CHAPTER 21: PLATELET AGGREGATION INHIBITORS

Question 1

Aspirin: cascade of the things released into plasma normally

Answer 1

start w arachidonic acid–> prostaglandin H2 formed by COX-1 –> thromboxane A2 released into plasma and promotes aggregation process

Question 2

Aspirin: MOA
- how long does it last
- repetitive administration effect

Answer 2

irreversibly inhibits COX-1–> therefore inhibits thromboxane A2 synth

• chemical mediator balance shifted to favor prostacyclin (favor anti-aggregation)
• lasts for life of platelet, 7-10 days
• give it repetitively, had cumulative effect on platelet func

Question 3

Aspirin: therapeutic use
- dose range

Answer 3

• prophylaxis of transient cerebral ischemia (stroke that lasts few mins)
• reduce recurrence of MI
• dec mortality in primary/secondary prevention of MI

dosage range 50-325 mg daily

Question 4

Aspirin: Adverse effects

Answer 4

high dose: inc drug-related toxicities/possible inhibit prostacyclin production (the thing that does anti-aggreg.)

prolonged bleeding time–> complications of inc hemmoraghic stroke & GI bleeding incidences

NSAIDS inhibit COX-1 competing to catalytic site
only take immediate release aspiring at LEAST 60 min before or 8 hours after ibuprofen

inc bleeding time, NSAIDS

Question 5

P2Y12 Receptor Antagonists
- names
- MOA

Answer 5

• clopidogrel, cangrelor, ticlopidine, ticagrelor, prasugrel
  (chloe can tickle tica’s prasu)

MOA: inhibit ADP binding to P2Y12 rec on platelets–> inhibit activation GP IIb/IIa rec needed for platelets to bind to fibrinogen and to each other

Question 6

P2Y12 Receptor Antagonists: therapeutic uses
- Clopidogrel

Answer 6

• prevent atherosclerotic events in PT w recent MI or stroke
• in PT w PAD
• prophylaxis of thrombotic events in acute coronary syndromes

Question 7

P2Y12 Receptor Antagonists: therapeutic uses
- ticlopidine

Answer 7

• prevent TIA (transient ischemic attacks) and stroke in PT w prior cerebral thrombotic events
• PT intolerant to other therapies (life-threatening hematologic adverse rxns)

Question 8

P2Y12 Receptor Antagonists: therapeutic uses
- prasugrel

Answer 8

dec thrombotic CV events in PT w acute coronary syndromes

Question 9

P2Y12 Receptor Antagonists: therapeutic uses
- ticagrelor

Answer 9

prevent arterial thromboembolism in PT w unstable angina/acute Mi
including those undergoing PCI

Question 10

P2Y12 Receptor Antagonists: therapeutic uses
- cangrelor

Answer 10

adjunct during PCI to reduce thrombotic events in select PTs

Question 11

P2Y12 Receptor Antagonists: Pharmacokinetics

Answer 11

• oral doses for quicker effect except cang (IV)
• food interferes ticlodipine
• bound to plasma proteins
• hepatic metab by CYP P-450
• elimination by renal/fecal routes

CLOPIDOGREL IS A PRO DRUG

Question 12

P2Y12 Receptor Antagonists: Adverse effects

Answer 12

ticlopidine: hematologic rxns limit use (agranulocytosis, TTP, aplastic anemia)

clopidogrel: fewer AE, TTP, but neutropenia risk lower

prasugrel: bleeding risk, TTP, contraindic PT w TIA or stroke history

ticagrelor: box warning for bleeding, less effect w concom use of aspiring above 100mg

cangrelor: bleeding risk

NO ANTIDOTE FOR BLEEDING CAUSED BY THESE DRUGS

Question 13

Glycoprotein IIb/IIa Inhibitors: MOA
- abciximab
- eptifibatide and tirofiban

Answer 13

abciximab (antibody fragment): inhibit IIb/IIa receptor complex
- blocks binding fibrinogen and vw factor, so aggregation doesn’t occur

eptifibatide/tirofiban: block receptors too
- epti is a cyclic peptide binds to GP site that ineracts w arg-gly-asp sequence in fibrinogen
- tiro blocks same site, not a peptide

Question 14

Glycoprotein IIb/IIa Inhibitors: therapeutic use and AE

Answer 14

• IV w heparin and aspirin
• adjunct to PCI for prevent cardiac ischemic complications
• approved for PT w unstable angina wo dont respond to conventional med therapy when PCI planned within 24 hrs

PCI= angioplasty (placing stent)

AE: bleeding, especially when used w anticoag

Question 15

Cilostazol: MOA

Answer 15

active metabolites inhibit phosphodiesterase type III, prevent degrading cAMP, inc cAMP levels in platelets/vasc tissues—> prevent platelet aggreg/promote vasodilation

Question 16

Cilostazol: therapeutic uses and AE (common and rare)

Answer 16

use: reduce symp of intermittent claudication (pain in legs bc of vasoconstriction/less blood bringing O2 to muscles)

AE:
common- headache and GI problems (diarrhea, dyspepsia)
rare- thrombocytopenia or leukopenia

inc mortality in PT w advanced HF
contraindic in PT w HF