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pharmacology
anticogulants
72
Medical
Graduate
12/11/2007

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Term
the four major components of the normal hemostatic system
Definition
vessel wall
platelets
the coagulation system
the fibrolytic system
Term
vessel wall response to injury
Definition
vasoconstriction,
formation of platelet plugs,
regulation of coagulation and fibrynolysis
Term
platelets response to vascular injury:
Definition
adhesion
aggregation
secretion
elaboration of procoagulant effects
Term
hemostasis
Definition
spontaneous arrest of blooding from damaged blood vessels
Term
How does the endothelial cell regulate clotting-3 factors?
Definition
vonWillebrands factor-procoagulant molecules and anticoagulant proteins such as tissue plasminogen activator(TPA) are secreted.
prostaglandins such as prostacycline inhibit platelet aggregation, but thromboxane A2 promotes aggregation.
Thrombomodulin reacts with thrombin to activate protein C and S->inhibit coagulation cascade.
Term
fibrinolytic system does what?
Definition
dissolves the clott to restore blood flow
Term
coagulation system does what?
Definition
forms a fibrin clot-fibrinogen cleavesd by thrombin to form mesh
Term
how is thrombin generated?
Definition
by both intrinsic and extrinsic pathways
Term
extrinsic system activated when factor VII comes in contact with tisue factor.
found where?
Definition
brain, lungs,kidneys, liver
Term
intrinsic system-proteins for coagulation found where?
Definition
are all present in the circulation. Contact by factor XII with the subendothelial wall initiates intrinsic
Term
Warfarin effects?
Definition
protein C and S which are Vit K dependendent proteins that inactivate factors V and VIII of the clotting cascade.
Term
common lab tests used to screen coagulation disorders?
Definition
platelet function study-
PT-prothrombin time
aPTT-activated partial thromboplastin time
TT-thrombin time
platelet count
Term
PT used to monitor?
Definition
measure Vit K dependent factors-VII.
synthitic capacity of the liver
vitamin K absorption,
inhibition of clotting factor synthesis of Warfarin
Term
platlet function study?
Definition
with normal platelet count-> thrombocytopathy.
-possible VonWillebrans Ds.
-ASA ingestion
uremia or dysproteinemia
Term
aPTT?
Definition
measures intrinsic and common pathways.
time to form clot after Ca and activating agent put in plasma.
monitors Heparing, leparubin
Term
thrombin time?
Definition
time for the formation and appearance of the fibrin clot.
monitors systemic fibrolytic therapy-ie:quality of the fibrinogen
Term
heparin and LMWH (low molecualr wt)
Definition
used when rapid anticoagulant effect is required. IV-onset immediate.
-prevents venous thromboembolism and PE, used for unstable engina, acute MI,
with CABG, vascular, or angioplasty, and select pt with DIC.
Term
Heparing mechanism of action?
Definition
requires antithrombin (AT)
binds to AT and changes AT from slow thrombin inhibitor to rapind inhibitor of thrombin & factor Xa-common pathway.
-inactivates coagulation enzymes ie:thrombin IIa, factors Xa, IXa, XIa, and XIIa. XA most inhibition.
LMWH doesn't bind at same time with AT and thrombin-able to inhibit thrombin
Term
drawback of heparin use?
Definition
decreased activity of AT (antithrombin) by 1/3 may lead to increased thrombosis.
with heparing resistance due to deficiency of AT, give FFP to promote anticoagulation from heparin
Term
heparin properties?
Definition
not very predictible because only 1/3 has anticoagulation effects. Size of molecule varies, heterogeneous
Term
heparing kinetics?
Definition
given SC or IV.
binds to plasma proteins which can require higher doses esp w/PE.
More predictible when given IV.
Has non-linear effects r/t doses.
SC onset-20 min. doesnt cross placenta.
appears in breast milk.
does not lyse established thrombi!
Term
heparin half life affected by?
Definition
obesity, renal fx, hepatic fx, malignancy, presence of PE and infection
Term
heparing warnings and precautions?
Definition
risk for bleeding-ulcers, menstration, severe renal,hepatic,or biliary dx.
use w/caution with white clot syndrome-(new thrombus r/t thrombocytopenia and hep resistance (HIT),
pts >60, esp women, more bleeding prob
Term
PTT measured when after heparin?
