Med Chem - ACS (Acute Coronary Syndrome)

Question 1

explain how lipid-enriched plaques are very bad to form in the arteries

Answer 1

restricts blood flow

also, when the plaque ruptures, platelets adhere and form a clot that can block the coronary artery and prevent blood flow to the heart

Question 2

what is ACS (acute coronary syndrome)

Answer 2

condition where blood flow to the heart is suddenly reduced or blocked (the coronary artery)

Question 3

unstable angina vs STEMI vs NSTEMI

Answer 3

unstable angina - chest pain that occurs when heart isnt receiving enough oxygen. does not cause damage to the heart, but can progress to heart attack

NSTEMI - MILD heart attack. there is some damage to the heart

STEMI - ST-segment elevation MI. a ruptured plaque COMPLETELY blocks a major coronary artery. extensive heart damage

Question 4

explain how GpIIb and Gp IIIa are involved in crosslinking platelets when activated

Answer 4

these change conformation when activated. This shape change allows the crosslinking of fibrinogen between platelets to form a platelet plug

Question 5

true or false

increase cAMP causes vasodilation

Answer 5

true

Question 6

MOA aspirin (as an antiplatelet)

Answer 6

inhibits COX1, thus inhibiting the conversion of arachidonic acid to PGH2.

this inhibition allows inhibits the release of TXA2, a vasocnstrictor and a platelet aggregator

Question 7

MOA of dipyridamole

Answer 7

increased cAMP levels which prevents platelet aggregation and also causes vasodilation

inhibits cAMP breakdown

Question 8

name 5 P2Y12 antagonists

Answer 8

clopidogrel
prasugrel
ticlodipine
ticragelor
cangrelor

Question 9

3 Gp IIb/Gp IIIa antagonists

Answer 9

abciximab
epifibatide
tirofiban

“ATE”

Question 10

explain the role of ADP in platelet plug formation

Answer 10

when a plaque ruptures, nearby platelets adhere to the site of injury

these platelets change shape and express receptors that release ADP - a second messenger that is a potent platelet agonist

ADP binds to PY212 receptor on other platelets, causing them to aggregate together – leads to THROMBUS formation which can cause a big issue!!

Question 11

P2Y12 receptor antagonists are also called….

Answer 11

purinergic receptor antagonists

Question 12

**name the 3 P2Y12 receptors that bind to the P2Y12 receptor irreversibly

what is the name of this class?
are they prodrugs??

Answer 12

ticlodipine
clopidogrel
prasugrel

they are PRODRUGS and are called the thienopyridine derivatives

Question 13

**EXPLAIN the MOA of thienopyridine derivatives as antiplatelet agents

Answer 13

THEY ARE PRODRUGS

they are activated by CYPs (3A4/2C19) – to be activated, the thienopyridine ring MUST BE OPEN to allow covalent, IRREVERSIBLE binding to cysteine amino acid on the P2Y12 receptor of platelets.

prevents ADP, an inducer of platelet aggregation, from binding

Question 14

**disadvantage of thienopyridine class of drugs

Answer 14

genetic polymorphisms in CYP2C19 and CYP3A4 affect the response to the thienopyridine derivatives – bc they need these CYPS for the drug to be active

Question 15

**true or false

if a patient has an underactive CYP3A4, they may be more prone to bleeding from clopidogrel

Answer 15

FALSE - it’s underactive, so they will have LESS OR NO EFFECT – bc clopidogrel needs to be converted to its active metabolite by CYP3A4

Question 16

**advantages of prasugrel over clopidogrel

Answer 16

1. solves the issue of 85% of clopidogrel dose getting hydrolyzed by adding a cyclopropyl group (metabolically stable)
2. No CYP needed to activate the prodrug. the thiolactone spontaneously opens to expose the SH