Anticoagulants are drug used to reduce the coagulability of the blood. Drugs that help prevent the clotting(coagulation) of blood

1. ANTICOAGULANTS
1Department of Pharmacology
Presented By – Gyanendra Kumar Prajapati
1st year M.Pharm
Department of Pharmacology
KLE University’s College of Pharmacy,
Bengaluru

2. Anticoagulants are drug used to reduce the coagulability of
the blood. Drugs that help prevent the clotting(coagulation)
of blood.
Coagulation will occur instantaneously once a blood
vessel has been severed.
Blood begins to solidify to prevent excessive blood loss
and to prevent invasive substances from entering the
bloodstream.
Introduction
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3. CLASSIFICATION
1. Used in Vivo:
–A) Parenteral anticoagulant
●Indirect thrombin inhibitors:
Heparin,
Danaparoid,
Low molecular weight heparin,
Fondaparinux.
●Direct thrombin inhibitors:
Lepirudin,
Bivalirudin,
Argatroban.
3Department of Pharmacology

4. ● Indandione derivatives:
Phenindione .
● Direct thrombin inhibitors:
Rivaroxaban,
Dabigatron.
(B) Oral anticoagulants:
● Coumarin Derivative:
Bishydroxycoumarin (dicumarol),
Warfarin sodium,
Acenocoumarol.
4Department of Pharmacology

5. 2.Used in Vitro:
A . Heparin: (150 U in 100 ml of blood)
B . Calcium complexing agents:
Sodium citrate 1.65 gm for 350 ml of blood; used to keep
blood in the fluid state for transfusion
Sodium oxalate
(10 mg for 1 ml blood and Sodium edetate – 2 mg for 1 ml)
of blood

6. Heparin as Prototype
Endogenous - strongest organic acid present in theBody
Present in mast cells (MW – 75,000) – lungs, liver andintestinal
mucosa
Commercially - from Ox lung and Pig mucosa
(slaughterhouse)
Chemically, non-uniform mixture of straight chain
mucopolysaccharides with MW 10,000 to 20,000
Carries strong electro-negative charges
Types - (i) Regular or unfractionated (UFH) Heparin (MW 5000 to
30,000) – IV or SC and (ii) LMWH (MW
2000 to 6000) – mostly SC
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7. Heparin Actions
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•
Indirect acting - Activates plasma antithrombin III (AT III)
Heparin-AT III complex inactivates clotting factors - Xa, IIa, IXa, XIIa
and XIIIa, but not VIIa (extrinsic pathway)
–
–
At low conc. Xa mediated conversion of Prothrombin to thrombin affected
Overall, Xa and IIa mediated conversion of fibrinogen to fibrin
• AT III (suicide inhibitor) – binds to clotting factors slowly to form
stable complex. Heparin enhances it by
1.Heaprin creates scaffolding to bind each (clotting
factors) other with AT III
2.A specific polysaccharide in heparin binds to AT III and
induce conformational changes – bind factors
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8. Heparin Actions – contd.
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•
•
•
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Inhibition of Xa needs only the 2ndmechanism (LMWH) -
fondaparinuxs
IIa needs both the mechanism
Antiplatelet action: High doses prevents platelet aggregation
prolongs Bleeding time
Lipaemic clearing
Pharmacokinetics:
– Highly ionized, not absorbed orally – given IV (instant action) and SC
(slow action)
– Does no cross BBB and placenta
– 100 U/kg dose half life is 1 Hr., but above this dose 1 – 4 Hrs
– Should not with – Penicillin, hydrocortisone or tetracycline
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9. Heparin mechanism of action
Heparin
Antithrombin III
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10. Heparin – Contd.
• Adverse effects:
1. Bleeding due to overdose – haematuria is 1st sign
2. Thrombocytopenia – aggregation of platelets
3. Hypersensitivity – urticaria, rigor, fever and
anaphylaxis etc.
4. Alopecia and osteoporosis
• Contraindications: Bleeding disorders, Severe
hypertension, GIT ulcer, Piles, SABE & malignancy,
Ocular & neurosurgery, Chronic alcoholism, cirrhosis
etc.
• Aspirin and antiplatelet drugs - caution
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11. Low Molecular
Weight Heparin
(LMWH)
•
•
MW : 2000 to 6000
MOA: Acts only by interfering with Xa –
inducing conformational change in AT III –
smaller effect on aPTT – whole blood
clotting time
–
–
–
– Lesser antipatelet action and lower
incidence of haemorrhagic complications
Better Bioavailability on SC administration
(once daily dosing)
Better half life (4-6 Hrs)
Laboratory monitoring not needed (aPTT
and clotting time affected little)
• Uses: (1) Prophylaxis of DVT and Pulmonary
embolism in Surgery, stroke and
immobilized patients
(2) DVT
(3) UA and MI
(4) RHD and AF
(5) Haemodialysis patients
Interfered PT aPTT
IP N P
EP P N
CP P P
11Department of Pharmacology

