Anticoagulants

Front 1

Events of hemostasis

Back 1

1. vasospasm
2. platelet plug formation (primary hemostasis)
3. blood coagulation (secondary hemostasis)
4. dissolution of the fibrin clot (tertiary hemostasis)

Front 2

Platelet secretions

Back 2

ADP, Ca, ATP, serotonin, vWF, platelet factor 4, TXA2

Front 3

Anticoagulant factors

Back 3

PGI2, antithrombin III, Proteins C and S, Tissue Factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA)

Front 4

Aspirin

Back 4

Platelet aggregation inhibitor

irreversible inhibition of COX enzymes (acetylation)
therefore no TXA2, prolongs bleeding time.

Use: reduce incidence of MI, decrease mortality in MI pts.

Front 5

Clopidogrel, Triclopidine

Back 5

ADP receptor Blockers

irreversibly bind to P2Y12- no platelet activation

U: prevent thrombosis in stent pts.
Ad: thromcytopenic purpura
inhibit cytochrome P450
Triclopidine- neutropenia

Clopidogrel preferred b/c of side effects

Front 6

Dipyridamole

Back 6

Phosphodiesterase Inhibitor

increases CAMP levels by inhibiting phosphodiesterase and/or blocking uptake of adenosine - no platelet activation

U: coronary vasodilator
+warfarin= prophyaxis of thromboemboli in prosthetic ht. valve pts.
+aspirin= prophylaxis of cerebrovascular disease

Front 7

Cilostazol

Back 7

Phosphodiesterase inhibitor

vasodilation, inhibition of platelet aggregation

U: tx of intermittent claudication

Front 8

if No GP IIb, IIIa receptor

Back 8

Glanzmann's thrombathenia

Front 9

Abciximab

Back 9

GP IIb, IIIa blocker

irreversible
t1/2= 18-24 hrs.

parenteral

Front 10

Eptifibatide

Back 10

GP IIb, IIIa blocker

reversible

peptide

parenteral

Front 11

Tirofiban

Back 11

GP IIb, IIIa blocker

reversible

nonpeptide tyrosine analog

parenteral

Front 12

Types of Anticoagulants

Back 12

1.unfractioned heparin, low molecular weight heparin
2. selective factor Xa inhibitors
3.direct thrombin inhibitors
4. coumarin anticoags.

Front 13

heparin mechanism

Back 13

binds to antithrombin III and causes rapid activity to inhibit:
1. thrombin
2. factor IXa
3. factor Xa

sequence of 5 carbohydrate residues is essential for heparin binding

accelerates rxn 1000x

Front 14

low molecular weight heparin

Back 14

inhibit activated factor X, less activity on thrombin

equal efficacy as unfractioned heparin, increased bioavail., and less freq. dosing

ex.= enoxaparin, dalteparin, tinzaparin

Front 15

Monitoring heparin levels

Back 15

use activated partial thomboplastin time(aPTT)- measures intrinsic pathway
-only for unfractioned heparin

-low mol wt. heparin has high therapeutic index therefore not necessary to monitor levels
-->use specialized assay for anti-factor Xa

Front 16

heparin uses

Back 16

prevent fibrin formation

prevention of venous thrombosis

Front 17

heparin adverse effects

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1. bleeding
2. hypersensitivity
3. heparin induced thrombocytopenia

Front 18

heparin induced thrombocytopenia

Back 18

2 types- I=mild small decrease in platelet number
II= systemic hypercoagulable state

caused by Ab's that recognize heparin and Platelet Factor 4
-IgG binds to Fc receptor which causes platelet degranulation and aggregation.
--> thrombocytopenia via platelet comsumption

if HIT, discontinue heparin, administer direct thrombin inhibitor or fondaparinux

Front 19

reversal of heparin administration

Back 19

discontinue drug

if bleeding, use protamine sulfate
-protamine does not reverse effect of fondaparinux

Front 20

Danaparoid

Back 20

low molecular weight heparin
contains heparan sulfate, dermatan sulfate, chondroiton sulfate
- DEVOID of heparin or heparin fragments

U: prophylaxis of deep vein thrombosis, Tx of HIT

Front 21

Fondaparinux

Back 21

Factor Xa inhibitor

binds to antithrombin III and induces conformation change req. for binding to factor Xa

