Drugs used in Coagulation Disorders Flashcards
Drugs used in clotting/bleeding disorders fall into two categories
- drugs used to decrease clotting or dissolve clots already present
- drugs used to increase clotting in patients at risk of a bleed
Anticoagulants are used for
- acute MI
- A-fib
- Ischemic stroke
- DVT
anticoag drugs and thromoboylitic drugs are effective againt
arterial and venous thrombi
antiplatelet drugs are used against
arterial thrombi only
List the categories of anticoagulants
heparins, direct thrombin inhibitors, direct Xa inhibitor, warfarin
name the thrombolytics
urokinase, TPA derivatives
name the antiplatlet drugs
aspirin, glycoprotein IIb/IIIa inh., ADP inihibitors, pde uptake inhibitors
dosage route of heparin
parenterally (IV or subQ)
dosage route of coumadin
oral
dosage route of thrombin/X inh
parenteral or oral
antidote to heparin
protamine
works well on unfract. hep, partially on LMWH and not at all on Fondaparinux
Advantages of LMWH
*more specific for ATIII and not II
greater F
longer duration
lower chance of HIT
example of a LMWH
enoxaparin sodium
heparin like products are measure
by APTT
APPT used to measure
effect of heparin and direct thrombin inhibitors
Antithrombin II inactivates
thrombin, X, 9, 11
Heparin MOA
increases ATIII’s activity by 1000 fold
GPIIb/IIIa is activated by
platelet release of ADP, TXA2, and serotonin–> cause upreg of GP2b3a on platelet surface
How does HIT happen
more common with unfractionated heparin–> IgG ab to PF4-Heparin complex–> results in marked thrombocytopenia
will APTT measure LMWH
no
Can heparin be used in pregnancy
yes–> does not cross placenta
Fondaparinux
mimics the bioactive pentasaccharide on heparin–> same effects, given sub Q once a day
onset of heparin
instant (minutes)
excretion of heparin
renal
choice anticoag during pregnancy
heparin
site of action for heparin
blood
site of action for coumadin
liver
onset of coumadin
slow–> days 10 mg 5 mg 5 mg–> then recheck INR–> decide what to do from there
protein C inhibits
factors 5 and 8
cleaved by thrombin
1, 5, 8, 11, 13
common uses of heaprin
ACUTE
PE, MI, DVT
prolonged use of unfractionated heparin is associated with
osteoporosis
inibited by heparin
11, 8, 5, *accoriding to the book
inhibited by coumadin
2, 7, 9, 10 c, s
Direct thrombin inhibitors
administered parenterally
Lepuridin
Desirudin
bivalirudin
argotroban
direct thrombin inhibitors
administered orally
Dabigatran
MOA of Lepuridin
bind simulatenously to the acitve site of thrombin and thrombin substrates
MOA of Argatroban
binds only the thrombin active site
reversal agents for dorect thrombin inhibitors and direct Xa inhibitors
none
Direct thrombin inhibitor that can also inhibit platelets
Bivalirudin
how do you monitor coumadin
PT–> turn it into INR
INR range for someone who needs coumadin
2-3
INR range for someone with persistent dvt
2.5-3.5
antidote for coumadin toxicity
vitamin K, FFP, prothombin complexes
MOAS for coumadin
inhibits Vitamin K epoxide reductase preventing Vit K from being replenished and therefore GAMMA carboxylation cannot occur for factors 2, 7, 9, 10 C or S
Direct Xa inhibitors
rivaroxaban
apixaban
do Direct Xa or Direct thrombin inhibitors require monitoring
no
preferred anticoagulant in pt.s with HIT
direct thrombin inhibitors
Rivaroxaban indication
pt.s undergoing hip/knee replacement and prevention of stroke for Afib pt.’s
Warfarin in the circulation
99% bound
*anything that causes it to come unbound will have a major impact
Warfarin broekn down in the liver by
CYP2C9
can coumadin be used in pregnant women
no
necrosis due to warfarin toxicity is due to
acute deficiency of factor C
inducers of CYP–> causing low coumadin and therefore hypercoaguability
rifampin, phenytoin, and barbituates
inhibitors of CYP causing warfarin to be too low–> blled risk
SSRI’s, cimetidine
explain INR
inr= patients test PT/ standard PT (12-13)
high INR=
pt is more anticoagulated than a “normal” person and at a risk for bleed *their pt is long=slow clot
low INR=
pt is hypercoagulated and at a risk thrombus
*their pt time is quick=fast clotter)
Thrombolytic agents
T-PA (alteplase)
streptokinase (protein made by streptococci)
Thrombolytic enzymes MOA’s
catalyze the cleavage of plasminogen to plasmin so it can cleave fibrin and free serum fibrinogen–> dissolving and preventing a clot
seletivity of TPa
only cleaves plasminogen when bound to fibrin (but selectivity is less than you would hope for)
streptokinase MOA
does not cleave plasminogen directly–>forms a complex with plasminogen and causes it to undergo conf. change where it is cleaved rapidly by normal TPA
does streptokinase show selectivity for fibrin
no
most important indication of thrombolytic agents
as an alternative to percuatenous coronary angioplasty in emergency tx of coronary artery thrombosis with 6 hours
- also Stroke if within 3 hours
- also severe PE
name the antiplasmin drugs
tranexamic acid and aminocaproic acid
side effect specific to streptokinase
those with prevoius infection to the bacteria may have ab’s specific for the drug–> immune response
major adverse event you’re concerned with about thrombolytic agents
cerebral hemorrhage and bleeding
how does PGI2 (prostacylin) inihibit platelet aggregation
increases cAMP which dereases free calcium levels–> this will inihibit platelet aggregation
Antipletelet drugs include
- aspirin and other NSADS (not tyelenol)
- GP2b3a inh, abciximab, tirofiban,
- ADP antagonists (clopidogrel)
- Phosphodiesterase inh. (dipyramidole)
dipyramidole MOA
prolong the platelet inhibiting action of cAMP by inhibiting phosphodesterase (which breaks down cAMP)–> Ca2+ stays low and pletelets dont aggregate
- increases cGMP levels–> a vasodilator
- inhibit the uptake of Adenosine–> increase plasma concentration of adenosine
Drug used to treat vitamin K deffieiency
phytonadione
most important agents to treat hemophillia A/B
FFP, and factor 8 (A), 9 (B)
increases plasma concentration of vWF
desmopressin and factor 8
when do you use desmopressin
hemophilia A or to prepare pt.’s non vW disease for elective surgery
antiplasmin agents do what
increas clotting for the prevention of acute bleeding apirsodes in patients with hemophillia and others with high risk of bleeding disorders
name he antiplasmin meds
aminocaproic acid and tranexamic acid
