LDL (most effective), decrease TG, increase HDL
What other benefits come from statins?
Decrease in CRP, increase plaque stability, decreases platelet aggregation
Which two statins are inactive and hydrolyzed to active form?
Lovastatin and simvastatin
When should statins be taken?
at night
Which drug for hyperlipidemia has a high first pass rate and liver metabolism, therefore has many drug interactions?
Statins
What are the adverse side effects of statins?
Increase in serum aminotransferase (reversible and often asymptomatic), increased serum CK, can lead to rhabdomyolysis (myoglobinuria)
Liver damage
What are absolute contraindications for the use of statins?
PREGNANCY and ACTIVE HEPATIC DISEASE
What are P450 inhibitors that will increase the plasma concentrations of statins?
Grapefruit juice, macrolides, ketoconazole, verapamil, cyclosporine
Wha are P450 activators that will decrease plasma concentration of statins?
phenytoin, griseofulvin, barbituates, rifampin
What other antihyperlipidemia drug will inhibit the metabolism of statins?
Gemfibrozil and other fibrates
What is the MOA of fibric acid derivatives?
Upregulate LPL and other genes involved to increase LPL activity and increase catabolism of VLDL
What is the overall effect of fibrates?
TO DECREASE TGs by lowering VLDL concentration, will also decrease cholesterol
What is a hallmark adverse effect of fibrates? What serum level of a lipid panel would also elevate with use of fibrates?
increased cholelithiasis or gallstones; increase LDL
What is the MOA for Ezetimibe (zetia)?
Selectively blocks the intestinal absorption of cholesterol and sterols
When is ezetimibe indicated? When does it work well?
To decrease moderate LDL; produces reductions as great as 25% of that achieved by a statin alone if combined with a statin
What can you do to prevent niacin flush?
Take aspirin beforehand (decrease PG)
