Hello friends.............Its me Vishnu, third year pharm.D student Compared to my previous ppt "Seminar on anti-coagulants and INR" (Published in slideshare too), this ppt covers three important aspects, excluding INR details in this edition....The aspects include: 1. Blood clotting factors 2. Pharmacological actions of Heparin 3. Drug interactions of Heparin As far as third year Pharmacology students are concerned, mainly HEPARIN and WARFARIN are important under this chapter....while u can some words on other newer and miscellaneous anti-coagulants too.... NOTE: This ppt is for reference purpose only....u can take it as study material or reference visual........ Hope the newer edition helps... Keep studying well..... Keep rocking !! @rxvichu-live4more !! :)

1. ANTI-COAGULANTS : A
BRIEF OUTLOOK
PRESENTED BY:
VISHNU.R.NAIR
PHARM-D THIRD YEAR
NATIONAL COLLEGE OF PHARMACY (NCP), KERALA
STATE
SUBJECT : PHARMACOLOGY

2. INDEX:
 DEFINITION OF ANTICOAGULANTS
 CLASSIFICATION
 BLOOD CLOTTING FACTORS
 BRIEF OUTLOOK OF PARENTERAL ANTICOAGULANTS
 BRIEF OUTLOOK OF ORAL ANTICOAGULANTS
 BIBLIOGRAPHY

3.  DEFINITION OF ANTICOAGULANTS  :
 “ Drugs, that are used to reduce the COAGULABILITY (coagulating
capacity) of blood “……………………………..

4.  Classification of anti-coagulants  :
IN – VIVO DRUGS :
- PARENTERALANTICOAGULANTS:
A. HEPARINS:
1. High molecular weight Heparins :
• Unfractionated heparin (UFH)
2. Low molecular weight Heparins :
• Enoxaparin
• Dalteparin
• Tinzaparin

5. CONTINUED………………………….
• Reviparin
• Danaparoid
B. HEPARINOIDS:
- Heparan sulphate
- Hirudin
- Lepirudin
- Bivalirudin
- Argatroban

6. CONTINUED……………………………..
- ORAL ANTICOAGULANTS:
1. COUMARIN DERIVATIVES:
• Bishydroxycoumarin (Dicumarol)
• Warfarin sodium
• Acenocoumarol (Nicoumalone)
• Ethyl biscoumacetate
2. INDANDIONE DERIVATIVES :
* Phenindione

7. CONTINUED……………………………..
IN – VITRO DRUGS:
1. Heparin
2. Sodium citrate (used in blood banks to store blood)
3. Sodium oxalate (used as anticoagulant in laboratory)
4. Sodium edetate (used as anticoagulant in
laboratory)………………….

8.  Blood clotting factors  :
 FACTOR I : FIBRINOGEN
 FACTOR II : PROTHROMBIN
 FACTOR III : TISSUE FACTOR / THROMBOPLASTIN
 FACTOR IV : CALCIUM
 FACTOR V : PROACCELERIN (LABILE FACTOR )
 FACTOR VI : NOT AN INDEPENDENT FACTOR
 FACTOR VII : PROCONVERTIN (STABLE FACTOR)
 FACTOR VIII : ANTI-HEMOPHILIC FACTOR (GLOBULIN) ‘A’
 FACTOR IX : ANTI-HEMOPHILIC FACTOR ‘B’ (CHRISTMAS
FACTOR)

9. CONTINUED…………………………………
 FACTOR X : STUART- PROWER FACTOR
 FACTOR XI : PLASMA PROTHROMBIN ANTECEDENT FACTOR
 FACTOR XII : HAGEMANN FACTOR
 FACTOR XIII : FIBRIN- STABILIZING FACTOR (LAKI-LORAND
FACTOR)…………………………

10.  PARENTERAL ANTICOAGULANTS  :
 Here , we will discuss on HEPARIN and associated
HEPARINOIDS………………….

11.  HEPARIN 

12. 1. GENERAL PROPERTIES :
 Discovered by McLean
 Howell and Holt named the word “HEPARIN” in 1918
 Mainly occurs in MAST CELLS
 Richest source of MAST CELLS:
1. Lungs
2. Liver
3. Intestinal mucosa
• Commercial heparin is synthesized from :
1. Porcine intestinal mucosa
2. Bovine lungs

13. CONTINUED……………………………….
 HEPARIN : A mixture of STRAIGHT CHAIN (ANIONIC)
GLYCOSAMINOGLYCANS, with a wide range of molecular weights
 Strongly acidic, due to the presence of sulphate and carboxylic acid
groups………………………..

