ANTICOAGULANTS, ANTIPLATELET, and FIBRINOLYTIC DRUGS Flashcards
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
10a i
apixaban PO
- indications
- ADRs
- DDIs
- indications: reduce stroke/embolism risk in afib pts
- ADRs: bleeding
- DDIs: CYP540 and p glycoprotein, other drugs that inc bleeding
10a i
apixaban
advantages: an use in pregnancy, less systemic bleeding than warfarin, no INR monitor, no renal dose adjustment
disadv: no antidote, BID bosing, dont use in Creatinine clearance<15 min
10a i
edoxaban
- indications
- ADRs
- DDI
- advantage/disadv
- indication: reduce stroke/embolism risk in nonvalvular afib, tx DVT and PE 5-10 days after initial tx w parenteral anticoag
- ADRs: bleeding, anemia, rash, abnormal LFTs
- DDIs: anticoag, antiplatelet, thrombolytics, SSRIs, SNRIs (all inc bleeding risk if used tog)
adv: QD dosing
disadv: no antidote
DOAC antidotes
10a and 2a
idarucizumab for dabigatran
andexanet for apixaban and rivaroxaban
ciraprantag- still being investigated for 10a and 2a for universal use
antiplatelet drugs
normal platelet aggregation
platelets adhere to damaged endothelium (1a and 1b glycoprotein receptors), synth and release mediators of aggregation (thomboxane A2/TXA2, ADPm and serotonin/5HT3
mediators inc expression of glycoportein receptors, promote aggregation via binding fibrinogen to 2b/2a receptors
antiplatelet
names
aspirin, dipyridamole, ticlopidine, clopidogrel, cilostazol, pentoxifylline, ticagrelor, cangrelor, glycoprotein 2b/2a inhibitors
antiplatelet
aspirin
- MOA
- indications
- ADRs
- MOA: inhibit prostaglandins (TXA2)
- indications: prevent arterial thrombosis pts w ischemic heart ds and stroke, unstable angina to prevent MI, post Mi thrombus prevention, etc
- ADRs: bleeding, GI irritation
more indications in chart
antiplatelet
dipyridamole + ASA
- MOA
- indication
- ADRs
- MOA: inhibit platelet aggregation
- indication: combo for secondary stroke prevention, IV for stress test to dilate coronary arteries
- ADRs: bleeding, angina, dyspnea, hypoten, HA, dizzy
antiplatelet
ticlodipine
- MOA
- ADR
- MOA: inhibit ADP
- ADRs: n/v/d, bone marrow suppression
antiplatelet
clopidogrel
- MOA
- indications
- ADRs
- DDI
- MOA: block ADP receptor
- indications: reduce MI, stroke, vasc death in atherosclerotic pts, PAD, prevent thromb after PCI, ACS
- ADRs: bleeding, GI, thrombocytopenia
- DDIs: PPIs
cilostazol
- MOA
- indications
- CI
- ADRs
- DDIs
- MOA: inhibit PDE3
- indications: add on tx for intermittent claudication
- CI: HF
- ADRs: dizzy, diarrhea, palpitations
- DDIs: ASA, coumadin, CYP450 substrate
pentoxifylline
MOA: alt RBC flexibility, dec blood viscosity
indication: IC
ADRs: dyspnea, n/v, HA
ticagrelor
- MOA
- pharm
- indications
- MOA - blocks platelet ADP P2Y12 receptor
- PHARM: Anticoagulants, Antiplatelets and Fibrinolytics
- Indications - ACS managed with PCI, combo w aspirin. dec risk Cv death, stroke and stent thrombosis
ticagrelor
- ADRs
- DDIs
- adv/disadv
ADRs – similar to clopidogrel.
- Others - bradycardia, dyspnea, and
gynecomastia in men
DDIs – CYP3A4 DDIs possible, but does not have CYP2C19 DDI that clopidogrel does
Advantage: Improved mortality rate compared to Plavix and Effient
Disadvantage: BID dosing. No generic available
cangrelor
- MOA
- ADRs
- DDIs
- adv/disadv
MOA - blocks platelet ADP P2Y12 receptor
indications - adjunct to (PCI) to reduce MI risk
ADRs – bleeding
DDIs – Do not administer with Clopidogrel or prasugrel (no antiplatelet
effect will be observed)
Advantage: IV
Disadvantage: IV. No generic available
