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Pharm test 3 > Anticoags > Flashcards

Anticoags Flashcards

1
Q

Oral antiplatelet aggregation

A

Aspirin, Ticlopidine, Clopidogrel, Prasugrel, & Ticagrelor (PT cat)

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2
Q

IV antiplatelet aggregation

A

Abciximab, Eptifibatide, & Tirofiban

ate

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3
Q

*Aspirin MOA

A

Cycloxygenase (COX) inhibitor
Prevents the production of Thromboxane A2
Action is irreversible, lifespan of a platelet 10 day

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4
Q

*ASA prevents what, dose diseases

A 
Recurrent Ischemic Events
Stroke
Myocardial infarction
Symptomatic peripheral arterial disease
Dosage: 81–325 mg qday
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5
Q

ASA precautions
drug interaction
tx for bleeding

A

Children (Reye’s)
Pregnancy
Asthmatics
Cardiovascular drugs
Blunts effect of ACE inhibitors, ß-blockers, & diuretics due to prostaglandin inhibition
Increased bleeding with other anticoagulants. Treatment of bleeding is platelet transfusion: have platelets circulation just don’t stick to each other so platelet count doesn’t matter

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6
Q

*Ticlopidine (ticlid) MOA

A

Thienopyridine - Blocks ADP receptor on platelet and inhibits fibrinogen binding

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7
Q

Ticlopidine (ticlid) use

restrictions

A

Used for prevention of recurrent ischemic events especially in cases of ASA intolerance
**Use is extremely restricted due to: Neutropenia, Thrombotic thrombocytopenic purpura, GI Upset, Teratogenesis

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8
Q

*Clopidogrel (Plavix) MOA

A

Thienopyridine – Irreversibly blocks ADP receptor on platelet and inhibits fibrinogen binding

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9
Q

*Clopidogrel (Plavix) prevention of

A

Used for prevention of recurrent
ischemic events:
Stroke prevention
Recent acute coronary syndrome (dual therapy better than ASA mono therapy)
Post-percutaneous coronary intervention (dual therapy better than ASA monotherapy)

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10
Q

which mono therapy is better ASA or Clopidogrel, but what the down side and doses of the 2

A

Clopidogrel monotherapy better than ASA monotherapy but cost may be prohibitive
Dosage
Loading dose of 300mg or 600mg
Daily dose of 75mg

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11
Q

Clopidogrel precautions

A

Metabolized via CYP2C19, genetic predisposition to poor metabolism along this pathway, may require increased dosing
**CYP-450 inhibitor
Dose adjustment for severe renal or
hepatic disease
Use in conjunction with other anticoagulants

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12
Q

Clopidogrel toxicities/bleeding

A 
Increased risk of bleeding
Serious bleeding seen most commonly in the elderly, the underweight, and pts with previous stroke or TIA
Treatment of Bleeding
Discontinuation of drug (at least
temporarily)
Platelet transfusion
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13
Q

*Prasugrel (effient)

A

New Thienopyridine
greater than clopidogrel at reducing risk of recurrent MI and in-stent thrombosis
greater risk of bleeding
works of clopidogrel non-responders

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14
Q

Prasugrel dose precautions

A

10mg qday
Precautions:
Active bleeding
Previous stroke/TIA, underweight, elderly (>75 yrs) – Consider decreasing dose to 5mg qday
*Surgery – Risk of bleeding during CV surgery was 4x greater than clopidogrel. Do not use pre-cardiac cath!

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15
Q

*Ticagrelor (brilinta) MOA

A

Blocks ADP receptors from different binding site (allosteric antagonist)

  • better than clopidogrel of MI and stroke
  • but higher rate of non-procedure bleeding–including intracranial hemorrhage
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16
Q

Ticagrelor uses dose

A

Prevention of recurrent ischemic events after myocardial infarction
Stroke prevention
Recent acute coronary syndrome
Post-percutaneous coronary intervention
Dosage: 180mg x 1, then 90mg bid
Always given as dual therapy with ASA unless ASA is contraindicated

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17
Q

Ticagrelor precautions contraindications

A 
Precautions:
Hepatic dysfunction
ASA use greater than 100mg/day
Hold for >5 days before surgery
bid dosing may have compliance considerations
Contraindications:
Active bleeding
History of intracranial hemorrhage
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18
Q

*GPIIb/IIIa inhibitors MOA

A

Block the GPIIb/IIIa receptor preventing fibrinogen binding

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19
Q

*GPIIb/IIIa inhibitors uses and drug names

A 
Acute Coronary Syndrome
Percutaneous Coronary Intervention
Drugs:
Abciximab (ReoPro)
Eptifibatide (Integrillin)
Tirofiban (Agrastat)
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20
Q

