Oral Anticoagulants: Pharmacodynamics, Clinical Indications and Adverse Effects

@article{Freedman1992OralAP,
  title={Oral Anticoagulants: Pharmacodynamics, Clinical Indications and Adverse Effects},
  author={Michael D. Freedman},
  journal={The Journal of Clinical Pharmacology},
  year={1992},
  volume={32}
}
  • M. D. Freedman
  • Published 1 March 1992
  • Medicine
  • The Journal of Clinical Pharmacology
Discovered early in this century consequent to investigations of a bovine hemorrhagic disease, the oral anticoagulants inhibit a post translational modification required for various hepatically derived serine proteases to become active. These include Factors II, V, VII and X. Through their effect on Proteins S and C, the extrinsic pathway is also effected. While most of these agents exist as optically active enantiomers, with differing kinetics and pharmacologic profiles, they are generally… 
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References

SHOWING 1-10 OF 147 REFERENCES
Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy
TLDR
The pharmacokinetics and pharmacodynamics of warfarin indicate that several days’ overlap with heparin on initiation ofwarfarin, and gradual (rather than sudden) discontinuation of warFarin, might theoretically be necesssary, however, those studies which have been performed have indicated that a long overlap and gradual discontinuation are not associated with greater safety or efficacy of the drug.
Kinetics of the anticoagulant effect of bishydroxycoumarin in man
TLDR
It is shown that there is an essentially linear inverse relationship between synthesis rate of prothrombin complex activity and the logarithm of plasma bishydroxycoumarin concentration.
Warfarin Sodium Derivative: (Coumadin® Sodium)
TLDR
Clinical experiences with an intravenously administered 4-hydroxycoumarin drug which induces therapeutic hypoprothrombinemia of several days duration following a single dose are reported.
Hemorrhagic complications of anticoagulant therapy.
TLDR
The frequency of bleeding increased with the intensity of treatment as reflected in daily determinations of "prothrombin activity," and epidemiologic factors possibly associated with an increased risk of bleeding included advanced age, urologic disorders, gynecologic problems, the postpartum state, and the initiation of therapy by administration of large oral doses of anticoagulant.
Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose-effect relationship.
  • N. Holford
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1986
TLDR
Empirical methods for warfarin dose prediction as well as those based on the combined pharmacokinetic-pharmacodynamic-physiological-prothrombin system have been proposed and only one has been adequately described and compared with the performance of an unaided physician.
The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin.
TLDR
The apparent dissociation between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factors activity, produced by warfarin, may reflect the insensitivity of functional clotting factor assays to a small reduction in clottingfactor concentration.
Effect of Warfarin on the Activated Partial Thromboplastin Time
TLDR
Outpatients followed in an anticoagulation clinic were studied retrospectively to determine the effect of warfarin on the activated partial thromboplastin time (APTT) and a good linear correlation was evident.
Oral anticoagulants controlled by the British comparative thromboplastin versus low-dose heparin in prophylaxis of deep vein thrombosis.
TLDR
The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin were equally effective in preventing deep vein thrombosis in a moderate-risk group.
Clinical Pharmacokinetics and Pharmacodynamics of Warfarin
TLDR
Empirical methods for warfarin dose prediction as well as those based on the combined pharmacokinetic-pharmacodynamic-physiological-prothrombin system have been proposed, but it remains to be demonstrated that any alternative method is superior to the traditional empirical approach to warFarin dose adjustment.
Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis.
TLDR
It is indicated that less intense anticoagulant therapy is associated with a low frequency of recurrent venous thromboembolism and a reduced risk of hemorrhage.
...
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