Transcript Therapeutic I - 9-3

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Therapeutics 1 Tutoring
Sarah Darby
[email protected]
September 3, 2016
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Lectures Covered
 Acute
Coronary Syndrome
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ACS
 Troponin
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assay
Cardiac specific
Rapid results
Detectable levels = myocardial damage
Rises in ~4 hours and remains elevated for several days
Collect 2 samples 6 hours apart
 BNP
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Rise = increased ventricular wall stress
 ST


segment
ST elevation = injury
T wave inversion = ischemia
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ACS
UA
NSTEMI
STEMI
Troponin
Negative
Positive
Positive
EKG
changes
ST depression or T
wave inversions
ST depression or
T wave inversions
ST elevation
Artery
Partial occlusion
Partial occlusion
Complete
occlusion
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ACS
 Catheterization

Use of small catheter threaded through femoral artery to gauge
health of heart

May simply view heart’s status without “intervening”

May perform PCI
 Percutaneous
coronary intervention (PCI)
 May be called angioplasty

With or without stent placement (usually with)
 Reperfusion
Therapy
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Thrombolytic therapy (t-PA, reteplase, tenecteplase)
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PCI
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ACS
 Initial
treatment
 Aspirin
 Nitrates
 Beta-blockers
 Anticoagulants
 Other
antiplatelet agents
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ACS
 Conservative
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AKA “Ischemia guided”
Not going to the cath lab, not intervening
Medication only
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Aspirin
P2Y12 inhibitor
Anticoagulant
 Invasive
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management strategy
strategy
Headed to the cath lab, intervening
Aspirin
P2Y12 inhibitor
Possibly GPI in high risk patients
Anticoagulant
Cath lab to determine need for PCI or CABG
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ACS
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ACS
 While
you are working in the ER, the physician
asks for your recommendation concerning
reperfusion therapy for a patient. What type of
patients are eligible for reperfusion therapy?
A. Unstable
NSTEMI
C. STEMI
B.
angina
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ACS
 Reperfusion

therapy
Either PCI or fibrinolytics
 Time
= Muscle!
 Door
to needle <30min
 Door
to balloon <90min
 PCI
> fibrinolysis
 Reduced
rates of death, second MI,
recurrent ischemia
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ACS
 Reperfusion
therapy with fibrinolysis
Tissue plasminogen activator
 Reteplase
 Tenecteplase
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All given in combination with heparin.
Major concern: intracranial bleeding
T-PA has shortest duration
When to use?
 ST elevation in at least 2 contiguous leads
 Patient presents within 12 hours of chest pain onset
Successful reperfusion
 Prompt relief of chest pain
 Prompt resolution of ST elevation
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ACS
 Which
agent acts by irreversible
acetylation in order to inhibit platelet
aggregation?
A.
Clopidogrel
B.
Aspirin
C.
LMWH
D.
Ticagrelor
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ACS

JH arrives at ER at 11:00 am by way of EMS.
Complains of CP and SOB onset 3 hours ago. JH
states he took ASA 81mg just before calling 911.
What is your first course of action when he arrives?
A.
Initiate heparin continuous infusion
B.
Immediately send the pt to the cath lab
C.
Administer Aspirin 325mg chew and swallow
D.
Administer enoxaparin SQ
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ACS
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JH arrives at ER at 11:00 am by way of EMS.
Complaints of CP and SOB onset 3 hours ago. JH
states he took ASA 81mg just before calling 911.
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After JH is stabilized, the physician discusses with you
the need for continual aspirin therapy at 162mg daily.
How would you respond?
A.
Great idea!
B.
I agree with daily aspirin therapy, but let’s use 325mg
daily for increased mortality benefit.
C.
I agree with daily aspirin therapy, but let’s use 81mg
daily for reduced risk of bleeding and similar CV
benefits.
D.
I disagree. Let’s use Warfarin 5mg daily.
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ACS
 In
the acute management of ACS, what
dose of Clopidogrel do you recommend?
A.
600mg load, followed by 75mg daily
B.
600mg load, followed by 150mg daily
C.
300mg load, followed by 150mg daily
D.
100mg load, followed by 75mg daily
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ACS
 Polymorphisms
in which CYP enzyme may
render Clopidogrel ineffective?
A.
CYP2B6
B.
CYP1A2
C.
CYP2C19
D.
CYP3A4
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ACS

