Digoxin-rifampin interaction

Digoxin doses required to maintain therapeutic serum concentrations rose substantially in two patients dependent on dialysis with the commencement of rifampin therapy. When rifampin was discontinued, doses fell to requirements before rifampin. Serum digoxin concentration may fall to ineffective levels with rifampin therapy and rise to potentially toxic levels when rifampin is discontinued.     

Lipoprotein-cyclodextrin interaction

Interaction of cyclodextrins with native and isolated lipoproteins was studied by electrophoretic and spectroscopic means. Reaction between these two biomolecules resulted in the formation of soluble and insoluble complexes. Cyclodextrin-mediated precipitation of lipoproteins was strongly affected by the concentration of the oligosaccharide and the presence of guest molecules capable of being entrapped within the cyclodextrin cavity. Lipoprotein precipitation by cyclodextrins was observed under acidic, neutral as well as alkaline conditions. The ionic strength of the medium did not significantly affect this interaction. Under appropriate experimental conditions, most types of cyclodextrins were able to form complexes with the various lipoprotein classes. The ability of cyclodextrins to precipitate lipoproteins was in the order of beta-cyclodextrin greater than alpha-cyclodextrin greater than gamma-cyclodextrin and hydroxyalkylated beta-cyclodextrin. Among the lipoproteins, the order of reactivity with a given cyclodextrin was: low density lipoproteins greater than high density lipoproteins greater than very low density lipoproteins. Competitive studies using L-phenylalanine and methanol, both of which form inclusion complexes with cyclodextrins, reveal that molecular encapsulation plays an important role in the stabilization of beta-cyclodextrin-lipoprotein complexes. The present data also suggests that the binding of cyclodextrins to lipoproteins may involve the formation of exclusion complexes.     

Ticlopidine-theophylline interaction

Ticlopidine, a new antithrombotic agent, and theophylline, a widely used bronchodilator drug, are both almost completely metabolized in the liver. To evaluate an interaction between these two drugs, we studied theophylline pharmacokinetics before, after 10 days of ticlopidine administration, and 1 month later in 10 healthy volunteers. We found a highly significant increase in the theophylline elimination half-life (P less than 0.001) and a comparable reduction in its total plasma clearance (P less than 0.001) after ticlopidine treatment. Pharmacokinetic parameters returned to initial values within 30 days after ticlopidine withdrawal. Moreover, no changes in theophylline pharmacokinetic parameters were observed 3 months later, before and after 10 days of placebo administration. Our results seem to exclude direct liver toxicity and may suggest a reversible inhibition of the liver metabolic capacity of theophylline.     

Capecitabine-warfarin interaction

OBJECTIVE: To report a case of concomitant warfarin therapy with consecutive cycles of capecitabine therapy, providing time of onset, magnitude, and assessment of the interaction. CASE SUMMARY: A 59-year-old man receiving chronic warfarin therapy for a mechanical mitral valve replacement was diagnosed with stage IV metastatic colon cancer. He was started on capecitabine/irinotecan after his cancer progressed with fluorouracil/leucovorin and the FOLFOX 6 regimen (oxaliplatin, leucovorin, and continuous fluorouracil infusion). He received 3 consecutive cycles of capecitabine/irinotecan with concomitant oral anticoagulation and, with each cycle, the warfarin dose was reduced. Over the course of these 3 cycles, the total weekly dose of warfarin was reduced by >85%. DISCUSSION: The capecitabine-warfarin interaction is clinically significant, requiring a black box warning in the package insert. The mechanism of action for the interaction is not clear, but may be related to down-regulation of CYP2C9 by capecitabine or its metabolites or a pharmacodynamic interaction with warfarin. A common response to this interaction, as discussed in previously published case reports, is the discontinuation of warfarin, capecitabine, or both. In this case, the Naranjo probability scale indicates a highly probable drug interaction between warfarin and capecitabine. CONCLUSIONS: As more patients require anticoagulation, and as chemotherapy agents such as capecitabine become available, the likelihood for these drug interactions increases. In our patient, close monitoring of therapy allowed successful use of warfarin and capecitabine.     

Nasobronchial interaction

Upper and lower airways can be considered as a unifiedmorphofunctional unit. In this paper, nasobronchial interactions are evaluated based on literature.To discuss nasobronchial interactions, literature review from Pub Med since 1982 is evaluated. Data base was including the terms nasobronchial interaction, nasal and bronchial. Asthma and rhinosinusitis may be associated with environmental factors and immunological predisposition. Treatment of rhinosinusitis may decrease asthma exacerbations. It was concluded that one airway, one disease-concept may be accepted when considering naso-bronchial interaction. Asthma treatment should also mean treating the nose as good as treating patients with nasal symptoms. To reach the succesful results it should be associated with evaluation of lung functions.     

