MT2_8_Antiplatelets Pharma Flashcards
What happens in primary hemostasis, vs secondary?
- primary: vasoconstriction reduces blood flow, and platelets come together, activate fibrin clot formation
- secondary: clotting factors form
Steps of thrombus formation?
- adhesion
- recruitment (via intracellular signaling pathways)
- aggregation G2b/3a complexes on platelets bind to fibrinogen to make thrombus
What is the MOA of aspirin, a cox 1 inhibitor?
- irreversible inhibition of cox 1 prevents thromboxane A2 from forming platelets
Main indications for aspirin?
- secondary prevention of major coronary events in patients with IHD
- Afib
- Stroke
- Peripheral vascular disease
- analgesic
Dosing of aspirin?
81 mg, equally effective as higher doses
higher doses 325, pt at higher risk for a bleed
Aspirin S/E
DDIs
-bleeding, increased risk with antithrombotic agents
- NSAID (ibuprofen, naproxen)
- increased risk of bleeding
- due to competitive inhibition of Cox 1
What drugs fall under phosphodiesterase inhibitors?
- dipyridamole
- cilostazol
MOA of dipyridamole?
High dose?
- PDE5 inhibitor, inhibits platelet aggregation
- increases adenosine, causing vasodilation
- vasodilation–>reflex tacky–>myocardial ischemia
Main indications for dipyridamole? IR vs ER
IR: prophylaxis of thromboembolism with cardiac valve placement
ER: secondary prevention of stroke + aspirin
For dipyridamole, why is the IR formulation not superior?
- has side effects, dizziness, hypotension, and tachy at high doses
MOA of cilostazol
- PDE3 inhibitor, increases cAMP
- reversible inhibition platelet aggregation
- vasodilatation
What is cilostazol indicated for?
- cramping in peripheral artery disease
- used in combo with ASA or clopidogrel improves walking distance in patients with PAD
Cilostazol dosing?
- 100mgBID, w high fat meal
How is cilostazol metabolized?
Caution in…
- cyp2c19/3A4
- hepatic and renal impairment (CrCl less than 25)
- if on a 3A4/2C19 inhibitor (zoles) reduce dose to 50 mg BID
SE of cliostazol?
CI?
- skin rash, GI, Headache, hypo,tachy
- heart failure
Name P2Y12 inhibitors with irreversible binding, and reversible binding
- irreversible: ticlopidine (not used, neutropenia), clopidogrel,prasugrel
- reversible: ticagrelor, cangelor
How do P2Y12 inhibitors work?
All agents need a…
- binds P2Y12 inhibitor
- prevents ADP from binding
- prevents GP2b3a activation
- block platelet aggregation
(except for ticagrelor, cangrelor, bind directly on receptor) - loading dose
How is clopidogrel metabolized?
- 85% active, 15% inactive
- converted into 2 steps via CYP2C19 to active metabolite
Indications for Plavix?
Dose?
- ACS, PCI, CABG
- Stroke, TIA
- PAD
- Stroke prevention w ASA
- alternative to ASA
- 600mg or 300mg po x1, then 75 mg po daily
Plavix SE, CI, Hold, BBW
- bleeding
- active bleeding (ulcers)
- hold 5 days
- poor metabolizer for CYP2C19 results in increased CV events
- omeprazole and esomeprazole inhibits 2C19, decreased efficacy)
Prasugrel vs Clopidogrel
- faster, more predictable anti platelet response (bc of higher absorption and metabolite BA)
- lack of DDI
- higher rates of bleeding though
- rapid on
Indications for prasugrel?
- ACS with PCI ONLY
- 60mg x1, 10mg/day, if less than 60kgs, dose of 5 mg ok
BBW of prasugrel?
Ci
Hold
- not recommend for older than 75 (increased bleeding)
CI in prior stroke, TIA
and active bleeding ulcer
hold 7 days before surgery
MOA of ticagrelor?
- reversible, so it binds directly to the receptor to inhibit G protein activation
Ticagrelor vs clopidogrel?
