ANTICOAGULANTS

These are the agents used to prevent and treat:

 arterial thrombus (white in colour) like in myocardial infarction
 venous thrombosis of limb veins
Anticoagulants may be
A. In vivo heparin
 parenteral (heparin, LMWH, fondaparinux)
 oral (dicumarol, warfarin, rivaroxaban)
B. in vitro-heparin
 sodium citrate - sodium oxalate
Contraindications for anticoagulant therapy
 Ongoing bleeding
 recent surgery
 invasive procedure
 severe trauma
 bleeding tendency
 intracranial haemorrhage
 pericarditis
 pericardial effusion
 severe hypertension
 GIT ulcer
 piles
 ocular and neurosurgery
Heparin (Unfractionated)
pharmacokinetics
 It is a natural anticoagulant (mucopolysaccharide)
 Commercial heparin is derived from lung and intestinal
mucosa of pigs and cattle.
 It prevents clotting of blood both in vivo and in vitro by acting on
all three stages of coagulation
 It activates plasma antithrombin Ill and so blocks extrinsic
 Pathway
 It has got antiplatelet action
 The onset of action is immediate after administration lasting for 4
hours.
 It is metabolized in the liver by heparinase.
 It does not cross placental barrier and is not secreted in breast milk
monitoring
 clotting time
 activated thromboplastin time
side effects
 hyperkalaemia
 thrombocytopenia
 osteoporosis
Dose
1. prophylaxis
 5,000 units/subcutaneously 8th hourly.
2. therapy
 10,000 units/IV 8th hourly. later changed to s.c dose
Precautions
 Heparin is not given orally
 not given intramuscularly
 not combine with penicillin and hydrocortisone.
 Heparin should be monitored with APTT
 Heparinoid is an anticoagulant used in patients where heparin is
contraindicated
 Danaparoid is an antifactor Xa
Heparin antagonist
 protamine sulphate
 given slow intravenous
 1 g reverses 100 units of heparin.
 It is given only after doing activated thromboplastin time.
 Overdosing may itself precipitate bleeding.
Low Molecular Weight Heparin (LMWH)
  It is a commercially prepared heparin with a low molecular weight
 It acts by inhibiting factor Xa.
 It shows lesser antiplatelet action
 lower incidence of hemorrhagic complications.
 It has got better bioavailability on s.c administration (once daily).
Drugs
Enoxaparin; Dalteparin; Parnaparin; Reviparin; Fraxiparine.
route
It is used as subcutaneous injection.
Advantages
 It has got longer duration of action once a day
 has better anticoagulant effect
 less interaction with platelets
 less antigenic
 monitoring is not necessary.
Disadvantages
 They are expensive
 only partially reversible by protamine sulphate
 it is monitored by anti-Xa assay which is not freely available.
Fondaparinux (Arixtra)
 It is a synthetic factor Xa inhibitor.
 It acts by binding antithrombin Ill.
 injected subcutaneously once daily dose
ORAL ANTICOAGULANTS
 given orally
 slow-acting
Types
A. Coumarin derivatives:
 Warfarin sodium: Most common oral anticoagulant used.
B. lndandione derivative
 Phenindione
pharmacokinetics
 suppressing synthesis of prothrombin, factors VII, IX and X.
  does not have in vitro action.
 They are slow-acting but and long-acting.
 They cross placental barrier (teratogenic)
 They are secreted in breast milk.
monitoring
 prothrombin time.
(PT comes to normal only 7 days after cessation of the drug).
 INR
(has to be maintained within 2- 3).
Indications
 maintenance therapy after cessation of heparin
Side Effects
 Bleeding (blood transfusion – FFP - vitamin K)
 Cutaneous gangrene.
 Fetal haemorrhage and teratogenicity.
 Drug interactions (NSAIDs, omeprazole, metronidazole)
WARFARIN
 the most common drug used.
 It has got lesser side effects.
 It has got cumulative action and so given in tapering dose.
 once a day.
 It should be discontinued 7 days before any surgery and
prothrombin time should return to normal level.
Non-vitamin K antagonist oral anticoagulants (NOACs)
A. Direct thrombin inhibitors (factor Ila)
 Natural: hirudin
 Synthetic: Argatroban
B. Direct factor Xa inhibitors
 Apixaban - Edoxaban
Contraindications for NOACs: Renal impairment
Anti-platelet Drugs
1. aspirin
 inhibits platelet synthesis of thromboxane A2.
2. Ticlopidine
 inhibits platelet aggregation.
3. Clopidogrel
 inhibits platelet aggregation
4. Dextran
 inhibits platelet aggregation.
5. Dipyridamole
 xanthine oxidase inhibitor