Warfarin properties

The distribution of the ionic species is determined by the molecular properties of the compound, but also by the nature and the concentration of the counterions present in the media [78]. For example, the influence of [Na ] on the transport kinehcs of warfarin through an octanol membrane has been reported [79]. 

Matricaria recutita, known as German chamomile, is also purported to have antispasmodic properties. It is taken most often as a tea up to four times a day. Benzodiazepine, alcohol, and warfarin users should be cautioned against taking this product because it can cause drowsiness, and it contains coumarin derivatives.20... 

The effect of relative humidity and temperature on the physical and structural properties of the 1 1 isopropanol solvatomorph of warfarin has been studied [58], Below the critical relative humidity of 60-68% the solid is not hygroscopic, but becomes deliquescent at higher values of relative humidity without exchange of water for isopropanol. Storage of the solvate-morph at elevated temperatures causes formation of an amorphous solid owing to loss of isopropanol, which may proceed through an intermediate crystalline phase. 

Hermans JJ, Thijssen HH. Properties and stereoselectivity of carbonyl reductases involved in the ketone reduction of warfarin and analogues. Adv Exp Med Biol 1993 328 351-360. 

The discovery of the anticoagulant properties of dicoumarin (j ) led to the development of the more potent anticoagulant warfarin (2), (Structure 1). The subsequent discovery that the anticoagulants can be successfully used as multiple dose... 

Kraak et al. (38) reported the first ACE application to study drug binding to a plasma protein. They used the model system warfarin-human serum albumin (HSA) to compare the suitability of the Hummel-Dreyer, frontal analysis, and vacancy peak methods. A more methodologically intended paper from Erim and Kraak (39) used VACE to study the displacement of warfarin from bovine serum albumin (BSA) by furosemide and phenylbutazone. They concluded that VACE is especially suited to examining competitive properties of simultaneously administered compounds toward a given protein-drug system. 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

As noted above, OC failure may lead to accidental pregnancy and exposure of the developing fetus to potentially teratogenic properties of CBZ ( 383). Therefore, OC levels should be closely monitored and patients should notify their physician of spotting, an indicator of OC failure. Prothrombin time and the International Normalized Ratio (INR) should be monitored when patients are on warfarin and CBZ concomitantly. Patients stabilized on an antipsychotic may decompensate when CBZ is added. This may necessitate an increase in the antipsychotic dose and is one indication for TDM of antipsychotic drug levels ( 384). Conversely, when CBZ is discontinued, the dose of these other agents may need to be lowered to avoid toxicity. In summary ... 

Drugs that are not absorbed from the gastrointestinal tract of the baby, such as warfarin, are safe for the mother to take. The administration of antibiotics to a breast-feeding mother usually poses no concern for the newborn infant. However, metronidazole, which has mutagenic properties, reaches concentrations in milk that equal or exceed maternal plasma levels. Caution is also advised with sulphonamides, nitrofurantoin, or naladixic acid since these can cause haemolysis in infants with glucose-6-phosphate dehydrogenase deficiency. 

Several natural products contain substances that have coumarin, salicylate, or exhibit antiplatelet properties. Therefore, a theoretical risk for potentiation of the pharmacological activity of warfarin exists when these herbs are taken with warfarin. Herbs thought to contain coumarin or coumarin derivatives include the following ... 

Structural features that promote biological activity are sometimes called biophores. They are divisible into pharmacophores and toxicophores. Pharmacophores impart desirable properties on a molecule (e.g., pharmacological activity or a particular fragrance). Toxicophores are responsible for undesirable effects such as toxicity (e.g., mutagenicity and skin sensitization). The same molecule can have more than one descriptor that can act as both a pharmacophore and a toxicophore in the same or different biological systems. Examples here are the toxic side effects of anti-cancer drugs and the use of Warfarin, a commercially available rat poison, to help reduce the formation of blood clots in human heart disease. 

---