This presentation easy to read for the all type of student ,Doctors and Medical to know the anticoagulant and mechanism and function of anticoagulants which are used in human body or blood

1. Anticoagulants
by
Haider zaman
Medical Lab Technology

2. Coagulation
• Coagulation =(also known as clotting)
• is the process by which blood changes from a liquid to
a gel, forming a clot.

4. Anticoagulants
• A substance that prevents blood from clotting by suppressing the
synthesis or function of various clotting factors.
• Anticoagulants are given to prevent thrombosis and used in drawing
and storing blood.
• There are two main types of anticoagulants:
Heparin
 vitamin K antagonists (e.g., warfarin).

5. Heparin
• Heparin is a naturally-occurring anticoagulant produced
by basophils and mast cells.
• Heparin acts as an anticoagulant, preventing the formation of clots and
extension of existing clots within the blood. While heparin does not break
down clots that have already formed (unlike tissue plasminogen activator),
it allows the body's natural clot lysis
• Highly ionized, not absorbed orally.
• it is given IV only.
• Heparin is one of the oldest drugs currently in widespread clinical use. It
was originally isolated from canine liver cells, hence its name Heparin.

6. Heparin structure
• heparin is heterogeneous of un branched polysaccharide chains
Alternating monosaccharide units of
L-iduronic acid and D-glucosamine
• one third of the polysaccharide chain contain a specific antithrombin
binding pentasaccharide sequence
Source
 preparation from porcine and bovine
intestinal mucous
 preparation from bovine lung

7. Heparin Actions
Heparin exerts parts of its anticoagulant activity through interaction
with antithrombin
antithrombin binds specifically to a pentsaccharide in heparin
binding to heparin induced a conformational change in the
antithrombin , which accelerate
enzyme inhibition

8. Heparin mechanism of action
Heparin
Antithrombin III
Thrombin

9. Adverse effects of Heparin
1. Bleeding due to overdose – hematuria 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

10. Pharmacokinetics Heparin
Absorption: Heparin is not absorbed from GI; must be given IV or
subcutaneously,
Metabolism: The liver and reticuloendothelial system are the sites of
biotransformation.
Elimination: The average half-life is 1.5 h
(range, 1 to 6 h) and is dose dependent Excreted in the
urine

11. Dosage and Administration:
 intravenously (immediate effect)
- 20 to 40 thousands units/day dose
 subcutaneously ( effect on 20-60 min )
-8,000 to 10,000 units every 8 h .

12. Drug interactions
• interaction with :
• Alteplase
• Antihistamines
• Antithrombin
• Cephalosporins (eg, cefazolin, ceftriaxone)
• Penicillins, parenteral (eg, ampicillin, penicillin G)

13. Warfarin
Warf Warfarin is an oral anticoagulant widely used to control and
prevent thromboembolic disorders.
Warfarin is clinically available as a racemic mixture of R- and S-warfarin.
The S-enantiomer has 3–5 times greater anticoagulation potency than
its optical congener R-warfarin.

14. Action of Warfarin
Warfarin acts by antagonizing the anti- hemorrhagic effect of vitamin
K.
It inhibits hepatic synthesis of vitamin K dependent coagulation factors
II, VII, IX, and X by inhibiting vitamin K1 -2,3 epoxide reductase
preventing vitamin K from being reduced to its active form.

16. Pharmacokinetic
 The oral bioavailability of warfarin is nearly 100%.
It is highly bound (approximately 99%) to plasma protein, mainly
albumin. (The high degree of protein binding is one of several mechanisms whereby other drugs
interact with warfarin)
Warfarin is distributed to the liver, lungs, spleen, and kidneys. It does
not appear to be distributed to breast milk in significant amounts. It
crosses the placenta and is a known teratogen.
The duration of anticoagulant effect after a single dose of warfarin is
usually 5-7 days.

17. Pharmacokinetic
Warfarin is metabolized by hepatic cytochrome P-450 (CYP)
isoenzyme to inactive metabolites, which are excreted in the bile. (It also
is metabolized by reductases to reduced metabolites “warfarin alcohols” , which
are excreted in the kidneys).
Warfarin metabolism may be altered in the presence of hepatic
dysfunction or advanced age but is not affected by renal impairment.

18. Indications
prophylaxis and/or treatment of venous thrombosis and its
extension, and pulmonary embolism.
prophylaxis and/or treatment of the thromboembolic complications
associated with atrial fibrillation and/or cardiac valve replacement.
to reduce the risk of death, recurrent myocardial infarction, and
thromboembolic events such as stroke or systemic embolization after
myocardial infarction.

19. Dosage and Administration
Adults: PO 2-5 mg/day initially; adjust daily dose according to PT or
INR determinations. Usual maintenance dose is 2-10 mg/day.
The IV dosages would be the same as those would be used orally.
Administer as a slow bolus injection over 1 to 2 min in a peripheral
vein.

20. Adverse Effects
Hematologic: hemoptysis, bruising, epistaxis, bleeding gums, hematouria
or blood in stool.
Cardiovascular: hypotension, syncope, vasculitis.
CNS: dizziness, fatigue, headache, lethargy.
Hepatic: elevated liver enzymes, hepatitis, jaundice.
Miscellaneous: hypersensitivity reactions, osteoporosis, chest pain, fever,
purple toe syndrome.

21. Drug Interactions
Divided into:
1. Pharmacokinetic mechanisms:
1) enzyme induction 2) enzyme inhibition 3) reduced
plasma protein binding.
2. Pharmacodynamic mechanisms:
1) synergism 2) competitive antagonism (vit K) 3) an altered
physiologic control for vitamin K (hereditary resistance to oral
anticoagulants).