JH is a 69 yo male with STEMI. He is started on DAPT
with Aspirin and Clopidogrel. Due to his increased
risk of bleeding, your team decides to add an agent
for GI protection. What do you recommend?
A.
Omeprazole
B.
Pantoprazole
C.
Esomeprazole
D.
Ranitidine
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ACS
Which
agent is not a prodrug?
A. Clopidogrel
B.
Ticagrelor
C. Prasugrel
ACS
Clopidogrel
•
300-600mg load,
followed by 75mg
daily
•
Prodrug
•
Slow onset
•
Irreversible
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Affected by
polymorphisms of
CYP2C19
Prasugrel
• 60mg load, followed
by 10mg daily
• PCI only!
• More efficient than
Clopidogrel
• More bleeding than
Clopidogrel
• CI: active bleed, history
of TIA/stroke
• Not recommended: 75
years and older,
weighing <60kg
• No polymorphism issues
Ticagrelor
• 180mg load, followed
by 90mg BID
• Not a prodrug
• Reversible
• Compliance
important
• Avoid with 3A4
inhibitors
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ACS
PCI w/stent
Clopidogrel
Prasugrel
Ticagrelor
Load
300-600mg
60mg
180mg
Maintenance
75mg daily
10mg daily
90mg BID
Duration
1 year
1 year
1 year
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ACS
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PR is a 70 yo female who is now on the medicine floor
s/p STEMI w/thrombolytic therapy. Her daughter states
she helps her mom take her medications in the
morning because she has trouble remembering by
herself. What medications do you recommend before
she is discharged?
A.
Aspirin 81mg indefinitely and Clopidogrel 75mg for 1 year
B.
Aspirin 81mg indefinitely and Prasugrel 10mg daily for 1 year
C.
Aspirin 81mg indefinitely and Ticagrelor 90mg BID for 1 year
D.
Aspirin 81mg and Clopidogrel 75mg for 6 months
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ACS
 Platelet
glycoprotein IIb/IIIa inhibitors (GPIs)
Inhibits final common pathway in platelet
aggregation
 Used for PCI w/stent
 Used with aspirin and heparin
 Highest evidence for high risk patients
 Positive troponin, previous MI, DM, LV
dysfunction
 Studies were before thienopyridine agents
available
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ACS
 Platelet
glycoprotein IIb/IIIa inhibitors (GPIs)
Abciximab
 Monoclonal antibody
 Reversed with platelet transfusion
 Eptifibatide
 Peptide
 Dose adjust in poor renal function
 Tirofiban
 Non-peptide
 Dose adjust in poor renal function
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ACS
 BD
is a 57 yo male with confirmed STEMI. The
team decides to use pharmacological
reperfusion. Which agent should not be used?
A.
Eptifibatide
B.
Enoxaparin
C.
Aspirin
D.
T-PA
E.
Metoprolol
APhA Complete Review for Pharmacy
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ACS
 Anticoagulation
Recommended for all patients regardless of
treatment strategy.
 Unfractionated Heparin (UFH)
 Enoxaparin
 Bivalirudin
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ACS
 UFH
 60
units/kg loading dose
 12 units/kg/h IV
 Goal: aPTT 50-70 seconds
 Duration: 48 hours or until PCI is completed
 Also used with thrombolytic therapy
 Usually preferred for use during PCI
 Watch out for HIT
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ACS
 Enoxaparin
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Preferred in UA/NSTEMI
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1mg/kg SQ every 12 hours
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CrCl < 30ml/min should use 1mg/kg SQ every 24 hours
STEMI w/ thrombolytic therapy
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IV bolus of 30mg, 1mg/kg SQ every 12 hours
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0.75mg/kg every 12 hours, no IV bolus
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<75 yo
 Creatinine <2.5mg/dl in men
 Creatinine < 2.0mg/dl in women
>75 yo
If CrCl is ever <30ml/min, use 1mg/kg SQ every 24 hours.
Watch out for HIT
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ACS
 Bivalirudin
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Used instead of heparin and GPI
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Only for invasive strategy
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0.75mg/kg loading dose, followed by 1.75mg/kg/h
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Initiate before PCI
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Used when patient has HIT
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ACS
 How
long should a patient take a P2Y12 inhibitor
after stent placement?
A.
1 month
B.
6 months
C.
12 months
D.
2 years
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ACS
 Which
is true for a DES?
A.
It releases antiproliferative agents that prevent
new endothelium from forming around the
stent
B.
DAPT therapy is crucial for at least 1 year
C.
The restenosis rate is lower than BMS
D.
All of the above
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ACS
 FD
is a 45 yo male who runs marathons. He
presents to the ED with CP after his morning run.
PMH: angina, hyperlipidemia, HTN. Current
meds: aspirin, rosuvastatin, nifedipine, and
clonidine. His EKG shows acute ischemia. HR=52.
BP=170/100. Which intervention is LEAST
appropriate?
A.
Enoxaparin 1mg/kg SQ every 12 hours
B.
Metoprolol 50mg BID
C.
Nitroglycerin SL PRN
D.
Continuation of aspirin
E.
Morphine if NTG does not relieve pain
APhA Complete Review for Pharmacy
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Post-MI (Sending patients home)

