Hematology pharmacotherapeutics Flashcards
List the antiplatelets that you know
Aspirin, clopidogrel, ticagrelor, dipyridamole
List the anticoagulants that you know
Dabigatran, apixaban, rivaroxaban, UFH, LMWH
List the fibrinolytics that you know
Alteplase, Tenecteplase
Which drugs are P2Y12 receptor inhibitors?
Clopidogrel, Ticagrelor
Which CYP enzyme is implicated in clopidogrel?
CYP2C19
What drugs interact with clopidogrel with reference to the CYP2C19 enzyme?
Inducers (increase efficacy): rifamycins
Inhibitors (decrease efficacy): PPI, fluoxetine, azoles
Which CYP enzyme is implicated in ticagrelor?
CYP3A4
What are the side effects of P2Y12 receptor inhibitors?
Adenosine SE: dyspnea, cough, bradycardia
Bleeding, ICH
What is the lifetime of a platelet?
7-10 days
What is the MoA of aspirin as an antiplatelet?
irreversible COX-1 inhibitor, reduces production of TXA2 and prevents platelet aggregation
Aspirin contraindicated in?
Children <16yo, asthma, active GI bleed, hypersensitivity
caution in renal impairment
Dipyridamole is often used as a first line antiplatelet (T/F)
False, dipyridamole has dose limiting SE and is used as an adjunctive agent
What is the DDI between dabigatran and rifampin?
decrease conc. of dabigatran
What is the MoA of apixaban and rivaroxaban?
Inhibit Factor Xa
What is the anticoagulant of choice for pregnancy? (Drug, dose, titration)
LMWH
SC enoxaparin 1mg/kg BD (adjust based on increasing BW)
How is LMWH cleared by the body? (Inc dose reduction with CrCL)
renally (dose reduce in CrCl <30 to 1mg/kg OD instead of 1mg/kg BD)
What genes are implicated in warfarin?
VKORC1 and CYP2C9
Which thrombolytic is indicated in treatment of VTE?
alteplase (not Tenecteplase!)
When should a thrombolytic be used in a patient with VTE / PE?
Severe cardiopulmonary compromise
In the treatment of VTE, anticoagulants can be used when there is an active bleed
No
For hospitalised pt with CrCl < 30, what is the recommended treatment for VTE?
UFH x 5 days overlap with warfarin
Outline the switch treatment for VTE, inc. dosing, frequency and duration
LMWH (1mg/kg BD) or UFH x5 days –> switch to dabigatran 150mg BD or edoxaban 60mg OD for 3m
For CrCl<30 LWMH 1mg/kg OD
Outline the Overlap treatment for VTE, inc. dosing, frequency and duration
Start warfarin (5mg - 5mg - INR) + cover with UFH/LMWH for 5 day AND INR >= 2.0
Then target INR 2-3
Outline the Oral only treatment for VTE, inc dosing, frequency and duration.
Apixaban: 10mg BD x7d -> 5mg BD (3m / 6m) -> 2.5mg BD (beyond 6m)
Rivaroxaban: 15mg BD x21d -> 20mg OD (3m / 6m) -> 10mg OD (beyond 6m)
When should the first follow up with a DVT pt be and what should be assessed?
3 months
Assess whether DVT is provoked or unprovoked
Bleeding risk
Outline whether DVT treatment should be initiated depending on location of clot
if clot is above knee, initiate treatment
if clot below knee, initiate or observe
Outline the changes (if any) to dosing of apixaban, rivaroxaban, and warfarin in VTE pt if they are taking these drugs beyond 6 months
Apixaban: 2.5mg BD
Rivaroxaban: 10mg OD
Warfarin: maintain INR 2-3
When should VTE treatment be extended beyond 3 months?
How long more before next follow-up?
DVT is unprovoked
Low bleeding risk
6m next follow up
What is considered high risk PE?
Hemodynamic instability
What is the treatment for high risk PE?
