Acute Coronary Syndrome lec Flashcards
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Oxygen supply and Oxygen Demand are not balanced
What is an Acute Coronary Syndrome?
It is a global term that encompasses:
- Non-ST segment elevation ACS
- Unstable Angina
- Non-ST segment MI (NSTEMI)
- ST segment elevation MI (STEMI)
What are the signs and symptoms of Acute Coronary Syndrome?
- *chest pain
- dyspnea “shortness of breath”
- syncope or lightheadedness
- diaphoresis “sweating”
How do we diagnosis an ACS?
with an electrocardiogram (ECG)
also looking at cardiac enzymes
With Unstable Angina (UA)
Cardiac enzymes-
ECG Changes-
Blockage-
Cardiac enzymes- (negative)
ECG Changes- None or Transient = P-QRS-T - ST depression
Blockage- partial blockage
With Non-ST segment elevation Myocardial Infarction (NSTEMI)
Cardiac enzymes-
ECG Changes-
Blockage-
Cardiac enzymes- (positive)
ECG Changes: None or Transient = P-QRS-T - ST depression
Blockage- partial blockage
With ST-segment elevation Myocardial Infarction (STEMI)
Cardiac enzymes-
ECG Changes-
Blockage-
Cardiac enzymes- (positive)
ECG Changes- ST elevation
Blockage- complete blockage of a coronary artery
If someone is thought to be having an Acute Coronary Syndrome, the guidelines recommend we get an _____________
12-lead electrocardiogram within 10 minutes of their first medical contact
What enzymes are most sensitive/specific towards ACS?
Troponins (Troponin I and Troponin T)
- these are detectable within 2-12 hours of an ACS and stay elevated for out to 2 weeks. (so they elevate quickly and stay elevated for a while)
Drug Treatment:
May involve medications alone (medical management)
or
Medications + (PCI) percutaneous coronary intervention
What medications will we use in a patient with ACS?
remember MONA-GAP-BA
Morphine GPIIb/IIIa antagonists Beta blockers
Oxygen Anticoagulants ACE inhibitors
Nitrates P2Y12 inhibitors
Aspirin
MONA- these are usually started right away
GAP - these agents will be determined depending if patient is going for a PCI or not
BA - within the first 24 hours we want to consider
What is the treatment for someone with NSTE-ACS?
**remember NSTE-ACS encompasses _____________
MONA-GAP-BA +/- PCI
(UA) Unstable Angina & NSTEMI
what is the treatment for someone with STEMI?
MONA-GAP-BA + PCI or fibrinolytic
PCI preferred
When should the MONA drugs be given in someone having an ACS?
What is the clinical benefit of each?
What other additional information should be known for each?
M- Morphine provides pain relief and helps anxiety.
Not for routine use; reserve for patients with unacceptable chest discomfort. Dose 2-5mg IV repeated at 5-to-30-minute intervals PRN. Monitor for hypotension, bradycardia, N/V, sedation and respiratory depression.
O- oxygen administer to patients with arterial oxygen saturation < 90% or respiratory distress
N- Nitrates: will dilate the coronary arteries, improve collateral blood flow and decrease preload/myocardial oxygen demand and afterload modestly. Also reducing chest pain. May consider IV infusion if patient is not improving.
A- Aspirin stops platelets from aggregating around atherosclerotic plaque. we want patient to chew a non-enteric coated aspirin. A couple baby aspirin or a 325mg chewable aspirin at the sign of chest pain.
Then a maintenance dose of aspirin 81-162mg daily continued indefinitely
DO NOT USE extended-release aspirin products. We want aspirin in blood stream fast!
When would we NOT consider IV nitroglycerin in someone with ACS?
if SBP is < 90mmHg, HR < 50bpm or patient
Contraindicated with PDE-5 inhibitors.
When should the GAP drugs be given in someone having an ACS?
What is the clinical benefit of each?
What other additional information should be known for each?
Choice of these drugs will be given as it relates to the plan/needs of the patient
G- GPIIb/IIIa receptor antagonists
-are for patient going for PCI or being medically managed. If used, then are used along with an anticoagulant.
