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AS - N929 Pharmacology II > Anticoagulants/Thrombolytics > Flashcards

Anticoagulants/Thrombolytics Flashcards

1
Q

Anticoagulants

A

Vitamin K antagonist (Warfarin)
Unfractionated heparin
Low molecular weight heparin
Direct oral anticoagulants

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2
Q

Warfarin (Coumadin)

A 
Vitamin K antagonist
Inhibits vitamin K dependent coagulation proteins (factors II, VII, IX, & X)
Prevent thromboembolisms
Rapid absorption
97% protein bound
Hepatic metabolism & conjugation
Excreted via bile & urine
Teratogenic - crosses placenta
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3
Q

Warfarin Onset & DOA

A

Onset 3-4 days
DOA 2-4 days
Elim 1/2 time 24-36hr after PO admin

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4
Q

Warfarin Dose

A

1.5-20mg PO

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5
Q

Warfarin Lab Values

A

PT/INR
2-3 Afib, treat VTE/PE, high risk surgery prophylaxis, tissue heart valves
2.5-3.5 mechanical heart valve, prevent recurrent MI, VTE history w/ INR 2-3

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6
Q

Warfarin Reversal

A

Minor surgery dc 1-5 days preop & restart 1-7 days postop
Immediate surgery 24-48hr or active bleeding admin vitamin K 2.5-20mg PO or 1-5mg IV
Emergency admin FFP or 4-factor concentrate K-centra

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7
Q

Unfractionated Heparin

A

Anticoagulant
Naturally occurring polysaccharide that inhibits coagulation
Released endogenously by mast cells & basophils
Binds to antithrombin & enhances AT ability to inactivate coagulation enzymes

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8
Q

Unfractionated Heparin DOA

A

DOA 1.5-4hr

Dose-dependent elimination 1/2 life

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9
Q

Unfractionated Heparin Dose

A

VTE prophylaxis 5,000u SC Q8-12hr
VTE treatment 5,000u IV + continuous infusion goal PTT 1.5-2.5x control value
Cardio-pulmonary bypass 400u/kg IV
Vascular interventions 100-150u/kg IV

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10
Q

Unfractionated Heparin Lab Values

A

aPPT 1.5-2.5x
Activated clotting time ACT
HEPTEM

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11
Q

Unfractionated Heparin Reversal

A

Protamine 1-1.5mg per 100u Heparin

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12
Q

Low Molecular Weight Heparin

A 
Anticoagulant
Enoxaparin (Lovenox)
Binds to antithrombin
Inhibits factors Xa & IIa
↓thrombin activity
Prevents fibrin clot formation
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13
Q

Enoxaparin Dose

A

Once daily

Elimination 1/2 time 24hr

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14
Q

Enoxaparin Advantages

A

↓dosing
More predictable PK response
↓effect on platelet function
Less monitoring required - no routine labs

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15
Q

Enoxaparin Disadvantages

A

More expensive
Surgery delay 12hr post-dose
Protamine only neutralizes 65%
More complete reversal w/ FFP

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16
Q

Direct Oral Anticoagulants (DOACs)

A 
Direct thrombin (IIa) inhibitors
Direct factor Xa inhibitors
- VTE treatment (Warfarin alternative)
- Prevent embolic stroke
- Surgical prophylaxis
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17
Q

DOACs Surgical Management

A

Minimal bleeding risk procedures continue
Low bleeding risk dc 24hr prior
High bleeding risk dc 48hr prior

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18
Q

Dabigatran (Pradaxa)

A

DOAC
Direct thrombin (IIa) inhibitor
Rapid onset w/ peak 24hr
1° renal elimination
Elim 1/2 time 12hr unless impaired renal function
Monitoring - coagulation assay, dilute thrombin time, aPPT, or ROTEM

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19
Q

Dabigatran (Pradaxa) Reversal

A

Idarucizumab (Praxbind)
Specific antidote
Binds w/ 350x ↑affinity than thrombin
Elim 1/2 time 45min

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20
Q

Direct Factor Xa Inhibitors

A

DOACs

  • Rivaroxaban (Xarelto)
  • Apixaban (Eliquis)
  • Edoxaban (Savaysa)

65-70% hepatic metabolism
Monitoring - coagulation assay (anti Xa), ROTEM, or PT (Rivaroxaban)

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21
Q

Antiplatelet

A

Cyclooxygenase inhibitors
P2Y12 receptor antagonists
Platelet glycoprotein IIb/IIIa antagonists

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22
Q

Aspirin

A

Antiplatelet COX inhibitor
Suppresses platelet function
Inhibits thromboxane A2 synthesis via interfering w/ COX 1 & 2 isoenzymes therefore present subsequent adenosine diphosphate release from platelets
IRREVERSIBLE

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23
Q

Aspirin Dose

A

81-325mg PO

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24
Q

Platelet Lifespan

A

8-12 days
Discontinue ASA at least 7 days prior to surgery d/t irreversible binding
New platelets required to reverse effects

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25
Q

Aspirin Clinical Indications

A

Prevent CVA (stroke)
Myocardial infarction prophylaxis
Vascular thrombosis complications

26
Q

Aspirin 1° vs. 2° Prophylaxis

A

1° hyperlipidemia w/o established CV disease
Continue ASA prophylaxis up to/including DOS hold few days per surgeon discretion

2° Afib, previous MI, or stents
Discontinue ASA requires explicit discussion w/ physician to consider cardiac vs. bleeding risk

27
Q

Cyclooxygenase Inhibitors

A 
Aspirin
NSAIDs
- Ketorolac
- Naprosyn
- Ibuprofen
28
Q

NSAIDs

A

Non-selective COX inhibitors
Antiplatelet temporary effects 24-48hr duration
Discontinue prior to surgery