U: prevention and Tx of deep vein thrombosis

subcutaneous injection

Front 22

Lepirudin

Back 22

Direct thrombin inhibitor
-binds directly to active site of thrombin

can inactivate both free and fibrin-bound thrombin since it is independent of antithrombin III activity

parenteral

monitor with aPTT

U: thrombosis related to HIT
AD: renal problems, no antidote exists

Front 23

Desirudin

Back 23

direct thombin inhibitor

U: prophylaxis against deep vein thrombosis

monitor with aPTT

Front 24

Bivalirudin

Back 24

direct thombin inhibitor

also inhibits platelet activation

aPPT

U:percutaneous coronary angioplasty

Front 25

Argatroban

Back 25

direct thombin inhibitor

small molecule thombin inhibitor

IV
U: HIT

monitor with aPTT

Front 26

Coumarin Anticoagulants

Back 26

warfarin, dicumarol

ORAL

antagonize cofactor function of vitamin K

Front 27

coumarin mechanism

Back 27

inhibit vitamin K epoxide reductase
- inhibits factors II, VII, IX, X

effects on seen for 8-12 hrs.

can be reversed by administration of Vit. K
- takes 24 hrs

Front 28

Warfarin

Back 28

Coumarin Anticoagulant

narrow therapeutic index

monitored by prothombin time (PT)
- extrinsic pathway

AD:
1. bleeding- if minor, withdraw drug and oral vit. K. if major, IV vit. K
2. Cutaneous necrosis.- reduced activity of Protein C. Pro. C is dependent on vit K also.
3.Crosses placenta- abnormal bone formation
4. many drug interactions

Front 29

Drug interactions of Warfarin

Back 29

Inhibit warfarin metabolism (potentiation):
cimetidine, chloramphenicol, disulfiram, fluconazole, mentronidazole, phenylbutazone, sulfinpyrazone, trimethoprim-sulfamethoxazole

Drugs stimulating warfarin metabolism:
barbiturates, carbamazepine, phenytoin, rifampin

Front 30

Thrombolytics

Back 30

Used to lyse formed clots and restore patency of vessel.

convert plasminogen to plasmin

U: unclotting catheters, unclotting shunts, strokes, in MI if angioplasty not available

AD:
1.bleeding
2. contradicted in healing wounds, pregnancy, history of cerebrovascular problems or metasaic cancer

Front 31

Streptokinase

Back 31

Thrombolytic

combines with plasminogen
- converts to plasmin
- degrades fibrinogen and factors V, VII

Front 32

Urokinase

Back 32

thrombolytic

converts plasminogen to plasmin

U: plumonary emboli

Front 33

Alteplase, Reteplase, Tenecteplase

Back 33

tissue plasminogen activator
- fibrin selective
- during therapeutic infusion of t-PA, higher concentrations of t-PA leads to higher concentrations of plasminogen

alteplase: t1/2= 3-6 min
- tx of acute MI, acute massive pulm. embolism, acute ischemic stroke

Reteplase: t1/2= 14-18min
-given in double bolus
-management in acute MI
- less fibrin specific than t-PA

Tenecteplase: t1/2= 20-24 min
-single IV bolus
- used to reduce mortality in acute MI
-more fibrin specific than t-PA

Front 34

Anistreplase

Back 34

complex of human plasminogen and bacterial streptokinase

DISCONTINUED IN USA

Front 35

Venous Thrombosis

Back 35

Prevention:
low dose of UF heparin, LMW heparin, or fondaparinux

also warfarin but needs to be monitored

Tx:
UF or LMW heparin for first 5-7 days with overlap of warfarin.
continue warfarin for 3-6 mo.

if in pregnant woman- just heparin

Front 36

Arterial thrombosis

Back 36

aspirin and clopidogrel or triclopidine
- TIA, strokes, unstable angina and acute MI

if angina and MI, combo with beta blockers, calcium channel blockers, and fibrinolytic drugs

Front 37

aminocaproic acid, tranexamic acid

Back 37

inhibit plasminogen activation, therefore no plasmin

U: therapy in hemophilia, bleeding from fibrinolytics

AD: thrombosis, hypotension

Front 38

Protamine sulfate

Back 38

chemical antagonist of heparin
-forms inactive complex with heparin

IV

most active on UF heparins
-inactive against fondaparinux

AD: hypersensitivity, dyspnea, flushing, bradycardia, hypotension

Front 39

Vitamin K

Back 39

stops bleeding due to oral anticoagulants (warfarin)

complete effect at 24 hrs. but starts after 6 hrs.

Front 40

Aprotinin

Back 40

Serine protease inhibitor
-blocks plasmin, plasmin-streptokinase complex

U: blood loss in bypass surgery

WITHDRAWN IN 2007

Front 41

Hemophilia A
Hemophilia B

Back 41

A= def of factor VIII
B= def of factor IX