Download - Drugs used in coagulation disorders
Drugs used in coagulation disorders
By S.Bohlooli, Ph.D.
Mechanism of blood coagulation
Thrombogenesis Blood coagulation Regulation of coagulation and
fibrinolysis Fibrin inhibition: 1-antiprotease, 2-
macroglobulin, 2-antiplasmin, antithrombin
Fibrinolysis: plasmin
Thrombogenesis
Blood coagulation
A model of blood coagulation
Fibrinolysis
Basic pharmacology of the anticoagulant drugs
Indirect thrombin inhibitors Direct thrombin inhibitors Warfarin and the Coumarin
anticoagulants
Indirect thrombin inhibitors
Unfractioned heparin Low molecular-weight heparin:
Enoxoparin, daltaparin, tinzaprin foundaparinux
Differences between fondaparinux, LMWH and HMWH heparin
The antithrombin-binding structure of heparin
Toxicity Bleeding Thrombocytopenia Caution in patient with allergy Contraindicated in:
Hypersensitive Actively bleeding Hemophilia Thrombocytopenia Sever Hypertension Intracranial hemorrhage Advanced renal or hepatic disease
Direct thrombin inhibitors
Hirudin, lepirudin Bivalirudin Agatroban Melagatran
Ximelagatran: oral prodrug
Warfarin and the Coumarin anticoagulants
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 :Mechanism of action
Warfarin: Toxicity bleeding Readily crosses the placenta
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 disorder5. Previous cerebrovascular accident or active
intracranial process6. Aortic dissection7. Acute pericarditis
Basic pharmacology of Antiplatelet agents
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
nausea, vomiting, and diarrhea severe neutropenia: 2.4% patients Fatal agranulocytosis with
thrombopenia
Clinical pharmacology of drugs used to prevent clotting Venous thrombosis
Risk factors: Inherited disorders Acquired diseases
Anithrombotic management Prevention Treatment of established disease
Arterial thrombosis Antiplatelet drugs
Drugs used in bleeding disorders
Vitamin K Plasma fractions Fibrinolytic inhibitors:
aminocaproic acid Serine protease inhibitors:
aprotinin
Vitamin K
Vitamin K to promote the biosynthesis of the -
carboxy-glutamate (Gla) forms of: 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 increased tendency to bleed Ecchymoses, epistaxis, hematuria,
gastrointestinal bleeding, and postoperative hemorrhage
fetal warfarin syndrome: vitamin K-dependent protein in bone
deficits in bone mineral density and fractures
Toxicity
Phylloquinone and the menaquinones are nontoxic
menadione and its derivatives: hemolytic anemia and kernicterus in
neonates, especially in premature infants