Alteplase 100mg over 2h + UFH
DOACs are recommend in pt with Anti-Phospholipid Syndrome
No, warfarin is rec
When should treatment for VTE be continued indefinitely?
recurrent VTE or Anti-Phospholipid Syndrome
What is prophylactic dose for enoxaparin?
40mg OM
Outline how to estimate stroke risk with CHA2DS2VA
C - Congestive HF / left ventricular dysfunction / hypertrophy
H - Hypertension
A2 - >=75yo
D - diabetes
S2 - previous stroke / TIA
V - vascular disease (prior MI, PAD, aortic plaque)
A - 65-74 yo
How to determine when to start treatment with CHA2DS2VA?
0 = no need to anticoagulate
1 = consider
2 = anticoagulate
DOACs are preferred over warfarin in SPAF
yes
When is warfarin still used?
LV thrombus
prosthetic heart valve / moderate - severe mitral stenosis
APS related VTE
What is the regular dosing regimen of dabigatran?
150mg BD
When are dose adjustments to dabigatran required?
110mg BD if:
- p-gp inhibitor
- >=80 yo
- high risk of bleeding
When is dabigatran contraindicated?
CrCl <30
What is the normal dosing regimen for rivaroxaban in SPAF?
20mg OD
When are dose adjustments to rivaroxaban required?
CrCl 30-50: 15mg OD
15-30: use with caution
When is rivaroxaban contraindication?
CrCl < 15
What is the normal dosing regimen for apixaban?
5mg BD
When are dose adjustments to apixaban required?
2.5mg BD if any 2/3 of the following:
- age >= 80
- body weight < 60kg
- SCr >= 133
CrCl 15-29
What is the normal dosing regimen for edoxaban?
60mg OD
When are dose adjustments to edoxaban required?
30mg OD if:
- CrCl 15-50
- Body weight < 60kg
- if concurrently taking verapamil, quinidine, dronedarone
When is edoxaban contraindicated?
CrCL < 15
In renal impairment, VKA is preferred over DOAC in SPAF (T/F)
False
Which anticoagulant can be used in hemodialysis patients for SPAF?
Apixaban
Which drugs are affect both p-gp and CYP3A4, causing DDI with anticoagulants?
ritonavir, clarithromycin, azoles
How do you switch between DOACs and Warfarin?
Warfarin -> DOAC: hold warfarin, wait for INR <2, then start DOAC
DOAC -> Warfarin: Stop DOAC and start warfarin immediately
Which anticoagulants are recommended in patients with high body weight?
Apix, rivarox
Which anticoagulants are recommended in elderly patients?
Apix, edoxaban
What should we normally do when we want to reverse DOACs non-urgently?
stop for 1-2 days
Outline how to estimate bleeding risk with HASBLED
H - HTN >160
A - abnormal renal (dialysis, transplant, SCr >200) / hepatic (cirrhosis, bilirubin > 2 ULN, LFTs > 3 ULN)
S - history of stroke
B - predisposition to bleeding
L - labile INR
E - elderly > 65yo
D - drugs (antiplatelet / aspirin) / alcohol (>14 [M] / 7 [F] units per week)
How do you start warfarin? What else do you need to add?
5-5-INR
cover with LMWH for 5 days / INR>2 (whichever is longer)
When should warfarin be held?
INR >4 –> hold until <= 3
How does gut bacteria interact with warfarin?
gut bact product vit K –> if killed –> INR increase
How does alcohol interact with warfarin?
binge –> CYP decrease –> INR increase
chronic –> CYP increase –> INR decrease
How does fever interact with warfarin?
increase turnover rate of clotting factors –> INR increase
How does physical activity interact with warfarin?
increase INR
How does smoking interact with warfarin?
increase CYP –> decrease INR
What drugs require warfarin to have pre-emptive adjustment when given together?
Bactrim: 25-50% reduce warfarin
Ciprofloxacin: 20-30% reduce warfarin
monitor INR 3-5 days later
How to reverse warfarin?
