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MDSC 3312 MB > Anticoagulants, Antithrombotic > Flashcards

Anticoagulants, Antithrombotic Flashcards

1
Q

What are anticoagulants?

A

Indirect thrombin inhibitors (Heparin – UFH, LMWHs)
Warfarin (Vitamin K antagonist)
Direct thrombin inhibitors
Direct Xa inhibitor

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2
Q

Thrombolytics

A

Streptokinase

Recombinant t-PA

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3
Q

Antiplatelets

A

Cyclooxygenase inhibitors
Phosphodiesterase inhibitors
ADP receptor pathway inhibitors
GPIIb/IIIa antagonists

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4
Q

Oral Anticoagulants

A

warfarin

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5
Q

Direct Thrombin Inhibitors

A

Bivalirudin
Argatroban
Dabigatran

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6
Q

Indirect Thrombin Inhibitors

A 
Unfractionated Heparin
LMW Heparin
Enoxaparin
Dalteparin
Tinzaparin 
Factor Xa selective 
Fondaparinux
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7
Q

Direct Xa inhibitors

A

Rivaroxaban
Apixaban
Edoxaban

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8
Q

COX inhibitor

A

aspirin

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9
Q

Phosphodiesterase Inhibitors

A

dypridomole cilostazol

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10
Q

ADP receptors

A

Clopidogrel
Ticlopidine
Prasugrel

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11
Q

Anti GPIIb/IIIa

A

Abciximab
Eptifibatide
Tirofiban

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12
Q

Thrombolytics

A 
Streptokinase
Urokinase
t-PA
Alteplase (human tPA)
Reteplase
Tenecteplase
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13
Q

Heparin Preparation and Indications- high dose, intermediate dose, sc

A

Prepared from:
Porcine intestinal mucosa
Bovine lungs

Indications:
DVT, VTE, PE, unstable angina (High dose)
Hip surgery, esp. implantation of prosthesis (intermediate dose)
Prophylaxis (sc) in patients undergoing major surgery or prolonged bed rest

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14
Q

Administration and Elimination of heparin

A

IV or SC - NOT IM- hematoma risk

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15
Q

Elimination of heparin is increased with

A

Hepatic dysfunction

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16
Q

M.O.A of heparin - factors involved, reversible or irreversible, spends on

A

depends on antithrombin - binds to 2a, 9a, 10 a (RLS)- increase the rate of the reaction and then it releases antithrombin unchanged after inducing a conformational change leading to exposure of the active site

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17
Q

Which factors are affected by the UFH and LMWH?

A

UFH- 10 a and 2a LMWH- 10A

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18
Q

How can UFH. LMWH be reversed and it is more effective with? Which factor is affected more?

A

Protamine sulphate iv (1mg for every 100units heparin).

Only anti-IIa affected; LMW heparin effect not fully and quickly reversed as UFH- Anti-2a

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19
Q

What are the advantages of LMW heparin?

A

Adv- high bioavailability, wide therapeutic index, lower 1/2 life, less Intra and inter-patient variability, less HIT, bone loss, hi induced osteoporosis, hemorrhagic complications

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20
Q

Disadv of LMW

A

Cannot be stopped as fully and quickly as UFH.

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21
Q

What is the difference in the APTT in a patient with UFH and LMWH?

A

APTT- INCREased with UFH - affect 10a and 2 a lwmh- no effect on 2a - no changes in aptt

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22
Q

What does Aptt measure and what is used to measure LMW heparin?

A

APTT- measures the ability to inhibit 2a (specifically UFH ability) LMWH- anti-10 assay-

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23
Q

Dosing of LWMH depends on and should be cautioned in

A

(weight-based dosing in normal renal function; caution in renal insufficiency, obesity and pregnancy).

24
Q

Mechanism of action of Fondaparinux and Indications

A

Antithrombotic , Bind to antithrombin strongly and selectively, no interaction with platelets Indicated for prophylaxis and treatment for VTE

