Warfarin gastrointestinal effects

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. 

Sulfasalazine s absorption can be decreased when antibiotics are used that destroy the colonic bacteria. Sulfasalazine also binds iron supplements in the gastrointestinal tract that can lead to a decreased absorption of sulfasalazine. The administration of these two agents should be separated temporally to avoid this interaction. Sulfasalazine can potentiate warfarin s effects by displacing it from protein-binding sites. Close monitoring of the patient s International Normalized Ratio is indicated. ... 

Many drug interactions (ethanol T gastrointestinal bleeding, T effects of sulfonylurea and warfarin, i effects of uricosurics)... 

ADRs are certainly the most important form of iatrogenic (i.e. doctor-induced) disease. Many of the serious reactions that occur are well-recognised and potentially preventable - e.g. bleeding with warfarin, the upper gastrointestinal effects of NSAIDs. In public health terms, it is not newly introduced drugs that are responsible for most of the population burden of adverse drugs reactions but those whose safety profile is well-established (see below). 

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. 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Anticoagulant drugs include heparin and warfarin (Coumadin ) —agents used to prevent deep vein thrombosis. They are also used to prevent formation of emboli due to atrial fibrillation, valvular heart disease, and other cardiac disorders. Heparin, which is not absorbed by the gastrointestinal tract, is available only by injection its effect is immediate. 

The principal adverse reaction to warfarin is hemorrhage. Prolonged therapy with the coumarin-type anticoagulants is relatively free of untoward effects. Bleeding may be observable (e.g., skin, mucous membranes) or occult (e.g., gastrointestinal, renal, cerebral, hepatic, uterine, or pulmonary). Rarer untoward effects include diarrhea, small intestine necrosis, urticaria, alopecia, skin necrosis, purple toes, and dermatitis. 

Studies have shown that gastrointestinal mucus presents a physical barrier to the diffusion of small molecules such as urea, benzoic acid, antipyrine, 1-phenylalanine and warfarin as well as to large protein molecules. Similarly, the passive absorption of testosterone was shown to be doubled upon ridding the intestinal epithelial cells of the overlying mucus layer. However, the situation regarding the effect of mucus on oral bioavailability is a complex one for example, it has been shown that drag binding to the mucosal surface is essential to the absorption of barbituric acid derivatives from the rat small intestine. 

Use of St. John s Wort is complicated by the lack of standardisation of the ingredients. Those who wish to take St. John s Wort should be made aware that it may cause dry mouth, dizziness, sedation, gastrointestinal disturbance and confusion. Importantly also, it induces hepatic P450 errzymes (CYP 1A2 and CYP 3A4) with the result that the plasma concentration and therapeutic efficacy of warfarin, oral contraceptives, some anticonvulsants, antipsychotics and HTV protease/reverse transcriptase inhibitors are reduced. Concomitant use of tr5 to-phan and St John s Wort may cause serotonergic effects including nausea and agitation. 

Pharmacokinetics. Warfarin is readily absorbed from the gastrointestinal tract and like all the oral anticoagulants, is more than 90% bound to plasma proteins. Its action is terminated by metabolism in the liver. Warfarin (t/ 36 h) is a racemic mixture of approximately equal amounts of two isomers S (t)/ 35 h) and R 50 h) warfarin, i.e. it is in effect two drugs. S warfarin is four times more potent than R warfarin. Drugs which interact with warfarin affect these isomers differently. 

Garlic Hypertension, hypercholesterolemia Gastrointestinal upset, gas, reflux, nausea, allergic reactions, and antiplatelet effects. May effect warfarin (increase INR)... 

Gastrointestinal side effects of warfarin therapy are uncommon and usually self-limited. Because warfarin interferes with vitamin K metabolism, there has been some theoretical concern that it may adversely affect bone formation and cause osteoporosis with long-term use. To date, the association between warfarin and osteoporosis is inconclusive, and the risk of fracture appears to be negligible. 

A potentially dangerous interaction may occur between fluvoxamine and warfarin. There is a 65% increase in plasma warfarin concentration and a significant prolongation of prothrombin time. The selective serotonin reuptake inhibitors (SSRIs) increase the risk of upper gastrointestinal bleeding, and this effect is potentiated by the concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. There are anecdotal reports of bleeding disorder with the concomitant use of nicoumalone (a coumarin derivate), ibuprofen, and warfarin. 

At least 7 reports have described increased prothrombin times or INRs in patients stabilised on warfarin who took flueonazole in doses of 50 to 400 mg daily. " Several patients had haemorrhagic effects (gastrointestinal bleeding, melaena, ocular haemorrhage, spinal epidural haemato-... 

Nizatidine 300 mg daily for 2 weeks had no significant effect on the prothrombin times, kaolin-cephalin clotting times, the activity of factors II, Vn, XI and X, or on steady-state semm warfarin levels in 7 healthy subjects taking warfarin. A lack of a pharmacokinetic interaction was also reported in the preliminary results of another study. An isolated case of gastrointestinal bleeding, associated with markedly prolonged prothrombin times, occurred after a 78-year-old took six doses of nizatidine 300 mg. ... 

---