Pharm - Anticoagulants

Question 1

Unfractionated Heparin

Mech, Route, TDM, +/-

Answer 1

M: binds AT, 1:1 AT:anti-FXa activity
R: inactivated in gut, must be IV, sc, sublingual
TDM: variable t1/2 in ppl, monitor with aPPT
+: immediate effect, good use in low-risk patients, reversed by PROTAMINE
-: bleeding risk (Cullen’s sign - periumbilical; Turner’s sign - flank), thrombocytopenia with thrombosis due to UH antibodies agglutinating platelets, osteoporosis (more bone resorption and less bone formation)

Question 2

LMWH

Mech, Route, +/-

Answer 2

Dalteparin, Enoxaparin, Tinzaparin
M: binds AT, 3:1 anti-FXa:AT activity due to smaller size
R: all sc (better absorption than UH)
+: no TDM necessary, more predictable, GOOD for DVT/PE, no thrombocytopenia or osteoporosis adverse rxns
-: Expensive, adverse rxn of bleeding/bruising

Question 3

Penta H

Mech, Route, +/-

Answer 3

Fondaparinux (Arixtra)
M: ultimate LMWH - only anti-FXa activity
R: once daily sc injection (long half life - may be bad if adverse rxns occur)
+: minimal platelet interaction, as effective as LMWH prophylaxis, equal to IV UH in efficacy for PE
-: not effective for pts with prosthetic devices, contraindicated in renal failure & low body weight bc eliminated ONLY KIDNEY, no reversal agent

Question 4

Warfarin

Mech, Interactions, TDM, Adverse Rxns

Answer 4

M: inhibits VKOR, can’t get clotting factors to bind charged phospholipids on membranes to assemble - affects FVII, IX, X, prothrombin (slow acting, requires 5 days to achieve therapeutic effect)
I: CYP2C19 metabolism, enhanced by antibiotics, cardiac meds, anti-inflammatories, GI meds, Ginkgo, St. Johns Wort, Garlic; reduced by ABx, anticonvulsants
TDM: INR: ratio of pt’s PT to control PT, raised to ISI - normalizes by thromboplastin reagent, needs TDM due to CYP2C9 polymorphisms, changes with age, changes b/w diet of vitamin K, VKOR mutations
Adverse Rxns: bleeding, teratogenic, necrosis/gangrene (inhibits anticoagulants to also cause thrombosis)

Question 5

DOACs

Mech, Indications, Contraindications, Reversal Agents, +, Interactions

Answer 5

Apixaban, Edoxaban, Rivaroxaban, Betrixaban, Dabigatran
M: small mLc inhibitors of FXa (Apixaban - Eliquis, -xabans) or Thrombin (Dabigatran)
Ind: AFib (all except betrixaban), CV events, acute DVT/PE, VTE
CI: prosthetic heart valves
RA: Andexanet (-xabans), Idarvcizumab (Dabigatran) - EXPENSIVE and thrombosis risk
+: no TDM, quick action, low interactions, less bleeding
I: drugs affecting PGP or CYP3A4

Question 6

Direct Thrombin Inhibitors

Mech, Use

Answer 6

Dabigatran + Argatroban: block only thrombin’s active site pocket, prolongs PT time, no cofactor needed
Desirudin + Bivalirudin: blocks thrombin active site pocket and fibrinogen binding exosite
Desirudin: prevention of DVT/PE post-hip surgery
Bivalirudin: shorter half life, used in coronary interventions