Flashcards in Atherosclerosis Pharm Deck (21)
What is the dominant mechanism for controlling LDL plasma concentration?
regulation of hepatic LDL receptor pathway
What are the three HMG CoA reductase inhibitors?
What is the mechanism of action of statins?
structural similarity to HMG CoA substrate; reversible competitive inhibitor
How do statins increase LDL receptor gene expression?
in response to reduced free cholesterol content within hepatocytes; SREBPs are cleaved and the transcription factor then bind to sterol responsive element of LDL receptor gene
What are the minor adveerse effects of statins?
GI symptoms, diarrhea, constipation, excess flatus, abdominal pain/cramps and nausea
What are the major adverse effects of statins?
What are the myopathy risk factors?
increased statin levels, increased age, hepatic, renal disease, hypothyroidism, or combination with drugs
Why are statins contraindicaated in younger women.
What are the cinical use of statins?
first line therapy in pts who are at high risk for MI due to hypercholesterolemia; statins are effective in almost all pts with high LDL_C levels except for homozygous familial hypercholesterolemia
What is the mechanism of action of cholestyramine?
anion-exchange resins that increase bile acid excretion; highly charged + and binds bile acid; in most individuals synthesis is insufficient to make up for increased excretion
What are the adverse effects of cholestyramine?
poor pt compliance bc of consistancy
most elevation in TG
interfere with abosrbance of other drugs
What is the mechanism of action of niacin?
not explained by a single mechansim; due to decreased cAMP levels, reducing VLDL production
What are the major adverse effects of niacin?
intesnse flush and pruritis, GI ffects
concurrent use of niacin and statins can cause myopathy
What are the clincial use of niacin?
hypertriglyceridemias adn elevated LDL-cholesterol
only ipid lowering drug that reduces Lp(a)
What is the mechanism of action of Ezetimibe?
inhibits cholesterol transfer from intestinal lumen into intestinal cell by binding to transporter called Niemann Pick Cl-like 1 protein within brush border membrane
What is the clinical use of Exetimibe?
monotherapy for treatment of primary hypercholesterolemia in pts that are resistant to statin therapy
What are the mechanism of action of PPAR activators?
Gemfibrozil and Fenofibrate; mediate action by interaction with proliferator activated receptros, bind to them and alter transcritption of genes
Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors mechanism of action is what?
a mediator of hepatic LDL receptor degradation, is inhibited by this drug
What are the adverse effects of PCSK9 inhibitors?
generally well tolerated, hwoever still experimental; used to tx hypercholesterolemia
What is the mechanism of action of apolipoprotein B-100 inhbiition?
used to tx familial hypercholesteromeia homozygous by preventing formation of LDL or VLDL