ACS Pharm and Therapeutics Flashcards
Thrombus type in STEMI-ACS?
Complete occlusion
Thrombus type in NSTEMI (Non ST elevation ACS)?
Non-fully occlusive, some patency w/ tissue damage or cardiac necrosis
Thrombus type in Unstable angina (Non ST elevation ACS)?
Non-fully occlusive, some patency
EKG for Unstable angina (Non ST elevation ACS)?
Non-specific EKG changes
EKG for NSTEMI (Non ST elevation ACS)?
ST-depression, T-wave inversions
EKG for STEMI-ACS?
ST-elevation, New LBBB
Enzymes for STEMI-ACS?
Troponin (Tn) positive
Enzymes for NSTEMI (Non ST elevation ACS)?
Troponin (Tn) positive
Enzymes for Unstable angina (Non ST elevation ACS)?
Within normal limits (WNL)
Thrombus formation?
-Glucose and fat will get stored along the lining of the lining of the lumen & create inflammation (endothelial injury) over time
-Fat plaque will build over endothelial matrix
-As plaque grows, artery gets more clogged
-Eventually increased BP from decreased area for blood to flow through lumen rips fat plaque from the wall
What does complete coronary occlusion cause?
Acute MI
What does spontaneous lysis, repair, and wall remodeling after occlusion cause?
Temporary resolution of instability, future high risk coronary lesion
What does incomplete coronary occlusion cause?
Unstable angina or non-Q-wave MI
How does a thrombus form?
Systemic thrombogenicity
Platelet activation, adhesion, aggregation
Coagulation pathway activation/thrombin formation
Fibrinogen conversion to fibrin w/ cross-linking of bands
Initial assessment for NSTEMI/STEMI?
12-lead EKG to differentiate, troponins, clinical presentation, TIMI risk score and GRACE scores
What do TIMI risk score and GRACE scores measure?
TIMI: risk of ischemic event/mortality in NSTEMI or unstable angina
GRACE: estimates in-hospital and 6 month to 3 year mortality risk of adverse events after ACS
Do all diabetics feel left arm pain?
No (due to neuropathies)
*can happen in T1DM and T2DM
What is the goal of ACS care?
Immediate relief of ischemia/prevention of further MI and death
Parmacotherapy plan for ACS care?
Early therapy –> Revascularization –> Long-term management
*appropriate therapies in all 3 areas minimizes morbidity & mortality
What happens if patients do not receive therapy for ACS management?
Increased chance of CV event in the next year
What should all ACS patients receive early in hospital care?
Anti-ischemic and analgesic medication
*MONA plus B-Blocker
What is MONA therapy?
Morphine
O2
Nitroglycerin
Aspirin (ASA)
Why is morphine given in MONA therapy? How often is it given?
To relieve stress, pain, provide vasodilation
Administer every 5-30 min
When should O2 be given in MONA therapy?
If SaO2 <90% (oxygen saturation of arterial blood), if pt in respiratory stress or has features of hypoxia
How can Nitroglycerin be administered for MONA therapy?
NTG spray under tongue, Sublingual tablet, or IV
Does nitroglycerin improve mortality in ACS?
No
Limitations in nitroglycerin therapy for ACS?
Vitals: SBP<90 mmHg, arrhythmias (ex. Severe bradycardia/tachycardia)
Should Nitroglycerine prevent other mortality reducing therapies?
No, should not prevent/preclude
(Ex. Alteplase, heparin)
How does aspirin benefit ACS in MONA therapy?
Helps stabilize plaque/clot
*inflammatory markers can promote clot expansion –> Aspirin helps regulate/reduce inflammation/prevent expansion
What does DAPT stand for?
Dual anti-platelet therapy
What is used for DAPT?
Aspirin PLUS a P2Y12 receptor inhibitor (clopidogrel, ticagrelor, or prasugrel)
How long is ASA taken after ACS?
For life
What can be taken in place of Aspirin if a patient is allergic?
Clopidogrel
How should B-Blocker be administered for ACS?
IV initially and then transition to PO
What does B-Blocker therapy improve in ACS patients?
Reduced mortality, re-infarction rate, and frequency of arrhythmias
Use caution with B-blocker therapy in which conditions?
New HFrEF or acute decompensated HF
Which B-Blocker is the most popular in early hospital care for ACS?
Metoprolol
Contraindications for B-blockers?
Pulmonary disease: carvedilol not ideal (Beta-2 R activity in the lungs)
Low HR/bradycardia
Hypoglycemia
What is indicated in treatment for a STEMI (completely blocked coronary artery)?
Urgent revascularization (either PCI or fibrinolytics)
Is PCI or fibrinolytic treatment preferred for revascularization of STEMI/complete blockage?
PCI
What kind of PCI is usually used for revascularization of STEMI/complete blockage?
Usually re-profusion w/ stent
When would fibrinolytics be indicated for revascularization of STEMI/complete blockage?
When PCI is unavailable/cannot be performed within 120 minutes of onset
What is indicated for early hospital care for NSTE-ACS (UA or NSTEMI)?
