Drugs used in coagulation
disorders
By S.Bohlooli, Ph.D.
Mechanism of blood
coagulation
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Thrombogenesis
Blood coagulation
Regulation of coagulation and
fibrinolysis
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Fibrin inhibition: 1-antiprotease, 2macroglobulin, 2-antiplasmin,
antithrombin
Fibrinolysis: plasmin
Thrombogenesis
Blood coagulation
A model of blood coagulation
Fibrinolysis
Basic pharmacology of the
anticoagulant drugs
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Indirect thrombin inhibitors
Direct thrombin inhibitors
Warfarin and the Coumarin
anticoagulants
Indirect thrombin inhibitors
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Unfractioned heparin
Low molecular-weight heparin:
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Enoxoparin, daltaparin, tinzaprin
foundaparinux
Differences between fondaparinux, LMWH
and HMWH heparin
The antithrombin-binding structure of heparin
Toxicity
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Bleeding
Thrombocytopenia
Caution in patient with allergy
Contraindicated in:
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Hypersensitive
Actively bleeding
Hemophilia
Thrombocytopenia
Sever Hypertension
Intracranial hemorrhage
Advanced renal or hepatic disease
Direct thrombin inhibitors
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Hirudin, lepirudin
Bivalirudin
Agatroban
Melagatran
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Ximelagatran: oral prodrug
Warfarin and the Coumarin
anticoagulants
Warfarin :Mechanism of action
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Block the -carboxylation of several
glutamate residue in prothrombine and
factors VII, IX, and X
As well as the endogenous
antigoagulant proteins C and S
There is 8- to 12-hour delay in the
action of warfarin
Warfarin :Mechanism of action
Warfarin: Toxicity
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bleeding
Readily crosses the placenta
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Hemorrhagic disorders
Abnormal bone formation
Cutaneous necrosis
Frank infarction of breast, fatty tissues
intestine, and extremities
Venous thrombosis
Basic pharmacology of the
Fibrinolytic drugs
Contraindications to Thrombolytic Therapy
1. Surgery within 10 days, including organ biopsy,
puncture of noncompressible vessels, serious
trauma, cardiopulmonary resuscitation
2. Serious gastrointestinal bleeding within 3 months
3. History of hypertension (diastolic pressure >110 mm
Hg)
4. Active bleeding or hemorrhagic disorder
5. Previous cerebrovascular accident or active
intracranial process
6. Aortic dissection
7. Acute pericarditis
Basic pharmacology of
Antiplatelet agents
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Clyclooxygenase inhibitors:Aspirin
ADP receptor antagonists: Clopidogrel,
ticlopidine
Blockers of GP IIB/IIIA receptors:
abciximab, eptifibatide, tirofiban
Phosphodiesterase inhibitors:
dipyridamole, cilostazol
Structure of ticlopidine and clopidogrel
Toxicity:Ticlopidine
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nausea, vomiting, and diarrhea
severe neutropenia: 2.4% patients
Fatal agranulocytosis with
thrombopenia
Clinical pharmacology of drugs
used to prevent clotting
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Venous thrombosis
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Risk factors:
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Anithrombotic management
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Inherited disorders
Acquired diseases
Prevention
Treatment of established disease
Arterial thrombosis
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Antiplatelet drugs
Drugs used in bleeding
disorders
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Vitamin K
Plasma fractions
Fibrinolytic inhibitors: aminocaproic acid
Serine protease inhibitors: aprotinin
Vitamin K
Vitamin K
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to promote the biosynthesis of the -carboxyglutamate (Gla) forms of:
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factors II (prothrombin), VII, IX, and X
anticoagulant proteins C and S, protein Z (a
cofactor to the inhibitor of Xa)
the bone Gla protein osteocalcin, matrix Gla
protein, growth arrest-specific protein 6 (Gas6)
four transmembrane monospans of unknown
function
Vitamin K Deficiency
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increased tendency to bleed
Ecchymoses, epistaxis, hematuria,
gastrointestinal bleeding, and
postoperative hemorrhage
fetal warfarin syndrome: vitamin Kdependent protein in bone
deficits in bone mineral density and
fractures
Toxicity
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Phylloquinone and the menaquinones
are nontoxic
menadione and its derivatives:
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hemolytic anemia and kernicterus in
neonates, especially in premature infants