vascular system Flashcards
atherosclerosis treatment: identify the drugs used in the prevention and treatment of atherosclerosis and the subsequent rupture of an atherosclerotic plaque
2 types of acute coronary syndromes
NSTEMI (non-ST elevated MI), STEMI (ST-elevated MI)
in NSTEMI, what does the ‘white’ thrombus signify
partially occluded coronary artery
treatment for NSTEMI
antiplatelets
in STEMI, what does the ‘white’ thrombus signify
fully occluded coronary artery
treatments for STEMI
antiplatelets, thrombolytics
3 causes of acute coronary syndromes
damage to epithelium, atheroma formation, platelet aggregation
what drugs treat atherosclerosis
antiplatelet drugs
3 categories, with examples, of antiplatelet drugs (can be used for prophylaxis or treatment of atherosclerosis)
COX inhibitors (aspirin), P2Y12 receptor antagonists (clopidogrel), GPIIb/IIIa receptor antagonists (abciximab)
if atherosclerotic plaque ruptures, what class of drugs is used to treat
thrombolytics
example of thrombolytic drug and mechanism of action
alteplase, which is a tissue plasminogen activator
‘white’ vs ‘red’ thrombus, and treatments
red (red cell rich) in lumen of blood vessel (vein; e.g. DVT) so treated with anticoagulants; white (high content of foam cells - macrophages digesting cholesterol) forms inside actual blood vessel (artery; e.g. (N)STEMI) wall, so treated with antiplatelets
5 drug therapies for lipid-lowering therapies
bile acid sequestrants, nicotinic acid, fibrates (gemfibrozil), statins, ezetimibe
mechanism of action of statins
inhibits HMG-CoA reductase (HMG-CoA to mevalonic acid); cholesterol synthesis in liver reduced, so expresses more LDL surface receptors, reducing LDL in circulation
“rule of 6” for statins, and impact of PCSK9 and inhibitors
if 2x dose, further 6% reduction in LDL (not huge decrease upon increasing dose), but increases PCSK9 which inhibits LDLR (not ideal, so inhibition of PCSK9 increases LDL lowering effects of statins - could be given as vaccine or therapy)
relative reduction in CHD risk using statins
30%
pleiotropic (multiple) effects of statins
separate effect in inflammation, decreasing inflammation in atherosclerosis, inflammatory bowel disease etc,
what do fibrates bind to
PPAR (peroxisome proliferator activated receptor) alpha receptors in nucleus; PPAR gamma activators are glitazones used in diabetes
mechanism of action of fibrates
bind to PPARS, increasing plaque stability (decrease thrombosis), decrease cell recruitment, decrease inflammatory response, increase cholesterol efflux, cause vasoconstriction
effect of fibrates
increase HDL, decreasing CHD and stroke risk
mechanism of action of nicotinic acid
ability to decrease LDL cholesterol and increase HDL cholesterol levels in plasma, and anti-inflammatory, but causes flushing and more side effects
ezetimibe mechanism of action
absorbed then activated as glucoronide, inhibiting cholesterol absorption
combining statins (e.g. simvostatin) and ezetimibe
combining gets past “rule of 6”, further decreasing LDL, but not hugely; however whilst LDL lowered, mortality increased, so abandoned
why aren’t CETP inhibitors as popular in clinical use
adverse effects (e.g. activate RAAS, causing hypertension)
