Acute Coronary Syndrome Flashcards
Acute Coronary Syndrome (ACS)
- Really an Acute MI from atherosclerosis, plaque etc.
- Consists of STEMI’s, Non-STEMI’s and unstable angina
- Life-threatening
DDx for ACS
- ACS
- Pulmonary Embolism
- Non- STEMI
- Aortic Dissection
- Gastroesophageal reflux
- STEMI
- Unstable angina
**Difficult!!! esp. cause you have to act fast to treat MI!
What do you give a STEMI (or new LBBB) or a Non-STEMI after taken history, physical exam and ECG?
ONAM!!!
- ) Oxygen
- ) Nitroglycerin
- ) Aspirin
- ) Morphine (controversy, possible increased mortality?)
- Others: Beta-blocker, Anithrombin
After meds for STEMI, what next?
Either:
- Emergent PCI, use with Glycoprotein IIb/IIIa inhibitors
OR
- Fibrinolytic Therapy
After meds for non- STEMI, what next?
Either:
- Early Intervention, use Glycoprotein IIb/IIIa inhibitors or bivalirudin with PCI
OR
- Medical management; consider Glycoprotein IIb/IIIa inhibitors or bivalirudin for high-risk patients
UNSTABLE ANGINA
- Secondary to reduced myocardial perfusion
- Three principle types:
1. Rest angina
2. New-onset severe angina
3. Crescendo angina (had it but getting worse and more frequent)
–> treat symptomatically
NSTEMI
Defined by ACC and ECC as:
- Rise and fall of serum troponin levels
- Fall of CK-MB levels
- Ischemic symptoms
- Development of pathologic waves on the ECG
- ST-segment changes indicative of ischemia
Intermediate risk (not fully occlusive, could progress quickly
STEMI
- Most lethal form of acute coronary syndrome
- Completely occlusive thrombus results in total cessation of coronary blood flow
- Accurate diagnosis vital because Immediate consideration of reperfusion by mechanical or drug methods
- Thrombolytics have potentially fatal outcomes so use has guidelines
Antiplatelets?
Aspirin
How aspirin works?
Affects Thromboxane A2 (on platelets) –> it suppresses it so platelets don’t stick well together –> stop/slow clots
Indications for Aspirin?
o Treatment of mild-to-moderate pain, inflammation, and fever
o Prevention and treatment of acute coronary syndromes (ST-elevation MI, non-ST-elevation MI, unstable angina)
o Acute ischemic stroke, and transient ischemic episodes
o Management of rheumatoid arthritis, rheumatic fever and osteoarthritis
o Adjunctive therapy in revascularization procedures (coronary artery bypass graft, percutaneous transluminal coronary angioplasty, carotid endarterectomy), stent implantation
Does aspirin work?
YES!!! 50% reduction in death of MI
- Shown to be effective (in combination) in reducing recurrent ischemic events in patients undergoing intracoronary stent placement
- CABG –> 50% reduction in early thrombotic graft occlusion
*** So take on regular basis to prevent MI!
ADR of aspirin
• Aspirin sensitivity
o Respiratory sensitivity
o Cutaneous sensitivity
o Systemic sensitivity
Aspirin maintenance dose prescription
81 mg
One tablet daily
Aspirin dose with ER presentation
160-325 mg
Must take chewable tablets and chew
Prescription for Clopidogrel maintenance dose
75 mg
One tablet daily
• Maintenance Dose, get effect in 10-11 days
Prescription for Clopidogrel for use with PCI
Load 300 mg and maintain at 75 mg once daily
How do the oral Antiplatelets (Clopidogrel) work?
o Stop ADP from binding to receptor (P2Y12)
o So the P2Y12 receptor can’t activate the Glycoproteins IIb/IIIa receptors to be made
Glycoproteins IIb/IIIa receptors normally link up platelets clot
• They can’t do this with this drug
Clopidogrel Metabolism
Prodrug- two step including 2C19, 3A4, 2B6, 1A2
Clopidogrel Indications
- Acute coronary syndrome (UA, NSTEMI, STEMI)
- Recent myocardial infarction, recent stroke or established peripheral vascular disease
What are the other antiplatelets beside Clopidogrel?