- rapid onset
- consistant inhibition
Ticagrelor indications and Dose
- indicated for ACS w/wo PCI
- alternative to ASA or P2y12 inhibitor
- dose: LD 180 mg x1, 90mg BID
Ticagrelor DDIs
- substrate and inhibitor of 3A4, so dose simvastatin/lovastatin high like at 40
- inhibits PGP, can increase digoxin levels
Ticagrelor SE, Hold
- dyspnea, bleeding
- increase in adenosine concentrations due to blocking nucleotide transporter..vasodilation
- hold 5 days before surgery
Ticagrelor BBW?
BBW: use only with low dose aspirin less than 100
CI: active bleeding, history of intracranial hemorrhage
severe hepatic impairment
Cangrelor …what makes this drug different?
MOA is the same as ticragelor….IV
Indication for cangrelor?
Dose?
- undergoing PCI, pt does not get P2y12 inhibitor or GP2b3a inhibitor
- LD 30mcg/kg bolus, then 4 mcg/kg/min
How long does platelet function return after dc cangrelor? When to give plavix
- 1 hour
- after to avoid a decrease in activity
SE of cangrelor
CI
Place in therapy
- bleeding, renal insufficiency,dyspnea
- CI inbleeding
- bridge
Example of a thrombin receptor antagonist (PAR1 antagonist)
- vorapaxar
MOA of vorapaxar?
- reversible competitive PAR1 receptor antagonist
- inhibits thrombin platelet aggregation, but does not interfere with coagulation cascade, therefore does not affect PT or aPTT
Vorapaxar indication? Dose?
- reduce the risk of major adverse cardiac events in patients with a previous MI or PAD
- Dose: 2.08mg QD, WITH aspirin/clopidogrel
Major DDI with Vorapaxar?
- avoid use w strong 3A4 inhibitors/inducers
Vorapaxar SE/CI/BBW?
-SE: bleeding, anemia, depression, rask, skin issues
- CI/BBW: Hx of stroke, TIA, ICH
- active bleeding
- severe hepatic impairment
Name the G2b3a receptor inhibitors
- abciximab
- eptifibatide
- tirofiban
ALL IV
How do GP 2b3a receptors work?
- inhibits fibrinogen from binding to GP 2b3a receptor on activated platelets
- used as an adjunct
When are GP2b3a inhibitors used?
- ACS with PCI
- usually given with an anticoagulant (heparin or LMWH) + aspirin
CI of GP2B3A inhibitors?
- Intercranial issues (aneurysm, mass)
- AV malformations
- HTN
- hemorrhagic stroke/recent stroke
- recent surgery/trauma
- GI bleed
- thrombocytopenia (platelets less than 100)
MOA of abciximab? ReoPro
- noncompetitive irreversible inhibitor of G2b3a
- antibody against GP2b3a receptor, which causes steric hinderance blocking access of fibrinogen
When is abciximab indicated?
- PLANNED PCI (STEMI and UNSTEMI if no response)
- Dose is 0.35 mg/kg bolus, then 0.125 mcg/kg/min
In what pop is abciximab good for? how long does it take to dissociate from receptors?
- good for renal
- up to 4 hours , therefore duration is a lot longer
SE of abciximab?
- bleeding, hypotension, nausea
- antibody development on readmit: anaphylaxis, thrombocytopenia, reduced efficacy
MOA of eptifibatide?
- LMW competitive and reversible G2B, 3A antagonist
- has high specificity, low affinity to the GP2B3A inhibitor
Eptifibatide indication and dose?
- indicated for ACS, PCI
- Dose is 180mcg/kg IV bolus, then 2 mcg/kg/min
CI for eptifibatide?
SE?
- ESRD , half the dose if CrCl is less than 50
- SE- bleeding, hypotension, thrombocytopenia
MOA of tirofiban?
- similar to eptifibide, high specificity, high affinity
Indication for Tirofiban?
- ACS
- PCI
- 25mcg/kg IV bolus, then 0.15 mcg/kg/min
Need to renallyadjust for tirofiban?
- yes, if CrCl is less than 60, has the infusion rate