Vit K 50-100mg if INR >= 1.5
How often should pt without renal impairment and <75 yo be monitored for SPAF?
annually
How often should pt with CrCL < 60 be monitored for SPAF?
CrCL / 10 months
How often should pt >75yo be monitored for SPAF?
4 months
Which drug is contraindicated with DOACs? How manage?
carbamazepine, valproate, rifampin. use warfarin instead
What is loaded on the ambulance on the way to the hospital when ACS is suspected and at what dose?
aspirin 100mg (taken) / 300mg (ASA naive)
What is loaded once ACS is confirmed and at what dose?
Ticagrelor 180mg (preferred)
Clopidogrel 600mg
What is given during primary angioplasty?
UFH / LMWH
GpIIb/IIIa
Cangrelor
What is the ‘solution’ to In-Stent Restenosis?
drug-eluting stent
What is the ‘solution’ to in-stent thrombosis?
DAPT
When is Clopidogrel given over Ticagrelor for coronary syndromes? (specify dose)
CCS: 600mg Clopidogrel –> 75mg OM for 6 months
ACS pt <=75yo receiving thrombolysis: 300mg clopidogrel
What is the treatment regimen for ACS pt with stent placement with low bleeding risk?
DAPT (ASA 100mg OD + tica 90mg BD / clopi 75mg OM) for 12 months then SAPT (usually ASA) or extended duration
What is the treatment regimen for ACS pt with high bleeding risk?
DAPT (ASA 100mg OD + tica 90mg BD / clopi 75mg OM) for 3 months then SAPT (usually ASA)
What is the treatment regimen for ACS pt with very high bleeding risk?
DAPT (ASA 100mg OD + tica 90mg BD / clopi 75mg OM) for 1 months then SAPT (clopi)
For CYP2C19 LoF not at high bleeding risk, which antiplatelet therapy is recommended?
Ticagrelor
For CYP2C19 LoF at high bleeding risk, which antiplatelet therapy is recommended?
Ticagrelor if assessed to be suitable
In decision making, which is a larger factor: bleeding risk or ischemic risk?
bleeding risk
What is the recommended treatment regimen for PCI for Stable IHD?
DAPT (clopi 75mg OM + ASA 100mg) for 6m then ASA lifelong or clopi monoT
What are the dosing regimen for extended duration DAPT (>12m) for clopi and tica?
Tica 60mg BD (up to 3 years)
Clopi 75mg OM (up to 30 months)
When can extended duration DAPT be considered?
low bleeding risk + high thrombotic risk according to risk criteria (FYI)
Typical doses for clopidogrel
loading: 600mg / 300mg
maintenance: 75mg OM
Typical doses for ticagrelor
loading: 180mg
maintenance: 90mg BD (12m) 60mg BD (>12m)
How are NIHSS and ABCD2 used in stroke / TIA?
NIHSS 0-3: minor stroke
ABCD2 >= 4: high risk TIA
What should be started in stroke pt after r-TPA and by when?
SAPT after 24h and within 48h
What stroke pt can be considered for r-tpa?
present within 3 hours of symptoms (4.5 hours with additional criteria)
disabling stroke symptoms
BP < 180/110, BG > 2.8
No ICH
For pt not eligible for r-TPA, how to determine DAPT vs SAPT?
minor stroke and high risk TIA
How long is DAPT duration for Minor stroke / high risk TIA?
21 days
What statin regimens should be started in stroke pt if no C/I? Include dose.
high intensity statin
atorva 40-80mg ON
rosuva 20-40mg ON
If stroke mechanism is evaluated to be cardioembolic, what are the next steps?
Stop antiplatelet, start oral anticoagulant
For non-cardioembolic, severe major ICAS, what should be added and for how long?
clopidogrel 75mg for 90 days
What are the 3 major arteries?
anterior, middle, posterior cerebral artery
What is the LDL goal for post-stroke pt?
<1.8
What options can be used as long-term SAPT in stroke pt?
Aspirin
Clopidogrel
When to stop clopi and tica before surgery?
clopi: 5d
tica: 2d
