drugs affecting clotting Flashcards
Hemostasis
Primary-platelet aggregation
Secondary -fibrin clot development
-platelet aggregation
caused by products of endothelial destruction
ADP, collagen,thrombin,prostaglandins, and thromboxane A2
Primary Hemostasis
plateletts become sticky and change shape with activation
Adherance to collagen and Von Willebrand Factor to form Plug in vessel (adhere to each other)
Secondary Hemostasis
Intrinsic and extrinsic Pathways
Both Result in activation of factor X -Xa
Secondary Hemostasis
Intrinsic path
Initiated in response to blood trauma or vessel damage Causes Smoking HTN Hypercholesterolemia Sickle cell
Secondary Hemostasis
Extrinsic path
Activated by external trauma
Clotting cascade **know
Factor Xa
Protein S and Protein C=SC complex
Factor 5A and 7A inactivates process.
converts inactive prothrombin to active thrombin ( to make clot)–thrombin cleaves fibrinogen –fibrin strands (active)–strands weave together to create a clot.
clotting cascade
control mechanism 1
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.
clotting cascade
control mechanism 2
Mechanism 2
as the clot develops (evolving fibrin clot ) it traps fibrin—then it is used up after being trapped.
clotting cascade
control mechanism 3
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
Heparin
Standard of treatment
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.
Heparin Dosing
No PO administration (IV SC)
Antidote –Protamine sulfate
Monitoring lab– PTT
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
Heparin SE
bleeding heparin induced thrombocytopenia- HIT Interactions drugs that influence clottting (NSAIDS, ASA) assess platelett and or H &H
Low molecular weight Heparin
smaller molecules
Enoxaparin (lovenox) no epidural
Dalteparin (fragmin)
Inhibits factor Xa and Thrombin
Low molecular weight Heparin
Advantages
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
Warfarin
Prevention
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.
Warfarin Monitoring
PT/INR goal 2-3
Warfarin indications
Heparin bridge tx until levels stabilize (takes 6 days to deplte clot factors)
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
Warfarin adverse effects
Contraindicated in pregnancy (teratogen)
Multiple drug to drug interactions–Highly but weakly protein bound.
2C93A4
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 ETOHPlatelett Inhibitor ASA
SE
GI bleeding hearing loss with OD, Reye syndrome, acidosis
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.
Pradaxa direct thrombin inhibitor
uses non valvular Afib
*****>reflex clotting if stopped
store in original bottle
no antidote
xarel
eloquist
Direct factor 10A inhibitors
(Plavix) clopidogrel ADP inhibitor
Blocks ADP receptor on plateletts
blocks fibrinogen binding to site
half life 7-8 hours
75 mg qd
plavix clopidogrel SE
interactions P4502c19enzyme
+prodrug metabolism is essential
common interactions
phenytoin/tamoxifen/warfarin/NSAIDS(select) and omeprazole
chest pain, edema, HTN, HA, Dizziness rash puritis, purpura, arthralgia and back pain, uRI cough
agranulocytosis/thrombocytopenia
(Effient) Prasugrel
10 mg qd
> effectiveness over Plavix but >risk of bleeding
less dependent on metabolism
not indicated >75 yo/prior hx stroke/TIA
