Drugs- Hemostasis Flashcards Preview

B&L > Drugs- Hemostasis > Flashcards

Flashcards in Drugs- Hemostasis Deck (41):
1

Virchow's triad

-Disruption of blood flow
-Hypercoagulable state
-Endothelial injury

2

Formation of clot

1- vasoconstriction
2- primary hemostasis (platelet adhesion, granule release, aggregation)
3- secondary hemostasis (Thrombin activation, fibrin polymerization)
-Activation of antithrombotic mechanisms (ATIII, plasmin, protein C and S)

3

Aspirin

-Inhibits synthesis of TxA2 by irreversible acetylation of COX-1 in platelets
-COX-1 irreversibly inactivated
-Antithrombotic effects last for duration of platelets life span

4

Ticlopidine

-Inhibits ADP receptors on platelets which prevents activation of GPIIb-IIIa
-Inh platelet adhesion
-Alternative to aspirin
-prophylaxis for M reinfarction
-Nausea, diarrhea, hemorrhage
-Assoc with TTP
-Severe BM toxicity

5

Clopidogrel

-Similar to ticlopidine but lower AE
-Reqs activation by CYP2C19 (PPI, anti-epileptics, propranolol; drug-drug int)
-Used in pts with hx of stroke, recent MI, PVD, stents

6

Abciximab

-Inh platelet aggregation by preventing binding of fibrinogen to gp IIb/IIIa
-IV to high risk pts undergoing coronary angioplasty
-Expensive, bleeding is common AE

7

Tirofiban, eptifibatide

-Small molecule platelet receptor GP inhibitors
-Constant infusion

8

PDE inhibitors

-Increased cAMP inhibits platelet activation
-Decreased conv of cAMP to AMP will inhibit platelet act
-Dipyriadol, cilostazol

9

Dipyridamol

-Vasodilator, inh platelet aggregation by inhibiting AMP formation from cAMP
-Combo with warfarin, inh embolism from heart valves

10

Cilostazol

-Antithrombotic, antiplatelet and vasodilation
-Inh PDE, increases cAMP

11

Anagrelide

-Red elevated platelet cts in essential thrombocytosis by inh megakaryocyte development

12

calcium chelators

-inh blood coag in vitro (sodium citrate, disodium edetate)

13

Heparin

-Accel action of ATIII to neutralize thrombin and other coag factors

14

Rudins

-Direct thrombin inhibitors

15

Coumarin

Interfere with hepatic synthesis of fxnal vit K dep clotting factors (II, VII, IX, X, protein C and S)

16

Standard Heparin

-From intestinal mucosa and bovine lung
-3k-30k g/ml
-Continuous infusion or intermittent subq
-Immediate onset
-Inactivates IIa mainly and Xa
-Clearance is dose-dependent bc plasma levels inc considerably once binding sites are saturated
-PTT 1.5-2.5 x normal
-Contraindicated in pts with bleeding disorders (hemophilia, thrombocytopenia), advanced liver or kidneyd isease, severe htn, active TB
-Lack of placental transfer, so good in pregnancy
-AE: bleeding, osteoporosis in long term therapy, allergic rxn since animal product

17

HIT

heparin induced thrombocytopenia; IgG against Hep-PF4

18

Antidote to standard hep

Protamine sulfate, binds to heparin (anion-cation interaction)
-Not as capable in reversing LMWH

19

LMWH

-Dose independent pharmacokinetics
-Subq, no monitoring needed
-Contraindicated in HIT
-Not reversed with protamine sulfate
-Monitored by anti-Xa activity assay

20

Fondaparinux

-Synthetic pentasaccharide anticoagulant
-No effect on thrombin (IIa)
-ATIII mediated selective inh of factor Xa
-Subq, once daily dosing bc elim half life is 18 hrs
-PE, DVT, venous thromboembolism prophylaxis

21

Warfarin

-Low volume of distribution bc of extensive plasma protein binding
-Long 1/2 life
-Metabolized to inactive by CYP2C(- drug interactions)
-Target vitamin K epoxide reductase (mutations)
-Slow onset
-Arterial and venous thrombi
-Prevent blood clots in pts with chronic afib
-Prolong PT
-AE: fatal bleeding in brain, stomach, intestine, pericardium
-Contra in pregnancy, teratogen, liver disease, bleeding disorders
-

22

Antidote to warfarin

-Vitamin K, FFP, Factor IX

23

Warfarin drug interactions that diminish response

-Drug drug interactions- cholestyramine, anticonvulsants (barbiturates, phenytoin, rifampin, st john's wort), diet (inc vit K will out compete warfarin), estrogens

24

Warfarin drugs that enhance response

-Displacement from plasma albumin- sulfonamides- more will reach liver and reach target
-Amiodarone, allopurinol, cipro, erythromycin
-Broad spectrum abx which will reduce vit K (less competition)

25

Hirudin

-Specific thrombin inhibitor from leeches

26

Lepirudin

Recomb yeast form of hirudin
-Anticoag in pts with HIT
-Can't use in pts with renal disease

27

Desirudin and bivalirudin

Recomb hirudin analog
Direct thrombin inh

28

Argatroban

2nd agent approved from HIT (1st is lepirudin)
-IV, anticoag it pts with HIT or at risk for HIT
-Cleared by liver and can be used in pts with end-stage renal disease

29

Dabigatram

Pradaxa
-Oral direct thrombin inhibitor
-Afib, DVT, PE
Excreted inurine
-Limited need for monitoring

30

Rivaroxaban

Xarelto
-FXa inhibitor
Oral, variable F
-Inactivated by CYP3A4/5
-Excreted in urine and feces

31

Apixaban

Eliquis
Fxa inhibitor
-Bioavailability 50%
-Excreted in urine and feces

32

Praxbind

Reversal agent for Pradaxa (Dabigatram)

33

Thrombolytics

Lyse by catalyzing formation of plasmin from plasminogen
-Circulating antiplasmin precludes possibility of using plasmin itself
-Thrombolytics convert plasminogen to plasmin inside thrombus
-Should be followed with anticoag therapy with heparin, then warfarin

34

Streptokinase

-Produced by Group c beta-hemolytic streptococci
-Activator complex with plasminogen that results in formation of plasmin
-Plasmin degrades fibrin, fibrinogen, Factors V and VIII
-hsn to streptokinase may occur

35

Urokinase

Parenteral thrombolytic agent from human cultured kidney cells
-Lysis of coronary artery thrombi
-Hsn less frequent than with strepokinase

36

Alteplase

-t-PA biosynthetic recombinant form
-More exp than streptokinase
-no hypersenstivity

37

Reteplase

-Longer 1/2 life than alteplase

38

-Tenecteplase

-Prolonged half life than alteplase, increased specificity for fibrin, inc resistance to PAI-1

39

Vitamin K

-Reqd for y-carboxylation of glutamade residues in prothrombin, factors VII, IX, X
-Treats warfarin excess and vit K def

40

Plasma fractions/ clotting factors

-tx hemophilia
-Threat of AIDs and viral hepatitis
-Recombinant factors preferred

41

Fibrinolytic inhibitors

-Aminocaproic acid treats hyperfibrinolysis, bleeding assoc with neoplastic disease, bleeding following cardiac surgery