ANTICOAGULANTS, ANTIPLATELET, and FIBRINOLYTIC DRUGS Flashcards
(40 cards)
venous thromboembolism
- manifests 2 ways
- DVT (lower ext) and PE (complication of DVT, thrombus lodges in pulm artery)
- virchows triad (venous stasis, hypercoagulability vascular injury)
peripheral arterial ds
- what is it
- characteristics
- tx goals
- ds of atherosclerosis
- characteristic–> intermittent claudication (IC), pain at rest in lower ext
- tx: dec impairment caused by SS of IC, optimize comorbid ds states (HLD, HTN, DM)
clotting cascade
- intrinsic v. extrinsic pathway factors
- what are they activated by
- common pathway (where they meet)
intrinsic: factors 12, 11, 9
- activated by contact with factor 12 with exposed colalgen from damaged vessels
extrinsic: 3, 7
- activated by exposure of blood to tissue thromboplastin (released after vasc injury that activates factor 7 and 10)
common- 10, 5, 2, 1 (where they both cross and join)
factors that are vit K dependent
- what inhibits them
- half life
factor 2, 7, 9, 10
- inhibited by warfarin
- half life ranges from 6 hrs (factor 7) to 50 hrs (factor 2)
anticoagulants
- categories
coumadin derivatives, heparin, low molecular weight heparins, direct thrombin inhibitors, selective factor 10a inhibitors
anticoag
wafarin/coumadin
- MOA
-
- MOA: inhibit vit K dep factor synthesis
- indications: proph and tx for DVT, PE, stroke prevention pts w Afib and artifical heart valves, stroke and MI, proph embolism post MI
- CI: pregnancy, hemorrhagic tendencies, hemophilia, uncontroll/severe HTN, severe hepatic ds
anticoag
warfarin/coumadin
- half life
- metabolism
- dosing
half life of vit K dep clotting factors
- factor 7–> 6 hrs
- factor 2–> 50 hours
metabolism: CYP450 2C9 substrate
dosing: 5 mg x3days then check INR, overlap w heparin by 4-5 days once INR is therapeutic
anticoag
warfarin/coumadin
- monitoring goals
monitor PT and INR
- pt should be 1.3-1.5 times control
- INR goal 2-3, higher (3-4.5) for mechanic prosthetic valves
- monitor daily until 2 therapeutic INRs, 2-3x week for 1-2 weeks
monitor labs
- CBC
- SS of bleeding
anticoag
warfarin/coumadin
- ADRs
- DDI
- food-drug
- ADRs: bleeding, CNs, Gi, allergy, hepatic, SKIN NECROSIS, PURPLE TOE SYNDROME (3-8 wks after initiation, discoloration persists)
- DDI-
food drug:
- DEC effect of warfarin: vit K, high protein fad diets, alcohol, st johns wort and COQ10, grapefruit/cranberry/mango juice
- INC effect of warfarin: herb/alt meds (ginseng, gingko, garlic)
anticoag
wafarin/coumadin
- tx for overdose
- 4 options, INR for each?