*Abciximab uses

A 
ACS with planned PCI
– If used with heparin keep aPTT 60-85 sec
PCI
Most expensive agent
Most prolonged effects
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21
Q

*Eptifibatide

A 
ACS
– IV bolus – Infusion
Serum Creatinine <2.0 mg/dl
2.0 mcg/kg/min for up to 72 hours
Serum Creatinine 2.0 to 4.0 mg/dl 
1.0 mcg/kg/min for up to 72 hours
PCI – Same as above
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22
Q

GPIIb/IIIa Inhibitors toxicities

A

Bleeding
Abciximab – reverse with platelets
Eptifibatide and Tirofiban – discontinue the drug
Interactions
Other antiplatelet and anticoagulant agents potentiate effects

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23
Q

Peri-op mgmt of anti platelet therapy

A

Temporary interruption of anti-platelet therapy should occur 7-10 days pre-op
Therapy should resume 24hrs (or next AM) post-op as long as hemostasis is achieved
Patients at high risk for cardiac events should continue ASA up and through the OR, clopidogrel should be stopped at least 5 days prior to OR

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24
Q

*Heparin MOA

A

Heterogenous mixture of polysaccharide chains
Activates Antithrombin III
Increases inhibition of Thrombin (IIa) and
Factor Xa by 1000 fold

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25
Q

*Heparin uses

A

DVT prophylaxis and treatment
Pulmonary Embolus treatment
Acute Coronary Syndrome
When warfarin started or contraindicated

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26
Q

Heparin doses

A

DVT prophylaxis: 5,000 Units SQ q8hrs
q12 hr dosing occasionally used in high-risk bleeding pts (i.e. Neurosurgery and ESRD)
Intravenous infusions
Weight-based bolus
Weight-based infusion
Adjusted based on aPTT or anti-Xa values q6hrs until stable, then qday

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27
Q

Heparin interactions/drawbacks

A

Increased risk of bleeding when used with other anticoagulant or antiplatelet agents
Drawbacks of use
Variable anticoagulant effect
Inability to inhibit clot-bound thrombin

28
Q

Heparin toxicities

A

*Bleeding
STOP THE HEPARIN! Look for hidden heparin!
Reverse with Protamine 1mg/100 U Heparin (or just give 50mg bolus)
*Benign thrombocytopenia
*Heparin-induced thrombocytopenia (HIT)
1% @ 7days ■ 3% @ 14days

29
Q

HIT non-immune mediated (type 1) and immune mediated (type 2)

A

1.Mild drop in platelets, usually within 4 days of start of heparin treatment, NOT progressive or associated with thrombosis
2. Follows heparin exposure (prophylactic or full)
Reduction in platelet count to < 150,000 or
a decrease of 50% from baseline (pre heparin)
Occurs 5 - 14 days after heparin exposure

30
Q

Thrombocytopenia

A

Occurs in 2-5% (UF>LMWH)
Most common: Surgery >medical > obstetric
Typical platelet count 38,000-60,000
Typical onset (66%): Exposure 5-14 days
Delayed onset (3-5%): Exposure 2-6 weeks
Rapid onset (25-30%): hours to days, usually due to residual circulating antibodies from heparin exposure within last 100 days)

31
Q

HITT venous, arterial

A

Thrombocytopenia with Thromboembolism (10 – 25% cases)
Venous:
(4 x more common)
DVT, PE, Venous limb gangrene, dural sinus
thrombosis
Arterial:
Cerebral infarction, limb ischemia, skin necrosis, myocardial infarctions, mesenteric ischemia, adrenal, renal, spinal artery infarctions
25 – 30% mortality, 25% amputation rate

32
Q

HIT lab

A

ELISA: (enzyme linked immunosorbent assay)
Antigen assay measures titer of IgG antibody to heparin-PF4 complex
Easy to do and readily available
Sensitivity 90%, Specificity 80% (detects other antibodies)
C-serotonin release assay (SRA):
Detects platelet activation
Labor intensive, Not readily available, Usually a “send-out” test
Sensitivity & Specificity 95%
Used primarily as a confirmatory test
**Do not delay treatment waiting for test results!

