Warfarin, toxicity

Fluvastatin may increase warfarin toxicity because both compete with P450 2C9 for metabolism. Cerivastatin can cause fatal rhabdomyolysis risk with other statins unclear. 

Warfarin also undergoes enterohepatic recycling, and its elimination can be enhanced by ion exchange resins (20) this has been used to treat warfarin toxicity (21). 

Scott, D.A., Netchvolodoff, C.V., Bacon, B.R. Delayed subcapsular hematoma after percutaneous liver biopsy as a manifestation of warfarin toxicity. Amer. J. Gastroenterol. 1991 86 503 - 505... 

Meisheri YV. Simultaneous phenytoin and warfarin toxicity on chronic concomitant therapy. J Assoc Physicians India (1996) 44, 661-2. 

I6I C. Warfarin baits need contain only 0 025% active principle, and rats are killed after ingesting about 5 doses the bait can be left down and the risk of acute toxicity to man or domestic animals is not serious. In common with other coumarin derivatives, warfarin reduces the clotting power of blood and death is caused by haemorrhages initiated by any slight injury. Warfarin is a vitamin K antagonist, and large oral doses of the vitamin can be given as an antidote. 

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Aulerich RJ, Ringer RK, Safronoff J. 1987. Primary and secondary toxicity of warfarin, sodium monofluoroacetate, and methyl parathion in mink. Arch Environ Contam Toxicol 16 357-366. 

Because of the delay in the appearance of hemorrhaging following exposure to warfarin and related ARs, a suitable interval must elapse between exposure of experimental animals to the chemical and the assessment of mortality in toxicity testing. Typically, this period is at least 5 days. Some values of acute oral LD50 of rodenticides to vertebrates are given in Table 11.2. 

The anticoagulant rodenticides warfarin and superwarfarins are toxic because they have high affinity for a vitamin K binding site of hepatic microsomes (Chapter 11, Section 11.2.4). In theory, an ideal biomarker would... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

The dose of capecitabine begins at 1250 mg/m2 twice a day when used by itself lower doses are used often when it is given in combination with irinotecan or oxaliplatin or in patients with renal insufficiency. The dose should be taken on a full stomach with breakfast and dinner. Capecitabine administered with warfarin can result in significant increases in the patient s INR and requires close monitoring to prevent bleeding. The convenience of oral administration and an improvement in toxicity make capecitabine a useful alternative to IV 5-FU both by itself and incorporated into other regimens used in colon cancer. 

The water-soluble and fat-soluble vitamins in the parenteral multivitamin mix are essential cofactors for numerous biochemical reactions and metabolic processes. Parenteral multivitamins are added daily to the PN. Patients with chronic renal failure are at risk for vitamin A accumulation and potential toxicity. Serum vitamin A concentrations should be measured in patients with renal failure when vitamin A accumulation is a concern. Previously, vitamin K was administered either daily or once weekly because intravenous multivitamin formulations did not contain vitamin K. However, manufacturers have reformulated their parenteral multivitamin products to provide 150 meg of vitamin K in accordance with FDA recommendations. There is a parenteral multivitamin formulation available without vitamin K (e.g., for patients who require warfarin therapy), but standard compounding of PN formulations should include a parenteral multivitamin that contains vitamin K unless otherwise clinically indicated. 

Decreased cigarette consumption in smokers, easier to stop smoking Exaggerated response to warfarin and phenytoin Increased efficacy of omeprazole, increased toxicity of mephenytoin Absence of codeine efficacy, no effect of encainide, increased levels of tricyclic antidepressants, fluoxetine, phenothiazines Sustained paralysis to succinylcholine, possible increased toxicity of cocaine Unknown... 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia. It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid. Synonyms for this drug are arlef, flexocutan, romazal, and others. 

Rodenticides are a broad class of chemicals designed to kill mammals, particularly rats and mice. Compounds that inhibit blood clotting, anticoagulants, are commonly used to control rat populations. One of the first was warfarin, which is related to the plant-derived coumadin (from spoiled sweet clover). In the 1950s rats developed resistance to warfarin, which prompted the development of more potent anticoagulants. Other rodenticides include fluoroacetic acid and zinc phosphide (very toxic) and thiourea-based compounds. The primary alternative to using rodenticides is trapping. 

Concentration dependent toxicity Aminoglycosides Cytotoxic agents Ciclosporin Digoxin Lithium Tacrolimus Theophylline Warfarin... 

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