Pharm - ACS Flashcards
What is the goal of therapy for a patient with UA or NSTEMI?
- prevent progression to STEMI and death
- prevent ischemia and life-threatening ventricular arrhythmias
- relief of ischemic pain
- prevent further thrombosis of or embolism from an ulcerated plaque
For a patient presenting with UA (or any ACS), what is the correct aspirin product to use? and the dose?
- chewable, uncoated aspirin
- 162-325 mg ASAP
- continued indefinitely
MoA of aspirin in treating UA/NSTEMI
- in cytosol AA (arachadonic acid) is converted to 2 prostaglandin intermediates by COX-1 and COX-2
- COX-1 is essential for synthesis of thromboxane A2 (TxA2)
- TxA2 stimulates platelet aggregation and vasoconstriction
- aspirin blocks COX-1, reducing production of TxA2 = decreased platelet aggregation
(flow chart on pg 6 if needed)
appropriate dosing of sublingual nitroglycerin for UA
- 3 sublingual nitroglycerin tabs 0.4 mg
- one at a time, spaced 5 min apart
MoA of nitroglycerin
- nitrates enter vascular smooth muscle and form NO
- NO stimulate an enzyme to form cGMP which does 2 things:
- inhibits Ca++ entry into cell (relaxation)
- causes downstream dephosphorylation of myosin = relaxation = vasodilation
(flow chart on pg. 7 if needed)
ADRs of sublingual nitro
- HA (intense) and flushing
- SL tingling
- postural hypotension
- occasional nausea
- tachycardia
ADRs of aspirin
(Letassy didn’t have specific list in packet)
- chewing aspirin can irritate mouth, make sure to rinse
- takes 7 days to reverse so stop 1 week before procedure to prevent bleeding
define the term cardioselectivity in context of a cardioselective beta blocker
- refers to the ability of a drug to preferentially block the B-1 receptor
- cardioselective beta blockers have the potential advantage of less likely to cause bronchoconstriction or peripheral vasodilation
- the selectivity is usually lost at higher doses
- best one is metroprolol tartrate**
define dual antiplatelet therapy (DAPT)
- all patients w/ NSTEMI should be treated w/ aspirin and a P2Y12 receptor blocker (ASA + P2Y12RB)
- it’s directed at limiting platelet adhesion and aggregation (early steps of coronary a. thrombus formation)
- it has been shown to significantly reduce the risk of cardiovascular death, nonfatal MI or stroke
what is the recommended duration of DAPT for patients w/ stent placement secondary to UA/NSTEMI
- at least 12 months
- unless high bleed risk
What are the P2Y12 receptor blockers? (the 4 that letassy gave us)
- clopidogrel (Plavix)
- prasugrel (effient)
- ticagrelor (brilinta)
- cangrelor (Kengreal)
MoA of clopidogrel (Plavix)
- P2Y12 ADP receptor inhibitor
- requires 2 steps for biotransformation to active metabolite
- irreversibly blocks the P2Y12 portion on the ADP receptor on platelet surface
- reduced platelet aggregation
MoA of ticagrelor
- noncompetitive, reversible, P2Y12 receptor antagonist
- reversibly binds to ADP receptors on platelet surface
- prevents ADP-mediated platelet activation and aggregation
In treating a patient with UA, what is the appropriate dose of clopidogrel?
- **Loading dose: 300-600 mg
- followed by 75 mg orally daily
In treating a patient with UA, what is the appropriate dose of prasugrel?
- **loading dose: 60 mg
- followed by 10mg orally daily
- 5mg daily if used in pts w/ high bleeding risk
In treating a patient with UA, what is the appropriate dose of ticagrelor?
- **Loading dose: 180 mg
- followed by 90 mg orally BID given w/ low dose ASA
In treating a patient with UA, what is the appropriate dose of cangrelor?
- IV bolus 30 mcg/kg prior to PCI
- followed by infusion (4 mcg/kg/min) continued for at least 2 hrs or duration of PCI
In treating a patient with UA, what is the appropriate dose of unfractionated heparin?
- **loading dose: IV bolus 60-70 units/kg (MAX 5000 units)
- followed by 12 units/kg/hr or until aPTT goal is achieved
In treating a patient with UA, what is the appropriate dose of LMWH?
- no loading dose
- 1 mg/kg subQ q 12
ADRs of clopidogrel
- bleeding (but less than aspirin)
- neutropenia
drug-drug interactions of clopidogrel
- it is an inactive prodrug requiring transformation by liver CYP3A and 2C19
- significant drug interaction:
- PPIs
- Statins
explain what can occur with the drug interactions of clopidogrel
- PPIs: may decreases serum concentrations of active metabolites; increases risk of decreasing effectiveness of clopidogrel; avoid
- statins: may diminish the antiplatelet effect of clopidogrel
ADRs of ticagreglor
- bleeding
- dyspnea** (unique):
- usually occurs in 1st week
- may be transient or persistant
- not linked to a deterioration in heart or lung function
drug drug interactions of ticagrelor
- it inhibits CYP3A4 so can increase serum concentrations of some drugs
- stronger CYP3A4 inhibitors can increase levels of ticagrelor and reduce speed of onset
- it reversibly inhibits platelet activation
black box warning for prasugrel
bleeding and TTP
contraindications for prasugrel
- 75 or older w/o high risk of sent thrombosis
- hx of prior stroke or TIA
- active or suspected bleeding
which antiplatelet agents are pro drugs?
- clopidogrel
- prasugrel
what are the anticoagulant agents?
- IV UFH
- LMWH
- direct thrombin inhibitors
MoA of UFH
- catalyzes the inactivation of thrombin and Xa
- prevents conversion of fibrinogen to fibrin and clot formation
- indirect thrombin inhibitor
MoA of LMWH
- inactivates Xa but w/ lesser effect on thrombin
- doesn’t prolong aPTT
- indirect thrombin inhibitor
MoA of fondaparinux (anticoag)
-selective inhibitor of Xa
MoA of bivalirudin (anticoag)
-reversible direct thrombin inhibitor
Given a pt w/ UA/NSTEMI and renal insufficiency, what is the appropriate anticoag?
- UFH
- b/c it’s not cleared by kidneys
Given a patient with STEMI, what is the appropriate time interval of admin of a fibrinolytic? and what is the expected benefit?
- should be administered w/i 30 min of hospital arrival
- benefit is greatest when administered w/i 2 hrs of symptom onset
- significant benefit associated w/ admin up to 12 hrs from onset of chest pain
- trend toward benefit when given 13-24hrs
MoA of fibrinolytics
catalyze the conversion of plasminogen to plasmin which degrades fibrin
indication of fibrinolytics in a pt w/ STEMI
-preferred agent if onset of sx is w/i 3 hrs and access to cardiac cath for PCI is delayed or unavailable
MoA of glycoprotein IIb/IIIa blockers
- bind to GP IIb/IIIa receptor
- causes conformational change that inhibits platelet aggregation