14. 2. MECHANISM OF ACTION (M.O.A) OF
HEPARINS :
• At low doses, heparin shows 2 actions:
a. Inactivates FACTOR Xa
b. Inhibits conversion of PROTHROMBIN to THROMBIN
• At high doses, heparin shows 2 actions:
a. Inactivates factors IX, X, XI, XII, and thrombin
b. Inhibits conversion of FIBRINOGEN to FIBRIN
• Drug  inhibits activation of FACTOR VIII
• Overall precisely:
Drug  binds to Antithrombin-III  forms ‘Heparin- AT-III complex’ 
inactivates clotting factors Xa, IIa, IXa, XIIa, and XIIIa…….

15. PICTORICAL REPRESENTATION
OF HEPARIN MOA:

16. 3. COMPARISON BETWEEN LOW AND
HIGH MOL. WT. HEPARINS:
CRITERIA HMW HEPARINS LMW HEPARINS
Molecular weight High (30,000 Daltons) Low (5,000 Daltons)
Biotransformation Low High (90%)
Half-life Shorter (dose- dependent) Longer (dose- independent)
M.O.A Inactivates both factor IIa,
and Xa
Inactivates Xa
Anti-coagulant effect More effective Less effective
Monitoring By a PTT ( Activated
prothrombin time )
Can be given once or twice
daily without monitoring
ADRs High risk of
thrombocytopenia, long
Less chance of
thrombocytopenia and long

17. 4. ADVANTAGES OF LMWH OVER HMWH
:
• Better s.c availability:
- LMWH : 70-90%
- HMWH : 20-30 %
• Better and consistent half life
• Since a PTT/ clotting times are not prolonged  LMWH requires fewer lab
monitorings
• Lower incidence of hemorrhagic complications
• LMWH  Decreased antiplatelet action  decreased interference with
thrombosis…………………………….

18. 5. PHARMACOKINETICS OF HEPARIN:
 HEPARIN  Highly charged  poorly crosses cell membranes  thus
given parenterally
 For low dose : give s.c
 For high dose : give s.c and i.v
 Metabolism : by liver
 Half-life depends on dose given………………………….

19. 6. PHARMACOLOGICAL ACTIONS OF
HEPARIN :
A. ANTICOAGULANT ACTIVITY:
- Powerful and instantaneous acting anti-coagulant
- Effective both in-vivo and in-vitro
- Sudden stoppage of conventional- dose therapy  causes rebound increase in
coagulability for few days
B. ANTI-PLATELET EFFECT:
- In high doses, heparin has 2 effects :
i. Inhibits platelet aggregation
ii. Prolongs bleeding time

20. CONTINUED……………………………….
3. IN LIPAEMIA CLEARING:
- HEPARIN (low dose), when injected  causes release of
LIPOPROTEIN LIPASE from vessel wall and tissues  Hydrolyzes
triglycerides of chylomicra and VLDLs to Free Fatty Acids  causes
clearing of post-prandial lipaemic plasma (plasma looks
clear)……………………………….