29
Q

P2Y12 Receptor Antagonists

A 
Clopidogrel (Plavix)
Ticagrelor (Brilinta)
Inhibit platelet activation & aggregation via irreversibly binding its active metabolite to P2Y12 class adenosine disphosphate receptors on platelets
30
Q

Clopidogrel (Plavix)

A

P2Y12 receptor antagonist
Pro-drug requires CYP450 metabolism to produce active metabolite
Irreversible effects
Platelet function studies are unreliable

31
Q

Ticagrelor (Brilinta)

A

P2Y12 receptor antagonist

Does not require hepatic activation

32
Q

P2Y12 Receptor Antagonists

Clinical Indications

A 
Prevent 2° MI or CVA
Coronary artery stent
Acute coronary syndrome
Peripheral artery disease
Bare-metal stents 2-6wk
Drug-eluding stents 6mos
33
Q

P2Y12 Receptor Antagonists

Reversal

A

Discontinue 7 days prior to elective surgery

Emergent surgery = platelet transfusion to reverse

34
Q

Platelet Glycoprotein IIb/IIIa Antagonists

A

Antiplatelet

  • Abciximab (ReoPro)
  • Tirofiban (Aggrastat)
  • Eptifibatide (Integrilin)
35
Q

Platelet Glycoprotein IIb/IIIa Antagonists

MOA

A

Act at corresponding fibrinogen receptor (important to platelet aggregation)
Blocks fibrinogen → prevents final common pathway in platelet aggregation

36
Q

Platelet Glycoprotein IIb/IIIa Antagonists

PK/PD

A

Renal excretion
Elim 1/2 life 2.5hr
Abciximab 1/2 life 12hr w/ clinical effects lasting 48hr

37
Q

Platelet Glycoprotein IIb/IIIa Antagonists

Clinical Indications

A

Acute coronary syndrome
Angioplasty failures
Stent thrombosis

38
Q

Platelet Glycoprotein IIb/IIIa Antagonists

Considerations

A
  • Monitor effects w/ ACTs
  • Maintain ACT b/w 200-400sec
  • Reversible w/ drug clearance
  • Thrombocytopenia <100,000 develops then discontinue
  • Reversed w/ platelet transfusion
39
Q

Garlic

A

Herbal anticoagulant
Inhibits platelet aggregation
Discontinue 7 days

40
Q

Ginkgo

A

Herbal anticoagulant
Inhibits platelet activating factor
Discontinue 36hr

41
Q

Ginseng

A 
Herbal anticoagulant
Inhibits platelet aggregation
↓blood glucose
Check PT/PTT & glucose
Discontinue 24hr (preferably 7 days)
42
Q

Black Cohosh

A

Herbal anticoagulant
Used to treat menopausal symptoms
Contains anti-inflammatory compounds including salicylic acid

43
Q

Fish Oil

A 
Herbal anticoagulant
Prevent/treat atherosclerotic CV disease
↓triglycerides
800-1500mg/day
Dose-dependent bleeding risk >3g/day
44
Q

Feverfew

A

Herbal anticoagulant
Prevent migraines & inhibits platelet aggregation
Additive effects w/ other antiplatelet drugs & Warfarin

45
Q

Thrombolytics

A

Converts plasminogen to active form → plasmin
Plasmin breaks down fibrin
More effective to dissolve newly formed platelet-rich clots w/ weaker fibrinogen bonds
Treatment window = 6hr

Urokinase
Alteplase (t-PA)
Streptokinase

46
Q

Thrombolytic Contraindications

A

Trauma
Severe HTN
Active bleeding
Pregnancy

Adverse Effects:

  • Hemorrhage or bleeding
  • Re-thrombosis
47
Q

Alteplase (t-PA)

A

Fibrin specific thrombolytic drug synthesized by endothelial cells
Elim 1/2 life 5min
Short DOA
IV bolus then infusion OR direct into embolism
Limited use w/in 1st 3-6hr ischemic stroke

48
Q

Streptokinase

A

Thrombolytic
Protein produced by β hemolytic streptococci
NOT an enzyme
Non-covalently binds to plasminogen & converts → plasminogen-activator complex that acts on other plasminogen molecules to generate plasmin
Elim 1/2 life 20min
Bacterial product → stimulate antibody production & subsequent allergic reactions
Least expensive thrombolytic

49
Q

Intrinsic Coagulation Cascade

A

Amplifies & propagates hemostasis
2° hemostasis
Key = thrombin (factor II)
XII → XI → IX → VIII → common pathway

50
Q

Extrinsic Coagulation Cascade

A 
Plasma mediated
Hemostasis INITIATION
1° hemostasis
Key = tissue factor (III)
III → VII → common pathway
51
Q

Common Pathway

A

Results in soluble fibrin clot

X → factor X activates prothrombin II → thrombin IIa → thrombin activates fibrinogen I → fibrin Ia → CLOT FORMATION

52
Q

Normal Platelet Count

A

150,000-300,000mm^3

53
Q

INR

A

0.9-1.2

54
Q

PT

A

12-14 seconds

55
Q

Thrombin Time

A

<30 seconds

56
Q

Activated Clotting Time (ACT)

A

80-150 seconds

57
Q

Fibrinogen

A

> 150mg/dL

58
Q

aPPT

A

25-35 seconds

59
Q

Hemophilia A

A

Factor VIII deficiency

60
Q

Hemophilia B

A

Factor IX deficiency

61
Q

Vitamin K Dependent Factors

A

II, VII, IX, & X

62
Q

Blood Coagulation Mechanism

A
  1. Vasoconstriction
  2. Platelet plug formation
  3. Blood clot formation
  4. Dissolution

AS - N929 Pharmacology II (10 decks)

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