- they block fibrinogen from binding to GPIIb/IIIa receptor that is on platelets. similar to aspirin in that they affect platelet aggregation.
A-Anticoagulants
- the agents here are the LMWH (enoxaparin) and UFH and bivalirudin
(preferred in STEMI)
- inhibit clotting factors and can reduce infarct size
P- P2Y12 inhibitors
- agents include clopidogrel/prasugrel/ticagrelor
-these inhibit the P2Y12 receptor also on platelets, which is another way of affecting platelet aggregation.
What ways are we targeting platelet aggregation with drug treatment in someone with ACS?
aspirin
GPIIb/IIIa receptor antagonists
P2Y12 inhibitors
When should the BA drugs be given in someone having an ACS?
What is the clinical benefit of each?
What other additional information should be known for each?
Once patient has stabilized, gone to cath lab. Give within 24 hours, have continue as an outpatient.
B- Beta-1 selective blocker without ISA
A- ACE inhibitor
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For this setting (ACS) especially, we want to AVOID _____________. There is increased risk of mortality. No oral or even IV formulations.
Should also AVOID IR ______________. Also associated with increased mortality.
NSAIDs
ex. like IV ketorolac
nifedipine
Plavix
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clopidogrel
class: antiplatelet, P2Y12 inhibitors (antagonist)
Indications: For ACS or as secondary prevention in patients with a Hx of MI, stroke or PAD.
MOA: irreversibly binds to the platelet ADP P2Y12 receptor, preventing ADP -mediated activation on the GPIIb/IIIa receptor complex. This inhibits platelet aggregation and clot formation.
Dosage forms: oral tablet
generic 75mg tablet & 300mg tablet
Dosing:
LD: 300-600mg PO (600mg for PCI)
MD: 75mg daily by mouth
- if patient > 75 years old and fibrinolytic therapy administered for STEMI, omit loading dose and start at 75mg daily
Boxed Warnings:
Effectiveness depends on the conversion to an active metabolite. Poor metabolizers of CYP2C19 exhibit higher cardiovascular events than patients with normal CYP2C19 function. Consider alternative in patients identified as poor metabolizers.
Contraindications:
Active serious bleeding (GI bleed, intracranial hemorrhage)
Warnings:
-Bleeding risk (stop 5 days prior to elective surgery) Do Not Use with omeprazole or esomeprazole.
-Premature discontinuation increases risk for thrombosis
-(TTP) thrombotic thrombocytopenic purpura
Side Effects:
Generally well tolerated, unless bleeding occurs
Monitoring:
Pearls/Notes:
Prodrug “gets metabolized to active metabolite by CYP2C19”
Drug-Drug/Food interactions: Avoid omeprazole & esomeprazole.
clopidogrel increases the effects of repaglinide, which can cause hypoglycemia. Avoid using this combination.
Others: Topotecan, Urokinase, abrocitinib
Effient
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prasugrel
class: antiplatelet, P2Y12 inhibitors (antagonist)
Indications: **Only For ACS managed with PCI
MOA: is a prodrug that is metabolized to its active form, allowing it to irreversibly bind to & block the P2Y12 component of the ADP receptors on platelets. This prevents activation of GPIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation.
Dosage forms: 5mg & 10mg oral tablets
Dosing:
LD: 60mg PO (no later than 1 hour after PCI)
MD: 10mg daily with ASA (5mg daily if patient weighs < 60kg)
Once PCI is planned, give the dose promptly and no later than 1 hour after the PCI.
Boxed Warnings:
- Do NOT initiate if CABG likely, STOP at least 7 days prior to elective surgery.
- Significant, sometimes fatal, bleeding
- Not recommended in patients > 75 years old due to high bleeding risk, unless patient is considered high risk (DM or prior MI)
Contraindications:
Active serious bleeding, history of stroke or TIA
Warnings:
-Bleeding risk (stop 5 days prior to elective surgery) Do Not Use with omeprazole or esomeprazole.
