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Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e
| XI. Drugs Acting on the Blood and the Blood-Forming Organs > |
Oral Anticoagulants
Sections: Warfarin, History, Chemistry, Mechanism of
Action, Dosage, Absorption, Distribution, Biotransformation
and Elimination, Drug and Other
Interactions, Resistance to
Warfarin, Sensitivity
to Warfarin, Toxicities, Bleeding, Birth Defects, Skin Necrosis, Other Toxicities, Clinical Use, Monitoring Anticoagulant
Therapy: The INR (International Normalized Ratio), Other Oral Anticoagulants, Phenprocoumon
and Acenocoumarol, Indandione Derivatives, Rodenticides, Ximelagatran.
Topics Discussed: acenocoumarol; anisindione; anticoagulants, oral; anticoagulation; blood coagulation; coagulation disorders; congenital abnormality; hemorrhage; hemostatic function; international normalized ratio; phenprocoumon; rodenticides; skin necrosis; thromboembolism; warfarin; warfarin resistance; ximelagatran.
Excerpt:
"Following the report of a hemorrhagic disorder in cattle
that resulted from the ingestion of spoiled sweet clover silage,
Campbell and Link, in 1939, identified the hemorrhagic agent as
bishydroxycoumarin (dicoumarol). In 1948, a more potent synthetic
congener was introduced as an extremely effective rodenticide; the
compound was named
warfarin
as an acronym
derived from the name of the patent holder, Wisconsin Alumni Research
Foundation. Warfarin's potential as a therapeutic anticoagulant
was recognized but not widely accepted, partly due to fear of unacceptable
toxicity. However, in 1951, an Army inductee uneventfully survived
an attempted suicide with massive doses of a preparation of warfarin
intended for rodent control. Since then, these anticoagulants have
become a mainstay for prevention of thromboembolic disease.Bleeding is the major toxicity of oral anticoagulant drugs (Hirsh et al., 2003).
The risk of bleeding increases with the intensity and duration of
anticoagulant therapy, the use of other medications that interfere
with hemostasis, and the presence of a potential anatomical source
of bleeding. Especially serious episodes involve sites where irreversible..."
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