Early invasive strategy usually done over ischemia guided strategy
Define the difference between early invasive strategy and ischemia guided strategy for NSTE-ACS (UA or NSTEMI)?
Early invasive strategy: stent/evaluation for cabg ASAP
Ischemia guided: med therapy w angiography only if pt has recurrent of refractory ischemic sx
*depends on severity/stability of patient, availability for procedure, etc.
Which treatments are antiplatelet agents?
DAPT (aspirin and P2Y12 inhibitor) and GPIIb/IIIa inhibitors
Which meds are GPIIb/IIIa inhibitors?
Abciximab (Repro), Eptifibatide (Integrilin), Tirofiban (Aggrastat)
What are the anticoagulation strategies for ACS?
UFH, Enoxaparin, Bivalirudin, Fondaparinux
Mechanism of action for clopidogrel (P2Y12 inhibitor)?
Blocks ADP from platelet by binding to P2Y12 R’s
Mechanism of action for aspirin?
Blocks arachidonic acid from platelet by inhibiting Cox-1
Mechanism of action for fibrinolytics?
Blocks fibrin from linking platelets
Converts plasminogen to plasmin that degrades fibrin
Mechanism of action for GPIIb/IIIa inhibitors?
Block IIb/IIIa receptors on platelet, inhibit fibrinogen binding
Mechanism of action for Heparin, LMWH, Fondaparinux, Direct thrombin inhibitors?
Block thrombin from platelet
Which anticoagulants are less commonly used due to cost ($$$)?
Fondaparinux, Direct thrombin inhibitors
When would fondaparinux or direct thrombin inhibitors be indicated over heparin?
Incidences of HIT (Heparin induced thrombocytopenia)
Which stent may be more prone to atherosclerosis/clogging?
Bare metal stent
Which stent can prevent atherosclerotic build-up/remains more open over time?
Drug eluting stent (releases meds)
What is extremely important for those undergoing drug eluting stent PCI?
Need to be compliant with DPT, if not death risk is increased 10 fold due to plaque formation
Which antiplatelet therapy is indicated before PCI revascularization procedure in a patient with STEMI?
Aspirin, all 3 P2Y12i’s (clopidogrel, prasugrel, ticagrelor), ?? check
Which antiplatelet therapy is indicated before PCI revascularization procedure in a patient with STEMI + fribinolytic administered?
Aspirin, Clopidogrel
Which antiplatelet therapy is indicated before PCI revascularization procedure in a patient with NSTEMI early invasive intervention?
Aspirin, all 3 P2Y12i’s (clopidogrel, prasugrel, ticagrelor)
Which antiplatelet therapy is indicated before PCI revascularization procedure in a patient with NSTEMI ischemia guided intervention?
Aspirin, Copidogrel or Ticagrelor
Peak platelet inhibition for Clopidogrel (Plavix)?
600mg load 2 hours
Peak platelet inhibition for Prasugrel (Effient)?
60mg load 1-1.5 hours
Peak platelet inhibition for Ticagrelor (Brilinta)?
180mg load <1 hour
Contraindications of Clopidogrel (Plavix)?
Active bleeding
(however no one will use these meds, or any anticoagulants if there is a major active bleed)
Contraindications of Prasugrel (Effient)?
History of stroke/TIA
Contraindications of Ticagrelor (Brilinta)?
Intracerebral hemorrhage (ICH), hepatic disease
Metabolism of Clopidogrel (Plavix)?
Pro-drug, 2 step process by CYP2C19 enzymes
Metabolism of Prasugrel (Effient)?
Pro-drug, several CYP pathways
Metabolism of Ticagrelor (Brilinta)?
Not a pro-drug
Half-life of Clopidogrel (Plavix)?
8 hours
Half-life of Prasugrel (Effient)?
3.5 hours
Half-life of Ticagrelor (Brilinta)?
8 hours
What might cause someone to have no response to Clopidogrel (Plavix)?
CYP2C19 polymorphisms/varients
Are there any incidences where there would be no response to Prasugrel (Effient) or Ticagrelor (Brilinta)?
No known issues that would cause lack of response
Drug-drug interactions of Clopidogrel (Plavix)?
PPI’s (omeprazole and esomeprazole)
Drug-drug interactions of Prasugrel (Effient)?
Limited data
Drug-drug interactions of Ticagrelor (Brilinta)?
3A4 substrates, avoid Simvastatin (competes for same substrate, increases concentration)
Bleeding risk of Clopidogrel (Plavix)?
Lower risk
Bleeding risk of Prasugrel (Effient)?
Higher risk
Bleeding risk of Ticagrelor (Brilinta)?
Higher risk
GP IIb/IIIa inhibition has the greatest benefit in which patients?
Those with highest risk features for DM2, high troponins, or recent ACS
Addition of IIb/IIIai reduces what?
Composite endpoint of MI, hospitalization, or death
Addition of IIb/IIIai increases risk of what?
Bleeding
In addition to DAPT, all patients with ACS should be administered what?
An anticoagulant (to reduce risk of intracoronary & catheter thrombus formation)
Class I recommendation for STEMI (PCI) anticoagulant treatment?
