Anticoagulants Flashcards
Heparin works on which pathway
-Extrinsic pathway (TF, binds to AntiThrombin III)
-HETEROGENOUS mix of polysach’s (pentasach), Unfractionated (short and long sachs)
-binds to Antithrombin III and activates it (ATIII is a natural inhibitor of coagulation cascade) (1000x)
- mainly affects Xa ! (converts prothrombin to thrombin) and THROMBIN ! (converts fibrinogen to fibrin)
- also affects 9a, 11a, and 12a
- Hep is active after releasing from inactivated clotting factor)
-
Heparin works by binding to
Antithrombin III (AT III) which is part of EXTRINSIC pathway
Heparin indications
- Anticoag in surgeries, IV catheters (only used in hospitals bc of hematoma - swelling of clotted blood within tissue?)
- prophylaxis ag thrombosis (DVT or PE) ( isn’t heparin used only in hospitals and warfarin is profilaxis?)
Pharm:
ONLY IV
ONSET OF ACTION IS IMM (bc antithrombin III is already there)
Heparin SE
HEMORRAGE: antidote: PROTAMINE SULFATE (binds heparin)
HEPARIN-INDUCED THROMBOCYTOPENIA (HIT): autoimmune response to plts due to AB crosslinkiing - get hypercoagulation and die bc of DIC (?)::::::: NEVER USE HEP AGAIN
CI:
RENAL OR HEPATIC DZ
DO NOT USE in bleeding pts, hemophilia, hypersensitivity, during or aftr surgery of the brain, spinal cord or eye
EnoXaparin = low molecular wgt (LMW) heparin
FondaParinux = synthetic pentasacch
Both similar to heparin except
action more specific against FACTOR Xa
CAN BE INJECTED SUBQ (NOT JUST IV) bc smaller in size (big diff’ce!)
- USED IN PREGS to replace warfarin
LOWER HIT (HEP INDUCED THROMBOCYTOPENIA), but still can’t use it if ever had!
ANTIDOTE PROTAMINE SULFATE doesn’t work as well as on hep and NO EFFECT at all on fondaparinux!
Lepirudin
is made from leeches
DIRECT INHIBITO OF THROMBIN (very specific), doesn’t require AT III
Alternative to those who have HIT (Hep induced thrombocytopenia)
IV only
cleared by KIDNEY (dont’ use if kid prob - use argatroban instead)
hypersensitivity (40%)
Which drugs are given as an alternative to Heparin in those who have HIT?
Lepirudin (for pts with liver dz cz its cleared by kid)
Argatroban (for pts with kid dz bc it’s cleared by liver)
Argatroban
- DIRECT INHIBITOR OF THROMBIN
- also given as an alternative to HIT with hepartin in ppl who have kid problems
- cleared by LIVER (so can use in pts with kid problems but use Lepirudin in pts with liver issues)
- continuous IV infusion
Dabigatran
ORAL DIRECT INHIBITOR OF THROMBIN
- prevention of stroke in pts with non-valvular AFib
- has PREDICTABLE ACTOCOAGULANT EFFECTS, not monitored by PTT.
- cleared by kid
BLACKBOX: Avoid ABRUPT Discontinuation without alternative anticoag immediately (warfarin stays in the system for a few days but not dabigatran)
Rivaroxaban (Xarelto), Apixaban (Eliquis)
- ORAL inh of FACTOR Xa (prothrombin to thrombin) !
- Riva - approved for DVT, PE and FUTURE CLOTS
- APi - more limited
- rapid onset
- part cleared by kidney (adjust dose with kdi dz)
- can’t use in kid dz (GFR <30), liver dz
Warfarin
- inh reduction of vit K (reduced K needed for carboxylation of prothrombin)
- interferes with SYNTHESIS of 2, 7, 9, X, protein C and S
- takes time before onset of effect (bc synthesis takes time) and effect lasts 4-5 days
- -TONS of drug interactions
- -MONITOR BY INR (2-3)
- -MANY CONDITIONS AFFECT IT
Warfarin indications, pharm, SE, CI
-CHRONIC ADMINISTRATION - ORAL (titrate over 1 wk, long plasma half life (36 hrs)
-PREVENT dev of emboli: used for DVT, Thromboembolism
-NO effrect on existing thrombi
SE:
-HEMORRHAGE, ESP INTO BOWEL !!!
-ANTIDOTES:
VIT K if dc warfarin (takes time, not acute)
FRESH FROZEN PLASMA = IMMEDIATE
-REDUCES PROTEIN C (anticoag with short 1/2 life) so at first get pro-coag effect instead of anticoag (high chance of warfarin-induced thrombosis) -> CUTANEOUSE NECROSIS AND INFARCTION
——must co-admin with HEPARIN for first 5 days——-
antidotes for warfarin and heparin
Heparin: Protamin Sulfate
warfarin: vit K(long) and fresh frozen plasma (immediate)
warfarin CI
- PREGS (CAT X) (crosses placenta)
- ———LOTS OF DRUG INTERACTIONS:
- ABX lower VIT K - increases warfarin effect
- birth control/increased estrogen/pregs - decrease CLOTTING FACTORS
- aspirin, NSAIDS: PLT AGGREGATION/FUNCTION
- INHIBIT MICROSOMAL LIVER ENZYMES
- INDUCE LIVER MICROSOMAL LIVER ENZYMES
Thrombolytics: AltePlase (tissue plasminogen activator or t-PA), RetePlase, TenectePlase
MOA:
! convert plasminogen to plasmin (internal plasmin is protected -> lyses thrombus from within)
Indications:
-lysis of clots (doesn’t prevent clots) - re-establish tissue perfusion post MI (orig used for strokes but
-severe PE, DVT adn arterial thrombosis
-IV or intra-arterial if needed
SE:
- serious BLEED (bc clot was stopping bleeding)
