Anticoagulants & Analgesics Flashcards
venous thromboembolism (VTE) - hereditary risk factors
*factor V Leiden mutation
*Protein C or S deficiency
*hyperhomocysteinemia
*prothrombin gene mutation
*decreased factor VIII levels
*dysfibroginemia
*antithrombin deficiency
venous thromboembolism (VTE) - acquired risk factors
*surgery
*trauma
*medical illness
*immobolization
*pregnancy
*contraception/HRT
*indwelling catheters
*malignancy
*air travel
venous thromboembolism (VTE) in malignancy
*key risk factor: HYPERCOAGULABILITY
-mucin production by adenocarcinomas
-tissue factor production
*risk is higher in certain tumor types: pancreatic cancer, lung cancer, breast cancer, CNS malignancies
4 classes of anticoagulants
- heparins
- vitamin K antagonists
- direct thrombin inhibitors
- factor Xa inhibitors
anticoagulant class: heparins - MOA
*activates antithrombin, which decreases action primarily of factors IIa (thrombin) and Xa
*has its predominant impact on the intrinsic pathway of the coagulation cascade
indications for heparin
*immediate anticoagulation for:
-VTE prophylaxis/treatment [pulmonary embolism, DVT]
-acute coronary syndrome
-MI
-percutaneous coronary intervention
heparins - ADEs
*heparin-induced thrombocytopenia (HIT)
*bleeding
note - monitor PTT of pts on heparin
what lab test should you monitor in patients on heparin
PTT
heparin-induced thrombocytopenia (HIT) - pathophysiology
*complication of therapy with heparins
*development of IgG antibodies against heparin-bound platelete factor 4:
-antibody-heparin-PF4 complex binds and activates platelets, leading to removal by splenic macrophages and therefore LOW PLATELET COUNTS
*tx - discontinue heparin and start an alternative anticoagulant
heparin-induced thrombocytopenia (HIT) - diagnosis
*serotonin release assay = diagnostic gold standard
*4T score: thrombocytopenia, timing of platelet fall coincides with heparin use, thrombosis, oTher causes (injury, fall, etc)
heparin-induced thrombocytopenia (HIT) - management
*stop all heparin products
*initiate therapy with alternative anticoagulant (bivalirudin, argatroban, fondaparinux)
*note - reexposure to heparin should be avoided
low molecular weight heparin - examples
*enoxaparin
*dalteparin
low molecular weight heparin - MOA
*activate antithrombin → act mainly on decreasing factor Xa
enoxaparin
*example of a low molecular weight heparin
*indications:
-VTE prophylaxis/treatment
-acute coronary syndrome
*ADEs: heparin-induced thrombocytopenia, bleeding
dalteparin
*example of low molecular weight heparin
*indications:
-VTE prophylaxis/treatment
-myocardial infarction
*ADEs: heparin-induced thrombocytopenia, bleeding
note - not as commonly used in the US
what is the reversal agent for heparin
PROTAMINE SULFATE
protamine sulfate
*reversal agent of heparin
*MOA: positively charged peptide that binds negatively charged heparin
*indications: unfractionated and low molecular weight heparin overdosage/associated hemorrhage
*ADEs:
-hypersensitivity
-pulmonary hypertension
-dyspnea
vitamin K antagonists (warfarin) - MOA
*inhibits vitamin K epoxide reductase
*inhibits vitamin K-dependent clotting factors: factors II, VII, IX, and X
*also inhibits proteins C and S (which are anticoagulants)
*has its predominant impact on the extrinsic pathway of the coagulation cascade
warfarin - MOA
vitamin K antagonist (inhibits vitamin K epoxide reductase → decreased production of factors II, VII, IX, and X and proteins C and S)
warfarin - indications
*VTE treatment
*chronic anticoagulation
warfarin - onset of action
*vitamin K inhibition: takes about 5 days
*HYPERcoagulability for 0-48 hours after 1st dose; therefore, you have to “bridge them”
what lab test should you monitor in patients on warfarin
PT/INR
INR monitoring for patients on warfarin
*goal of therapy = INR
*INR monitoring:
-weekly during initiation/major dose adjustment
-monthly during maintenance
warfarin drug-drug interactions
*CYP2C9 inhibitors/inducers (fluconazole, amiodarone, rifampin)
*chemotherapy agents (capecitabine, aprepitant)
*oral contraceptives
warfarin food interactions
*green, leafy veggies (kale, turnip greens, iceberg lettuce)
*cereal
*lamb
essentially, you would need to eat these regularly and in consistent amounts; if not, there will be INR fluctuations
warfarin ADEs
*teratogenic effects
*skin/tissue necrosis (due to hypercoagulable state)
*vasculitis
reversal of warfarin
*Vitamin K (slow reversal)
*Kcentra (rapid reversal):
-4 factor prothrombin complex
-ADEs: headache, N/V, arthralgia, hypotension, stroke, DVT,PE
examples of direct thrombin inhibitors
*bivalirudin
*argatroban
*dabigatraban
bivalirudin - MOA
*directly inhibits thrombin (factor IIa)
bivalirudin - indications & ADEs
*indications: percutaneous coronary intervention; treatment of HIT
*ADEs: back pain, bleeding
argatroban - MOA
*directly inhibits thrombin (factor IIa)
argatroban - indications & ADEs
*indications: percutaneous coronary intervention, treatment of HIT
*ADEs: hypotension, bleedingg
*note - with co-administration with warfarin, argatroban can cause artificially high INR but it is purely lab artifact