33
Q

HIT clinical mgmt

A

Stop all drugs known to cause thrombocytopenia
STOP Heparin and START non-heparin anticoagulant (usually Argatroban)
Look for any history of heparin exposure
Look for unrecognized heparin sources
Heparinized flush bags
Heparin-coated catheters
Prophylactic sq heparin

34
Q

*Low Molecular Weight Heparin (enoxaparin) MOA/uses

A 
Saccharide chains ~ 5,000 daltons
Binds with Antithrombin III and inhibits
Factor Xa
Uses:
DVT prophylaxis
Acute Coronary Syndrome
VTE treatment
35
Q

Low Molecular Weight Heparin dose

A

Dosage (subcutaneous injection) Depends on indication
DVT Prophylaxis
Standard: 40mg q24hrs
Hip or knee replacement: 30 mg q12hrs
DVT Treatment: 1 mg/kg q12h or 1.5 mg/kg qd
Acute Coronary Syndrome: 1mg/kg q12h
*Dosage effects not routinely monitored, can check anti-Xa levels

36
Q

Low Molecular Weight Heparin precautions, tx

A

Precautions
Pregnant women – monitor anti-Xa levels
Obese patients – use weight-based dosing
*Not recommended in severe renal insufficiency (Cr Cl <30 ml/min). If no other alternative, reduce dose by 50%
Not for use with spine surgery patients or patients with epidural catheters
*Treatment of bleeding – Protamine provides ~60% reversal

37
Q

*Fondaparinux (Arixtra) MOA, uses

A 
Synthetic Factor Xa inhibitor
Binds with Anti-thrombin III to
potentiate Xa inhibition (by 300 times)
No direct effect on IIa (thrombin)
Uses:
Acute Coronary Syndrome
PE/DVT tx
DVT prophylaxis
38
Q

Fondapariunx dosage, contraindications, *tx

A 
Dosage
7.5mg subcutaneous qd for prophylaxis, 10mg for VTE or wt > 100kg, duration depends on reason for use
Contraindications:
CrCl < 30 ml/min
Spinal anesthesia or lumbar puncture
Treatment of bleeding
No known reversal agent
FFP is ineffective in reversal
Discontinue the drug and provide supportive care
39
Q

*IV direct Thrombin (IIa) inhibitors MOA, uses

A

Do not require Antithrombin III
IV Agents include Hirudin, Lepirudin, Desirudin, Hirulog, Argatroban (reversible), Bivalirudin
Uses: HIT (Argatroban, Lepirudin)
Percutaneous coronary intervention (Bivalirudin)

40
Q

IV direct Thrombin (IIa) inhibitors toxicities, Interactions, *Tx of bleeding

A

*Toxicities:
Bleeding
Lepirudin and Desirudin can only be used once d/t problems w/ anaphylaxis
*Interactions:
Increased bleeding with additional anticoagulants, thrombolytics, or anti platelet agents
*Treatment of bleeding:
Stop the infusion
May respond to a combination of Factor VII, FFP, and cryoprecipitate

41
Q

*Warfarin MOA

A

Interferes with the production of Vitamin K-dependent clotting factors (II, VII, IX, & X)
Interferes with the carboxylation of natural anticoagulants Protein C and Protein S

42
Q

*Warfarin uses

A 
Prevention of thrombosis/embolism
DVT
Atrial fibrillation
Mechanical heart valves
Long-term treatment of VTE
43
Q

Warfarin dosage

A

Start with 5-10mg/day x 2-5 days, then
**Dose based on Prothrombin time/INR
Most indications, therapeutic INR goal is 2.0–3.0
High risk patients (i.e. mechanical heart valves, previous thrombus, anti- phospholipid syndrome) goal of 2.5-3.0
**Overlap with heparin or LMWH for 1-2 days
Duration of therapy for uncomplicated DVT and PE = 3 months

44
Q

Warfarin toxicities,

A

Toxicities:

Bleeding, Birth defects, Cutaneous necrosis

45
Q

Warfarin interactions increased effect

A

Amiodarone
Cimetidine
Acetaminophen
Phenylbutazone

46
Q

Warfarin interactions decreased effects

A 
Sucralfate
Cholestyramine
Spironolactone
Barbituates
Vitamin K containing foods
47
Q

Warfarin precautions

A

Concomitant anti-platelet therapy and/or NSAID use

48
Q

Warfarin INR

A

Sub-therapeutic INR: Continue same dose, recheck in 1-2 wks: Super-therapeutic INR without bleeding, Hold next dose, recheck within 1 wk
Reversal/Treatment of bleeding: Vitamin K – either oral or IV, FFP -(1.4 to 1.5 of INR) can’t get INR below 1.5 with FFP

