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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
Aspirin Clinical Indications
Prevent CVA (stroke) Myocardial infarction prophylaxis Vascular thrombosis complications
26
Aspirin 1° vs. 2° Prophylaxis
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
Cyclooxygenase Inhibitors
``` Aspirin NSAIDs - Ketorolac - Naprosyn - Ibuprofen ```
28
NSAIDs
Non-selective COX inhibitors Antiplatelet temporary effects 24-48hr duration Discontinue prior to surgery
29
P2Y12 Receptor Antagonists
``` Clopidogrel (Plavix) Ticagrelor (Brilinta) Inhibit platelet activation & aggregation via irreversibly binding its active metabolite to P2Y12 class adenosine disphosphate receptors on platelets ```
30
Clopidogrel (Plavix)
P2Y12 receptor antagonist Pro-drug requires CYP450 metabolism to produce active metabolite Irreversible effects Platelet function studies are unreliable
31
Ticagrelor (Brilinta)
P2Y12 receptor antagonist | Does not require hepatic activation
32
P2Y12 Receptor Antagonists | Clinical Indications
``` Prevent 2° MI or CVA Coronary artery stent Acute coronary syndrome Peripheral artery disease Bare-metal stents 2-6wk Drug-eluding stents 6mos ```
33
P2Y12 Receptor Antagonists | Reversal
Discontinue 7 days prior to elective surgery | Emergent surgery = platelet transfusion to reverse
34
Platelet Glycoprotein IIb/IIIa Antagonists
Antiplatelet - Abciximab (ReoPro) - Tirofiban (Aggrastat) - Eptifibatide (Integrilin)
35
Platelet Glycoprotein IIb/IIIa Antagonists | MOA
Act at corresponding fibrinogen receptor (important to platelet aggregation) Blocks fibrinogen → prevents final common pathway in platelet aggregation
36
Platelet Glycoprotein IIb/IIIa Antagonists | PK/PD
Renal excretion Elim 1/2 life 2.5hr Abciximab 1/2 life 12hr w/ clinical effects lasting 48hr
37
Platelet Glycoprotein IIb/IIIa Antagonists | Clinical Indications
Acute coronary syndrome Angioplasty failures Stent thrombosis
38
Platelet Glycoprotein IIb/IIIa Antagonists | Considerations
- 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
Garlic
Herbal anticoagulant Inhibits platelet aggregation Discontinue 7 days
40
Ginkgo
Herbal anticoagulant Inhibits platelet activating factor Discontinue 36hr
41
Ginseng
``` Herbal anticoagulant Inhibits platelet aggregation ↓blood glucose Check PT/PTT & glucose Discontinue 24hr (preferably 7 days) ```
42
Black Cohosh
Herbal anticoagulant Used to treat menopausal symptoms Contains anti-inflammatory compounds including salicylic acid
43
Fish Oil
``` Herbal anticoagulant Prevent/treat atherosclerotic CV disease ↓triglycerides 800-1500mg/day Dose-dependent bleeding risk >3g/day ```
44
Feverfew
Herbal anticoagulant Prevent migraines & inhibits platelet aggregation Additive effects w/ other antiplatelet drugs & Warfarin
45
Thrombolytics
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
Thrombolytic Contraindications
Trauma Severe HTN Active bleeding Pregnancy Adverse Effects: - Hemorrhage or bleeding - Re-thrombosis
47
Alteplase (t-PA)
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
Streptokinase
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
Intrinsic Coagulation Cascade
Amplifies & propagates hemostasis 2° hemostasis Key = thrombin (factor II) XII → XI → IX → VIII → common pathway
50
Extrinsic Coagulation Cascade
``` Plasma mediated Hemostasis INITIATION 1° hemostasis Key = tissue factor (III) III → VII → common pathway ```
51
Common Pathway
Results in soluble fibrin clot | X → factor X activates prothrombin II → thrombin IIa → thrombin activates fibrinogen I → fibrin Ia → CLOT FORMATION
52
Normal Platelet Count
150,000-300,000mm^3
53
INR
0.9-1.2
54
PT
12-14 seconds
55
Thrombin Time
<30 seconds
56
Activated Clotting Time (ACT)
80-150 seconds
57
Fibrinogen
>150mg/dL
58
aPPT
25-35 seconds
59
Hemophilia A
Factor VIII deficiency
60
Hemophilia B
Factor IX deficiency
61
Vitamin K Dependent Factors
II, VII, IX, & X
62
Blood Coagulation Mechanism
1. Vasoconstriction 2. Platelet plug formation 3. Blood clot formation 4. Dissolution

AS - N929 Pharmacology II (10 decks)

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