vascular system

Question 1

2 types of acute coronary syndromes

Answer 1

NSTEMI (non-ST elevated MI), STEMI (ST-elevated MI)

Question 2

in NSTEMI, what does the ‘white’ thrombus signify

Answer 2

partially occluded coronary artery

Question 3

treatment for NSTEMI

Answer 3

antiplatelets

Question 4

in STEMI, what does the ‘white’ thrombus signify

Answer 4

fully occluded coronary artery

Question 5

treatments for STEMI

Answer 5

antiplatelets, thrombolytics

Question 6

3 causes of acute coronary syndromes

Answer 6

damage to epithelium, atheroma formation, platelet aggregation

Question 7

what drugs treat atherosclerosis

Answer 7

antiplatelet drugs

Question 8

3 categories, with examples, of antiplatelet drugs (can be used for prophylaxis or treatment of atherosclerosis)

Answer 8

COX inhibitors (aspirin), P2Y12 receptor antagonists (clopidogrel), GPIIb/IIIa receptor antagonists (abciximab)

Question 9

if atherosclerotic plaque ruptures, what class of drugs is used to treat

Answer 9

thrombolytics

Question 10

example of thrombolytic drug and mechanism of action

Answer 10

alteplase, which is a tissue plasminogen activator

Question 11

‘white’ vs ‘red’ thrombus, and treatments

Answer 11

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

Question 12

5 drug therapies for lipid-lowering therapies

Answer 12

bile acid sequestrants, nicotinic acid, fibrates (gemfibrozil), statins, ezetimibe

Question 13

mechanism of action of statins

Answer 13

inhibits HMG-CoA reductase (HMG-CoA to mevalonic acid); cholesterol synthesis in liver reduced, so expresses more LDL surface receptors, reducing LDL in circulation

Question 14

“rule of 6” for statins, and impact of PCSK9 and inhibitors

Answer 14

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)

Question 15

relative reduction in CHD risk using statins

Answer 15

30%

Question 16

pleiotropic (multiple) effects of statins

Answer 16

separate effect in inflammation, decreasing inflammation in atherosclerosis, inflammatory bowel disease etc,

Question 17

what do fibrates bind to

Answer 17

PPAR (peroxisome proliferator activated receptor) alpha receptors in nucleus; PPAR gamma activators are glitazones used in diabetes

Question 18

mechanism of action of fibrates

Answer 18

bind to PPARS, increasing plaque stability (decrease thrombosis), decrease cell recruitment, decrease inflammatory response, increase cholesterol efflux, cause vasoconstriction

Question 19

effect of fibrates

Answer 19

increase HDL, decreasing CHD and stroke risk

Question 20

mechanism of action of nicotinic acid

Answer 20

ability to decrease LDL cholesterol and increase HDL cholesterol levels in plasma, and anti-inflammatory, but causes flushing and more side effects

Question 21

ezetimibe mechanism of action

Answer 21

absorbed then activated as glucoronide, inhibiting cholesterol absorption

Question 22

combining statins (e.g. simvostatin) and ezetimibe

Answer 22

combining gets past “rule of 6”, further decreasing LDL, but not hugely; however whilst LDL lowered, mortality increased, so abandoned

Question 23

why aren’t CETP inhibitors as popular in clinical use

Answer 23

adverse effects (e.g. activate RAAS, causing hypertension)