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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
Q

Dosing and Administration fondaparinux

A

half life- 15 hrs, 1 daily and SC

26
Q

Increased bleeding is seen in fondaparinux and Is protamine sulphate able to reverse it?

A

given <6 postoperatively
<50kg

Protamine not useful to reverse effect, 100% anti-Xa effect

27
Q

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?

A

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
Q

A person is taking heparin along with an ACE inhibitor, in terms of electrolytes, what should be monitored and why?

A

Hyperkalemia- Ace inhibitors - increase K+ levels and long term heparin decreased aldosterone secretion- hyperkalemia

29
Q

What lab monitoring is done with heparin? Why?

A

Frequent platelet count important to determine thrombocytopenia. Heparin-associated (HAT; transient) or heparin-induced (HIT; life-threatening systemic hypercoagulable state).

30
Q

If HIT is suspected, what is the plan, is it life-threatening and what predominate?

A

Suspicious HIT: stop heparin, add direct thrombin inhibitor argatroban.

NB: predominantly Xa effect of LMW heparins.

31
Q

Heparin is contraindicated In

A 
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
Q

Heparin, surgery and pregnancy

A

cautionAvoid after surgery to eye, CNS or critical areas

33
Q

What are THE Vitamin K dependent factors?

A 
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
Q

What is the mechanism of action of warfarin?

A

. Recycling is necessary to

maintain sufficient intracellular [Vitamin K] to serve as a cofactor in this reaction.

35
Q

Bioavailability, half-life and dose adjustment warfarin

A

100% bioavailability; 99% bound to plasma protein; t1/2 ~ 36hrs.

Dose adjusted to ↑PT to 25% normal prothrombin activity over long-term

36
Q

INR goal and therapeutic index-warfarin

A

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
Q

Contraindication and indication of warfarin

A

Indications:
VTE – chronic prophylaxis
Systemic embolism – chronic prophylaxis
MI

Contraindications:
NEVER IN PREGNACY:
hemorrhagic disorder, teratogenic (abnormal bone formation)
Protein C deficiency

38
Q

Why is the maximal effect of warfarin seen within 1 week?

A

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
Q

How is warfarin used in acute DVT or PE? oVERLAP TIME?

A

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
Q

Warfarin Adverse Effects

A 
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
Q

Reversal

A

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
Q

What substances increase INR?

A 
Allopurinol
Amiodarone
Cimetidine
Clofibrate
Lovastatin
Tamoxifen
Omeprazole
Gemfibrozil
Isoniazid
Quinidine
43
Q

What decreases INR?

A 
Cholestyramine
Phenobarbital
Phenytoin
Sucralfate
Rifampin
Vitamin K
44
Q

Increase bleeding risk?

A 
Aspirin 
Argatroban
Clopidogrel
Danaparoid
NSAIDs
Ticlopidine
UFH/LMWHs
45
Q

Bioavailability, onset and half-, monitoring of Direct Xa inhibitor life

A

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
Q

Andexanet alfa

A

Andexanet alfa (Xa “decoy”, iv infusion) reverses rivaroxaban and apixaban action.

47
Q

Rivaroxaban use

A

Prophylaxis/tx of DVT and PE in hip and knee surgery.
Embolic stroke prophylaxis in nonvalvular AFib.
Tx of VTE.

48
Q

Apixaban

A

Embolic stroke prophylaxis in nonvalvular AFib.

Prophylaxis of DVT and PE in hip and knee surgery

49
Q

Edoxaban

A

DVT and PE in patients initially treated with parenteral anticoagulant for 5-10 days

50
Q

Xa factor inhibitors

A

Contraindication:

Severe hepatic or kidney dysfunction (significant portion excreted unchanged in urine)

51
Q

Bivalirudin- class, onset, half-life, indication, administer, moa

A

Short t1/2
Rapid onset/offset
Indication: percutaneous coronary angioplasty
Inhibits platelet activation

52
Q

What drug can be used for prophylaxis of HIT w/o with thrombosis? monitor

A

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
Q

Bioavailability, metabolism and Indications of dabigatran

A

Prodrug, low VTE following 5-7 days tx with heparin/LMWH
↓risk of recurrent VTE
VTE prophylaxis in major orthopedic surgery

54
Q

Clearance and Reversal of Dabigatran

A

Renal dysfunction prolongs drug clearance

Reversal: Idarucizumab (humanized monoclonal antibody)

55
Q

Direct XA AND thrombin vs warfarin advantages

A

Equivalent antithrombotic, lower bleeding rates compared with warfarin
Rapid therapeutic effect
No monitoring!
Fewer drug-drug interactions

56
Q

Direct XA AND thrombin vs warfarin disadvantages

A

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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