Agents that affect the clotting system Flashcards
initial activation of platelets causes what?
platelet plugs
3 receptors on a platelet
thrombin
TXA2
ADP
which go on to further actuvate the platelet?
TXA2 and ADP
what inhibits platelet aggregation?
cAMP
what connects two platelets thus activating them?
fibrinogen
fibrinogen binds to what receptor on the platelet?
glycoprotein (GPllB/GPlllA) receptors
what is a clot mosty formed out of?
fibrin
all factors are circulating ______, when activated become ______
proteins,
proteolytic enzymes
all factors require _____ for synthesis?
vitamin K
clotting cascade main ion
Calcium
prothrombin ll —> _______
thrombin lla
thrombin lla does what?
activates platelets, factors Vll, Vlll, Xlll
converts fibrinogen to fibrin, and as we know fibrin forms clots
what stabilizes clots?
Xlll –> Xllla
to reverse clot formation
plasminogen –> plasmin –> clot lysis
to localize the clotting
antithrombin lll –> causes inactivation of thrombin, factors 9, 10, 11, 12
too much clotting called what?
thrombus
clotting in arteries?
called white thrombi- associated with artharosclerotic plaque
- platelets + fibrin strands
clotting in veins?
red thrombi, associated with pooling of blood in extremities.
rbc + fibrin
thromboembolus
piece of thrombus breaks off and travels through the blood stream
conditions for which anticoagulants are used?
- thromboembolic disease- prevents formation and extension of clots in venous system
- after most kinds of surgery
- during transfusions
- pt’s with heart disease- arrhythmias
thrombophlebitis
due to deep venous thrombosis
anticoagulants do what
prevent clot formation
what are some in vitro anticoagulants?
calcium chelators- citric acid, ETDA, EGTA,
all bind calcium, remove from cascade. DONT GIVE TO PEOPLE, they are in blood bags.
main anticoagulant
heparin
heparin properties and location
located in mast cells
strong negative charge
large polymers 3-30 kd
heparin physiological effects
inhibits clotting by activating lipoprotein lipases.
heparin mechanism of action
binds to antithrombin lll, and increases its affinity for clotting factors by 1000x at low dose. also inhibits factor Xa., thus decrease thrombin.
does heparin lyse existing clots?
no
how is heparin administered?
IV or sublig. too big to be absorbed by gut. also too big to be passed by placenta.
onset of action of heparin is what?
fast, t 1/2 = 1 hours.
heparin is degraded by what?
heparinsase.
overdose of heparin treated with what?
protamine sulfate
long term use of heparin causes what?
osteoporosis
thrombocytopenia (HIT)
hypersensitivity.
low molecular weight heparins
enoxaparin
dalteparin
fondaparinux
does heparin have a predictable dose response?
no
low molecular weight heparins
4-5 kd- still too big for oral longer t 1/2 though = 4 hours more effect on 10a less HIT, osteoporosis more predictable D-R
fondaparinux
t 1/2 = 17 hours
acts only on 10a,
given subling
SE of low molecular weight heparins
(more expensive)
not reversed by protamine
may cause spinal hematoma in pt’s who have had spinal tap or anesthesia
what is used when pt has heparin induced thrombocytomepnia (HIT)
leech hirudin anticoagulant analogs- inhibits thrombin
3 analogs of leech hirudin
BAD
bivalirudin
argatroban
desirudin.
main oral anticoagulant
warfarin
Mech of action of warfarin
inhibits an enzyme that recycles vitamin K. so you get a deficiency, vit. K is used to make many factors in the blood clotting cascade.
does warfarin break up existing clots or just prevents new ones?
prevents new ones from forming.
how long does it take warfarin to have an effect?
long time, t 1/2 life of factor X is 40 hours, prothrombin 60 hours
what do you have to worry about with taking warfarin?
any drug that effects P450 can effect concentrations (barbiturates induce P450) also monitor diet
can warfarin pass the placenta?
yes
anything that inhibits factors is a what
enzyme inhibitor
direct thrombin inhibitor
dabigatran
dabigatran
prodrug enzyme inhibitor direct inhibitor works fast. taken orally
dabigatran SE
hemorrhage
warfarin is a direct or indirect mechanism
indirect. induces vit K deficiency
Factor Xa inhibitors
rivaroxrudin
apixarudin
SE of factor Xa inhibitors
bleeding after spinal tap or spinal surgery
platelet inhibitors: thrombin receptor blocker
vorapaxar
contraindication of vorapaxar
pt’s with history of inter cranial bleeding.
platelet inhibitors: ADP inhibitors
TIC TIC CLO PRA ticlopidine ticagrelor clopidogrel prasugrel
side affect of ticlopidine
neutrapenia- low neutraphils
agranulocytosis
platelet inhibitors: fibrinogen receptor inhibitors
abciximab
tirofiban
eptifibatide
fibrinogen general mechanisms, all given how? and SE
prevent platelet aggregation
all IV
all cause thrombocytopenia (lots of platelets)
COX inhibitors
aspirin
COX mechanism of action
inhibits thromboxane All synthesis by
cyclooxygenase inhibitor….decrease in platelet aggregation
phosphodiesterase inhibitors
cilostazol
dipyridamole
phosphodiesterase inhibitors mech of action
inhibit enzyme that breaks down cAMP, so increase in CMP
platelet count reducer
anagrelide
anagrelide mech of action
decrease platelet formation, maturation, and number
contraindications for all anticoagulants
bleeding disorders
sever hypertension
after surgery on eye, brain, spinal cord
thrombolytic agents
streptokinase
urokinase
Tissue plasminogen activator (TPA)
all thrombolytic agents are what? and work how
enzymes
convert plasminogen to plasmin
what does plasmin do
hydrolyzes fibrin
how are thrombolytic agents given
IV
hemostatic agents
aminocaproic acid
tranexamic acid
aminocaproic acid
enzyme inhibitor
inhibits plasminogen activation
tranexamic acid
more potent that aminocaproic, same mech of action.