21. 7. ADRs OF HEPARIN:
a. Bleeding (most common)
b. Allergy
c. Anaphylaxis
d. Alopecia
e. Long term osteoporosis  spontaneous susceptibility to fractures
f. Thrombocytopenia:
- Once thrombocytopenia is determined  stop heparin  give DIRECT
THROMBIN INHIBITOR
- Do not give platelets  platelets react with antibody already being produced by
human  increased chance of thrombosis………………

22. 8. DRUG INTERACTIONS OF HEPARIN :
A. HEPARIN + CORTICORELIN  Increased toxicity of CORTICORELIN 
increased risk of SEVERE HYPOTENSION
B. HEPARIN + MIFEPRISTONE  Excessive post abortion bleeding
C. HEPARIN + ASPIRIN  Both increase anticoagulation  dangerous interaction
D. HEPARIN + FLUOROURACIL  Both increase bleeding effects
E. HEPARIN + MIPOMERSEN  Increased hepatic enzymes
level…………………..

23. 9. HEPARIN IN PREGNANCY :
 Drug  does not cross placenta  should be used instead of warfarin in pregnancy
 Warfarin  crosses placenta  causes changes in fetus to cause fetal warfarin
syndrome  not good…………………..

24. 10. CONTRAINDICATIONS OF HEPARIN :
 Documented hypersensitivity
 Bleeding disorders (hemophilia)
 Thrombocytopenia
 Intracranial hemorrhage
 GI ulcerations
 Threatened abortion
 Advanced renal/ hepatic disease……………………..

25. 11. FOR HEPARIN TOXICITY :
 Give antidote as PROTAMINE SULPHATE
 Protamine  combines with heparin  forms stable complex 
devoid of anticoagulant activity
 Also used to reverse hemorrhage if 1 mg of protamine is given / 100 U
of heparin……………………

26. 12. USES OF HEPARIN :
a. Treatment and prevention of DEEP VEIN THROMBOSIS (DVT) in:
- Immobilized patients (bedridden)
- Old people
- Post-operative
- Post-stroke patients
- Leg fractures
- Elective surgery
b. In IHD:
- For unstable angina, Post MI
- After angioplasty, CABG, Stent replacement  For prophylaxis

27. CONTINUED…………………………………….
c. In Rheumatic Heart Disease/ Atrial Fibrillation:
- Decreases stroke due to emboli
d. In cerebrovascular diseases:
- In cerebral emboli (to prevent recurrence)
e. In vascular surgery, prosthetic heart valves, hemodialysis :
- To prevent thromboembolism
f. In Defibrination syndrome/ DIC:
- To prevent malignancies / infections…………………

28.  ASSOCIATED HEPARINOIDS


29. 1. They are drugs, that bind to thrombin without additional binding proteins such as
anti-thrombin
2. HIRUDIN and BIVALIRUDIN :
- Bind at both catalytic and / active site of thrombin
- Also bind at substrate recognition site
3. ARGATROBAN :
- Binds only at thrombin active site
4. LEPIRUDIN :
- Monitored by a PTT
- Action independent of anti-thrombin

30. CONTINUED……………………………………..
- Used in thrombosis related to heparin induced thrombocytopenia
- No antidote available
- ADR: Antibody formation against thrombin-Lepirudin complex
5. BIVALIRUDIN :
- Inhibits platelet activation
- Used in percutaneous coronary angiography
6. ARGATROBAN :
- Used in heparin induced thrombocytopenia , with/ without thrombosis
- Monitored by a PTT
- Dose is reduced in liver disease………………………

31.  Oral anticoagulants 
Here, we are focusing mainly on
WARFARIN……………………….

32. 1. M.O.A OF WARFARIN :
- WARFARIN  Interferes with hepatic synthesis of Vitamin K
dependent clotting factors ( II, VII, IX, and X) , as well as
anticoagulant proteins ‘C’ and ‘S’
- Drug  depletes functional Vit. K reserves  Competitively inhibits
subunit 1 of multi unit Vitamin K epoxide reductase complex 1 (VKOR
1 )  Reduces synthesis of active clotting factors ……………..

33. 2. PHARMACOKINETICS OF WARFARIN :
- Rapidly and completely absorbed after oral administration
- 100% bioavailability
- High plasma protein binding capacity : 99%
- Crosses placenta  TERATOGENIC
- Drug  appears in milk  thus, infants are given Vitamin K
- Shows hepatic clearance
- Metabolism: By liver , via oxidation, glucuronidation
- Take 12-16 hours before effect is observed………………..