- Ticlopidine
- Prasugrel
- Ticagrelor
Clopidogrel resistance
Genetic basis affected by CYP2C19
- Metabolize too fast –> don’t get therapeutic effect
- Not enough, so don’t metabolize fast enough –> toxic levels
Drug interactions of Clopidogrel ?
- Genetic basis affected by CYP2C19
- The Great Debate- Clopidogrel and the Use of Proton Pump Inhibitors (PPIs)
- PPIs suppress CYP2C19, and Clopidogrel levels too low –> clot possibility
Clopidogrel Works?
- CURE/COMMIT- relative risk reduction primary outcome was 20% and 7%
- CHARISMA- “failed to demonstrate a reduction…of the primary endpoint
ADR of Clopidogrel
o Bleeding - Wide variances seen in studies - All significantly lower than 5% • Labeled at 4% major and 5% minor o Rash, pruritus o Gastrointestinal hemorrhage o Thrombotic thrombocytopenic purpura
• Ticlopidine (Ticlid™)
o Life-threatening hematologic reactions
• Prasugrel (Effient™)
o Similar action to clopidogrel but reduced number of biotransformation steps
o Not intended for use in:
Patients 75 years of age or older
Patients who weigh less than 60 kg
• Ticagrelor (Brilinta™)
o Faster onset compared to clopidogrel
o Load and then twice a day dosing
What are the IV antiplatelets
- Abciximab
- Eptifibatide
- Tirofiban
Indication for Abciximab
- Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention
- Prevention of cardiac ischemic complications in patients with unstable angina/non-ST-elevation myocardial infarction unresponsive to conventional therapy when PCI is scheduled within 24 hours
Indication for Eptifibatide?
Treatment of patients with acute coronary syndrome including patients who are to be managed medically and those undergoing percutaneous coronary intervention
Indication for Tirofiban?
Treatment of acute coronary syndrome (ie, unstable angina/non-ST-elevation myocardial infarction ) in combination with heparin
How the IV antiplatelets work?
o Block binding of fibrinogen and von Wilebrand factor to glycoproteins IIb/IIIa on platelets
ADR of IV antiplatelets
o Bleeding Major bleeding at 10% Thrombocytopenia 0.5 to 1% o Abciximab’s problem Acute profound thrombocytopenia • Due to long activity, reversal may be needed by administering platelets o
Prescription for Eptifibatide
Integrilin
180 mcg/kg IV bolus over 1-2 minutes then infuse
2 mcg/kg/min intravenously
PA’s can’t write for
How Nitrates work
o ↑ nitric oxide levels
Potent vasodilator
Differences between nitrates
- *Dosage forms and kinetics
1. ) Rapid onset and short duration - Nitroglycerin sublingual
- Isosorbide dinitrate sublingual
2. ) Slower onset and sustained duration - Nitroglycerin transdermal patch
- Isosorbide mononitrate tablets
Uses for Nitrates
o Useful in reducing vasospasm and myocardial oxygen demand in acute situations
Intravenous administration quick and safe
o Relief of ischemic pain
Does the use of a nitrate reduce mortality rates?
o
• Route of Administration for Nitrates
o Emergent use requires sublingual administration
Peak plasma concentrations in 4 minutes
Sublingual spray faster than sublingual tablets
o Oral and cutaneous for prophylaxis
• Tolerance of nitrates (aka The “drug-free” zone)
cells become refractory to it and don’t respond to nitric oxide, so need drug free zone for maintenance doses (patch on in 8 am, off at 8pm, don’t put new 1 on)
Drug free for 12 hours
ADR of Nitrates
o Headache
o Dizziness, weakness, effects of postural hypotension
Nitroglycerin prescription
0.4 mg sublingually
One tablet under the tongue every 5 minutes for 3 doses
• Don’s Rule: If 1st dose doesn’t work call 911
Nitroglycerin patch prescription
0.4 mg/hour
Apply patch in the morning, remove at 8 PM and repeat each day
Nitrites
Amyl Nitrite
Amyl Nitrite administration
- Inhalation only
- Same mechanism of action as the nitrates
Amyl Nitrite as a Combination drug?
