drugs affecting clotting

Question 1

Hemostasis
Primary-platelet aggregation
Secondary -fibrin clot development

Answer 1

-platelet aggregation
caused by products of endothelial destruction
ADP, collagen,thrombin,prostaglandins, and thromboxane A2

Question 2

Primary Hemostasis

Answer 2

plateletts become sticky and change shape with activation

Adherance to collagen and Von Willebrand Factor to form Plug in vessel (adhere to each other)

Question 3

Secondary Hemostasis

Answer 3

Intrinsic and extrinsic Pathways

Both Result in activation of factor X -Xa

Question 4

Secondary Hemostasis

Intrinsic path

Answer 4

Initiated in response to blood trauma or vessel damage
 Causes
   Smoking
   HTN
   Hypercholesterolemia
   Sickle cell

Question 5

Secondary Hemostasis

Extrinsic path

Answer 5

Activated by external trauma

Question 6

Clotting cascade **know
Factor Xa

Protein S and Protein C=SC complex
Factor 5A and 7A inactivates process.

Answer 6

converts inactive prothrombin to active thrombin ( to make clot)–thrombin cleaves fibrinogen –fibrin strands (active)–strands weave together to create a clot.

Question 7

clotting cascade

control mechanism 1

Answer 7

Mechanism I
Clotting limited to injured site by antithrombin III. Antithrombin II constantly in circulation. —–Antithrombin III binds thrombin and inactivates it–stopping the clotting cascade.

Question 8

clotting cascade

control mechanism 2

Answer 8

Mechanism 2

as the clot develops (evolving fibrin clot ) it traps fibrin—then it is used up after being trapped.

Question 9

clotting cascade

control mechanism 3

Answer 9

Mechanism 3
Endothelial cells in injured area secrete thrombomodulin—which complexes with thrombin–thrombomodulin/thrombin complex—-activates Protein C–complexes with protein S—s/c protein complex– 1 cleaves factor VA and VII A, inactivating them. 2. inactivates an inhibitor of tPA (which converts plasminogen to plasmin which lyses the clot)==inhiniting the inhibitor of tPA= more tPA=more plasmin=more clot breakdown. (TPA is given to breakdown clots

Question 10

Heparin

Standard of treatment

Answer 10

MOA
Potentiates the action of antithrombin III (binds and inactivates), >affinity of antithrombin III for thrombin by factor 1000, no thrombin available to cleave fibrinogen –inhibits clotting. (clotting cannot occur)-also inhibits factor 10A, 9A and 12A.

Question 11

Heparin Dosing
No PO administration (IV SC)

Antidote –Protamine sulfate
Monitoring lab– PTT

Answer 11

Isolated from bovine lung or porcine intestinal mucosa–> risk of auto immune (type II reaction)
1-2 hour half life
deficiency.
Poor results if pt has an antithrombin III
Genetics, liver cirrhosis

Question 12

Heparin SE

Answer 12

bleeding 
heparin induced thrombocytopenia- HIT
Interactions
  drugs that influence clottting (NSAIDS, ASA)
assess platelett and or H &H

Question 13

Low molecular weight Heparin

smaller molecules

Answer 13

Enoxaparin (lovenox) no epidural
Dalteparin (fragmin)

Inhibits factor Xa and Thrombin

Question 14

Low molecular weight Heparin

Advantages

Answer 14

less binding endothelial cells and plasma protein.-<drug interactions
greater bioavailability
dose dependent clearance
longer half life qd or bid dosing
no need for PTT monioring
Ease of administration SQ9 site rotation, no rubbing)
weight based dose

Question 15

Warfarin

Prevention

Answer 15

MOA
Blocks vitamin K medicated clot factors II (thrombin) VII, IX, and X—inhibits conversion of prothrombin to thrombin
Inhibits Protein C synthesis (anticoag)
highly protein bound—protein binding medication interactions.
Half life 42 hours.

Question 16

Warfarin Monitoring

Answer 16

PT/INR goal 2-3

Question 17

Warfarin indications

Heparin bridge tx until levels stabilize (takes 6 days to deplte clot factors)

Answer 17

prophylaxis and treatment of DVT
prophylaxis and tx of Afib with embolism
prophylaxis and tx of PE

Initail dose 5mg qd with diaily PT/INR x 7days
usual maintenannce dose 2-5 mg qd

Question 18

Warfarin adverse effects
Contraindicated in pregnancy (teratogen)

Multiple drug to drug interactions–Highly but weakly protein bound.
2C93A4

Answer 18

bleeding 
anorexia
N/V/D abdominal cramps
purple toe syndrome
skin necrosis  (+ heredity Protein C deficiency)
     check Protein C  prior to admin
changes r/t vitamin K status
careful with ASA and ETOH

Question 19

Platelett Inhibitor ASA
SE
GI bleeding hearing loss with OD, Reye syndrome, acidosis

Answer 19

MOA clotting inhibition
blocks change of arachindonic acid to PGG—-blocks inhibits cox 1/cox2(non selective NSAID)–blocks cellular mediators–thrombaxane A2, PG2—-decreased thromboxane release form plateletts—no stickiness of plateletts–no clotting for life of pltelett–more constant anticoag effect.

Question 20

Pradaxa direct thrombin inhibitor

uses non valvular Afib
*****>reflex clotting if stopped

Answer 20

store in original bottle

no antidote

Question 21

xarel

eloquist

Answer 21

Direct factor 10A inhibitors

Question 22

(Plavix) clopidogrel ADP inhibitor

Answer 22

Blocks ADP receptor on plateletts
blocks fibrinogen binding to site
half life 7-8 hours
75 mg qd

Question 23

plavix clopidogrel SE

interactions P4502c19enzyme
+prodrug metabolism is essential

common interactions
phenytoin/tamoxifen/warfarin/NSAIDS(select) and omeprazole

Answer 23

chest pain, edema, HTN, HA, Dizziness rash puritis, purpura, arthralgia and back pain, uRI cough
agranulocytosis/thrombocytopenia

Question 24

(Effient) Prasugrel

10 mg qd

Answer 24

> effectiveness over Plavix but >risk of bleeding
less dependent on metabolism
not indicated >75 yo/prior hx stroke/TIA