discontinue, hold dose, or dec dose
- INR 3-5 no bleeding- omit 1 dose, resume w lower dose once INR approaches therapeutic range
- INR 5-9 no bleeding- omit 1-2 doses, resume at lower once INR reaches therapeutic, give vit K PO
phytonadione SC (vit K1)
- dose/duration depend on INR level and +/- bleeding
- give for 3 days to allow vit K to synth
phytonadion PO (vit K)
- use if INR inc but no significant bleeding
FFP, factor 9, or whole blood
- for significant bleeding or INR >20
anticoag
heparin (UFH)
- MOA
- indications
- CI
- MOA: inactivate thrombin (2a), other (9,10,11, 12), and fibrin (fibrinogen to fibrin)
- indications: tx and proph DVT & PE, unstable angina, acute MI, cardiac bypass, vasc surgery, angioplastly, stents, DIC
- CI: thrombocytopenia, uncontrolled bleeding
random fact- extracted from animal lung
anticoag
heparin
- ADRs
- tx for ADRs
- others
ADRs: bleeding (inc PTT), HIT, immune mediated HIT
- TYPE 1: HIT: 2-4 day onset, non immune, mild platelet reduction
- TYPE 2: immune HIT: 5-14 day onset, IgG mediated, severe platelet reduction (<100k) and thromboembolic complications (skin necrosis, PE, gangrene, stroke/MI)
tx: d/c heparin, use direct thrombin inhibitors (lepirudin or orgatroban) to tx underlying condition
OTHER ADRs
- GI, osteoporosis, hyperkalemia, local injx effects
anticoag
heparin
- pharmacokinetics (preferred route)
- monitoring
pharmacokinetics
- absorbed parenterally, NOT PO or IM
- IV and SC, short half life, instant onset IV, 1-2 hrs SC
- hepatic metabolism
monitor
- aPTT
- should be 1.5-2.5x patients baseline (normal is 30 seconds)
- monitor for SS of bleeding
anticoag
heparin
- DDIs
- Dosing (proph v. tx)
- tx for overdose
DDIs- inc risk of bleeding w other anticoag or ASA/clopidogrel, tetracycline, antihistamines, nictoine, digoxin (ALL inc heparin effect)
dosing: low dose prophylaxis 5000 units SC, tx IV dose
tx overdose: dc heparin, start protamine sulfate (inactive comlpex w heparin so antithrombin 3 cant be formed, immediate effect)
anticoag
low molecular weight heparins (LMWH)
- types
- MOA
- includes Dalteparin, exoaparin, and tinzaparin
- MOA: inactivate thrombin to lesser extent than UFH, enhance affinity to factor 10a
anticoag
LMWH
- indications
- monitor?
- tx overdose
- indications: prevent and tx DVT assoc w ORTHO and ABD surgery, PE, unstable angina, non Q wave MI
- better pharmacokinetics than UFH– LESS bleeding, dont need to monitor aPTT
- can use outpatient
- tx oversose- protamine
anticoag
direct thrombin inhibitors
- indication
- monitoring
- names
- indication: used in place of heparin in pt with HIT
- monitoring: creatinine, +/- aPTT
- types: hirudin, bivalirudin, lepirudin, argatroban, dabigatran
anticoag- direct thrombin inhibitors
hirudin, bivalirudin (indication), lepirudin, argatroban
give route
hiurdin: component of leech saliva
bivalirudin: synthetic derivative of hirudin, not for IM use, directly inhibits thrombin/little effect on bleeding time or platelets
- use with ASA for unstable angina undergoing PTCA
- lepirudin IV
- argatroban IV
anticoag- direct thrombin inhibitors
dabigatran
- indications
- ADRs
- DDIs
- indications: reduce stroke or syst embolism risk in pts w non valvular afib
- ADRs: bleeding, Gi bleed, GI effect
- DDIs: other drugs that cause bleeding
anticoag- direct thrombin inhibitors
dabigatran
- advantages and disadvantages
- antidote
- advantage: quick onset, reaches steady state in 2-3 days, np need to monitor PT/INR, less systemic and intracranial bleeds no hepatotox
- disadvantages: BID dosing, inc GI bleeds and GI effects, renal elimination
- antidote: idarucizumab
anticoag- factor xa inhibitors
factor 10a inhibitors
- names
fondaparinux, rivaroxaban, apixaban, edoxaban
anticoag- direct 10a i
fondaparinux
- indication
- route
- indications: prevent DVT in hip and knee replacement surgery
- NOT FOR IM USE
- only SC
may be more effective than LMWH
not yet FDA approved for dvt/pe tx
anitcoag- 10ai
rivaroxaban PO
- indications
- ADRs
- DDIs
- indications: reduce stroke/embolism risk in afib pts, prevent thrombosis post hip/knee surgery , DVT/PE tx and prevention
- ADRs: bleeding
- DDIs: CYP540 and p glycoprotein, other drugs that inc bleeding
10ai
rixaroxaban
- advantages and disadvantages
advantages: less systemic bleeding than warfarin, no INR monitoring
dis: no antidote, may need BID dosing, renal elimination, elderly/underweight pt susceptible to bleeding
