ANTI COAGULANT

DRUGS

By CH. Yaswanth kumar

 ANTI COAGULANT DRUGS
‣ These are the drugs that prevent or reduce the coagulability of
blood.

‣ These are classified as PARENTERAL and ORAL anticoagulants (IN-

VIVO)
 Heparin

‣ Heparin is a non-uniform mixture of straight chain

mucopolysaccharides with MW 10,000 to 20,000
‣ It contains polymers of two sulfated disaccharide units:
D-glucosamine-L-iduronic acid
D-glucosamine-D-glucuronic acid
‣ It is present in all tissues containing mast cells; richest
sources are lung, liver and intestinal mucosa.
 Actions of Heparin
HEPARIN

Activates plasma AT III

Heparin-AT Ill complex

Binds to clotting factors of intrinsic and common pathways

(Xa, Ila, IXa, XIa, XIla and XIlla) and inactivates them
‣ Heparin in higher doses inhibits platelet aggregation and
prolongs bleeding time.
‣ Heparin in lower doses helps in lipaemia clearing.
 PHARMACOKINETICS
‣ Heparin is not absorbed orally.
‣ If Injected i.v. - acts instantaneously.
‣ After s.c. injection anticoagulant effect develops after ~60 min.
‣ Bioavailability of s.c. heparin is inconsistent.
‣ Heparin does not cross blood-brain barrier or placenta (it is the
anticoagulant of choice during pregnancy).
‣ It is metabolized in liver by heparinase.
‣ Fragments are excreted in urine.
‣
‣ Heparin should not be mixed with penicillin, tetracyclines,
hydrocortisone or NA in the same syringe or infusion
bottle.
‣ Heparinized blood is not suitable for blood counts (alters
the shape of RBCs and WBCs), fragility testing and
complement fixation tests.
 ADVERSE EFFECTS

‣ Bleeding due to overdose - most serious complication.

‣ Thrombocytopenia - mild and transient.
‣ Transient and reversible alopecia is infrequent. Serum
transaminase levels may rise.
‣ Osteoporosis - long-term use of relatively high doses.
‣ Hypersensitivity reactions - rare.
 Contraindications

‣ Bleeding disorders, history of heparin induced

thrombocytopenia.
‣ Severe hypertension, threatened abortion,piles,GIT
ulcers.
‣ Subacute bacterial endocarditis, large malignancies,
tuberculosis.
‣ Ocular and neurosurgery, lumbar puncture.
Chronic alcoholics, cirrhosis, renal failure.
 Low molecular weight (LMW)
heparins

‣ Heparin has been fractionated into LMW forms (MW

3000-7000) by different techniques.
‣ LMWHs are defined as heparin salts having an average
molecular weight of less than 8000 Da.
‣ These are obtained by various methods of fractionation
or depolymerisation of polymeric heparin.
 Mechanism of action
‣ Selectively inhibit factor Xa with little effect on lla.
‣ Act only by inducing conformational change in AT III
‣ Hence LMW heparins have smaller effect on aPTT and
whole blood clotting time than unfractionated heparin
(UFH)
‣ they have lesser antiplatelet action-less interference with
haemostasis.
‣ Lower incidence of haemorrhagic complications
compared to UFH
Elimination - primarily by renal excretion.
Advantages of LMW heparin
‣ Better subcutaneous bioavailability (70-90%) compared
to UFH (20-30%)
‣ Longer and more consistent monoexponential t½(4-6
hours)
‣ Since aPTT/clotting times are not prolonged, laboratory
monitoring is not needed.
‣ Risk of osteoporosis after long term use is much less.
 Indications

‣ Prophylaxis of deep vein thrombosis and pulmonary

embolism in high-risk patients undergoing surgery.
‣ Treatment of established deep vein thrombosis.
‣ Unstable angina and MI: they have largely replaced
continuous infusion of UFH.
‣ To maintain patency of cannulae and shunts in dialysis
patients.
LMW HEPARINS (marketed)

Enoxaparin

Reviparin

Nadroparin

Dalteparin

Parnaparin

Ardeparin
 Fondaparinux

‣ The pentasaccharide with specific sequence that binds to

AT Ill with high affinity to selectively inactivate factor Xa
without binding thrombin (factor lla), has been recently
produced synthetically.
‣ Bioavailability - If injected s.c. is 100%
‣ Excreted unchanged by the kidney.
 Direct thrombine inhibitors

‣ Unlike heparin, these recently developed anticoagulants

bind directly to thrombin and inactivate it without the need
to combine with and activate AT III.
‣ Lepirudin
‣ Bivalirudin
‣ Argatroban
 Oral anticoagulants
‣ Act indirectly by interfering with the synthesis of vit K
dependent clotting factors in liver.
‣ Apparently behave as competitive antagonists of vit K and
lower the plasma levels of functional clotting factors in a dose-
dependent manner.
‣ they inhibit the enzyme vit K epoxide reductase (VKOR) and
interfere with regeneration of the active hydroquinone form of
vit K which acts as a cofactor for the enzyme v-glutamyl
carboxylase.
MECHANISM OF ACTION OF ORAL
ANTICOAGULANTS
 Direct factor XA inhibitors

‣ Act rapidly without a lag time

‣ Have short-lasting action

‣ Rivaroxaban
Oral direct thrombin inhibitor
Dabigatran etexilate

‣ Reversibly blocks the catalytic site of thrombin and

produces a rapid (within 2 hours) anticoagulant action.
Oral bioavailability is low.
‣ No laboratory monitoring is required.
‣ The plasma t½ is 12-14 hours.
‣ Duration of action 24 hours.
 USES OF ANTICOAGULANTS

‣ Deep vein thrombosis (DVT) and pulmonary embolism

(PE)
‣ Myocardial infarction (MI)
‣ Unstable angina
‣ Rheumatic heart disease; Atrial fibrillation(AF)
‣ Cerebrovascular disease
‣ Vascular surgery, prosthetic heart valves, retinal vessel
thrombosis, extracorporeal circulation, haemodialysis
‣ Defibrination syndrome or 'disseminated intravascular
coagulation'