34. 3. ADRs OF WARFARIN :
- BLEEDING:
• Common ADR
• Hematuria
• GI bleeding
• Internal hemorrhages
- CUTANEOUS NECROSIS :
• Due to decreased activity of Protein ‘C’
- INFARCTION OF BREAST, FATTY TISSUES,INTESTINE and
EXTREMITIES:
• Decreased activity of Protein ‘C’  venous thrombosis occurs  causes
above symptoms……………………………..

35. 4. HYPO-ACTIVITY OF WARFARIN
CAUSES…………..
a. Affected pregnancy (due to increase in clotting factors)
b. Nephrotic syndrome
c. Warfarin resistance (Genetic)…………………

36. 5. HYPER-ACTIVITY OF WARFARIN
CAUSES……………
a. Malnutrition
b. Debility
c. Affects newborns (due to Vitamin K deficiency)
d. Liver disease
e. Chronic alcoholism (due to decrease in clotting factors)
f. Hyperthyroidism (due to increased degradation of clotting
factors)………………………………

37. 6. FOR WARFARIN TOXICITY…………………
- Stop warfarin
- Administer Vitamin K (Antidote)
- The following can also be given :
a. Fresh frozen plasma
b. Prothrombin complex concentrates
c. Recombinant factor VIIa……………………..

38. 7. CONTRAINDICATIONS OF WARFARIN:
- In pregnancy:
a. Fetal protein in bone and blood affected
b. Birth defects
c. Abnormal bone formation
d. Bone hyperplasia
e. CNS defects
f. Fetal hemorrhage
g. Fetal hypoprothrombinemia
h. Fetal death
- Other contraindications same as that of heparin………………

39. 8. DRUG INTERACTIONS OF WARFARIN:
A. PHARMACOKINETIC INTERACTIONS:
i. Drugs, that inhibit warfarin metabolism:
- Cimetidine
- Imipramine
- Co-trimoxazole
- Chloramphenicol
- Ciprofloxacin
- Amiodarone
- Metronidazole

40. CONTINUED………………………………..
ii. Drugs, that increase warfarin metabolism:
- Barbiturates
- Rifampin
iii. Drugs, that displace warfarin from binding sites on plasma albumin :
- Chloral hydrate
- NSAIDs
iv. Drugs, that decrease GI absorption of warfarin:
- Cholestyramine

41. CONTINUED………………………………….
B. PHARMACODYNAMIC INTERACTIONS:
- Shows synergistic effects with heparin and aspirin
- Antibiotics +warfarin  decreased bacterial flora  decreased
Vitamin K synthesis  increased warfarin effects……………….

42. 9. USES OF WARFARIN :
- Same as that of heparin and other anticoagulants
- Monitoring is necessary, due to low therapeutic index
- Prothrombin Time (PT) should be noted (Time taken for blood to clot)
- Usually, patients on heparin are shifted to oral warfarin only after 3-5
days…………………………………..

43. 10. GENERAL COMPARISON BETWEEN
WARFARIN AND HEPARIN :
CRITERIA HEPARIN WARFARIN
ROUTE OF
ADMINISTRATION
Parenteral Oral
POLARITY Polar charged molecule Uncharged
ONSET OF ACTION Rapid 12-16 hours
M.O.A Inactivates clotting factors
by AT- III
Inhibits gamma-
carboxylation of glutamic
acid residues of clotting
factors
THERAPEUTIC INDEX Not low  safe Low  not safe
MONITORING Via a PTT Via PT

44.  BIBLIOGRAPHY  :
1. Nichols.W.L ; Bowie E.J.W ; Standardization of Prothrombin Time ;
Mayo Clinical Procedure 1993 ; 68 : 897-98
2. Lippincott’s Pharmacology Reviews
3. Essentials of Medical Pharmacology by Dr. Tripathi. K. D
4. The Pharmacological basis of Therapeutics by GOODMAN and
GILMANN
5. www.emedicine.net
6. www.healthline.com

45. THANK YOU !!!
  