25
Dosing and Administration fondaparinux
half life- 15 hrs, 1 daily and SC
26
Increased bleeding is seen in fondaparinux and Is protamine sulphate able to reverse it?
given <6 postoperatively <50kg Protamine not useful to reverse effect, 100% anti-Xa effect
27
A 60 yr old female has been taken X for PEas well as prophylaxis treatment for upcoming surgery she has been experiencing alopecia and bleeding, what drug is she taken and what are other side effects of the drug?
Bleeding – elderly (esp females) and renal failure patients more prone. Allergy Alopecia Heparin-induced thrombocytopenia (1-4%): transient, severe. Chronic therapy: Osteoporosis, ↑ risk of spontaneous fractures aldosterone secretion - hyperkalemia
28
A person is taking heparin along with an ACE inhibitor, in terms of electrolytes, what should be monitored and why?
Hyperkalemia- Ace inhibitors - increase K+ levels and long term heparin decreased aldosterone secretion- hyperkalemia
29
What lab monitoring is done with heparin? Why?
Frequent platelet count important to determine thrombocytopenia. Heparin-associated (HAT; transient) or heparin-induced (HIT; life-threatening systemic hypercoagulable state).
30
If HIT is suspected, what is the plan, is it life-threatening and what predominate?
Suspicious HIT: stop heparin, add direct thrombin inhibitor argatroban. NB: predominantly Xa effect of LMW heparins.
31
Heparin is contraindicated In
``` Hypersensitivity Severe thrombocytopenia Hemophilia and acquired coagulation disorders Active bleeding: GI ulceration bleeding hemorrhoids intracranial hemorrhage Severe liver disease Infective endocarditis Active tuberculosis Threatened abortion Visceral carcinoma ```
32
Heparin, surgery and pregnancy
cautionAvoid after surgery to eye, CNS or critical areas
33
What are THE Vitamin K dependent factors?
``` Factors II (prothrombin), VII, IX, and X; proteins S and C . Recycling is necessary to maintain sufficient intracellular [Vitamin K] to serve as a cofactor in this reaction. ```
34
What is the mechanism of action of warfarin?
. Recycling is necessary to | maintain sufficient intracellular [Vitamin K] to serve as a cofactor in this reaction.
35
Bioavailability, half-life and dose adjustment warfarin
100% bioavailability; 99% bound to plasma protein; t1/2 ~ 36hrs. Dose adjusted to ↑PT to 25% normal prothrombin activity over long-term
36
INR goal and therapeutic index-warfarin
INR goal related to coagulation risk: 2.0 – 3.0 for thrombotic prophylaxis and tx 2.5 – 3.5 for prosthetic valves and higher thrombotic risk cases (Warfarin has narrow therapeutic index, monitor regularly every 2-4 weeks)
37
Contraindication and indication of warfarin
Indications: VTE – chronic prophylaxis Systemic embolism – chronic prophylaxis MI Contraindications: NEVER IN PREGNACY: hemorrhagic disorder, teratogenic (abnormal bone formation) Protein C deficiency
38
Why is the maximal effect of warfarin seen within 1 week?
8-12hr delay in warfarin action, maximal effect within 1 week; resulting anticoagulant effect dependent on degradation t1/2 of Vit K-dependent clotting factors, ranging from 6 - 60 hrs
39
How is warfarin used in acute DVT or PE? oVERLAP TIME?
In patients with acute DVT or PE, UFH or LMW heparins always used for immediate anticoagulation until adequate warfarin-induced depletion of the pro-coagulant clotting factors is achieved. Duration of overlapping therapy is 5-7 days
40
Warfarin Adverse Effects
``` Hemorrhage Skin necrosis (within 1st week; very rare) Protein C inherited deficiency Rarely, infarction of breast, fatty tissue, intestines, extremities (purple toes syndrome) – hypercoagulable state) ```
41
Reversal
Reversal of action (Reestablish normal clotting factors activity): Stop warfarin; administer Vitamin K1, fresh-frozen plasma, prothrombin complex concentrate and recombinant Factor VIIa (rFVIIa). A new four factor concentrate (II, VII, IX and X) available
42
What substances increase INR?
``` Allopurinol Amiodarone Cimetidine Clofibrate Lovastatin Tamoxifen Omeprazole Gemfibrozil Isoniazid Quinidine ```
43
What decreases INR?
``` Cholestyramine Phenobarbital Phenytoin Sucralfate Rifampin Vitamin K ```
44
Increase bleeding risk?
``` Aspirin Argatroban Clopidogrel Danaparoid NSAIDs Ticlopidine UFH/LMWHs ```
45
Bioavailability, onset and half-, monitoring of Direct Xa inhibitor life
Relatively high oral bioavailability, rapid onset of action, shorter t1/2 than warfarin. Fixed dosing, no monitoringRelatively high oral bioavailability, rapid onset of action, shorter t1/2 than warfarin. Fixed dosing, no monitoring
46
Andexanet alfa
Andexanet alfa (Xa “decoy”, iv infusion) reverses rivaroxaban and apixaban action.
47
Rivaroxaban use
Prophylaxis/tx of DVT and PE in hip and knee surgery. Embolic stroke prophylaxis in nonvalvular AFib. Tx of VTE.
48
Apixaban
Embolic stroke prophylaxis in nonvalvular AFib. | Prophylaxis of DVT and PE in hip and knee surgery
49
Edoxaban
DVT and PE in patients initially treated with parenteral anticoagulant for 5-10 days
50
Xa factor inhibitors
Contraindication: | Severe hepatic or kidney dysfunction (significant portion excreted unchanged in urine)
51
Bivalirudin- class, onset, half-life, indication, administer, moa
Short t1/2 Rapid onset/offset Indication: percutaneous coronary angioplasty Inhibits platelet activation
52
What drug can be used for prophylaxis of HIT w/o with thrombosis? monitor
ARGATROBAN Short t1/2 Indication: tx or prophylaxis of HIT with or without thrombosis, coronary angioplasty with HIT Monitor aPTT. High INR, difficult transition to warfarin
53
Bioavailability, metabolism and Indications of dabigatran
Prodrug, low VTE following 5-7 days tx with heparin/LMWH ↓risk of recurrent VTE VTE prophylaxis in major orthopedic surgery
54
Clearance and Reversal of Dabigatran
Renal dysfunction prolongs drug clearance Reversal: Idarucizumab (humanized monoclonal antibody)
55
Direct XA AND thrombin vs warfarin advantages
Equivalent antithrombotic, lower bleeding rates compared with warfarin Rapid therapeutic effect No monitoring! Fewer drug-drug interactions
56
Direct XA AND thrombin vs warfarin disadvantages
Shorter t1/2 means non-adherence would lead to loss of anticoagulant effect and increase thromboembolic risk.

MDSC 3312 MB (7 decks)

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