- With cocaine or ecstasy euphoric state intensified and prolonged
- “poppers”
Once actually considered to be the genesis of AIDS in the gay community
Beta Blocker for ACS?
Metoprolol
Metoprolol acute dose?
Acutely 5 IV mg every 2 minutes for three doses then
Metoprolol dose after acute dose?
50 mg orally every 6 hours starting 15 minutes after the last IV dose
Metoprolol maintenance dose
100 mg twice a day
Anticoagulants
- Heparin (unfractionated heparin and Low Molecular weight heparin)
- Enoxaparin
- Fondaparinux
- Bivalirudin
How do the Anticoagulants work?
o Inactivates factor Xa and inhibits conversion of prothrombin to thrombin
• Enoxaparin (Lovenox™) info and dose
o Low Molecular weight heparin –> adjust for renal function
o NSTEMI- 1 mg/kg SC every 12 hours
o STEMI- 30 mg IV bolus and then 1 mg/kg every 12 hours
• Fondaparinux (Arixtra™) info and dose
o Factor Xa Inhibitor –>adjust for renal function
o NSTEMI- 2.5 mg SC once daily for 8 days or discharge
o STEMI- 2.5 mg IV once then 2.5 mg once daily for 8 days or discharge
• Bivalirudin (Angiomax™) info and dose
o Direct Thrombin Inhibitor PCI only
o NSTEMI*- 0.1 mg/kg IV bolus then 0.25 mg/kg/hour
o STEMI**- 0.75 mg/kg bolus then 1.75 mg/kg/hour
o
• Heparin (unfractionated heparin) info
o Monitor the aPTTs constantly
q. 4-6 hours 1.5-2 times the controlled value
ADR of Anticoagulants
Bleeding
Heparin Prescription
Heparin sodium
Give X units IV push now and start an infusion of heparin at X units/hour
Units driven by weight
Fibrionlytics
- Altepase (Activase)
- Reteplase (Retevase)
- Tenecteplase (TNKase)
How the Fibrionlytics work
o Activate Plasmin to break down the Fibrin clot –> clot busters
Contraindications for Fibrionlytics
o Any prior intracranial hemorrhage
o Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
o Known malignant intracranial neoplasm (primary or metastatic)
o Ischemic stroke within 3 months except acute ischemic stroke within 3 hours
o Suspected aortic dissection
o Active bleeding or bleeding diathesis (excluding menses)
o Significant closed-head or facial trauma within 3 months
Altepase other indications
- Management of acute ischemic stroke
- Management of acute pulmonary embolism
- Different dosing schemes
Fibrinolytics reversal agent?
• No specific reversal agent
o Unlabeled- will tranexamic acid work?
ADRs of Fibrinolytics
o Bleeding
o Rapid lysis causing reperfusion-related atrial or ventricular arrhythmias
o Cardiovascular events reported
o
Alteplase Prescription
15 mg IV bolus over 1-2 minutes then infuse 50 mg over 30 minutes and then 35 mg over one hour
Post ACS/MI care
• Aspirin
o Clopidogrel option (only if aspiring sensitivity or contraindicated)
• Beta blocker: ↓ post MI mortality
• ACE Inhibitor
o If history of known coronary heart disease
• Lipid-lowering
o HMGCoA reductase inhibitors (Statins aka Lipitor)
Help stabilize plaques so don’t rupture and get MI
Target LDL less than 100 mg/dL, HDl greater than 40 mg/dL and triglycerides less than 200 mg/dL
•