Definition
baseline and Q6 hrs, IV for steady state
Term
what to monitor when using heparin?
Definition
PTT, platelet count, hgb, hct, signs of bleeding.
Term
reversal of heparin?
Definition
protamine-binds heparin to state that has no anticoagulation effects. Given at 1.3 mg/kg for each 100u of Hep.
Term
cautions with protemine?
Definition
rapid IV inj-histamine release-> flushing, tachy, hypotension.Give over 5 min.
Rare-pulmonary vasoconstriction leading to pulmonary HTN, and bronchoconstriction-pretreat with ASA of NSAID to blunt effect.
allergic rx more common w/diabetics or allergies to fish
Term
Side effects of Heparin?
Definition
fever, chills, HA, ^K+ r/t decreased aldosterone, osteoporosis w/long term use. ^LFTs, anaphalaxis.
HIT, bleeding.
don't use prior to eye or cranial surg or placement of epidural->hematoma
Term
compare thrombocytopenia and HIT-heparin induced thrombocytopenia.
Definition
Normal-platelet count <100,000 r/t induced platelet aggregation. occurs 3-15 days after treatment-transient-stablizes in 4 days of D/C hep.
HIT-more severe and life-threatening. Occurs in 0.5-6% of pts. on day 6 of tx. platelets <50,000 and develope hypercoaguable state resistant to hep.
Pts develope HITT-thrombotic disease.
develop anti-platelet assc antibodies.
IgG mediated-immune response.
Term
treastment of H.I.T.
Definition
leparudin or argatroban(esp.w/renal pt)
treat until platelets >100,000.
do not use Warfarin(gangrene)or LMWH.
Do not give transusions for tx of HIT.
start warfaring once platelets ^.
Term
Heparin drug interactions?
Definition
NTG decreases effects,
increased cephalosporins, PCN may increase bleeding time, thrombolytics increase risk of hemorrhage.
Term
LMWH-low molecular weight heparin
Definition
heparin broke into small pieces.
less ginding to circulating proteins resulting in better bioavailability and a longer half life. More predictible anticoagulation and longer duration of action that UFH.
Can't bind w/thrombin and antithrombin III at same time. Works by inhibiting Factor Xa.
Term
LMWH-monitoring and excretion.
Definition
cleared by renal route-prolong with renal failure-^risk of bleeding.
Monitoring, ie: PTT not needed unless in renal failure or morbidly obese.
Term
Benefits of LMWH?
Definition
convenient, long 1/2 life=less frequent dosing.useful-DVT prophylaxis
less incidence of HIT and osteoporosis
Term
LMWH and orthopedic surgery.
Definition
1st dose 12-24 after surg.safer after epidural removed.Remove 8 hours after last injection of LMWH.
Avoid with NSAIDS (toradol)
Term
Names of LMWH? (#3)
Definition
daltaperin,
enoxaparin,
tinaparin
Term
fondaparinux
Definition
Selective Factor Xa inhibitor.
Indications:DVT prophylaxis after hip or knee surg.
Term
contraindications for fondaparinex?
Definition
active bleeding, CC<30, Wt <50kg, bacterial endocarditis, low platelets from antiplatelet antibodies, indwelling epidural,
Caution: renal insufficiency, uncontrolled HTN, bleeding tendancies, Hx of GI bleed, hemorrhagic stroke, HIT, elderly.
Term
Lepirudin
Definition
made from leech saliva! Irreversibly complexes with thrombin-therefore no antidote available. Use FFP if bleeding occurs.
Term
direct thrombin inhibitors (lepirudin, argatroban, bivalirudin) advantages over heparin?
Definition
inhibits thrombin that is bound to fibrin or fibrin degredation products.
more predictable anticoagulation response.
Not neutralized by Factor 4 (highly cationic, heparin binding protein released by platelets)
Term
Argatroban
Definition
selective thrombin inhibitor that binds directly to thrombin.
Tx HIT, IV infusion.
safer for renal insufficiency.
Monitor aPTT.
Can falsely elevate INR-should be >4
Term
Bivalirudin
Definition
directly,reversibly inhibits thrombin.