-Premature discontinuation increases risk for thrombosis
-(TTP) thrombotic thrombocytopenic purpura
Side Effects:
Generally well tolerated, unless bleeding occurs (higher risk than clopidogrel)
Pearls/Notes:
**Prodrug “gets metabolized to active metabolite by primarily CYP3A4”
**Dispense in original container!
Drug-Drug/Food interactions:
Brilinta
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ticagrelor
class: antiplatelet, P2Y12 inhibitors (antagonist)
Indications: For ACS
MOA: reversibly binds to & block the P2Y12 component of the ADP receptors on platelets. This prevents activation of GPIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation.
Dosage forms: Oral tablet 60mg & 90mg
Dosing:
LD: 180mg
MD: 90mg PO BID for 1 year, then 60mg BID.
“tablets can be crushed and mixed with water to be swallowed or given via NG tube”
Boxed Warnings:
- Significant, sometimes fatal, bleeding
-
After the initial dose of 162-325mg of aspirin, DO NOT EXCEED a maintenance dose of aspirin 100mg daily because higher daily doses reduce the effectiveness of ticagrelor
-** Avoid use when CABG likely, stop 5 days before any surgery
Contraindications:
active serious bleeding, history of intracranial hemorrhage
Warnings:
Side Effects:
Bleeding, dyspnea (>10%), increased SCr, increased uric acid.
Monitor:
monitor digoxin levels with initiation of or any change in ticagrelor dose
Pearls/Notes:
Not a Prodrug
Not a thienopyridine
Keep Maintenance Aspirin Dose to less than < 100mg daily
Drug-Drug/Food interactions:
Avoid with other strong CYP3A4 inhibitors or inducers, avoid with simvastatin and lovastatin doses greater than 40mg/day
Kengreal
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cangrelor
class: antiplatelet, P2Y12 inhibitors (antagonist)
Indications: Indicated as an adjunct to PCI in patients who are P2Y12 inhibitor naive and are not receiving a GPIIb/IIIa inhibitor
MOA:
Dosage forms: solution for reconstitution of 50mg/5mL vial sterile water. For injection
Dosing: Is in mcg
30mcg/kg IV bolus prior to PCI,
- then 4mcg/kg/min IV infusion for 2 hours or for duration of the procedure (whichever is longer)
Contraindications:
Significant active bleeding
Warnings:
Side Effects:
bleeding
Pearls/Notes:
- effects are gone 1 hour after drug discontinuation
-** Transition to one of the oral P2Y12 inhibitors after PCI**
Drug-Drug/Food interactions:
So, if you have an ACS patient and, on their profile, they have a past Hx of a stroke then which P2Y12 inhibitor CAN’T be used?
Effient prasugrel
Which P2Y12 inhibitor needs to be dispensed in its original container?
Effient prasugrel
When we use P2Y12 inhibitors, once we initiate in the setting of ACS. How do we initiate?
We give a big Loading Dose with these agents in order to inhibit platelet aggregation.
Which P2Y12 inhibitor is available as an injection?
cangrelor (Kengreal)
ReoPro
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abciximab
class: (GPIIb/IIIa) Glycoprotein IIb/IIIa receptor antagonists
Indications: Is only indicated for PCI +/- stent
MOA: these drugs block the GPIIb/IIIa receptor on platelets, which is where fibrinogen is supposed to bind. This results in inhibition of platelet aggregation and clot formation.
Dosage forms: IV injection
Dosing:
Contraindications:
- thrombocytopenia (platelets < 100,000 cells/mm3)
- Hx of bleeding diathesis (bleeding disposition)
- active internal bleeding
- severe uncontrolled hypertension
- recent major surgery or trauma (within the past 6 weeks)
- Hx of stoke within 2 years
-*- recent (within 6 weeks) clinically significant GI or GU bleeding
-increases prothrombin time
- hypersensitivity to murine proteins
- intracranial neoplasm, arteriovenous malformation or aneurysm
Side Effects: bleeding, thrombocytopenia
Monitoring: Hgb, Hct, platelets, s/sx of bleeding, renal function
Pearls/Notes:
- has irreversible blockade
- if used in PCI, the GPIIb/IIIa antagonist is given with Heparin
- must be filtered
- do NOT shake vials
- platelet function returns in ~24-48 hours after stopping drug
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Integrilin
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eptifibatide
class: (GPIIb/IIIa) Glycoprotein IIb/IIIa receptor antagonists
Indications:
MOA: these drugs block the GPIIb/IIIa receptor on platelets, which is where fibrinogen is supposed to bind. This results in inhibition of platelet aggregation and clot formation.