Rosuvastatin-acenocoumarol interaction

BACKGROUND: Previous evidence suggests that hydroxymethylglutaryl coenzyme A-reductase inhibitors (statins) might potentiate the effect of oral anticoagulants, but a MEDLINE search (key terms: stains, rosuvastatin, anticoagulants, acenocoumarol, and interaction; years: 1980-2005) revealed no reports of an interaction between rosuvastatin and acenocoumarol. OBJECTIVE: The aim of this article was to describe a case of possible interaction between rosuvastatin and acenocoumarol. METHODS: We report the case of a 36-year-old male patient receiving long-term oral treatment with acenocoumarol, a synthetic coumarin anticoagulant, who experienced an increase in international normalized ratio (INR) and a hematoma in the left leg approximately 45 days after the initiation of treatment with rosuvastatin. RESULTS: After discontinuation of both drugs, an unexpectedly rapid decrease in INR was observed. CONCLUSIONS: Based on the results of this case, a possible pharmacologic interaction between rosuvastatin and acenocoumarol should be considered. Rosuvastatin might enhance the anticoagulant effect of acenocoumarol, and a rebound effect in cases of simultaneous discontinuation of both drugs might occur. Rosuvastatin should be administered with extreme caution in patients receiving long-term acenocoumarol therapy.     

Fluconazole-carbamazepine interaction

The patient we describe had elevated carbamazepine serum concentrations during concomitant fluconazole administration (400 mg/day), including serial concentrations both before and after antifungal therapy. Since fluconazole is a known inhibitor of the cytochrome P450 enzyme system, this suggests an inhibition of carbamazepine metabolism.     

Patient-ventilator interaction

Patient-ventilator interaction has been the focus of increasing attention from both manufacturers and researchers during the last 25 years. There is now compelling evidence that passive (controlled) mechanical ventilation leads to respiratory muscle dysfunction and atrophy, prolonging the need for ventilatory support and predisposing to a number of adverse patient outcomes. Although there is consensus that the respiratory muscles should retain some activity during acute respiratory failure, patient-ventilator asynchrony is now recognized as a cause of ineffective ventilation, impaired gas exchange, lung overdistention, increased work of breathing, and patient discomfort. Far more common than previously recognized, it also predisposes to respiratory muscle dysfunction and other complications, leads to excessive use of sedation, increases the duration of ventilatory support, and interferes with weaning. Appropriate recognition and management of patient-ventilator asynchrony require bedside assessment of ventilator graphics as well as direct patient observation. Among currently available ventilation modes and approaches, none has been shown to be clearly superior to all the others with respect to patient-ventilator interaction, and strongly held preferences among investigators have led to controversy and difficulties in carrying out appropriate studies evaluating them. As a result, marked practice variation exists among different specialties as well as in different institutions and geographical areas. The respected authorities on mechanical ventilation who participated in this conference differed in the modes they preferred but agreed that proper understanding and use according to the individual patient's needs are more important than which mode is chosen. Conference participants discussed the determinants, manifestations, and epidemiology of patient-ventilator asynchrony, and described and compared several ventilation modes aimed specifically at preventing and ameliorating it. The papers arising from these discussions represent the most thorough examination of this important aspect of respiratory care yet published.     

Tolterodine-warfarin drug interaction

OBJECTIVE: To report two cases of warfarin therapy in which the addition of tolterodine resulted in prolonged international normalized ratios (INRs). CASE SUMMARY: Two patients, each receiving warfarin for stroke prophylaxis in association with chronic atrial fibrillation, developed adverse effects after the initiation of tolterodine for urinary disorders. Other medications for concurrent medical diagnoses had remained unchanged. One patient had an episode of prostatitis, which was treated with levofloxacin immediately prior to tolterodine initiation. The warfarin dosage had remained constant for many weeks in both patients prior to and during the tolterodine trials. In each patient, the initiation of tolterodine was associated with a significant increase in the patient's INR measured 10-14 days later. Thus, tolterodine was ineffective in both patients and was discontinued one to two days before the elevated INRs were determined during routine clinic visits. INRs determined approximately two weeks after tolterodine was discontinued were similar to those obtained during the period before the use of the drug; the warfarin dosage remained unchanged. Rechallenge with tolterodine was not attempted in either patient. DISCUSSION: Several aspects of the reported cases support the validity of a proposed drug interaction when tolterodine is initiated in a patient stabilized on warfarin therapy. The temporal association of the course of tolterodine with an elevated INR, the return to the previous warfarin dose-INR response relationship after tolterodine discontinuation, and the absence of other causes for the elevated INR were factors found in both patients. Possible mechanisms to explain the suggested drug interaction are explored. CONCLUSIONS: Until further data are available, clinicians should be vigilant for a possible drug interaction when tolterodine therapy is initiated in a patient maintained on warfarin therapy.