Used with glycoprotein IIb/IIIa inhibitor with cardiac cath.
Use with hx if HIT. Caution with active bleeding and renal disease
Term
Warfarin? Where it works and onset?
Definition
interferes with the conversion of Vitamin K therefore inhibits cofactors II, VII, IX, and X. Racemic mixture. Onset-36-72 hours, peak 5-7 days, metabolized in the liver.
Highly protein bound to albumin.
Term
Test to monitor warfarin?
Definition
INR-goal 2.0-3.0, 2.5-3.5 for mechanical or prosthetic valves.
PT 1.5-2 times normal.
hematocrit.
signs of bleeding.
Term
Warfarin warnings/precautions?
Definition
stop 3 days prior to invasive surgery.
check PT/INR prior to surg.
Many drug interactions-ASA, NSAIDS, high dose PCN,& moxolactams^bleeding
drugs that induce or inhibit liver metabolism can effect response to warfarin.
Term
warfarin dose decreased for?
Definition
elderly, impaired nutritional status, liver disease, high risk of bleeding
Term
Warfarin therapy-INR >5.0 but <9.0?
Definition
omit 1-2 doses, monitor INR more frequently and resume at lower dose.
Can give 1-2.5 mg Vit K po, or faster decrease give 2-4 mg Vit K, if not down in 24 hrs, repeat 2 mg po
Term
Warfarin therapy-INR >5 but <9-no significant bleeding
Definition
omit 1-2 doses,monitor frequently, resume at lower dose, give vit K 1-2.5 mg po if risk of bleeding, More rapid decrease in INR give 2-4 mg VIT K, if not down in 24 hours, 2 mg Vit K po
Term
Warfaring therapy-INR >9, no significant bleeding.
Definition
Hold warfarin, give 3-5 mg Vit K to lower in 24-48 hours, monitor Vit K more frequently, give more Vit K. resume therapy at lower dose.
Term
Warafrin therapy- INR >20 with significant bleeding.
Definition
Hold warfarin, give 10 mg slow IVP, Give FFP, Repeat Vit K Q12hrs.
If ever any bleeding-give 10 mg Vit K
Term
For life threatening bleeding give?
Definition
Give Prothrombin complex concentrate, VIT K 10 mg IV, FFP, repeat.
Term
Warfarin prior to invasive procedures?
Definition
If low risk of thromboembolism (No DVT x 3 months, a-fib without Hx of CVA) hold for 4 days prior to surg, INR to norm., post-op prophylaxis-give low dose Heparin concurrently with starting warfarn therapy
Term
Pts with intermediate risk of thromboembolism prior to surgery?
Definition
Stop Warfarin 4 days prior. cover with Heparin 5000u SC 2 days prior or LMWH, post-op give low dose or LMWH and warfarin.
Term
Pts w/high risk of thromboembolism (a-fib with Hx of CVA, heart valves, <3 months DVT) prior to surg?
Definition
Stop warfarin 4 days prior to surg. Inr to norm., cover with full dose heparin 2 days prior to surg, SC for outpatient, IV for inpatient, stop IV heparin 5 hours prior to surg,SC 12-24 hrs prior.
Term
Pts with low risk of bleeding on Warfarin therapy. Rx prior to surg?
Definition
Cont. warfarin at lower dose to INR of 1.3-1.5 for gyno or ortho surgeries.
Lower dose 4-5 days prior to surg, re-start post-op, supplement with low dose Heparin if necessary.
Term
ASA-how does it work?
Definition
Causes irreversible inhibition of platelet cyclooxygenase, which prevents the formation of thromboxane A2, a potent platelet aggregant and vasoconstrictor. Effect lasts the lifetime of the platelet.
Term
ASA dose for acute coronary syndrome?
Definition
160-325 mg chew and swalllow even if CP persists after 3 doses of NTG. Accounts for 20% decrease in vascular deaths. Daily use can decrease mortality in pts with hx of acute MI by 21%.
Term
Clopidogrel-how does it work?