Dosage forms: IV injection
Dosing:
Contraindications:
- thrombocytopenia (platelets < 100,000 cells/mm3)
- Hx of bleeding diathesis (bleeding disposition)
- active internal bleeding
- severe uncontrolled hypertension
- recent major surgery or trauma (within the past 6 weeks)
- Hx of stroke within 30 days or any history of hemorrhagic stroke
-*- dependency on renal dialysis
Side Effects: bleeding, thrombocytopenia
Monitoring: Hgb, Hct, platelets, s/sx of bleeding, renal function
Pearls/Notes:
- has reversible blockade
- if used in PCI, the GPIIb/IIIa antagonist is given with Heparin
- platelet function returns in ~4-8 hours after stopping drug
-do NOT shake vials
Drug-Drug/Food interactions:
Contraindications with these agents all relate to _____
bleeding risk
Aggrastat
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tirofiban
class: (GPIIb/IIIa) Glycoprotein IIb/IIIa receptor antagonists
Indications:
MOA: these drugs block the GPIIb/IIIa receptor on platelets, which is where fibrinogen is supposed to bind. This results in inhibition of platelet aggregation and clot formation.
Dosage forms: IV injection
Dosing:
Contraindications:
- thrombocytopenia (platelets < 100,000 cells/mm3)
- Hx of bleeding diathesis (bleeding disposition)
- active internal bleeding
- severe uncontrolled hypertension
- recent major surgery or trauma (within the past 4 weeks)
Side Effects: bleeding, thrombocytopenia
Monitoring: Hgb, Hct, platelets, s/sx of bleeding, renal function
Pearls/Notes:
- has reversible blockade of receptor
– if used in PCI, the GPIIb/IIIa antagonist is given with Heparin
- platelet function returns in ~4-8 hours after stopping drug
- do NOT shake vials
Drug-Drug/Food interactions:
Activase
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alteplase
“recombinant tissue plasminogen activator”
class: fibrinolytic
Indications: Used ONLY FOR STEMI, also used for acute stroke (different dosing)
MOA: medication causes fibrinolysis (clot breakdown) by binding to fibrin and converting plasminogen to plasmin.
Timing:
- PCI preferred (optimal door to balloon time: 90 minutes)
- If NOT able to receive PCI within 120 minutes of first medical contact, use fibrinolytic therapy! Must be started within 30 minutes of hospital arrival (door-to-needle time).
Dosage forms: IV
Dosing: Given as accelerated infusion
Contraindications:
- active internal bleeding or bleeding diathesis (bleeding predisposition)
- Hx of recent stroke
- any prior intracranial hemorrhage (ICH)
- severe uncontrolled hypertension (unresponsive to emergency therapy)
- recent intracranial or intraspinal surgery or trauma (in the last 2-3 months)
Side Effects: Bleeding (including ICH)
Monitoring: Hgb, Hct, s/sx of bleeding
Pearls/Notes:
- When fibrinolytic therapy is used, it should be given within 30 minutes of hospital arrival (door-to-needle time).
- In the absence of contraindications, and when PCI is not available, fibrinolytic therapy is reasonable in STEMI patients who are still symptomatic within 12-24 hours of symptom onset.
- Alteplase contraindications & Dosing differ when used for ischemic stroke
Drug-Drug/Food interactions:
Cathflo Activase
(single use 2mg vial) used to restore function of potentially clotted central lines and devices.
The abbreviation tPA is prone to errors; though it is commonly used, it is NOT recommended by _____________
ISMP
TNKase
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tenecteplase
class: fibrinolytic
Indications: Used ONLY FOR STEMI = (complete blockage)
MOA: medication causes fibrinolysis (clot breakdown) by binding to fibrin and converting plasminogen to plasmin.