49
Q

Periop mgmt of Warfarin Therapy

A
  • Pts who require temporary interruption of warfarin and normalization of INR, warfarin should be held 5 days prior to OR
  • Warfarin should be resumed 12-24 hours post-op as long as hemostasis has been achieved
  • For high-risk patients bridging with heparin up until 4-6hrs of surgery is recommended
50
Q

*Dabigatran (pradaxa) MOA, uses, dosage

A

Direct Thrombin Inhibitor (IIa)
Uses: Prevention of stroke in non-valvular atrial fibrillation (2010) and treatment of DVT/PE (2014)
Dosage: 110mg bid vs 150mg bid
Lower dosing suggested if high-risk for bleeding, elderly, or mod/severe renal impairment

51
Q

Dabigatran

A

superior to 150mg bid of warfarin for stroke and systemic embolism, no significant difference in major bleeding
*110mg bid just as good as warfarin for preventing with a 20% relative risk reduction for major bleeding

52
Q

Dabigatran advantages

A

No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Rapid time to peak action (1 hr)
Short half-life (12-14 hrs) in pts with normal renal function

53
Q

Dabigatran disadvantages

A

High cost and bid dosing which may impact compliance
No antidote yet
– Idarucizumab, an antibody, is currently under investigation. May be a potentially effective and rapid antidote
No assay for monitoring of anticoagulant effect
No long term data – Several reports of post- marketing serious or fatal bleeding events that requires investigation

54
Q

*Rivaroxaban (Xarelto) MOA uses dose

A

Direct Factor Xa inhibitor
Uses: Stroke and systemic embolism prevention in
non-valvular atrial fibrillation
Prevention of DVT after hip or knee replacement surgery
Treatment of PE/DVT
Dosage: 20mg qday

55
Q

Rivaroxaban *

A

just as good as warfarin for prevention

overall risk of bleeding same by decreased risk of intracranial and fatal bleeding compared to warfarin

56
Q

RIvaroxaban advantages

A

No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Once daily dosing may improve compliance
Rapid time to peak action (2.5-4 hrs)
Short half-life (7-11 hrs)

57
Q

Rivaroxaban disadvantages

A

High cost which may impact compliance
No antidote: Andexanet, a Factor Xa decoy currently under
investigation, may assist in reversal of the effects
No assay for monitoring of anticoagulant effect
No long term data

58
Q

*Apixaban (Eliquis) MOA uses dose

A

Direct Factor Xa inhibitor
Uses: Stroke and systemic embolism prevention in non-valvular atrial fibrillation, prevention of DVT in hip and knee replacement surgery, and treatment of DVT/PE
Dosage: 5mg bid

59
Q

*Apixaban

A

clear benefit over ASA for pt who are not candidates for warfarin
superior to warfarin in prevention and has significant decreased in bleeding risk

60
Q

Apixaban advantages

A

No routine monitoring required, predictable pharmacokinetics
Less influence by diet and drug interactions
Rapid time to peak action (3 hrs)
Short half-life (12 hrs)

61
Q

Apixaban disadvantages

A

High cost and bid dosing which may impact compliance
Reversed only with prothrombin complex concentrate
No assay for monitoring of anticoagulant effect
No long term data

62
Q

*Fibrinolytic what they do and drug names

A 
Plasminogen activators convert plasminogen to plasmin
Plasmin causes fibrinolysis
*Agents:
Streptokinase
Urokinase
Tissue-type Plasminogen Activator (t-PA)
Recombinant t-PA (Alteplase, Reteplase)
Tenecteplase (TNK-ase)
63
Q

*Fibrinolytic use

A 
Acute ST-elevation myocardial infarction
Acute ischemic stroke (within 6 hours of onset of symptoms) - tPA
Urokinase
Central venous catheter de-clotting
Pulmonary embolism
64
Q

Fibrinolytics dose, toxicities

A

Recombinant tPA: 10 Units over 2 min; Repeat in 30 min
TNKase: 30 – 50 mg single bolus over 5 seconds (wt-
based)
Toxicities
Bleeding - Evaluate absolute versus relative contraindications for the administration of fibrinolytics

65
Q

Firbinolytics absolute contraindications

A

Previous hemorrhagic stroke
Ischemic stroke within 3 months
Known intracranial neoplasm
Active internal bleeding (excluding menses)
Suspected aortic dissection
Significant closed head or facial trauma within 3 months

66
Q

Fibrinolytics relative contraindications

A

Recent trauma within 2-4 weeks (including
traumatic CPR)
Major surgery < 3 weeks
Recent (2-4 weeks) internal bleeding or active PUD
Pregnancy
For streptokinase - allergy or prior exposure (5 days to 2 years)

Pharm test 3 (6 decks)

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