UFH
Class I recommendation for STEMI w/ fibrinolytic therapy anticoagulant treatment?
UFH or enoxaparin
Class I recommendation for NSTE-ACS w/ early invasive strategy anticoagulant treatment?
UFH, enoxaparin, bivalirudin, or fondaparinux
Class I recommendation for NSTE-ACS w/ ischemia guided strategy anticoagulant treatment?
UFH or enoxaparin
If a patient is considered high risk for poor outcomes, and GP IIb/IIIa inhibitors are used, what is the preferred anticoagulant?
UFH
If a patients is considered high risk for poor outcomes, and has a risk of bleeding then what medication is recommended?
Bivalirudin (instead of UFH and GP IIb/IIIai)
When is Fondaparinux most commonly used for anticoagulation?
Allergy to UFH or enoxaparin (ex. HIT)
Is anticoagulation treatment continued or discontinues after PCI is completed?
Discontinued
What is Enoxaparin (Lovenox) classified as?
LMWH
What is Fondaparinux (Arixtra) classified as?
Factor Xa inhibitor
What is Bivalirudin (Angiomax) classified as?
Direct thrombin inhibitor
What are the dose adjustments for UFH in renal failure?
None
What are the dose adjustments for Enoxaparin (Lovenox) in renal failure?
If CrCl <30ml/min reduce dose by 50%
What are the dose adjustments for Fondaparinux (Arixtra) in renal failure?
CONTRAINDICATED if CrCl <30ml/min
What are the dose adjustments for Bivalirudin (Angiomax) in renal failure?
If CrCl <30ml/min: infusion must be reduced (see clinical protocol)
What should be monitored in UFH therapy?
aPTT to about 50-70 seconds
When should UFH be avoided?
If history of HIT
When should fibrinolytics be given to patients?
If the patient has STEMI (symptoms w/in 12 hours) and PCI cannot be performed within 120 min of first medical contact
What some commonly used fibrinolytic agents?
Alteplase, Reteplase, Tenecteplase
Which fibrinoltic out of Alteplase, Reteplase, & Tenecteplase has the most efficacy?
They all have similar efficacy
What should be administered along with fibrinolytics and for how long?
Anticoagulant therapy for minimum 48hrs (preferable for the duration of hospitalization)
What are the relative contraindications of fibrinolytic therapy?
BP>180/110
Hx of ischemic stroke w/in last 3 months
Dementia
Oral anticoagulant therapy (ex. Warfarin)
Absolute contraindications of fibrinolytic therapy?
Prior hemorrhagic stroke
Ischemic stroke w/in last 3 months
Cranial or spinal surgery w/in last 2 months
Severe uncontrolled HTN (unresponsive to emergency therapy)
How long is ASA taken for long term management post-ACS?
Indefinitely (Baby aspirin)
How long is P2Y12 inhibitor therapy administered along with ASA (DAPT) for long term management after ACS?
P2Y12 inhibitors minimum of 12 months
What is the harm in stopping anticoagulation early/patient non compliance with a bare metal stent?
Lowest risk if non-compliant, Re-stenosis or buildup of atherosclerosis
What is the harm in stopping anticoagulation early/patient non compliance with a drug eluting stent?
High risk of death if non-compliant/stopped early, Re-thrombosis/clotting
30 day mortality rates of drug therapy compliant patients post ACS vs. non-compliant?
Compliant: 0.7%
Non-complient: 7%
Which is more expensive: clopidogrel or ticagrelor?
Ticagrelor
Which has better efficacy: clopidogrel or ticagrelor?
Ticagrelor
When is early discontinuation of post-ACS therapy reasonable?
When risk of morbidity exceeds the benefits of therapy
What medication is indicated for all post-ACS patients?
Beta blocker unless contraindicated
When should beta blocker therapy be started for post-ACS patients?
ASAP
Which beta blockers can be used for post-ACS patients?
Metoprolol, Atenolol, Carvedilol, or Bisoprolol
If EF<40% which beta blocker should be used (HFrEF)?
Metoprolol, Carvedilol, Bisoprolol preferred
When are ACEi’s appropriate for post-ACS patients?
In HTN, CKD, DM, or EF<40% (Entresto)
If post-ACS patients have a cough while taking ACEi’s, what can be used instead?
ARB
When are aldosterone receptor blockers indicated in post-ACS patients?
If patients already on BB and ACEi who have EF<40%
Contraindications of aldosterone receptor blocker therapy?
Elevated K+, impaired renal function
What pain relievers should be avoided in post-ACS patients? Why?
NSAIDs (ibuprofen, naproxen, celecoxib)
**Increase risk of recurrent ACS
What pain relievers should be considered for post-ACS patients?
Tramadol or Acetaminophen
Which 2 lipid management drugs are appropriate for post-ACS patients?
Atorvastatin (higher doses 40-80mg/day) and Rosuvastatin (40mg/day)
*Dose specific
Worst place to get atherosclerosis/complete blockage?
Left coronary artery (The widow maker)