Timing:
- PCI preferred (optimal door to balloon time: 90 minutes)
- If NOT able to receive PCI within 120 minutes of first medical contact, use fibrinolytic therapy! Must be started within 30 minutes of hospital arrival (door-to-needle time).
Dosage forms: given as a single IV bolus dose dosed on patients weight(kg)
Dosing:
Contraindications:
- active internal bleeding or bleeding diathesis (bleeding predisposition)
- Hx of recent stroke
- any prior intracranial hemorrhage (ICH)
- severe uncontrolled hypertension (unresponsive to emergency therapy)
- recent intracranial or intraspinal surgery or trauma (in the last 2-3 months)
Side Effects: Bleeding (including ICH- intracranial hemorrhage “bleeding in head”)
Monitoring: Hgb, Hct, s/sx of bleeding
Pearls/Notes:
- When fibrinolytic therapy is used, it should be given within 30 minutes of hospital arrival (door-to-needle time).
- In the absence of contraindications, and when PCI is not available, fibrinolytic therapy is reasonable in STEMI patients who are still symptomatic within 12-24 hours of symptom onset.
Drug-Drug/Food interactions:
Retavase
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reteplase
class: fibrinolytic
Indications: Used ONLY FOR STEMI
MOA: medication causes fibrinolysis (clot breakdown) by binding to fibrin and converting plasminogen to plasmin.
Timing:
- PCI preferred (optimal door to balloon time: 90 minutes)
- If NOT able to receive PCI within 120 minutes of first medical contact, use fibrinolytic therapy! Must be started within 30 minutes of hospital arrival (door-to-needle time).
Dosage forms: IV
Dosing:
Contraindications:
- active internal bleeding or bleeding diathesis (bleeding predisposition)
- Hx of recent stroke
- any prior intracranial hemorrhage (ICH)
- severe uncontrolled hypertension (unresponsive to emergency therapy)
- recent intracranial or intraspinal surgery or trauma (in the last 2-3 months)
Side Effects: Bleeding (including ICH)
Monitoring: Hgb, Hct, s/sx of bleeding
Pearls/Notes:
- When fibrinolytic therapy is used, it should be given within 30 minutes of hospital arrival (door-to-needle time).
- In the absence of contraindications, and when PCI is not available, fibrinolytic therapy is reasonable in STEMI patients who are still symptomatic within 12-24 hours of symptom onset.
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Zontivity
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vorapaxar
class: Protease-Activated Receptor-1 Antagonist
Indications: For patients with a Hx of MI or PAD to reduce thrombotic cardiovascular events (CV death, MI, stroke, urgent coronary revascularization). Used for ACS.
MOA:
Dosage forms: oral tablet
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- an inhibitor of P-gp & a substrate for 3A4, so Avoid with strong CYP2A4 inhibitors and inducers.
- this drug was used with aspirin and/or clopidogrel in clinical trials
Drug-Drug/Food interactions:
How we manage the patient after they have had an ACS:
Secondary Prevention After ACS: Patients should be on_
- Look over patient profile, if we see something say, patient had an MI or patient had a STEMI. or patient had an ACS.
Make sure all medications are appropriate for patient.
1) Aspirin 81mg daily (81-325mg) indefinitely
2) P2Y12 inhibitor (**duration & choice of agent depends on how patient was managed in hospital)
—- If patient only received “medical management”, then: clopidogrel or ticagrelor + ASA for at least 12 months
—- If patient was “PCI-treated”, then: any oral P2Y12 inhibitor + ASA for at least 12 months
3) NTG (tabs or spray) indefinitely (use as needed), patient should always have available and be educated about how to use
4) Beta-blockers daily (target HR 50-60 BPM) for 3 years (indefinitely for some patients)
5) ACE inhibitor - we are looking for reduced EF, HTN, CKD, or DM
6) Aldosterone antagonist - reduced LVEF & symptomatic HF or DM
7) Statin- most will be on a high intensity statin
Other considerations:
Pain
Triple antithrombotic therapy
Lifestyle counseling
DAPT
Dual Antiplatelet Therapy
ex. aspirin + P2Y12 inhibitor