How can we reduce CV risk factors, prevent heart failure,
prevent another MI or stroke, and prevent death?
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Modifiable: smoking cessation, weight loss, exercise, healthy
diet, control of DM and HTN, and medication adherence
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Beta-blockers – reduce mortality, avoid ISA
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Aspirin 81 mg daily – prevent platelet aggregation
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Reduce mortality, avoid NSAIDs
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P2Y12 inhibitors – Clopidogrel, Prasugrel, Ticagrelor
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ACE inhibitors
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UA/NSTEMI: HF, EF<40%, HTN, DM
STEMI: all patients
If ARB needed: Candesartan or Valsartan
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Post-MI (Sending patients home)
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Oddballs
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Eplerenone – LVEF <40% with HF/DM
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Not for renal dysfunction or hyperkalemia
Nitrates
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All patients should receive Rx for sublingual NTG and
counseling on appropriate use
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Lipid lowering therapy – statins
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CCB – no mortality or morbidity benefit post-MI
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ACS

59 yo female presents to ED with chest pain, SOB, n/v that
started 2 hours ago. Her initial troponin is negative. What
problem does she have?
A.
Stable angina
B.
Unstable angina
C.
NSTEMI
D.
STEMI
E.
I have no idea.
F.
Too early to tell
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ACS
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59 yo female presents to ED with chest pain, SOB, n/v that
started 10 hours ago. Her initial troponin is negative, and
there are non-specific ST-T wave changes on her EKG.
What problem does she have?
A.
Stable angina
B.
Unstable angina
C.
NSTEMI
D.
STEMI
E.
I have no idea.
F.
Too early to tell
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ACS

64 yo male presents to ED with crushing chest pain that
started 5 hours ago. The EKG shows ST elevation and the
troponin level is 0.06ng/ml. What problem is he having?
A.
Stable angina
B.
Unstable angina
C.
NSTEMI
D.
STEMI
E.
I have no idea.
F.
Too early to tell
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ACS

64 yo male (80kg) presents to ED with crushing chest pain
that started 5 hours ago. The EKG shows ST elevation and
the troponin level is 0.06ng/ml. What do you
recommend?
A.
Aspirin 81mg
B.
Aspirin 325mg
C.
Metoprolol 100mg
D.
Clopidogrel 75mg
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ACS

64 yo male (80kg) presents to ED with crushing chest pain
that started 5 hours ago. The EKG shows ST elevation and
the troponin level is 0.06ng/ml. The healthcare team
determines that Alteplase will be used for
pharmacological reperfusion. What is the appropriate
simultaneous therapy?
A.
4,800 unit bolus UFH, followed by 960 units/h infusion
B.
4,800 unit bolus UFH, followed by 1000 units/h infusion
C.
4,000 unit bolus UFH, followed by 960 units/h infusion
D.
4,000 unit bolus UFH, followed by 1000 units/h infusion
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ACS
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67 yo male presents to ED with crushing chest pain that
started 5 hours ago. The EKG shows ST elevation and the
troponin level is 0.07ng/ml. PMH: DM, HTN, TIA. The
healthcare team determines he will be going to the cath
lab for PCI. Along with Aspirin, what treatment do you
recommend?
A.
Prasugrel 60mg
B.
Clopidogrel 75mg
C.
Clopidogrel 600mg
D.
Ticagrelor 90mg
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ACS

63 yo female (60kg) presents to ED with chest pain that
started 4 hours ago. The EKG shows no ST elevation but
the troponin level is positive. PMH: HTN, DM,
hyperlipidemia, HF, HIT. Her CrCl=55ml/min. The
healthcare team decides to be proactive and take the Pt
to the cath lab for PCI. Along with Aspirin 325mg and
Prasugrel 60mg, what therapy is appropriate?
A.
Heparin 3600 unit bolus and Eptifibatide
B.
Bivalirudin 45mg loading dose, followed by 105mg/h
C.
Enoxaparin 30mg loading dose IV, followed by 60mg SQ
daily
D.
Heparin 3600 unit bolus
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ACS
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BT is 65 yo female weighing 70kg who is post-ACS with
DES placement and preserved LVEF. What is the best
medication regimen for her?
A.
Aspirin 325mg daily, Clopidogrel 75mg daily, Diltiazem 240mg
daily, Simvastatin 40mg daily
B.
Aspirin 81mg daily, Ticagrelor 90mg BID, Metoprolol tartrate
50mg BID, Atorvastatin 80mg daily
C.
Prasugrel 5mg daily, Metoprolol succinate 100mg daily,
Simvastatin 40mg daily, Enalapril 10mg BID
D.
Aspirin 81mg daily, Prasugrel 10mg daily, Metoprolol tartrate
100mg BID, SL NTG
E.
Aspirin 325mg daily, Morphine 2-4mg IV PRN, oxygen, SL NTG
APhA Complete Review for Pharmacy
+
Therapeutics 1 Tutoring
Questions?
Sarah Darby
[email protected]
September 3, 2016