Definition
thienopyridine that impedes platelet activation and subsequent aggregation by blocking adenosine diphosphate receptors on platelet cells. This effect hinders glycoprotein IIb/IIIa receptors that are necessary for aggregation. Used with PTCA. Indicated for pts who benefit from antiplatelet therapy,but are sensitive to ASA. Less severe and
Term
ticlopidine-how does it work?
Definition
platelet aggregation inhibitor used for tx of ischemic heart disease for pts having PTCA.
Term
ticlopidine-side effects and precautions?
Definition
can cause neutropenis-get CBC Q2wks for 1st 3 months of therapy.
D/C if ANC <1200. Also monitor LFTs.
D/C tx 10-14 days prior to elective surgery.
Term
Glycoprotein IIb/IIIa inhibitors?
Definition
Abcixamab and eptifbatide.
Used with unstable angina, with thromolytics after PTCA.
Block final common pathway of platelet aggregation regardless of the initiating stimuli.
Term
Glycoprotein IIb/IIIA inhibitors-contraindicaation?
Definition
Active or recent GI or GU bleeding, recent trauma or surg.(within 6 wks), Hx of CVA within 2 years w/neurological defecit,bleeding diathesis or anticoagulant therapy with in 7 days unless PT <1.2Xnorm. Platelet count <100,000, cerebral tumor, AVM or aneurysm, Severe HTN, use of Dextran prior to PTCA, Hx of vasculitis, <75kg, >65 yo, Hx of GI disease
Term
Glycoprotein IIb/IIIa inhibitors use and treatment recomendations?
Definition
Given IV bolus then infusion. For ACS given with ASA, heparin, or clopidegrel. Major risk of bleeding and thrombocytopenia-1-2% will developplatelet count <50,000. Can be seen within the 2nd hr of admin. therefore draw count 2-4 hours after initialting abcixamab. Give platelets if thrombocytopenia or bleeding developes.
Term
Thrombolytics-how they work? name 1st (direct) and 2nd generation (indirect)
Definition
They convert plasminogen to plasmin that degrades fibrin mesh.(plasminogen activators)
Direct: streptokinase & anistreplase.
Indirect: alteplase, retaplase, tenecteplase, and lanoteplase.
Term
Streptokinase?
Definition
Indirect fibrinolytic agent. Depletes fibrogen abd Factors V and VIII. This "lytic" state make pt hypocoagulable to prevent rethrombosis.
may lead to antistreptococcal antibodies, therefore should not be used more than 1X/yr. Causes hypotension in >10% of patients.
<1% serious bleed.
Term
Anistreplase?
Definition
Modified streptokinase molecule,, longer half-life allows single bolus dosing. Genetic profile same, but more expensive.
Term
Altepase-description.
Definition
direct acting, naturally occuring plasminogen activator.It is not antigenic and does not cause allergic reactions. More fibrin specific than streptokinase, but can still lead to mild fibrinogen depletion. Lyses more highly cross-linked fibrin-able to break up long standing clots!
Term
Reteplase-describe.
Definition
Direct acting thrombolytic. Half life is 2X alteplase, permits double bolus dosing 10-30 min apart. Fibrinogen depletion >alteplase, but
Term
Tenecteplase-describe.
Definition
direct acting thrombolytic. longer half-life that others so allows for single bolus dosing. More fibrin specific than alteplase and has ^ resistance to plasminogenactivator inhibitors-1.
Term
Alteplase indications.
Definition
AMI for the lysis of thrombin in coronary arteries..
Acute massive PE in adults.
Acute ischemic stroke.
Unlabled use-peripheral arterial thrombi and central line clearance.
Term
accp 1998 CONTRAINDICATIONS for thrombolytic therapy-absolute.
Definition
aortic dissection, acute pericarditis, active bleeding, previous cerebral bleed, cerebral aneurysm, neoplasm or AVM,
Term
ACCP 1998 contraindications for thrombolytic therapy-relative.
Definition
nonhemorrhagic stroke, GI or GU bleeding in past 6 months, Major surgery, organ biopsy, puncture of non-compressible vessel, prolonged CPR with chest trauma or unconscious. Major trauma within 2-4-wks,severe HTN, Hx of bleeding diathesis, hepatic dysfunction, CA, and pregnancy. Diabetic retinopathy and menstration are NOT contraindications.
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