12. Dosage of Heparin
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•
•
•
•
•
Unitage: Expressed in units as it is standardized by bioassay –
variable molecular size
1 mg = 120-140 U activity
Administered as IV bolus 5000-10,000 u followed by 1000 u
/hr IV drip – adjusted with aPTT value
– Pretreatment aPTT value and followed by 1.5 to 2.5 times during
therapy
Alternate: 10,000-20,000 deep SC every 8 Hrly (fine needle)
Or, Low dose SC – 5000 SC 8-12 Hry before and after surgery
to prevent DVT
Protamine Sulfate: Heparin antagonist – given IV (1mg =
100U) – cardiac and vascular surgery
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13. Oral Anticoagulants
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14. Warfarin
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In vivo not in vitro
MOA: Competitive antagonist of
Vit.K – lowers the plasma level of
vit. K dependent clotting factors
– Inhibits VKOR needed to
generate active Vit.K
Synthesis of clotting factors
diminishes within few hours- at
different times by diff. factors
But anticoagulant action starts in
1-3 days only
Commercially, mixture of R and S
enantiomers
14Department of Pharmacology

15. Warfarin – contd.
• Kinetics: Completely absorbed from intestine and
99% plasma protein bound – only 1% free (many
drugs can displace (sulfonamides, phenytoin –
toxicity) – half life 36 hrs.
• Dosing: Risky – calculate risk-benefit ratio
– Dose is individualized by repeated measurement of PT
– Optimum ratio of PT: 2-2.5 in prophylaxis of DVT, 2-
3 in DVT treatment and 3-3.5 in MI etc.
• Uses: DVT, Pulmonary embolism and atrial
fibrillation (drug of choice – 3-4wks before and
after conversion)
15Department of Pharmacology

16. Warfarin
• ADRs: Bleeding – epistaxis, haematuria, bleeding
GIT Intracranial haemorrhage
– Minor bleeding – Vit K (takes long)
– Fresh blood transfusion or blood factors
– Other ADRs: Alopecia, dermatitis and diarrhoea etc.
• Contraindications: Same as heparin
– Foetal warfarin syndrome: skeletal abnormality –
hypoplasia of nose, eye socket, hand bones and
growth retardation
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17. Warfarin
Factors enhancing warfarin effect: (1) Debility, malnutrition
etc. (2) Liver diseases, chronic alcoholism (3) Newborn (4)
prolonged antibiotic therapy
Factors decreasing warfarin effect: Pregnancy, Nephrotic
syndrome and genetic warfarin resistance
Drugs enhancing anticoagulant action: Broad spectrum
antibiotics, Aspirin (platelet aggregation inhibition and
hypoprothobinemic action), Newer cephalosporins
(hypoprothobinemic; Chloramphenicol, allopurinol,
tolbutamide and phenytoin (inhibits metabolism)
Drugs reducing effect: Barbiturates, carbamazepine, OCP and
Rifampicin
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17Department of Pharmacology

18. Reference
• Principles of pharmacology – HL Sharma & KK Sharma.
• Pharmacology – Rang & Dale 5th Edition.
• Text book of pharmacology – K. D. Tripathi.7th Edition.
• Basics & clinical pharmacology – Katzung 11th edition.
• Pharmacology & Pharmacotherapeutics - Satoskar-21st
edition.
• Pharmacological basis of Therapeutics – Goodman &
Gilman 12th Edition.

19. THANK
YOU
19Department of Pharmacology