Helping a patient to quit smoking requires accurate identification of the problem, development of an individualized management plan and careful follow-up of the patient's response to treatment. Tools such as the Fagerstrom Test for Nicotine Dependence can help the physician learn about the patient's smoking habit and develop an effective treatment plan. Support from physicians, health care providers, family and smoking cessation groups can help patients quit smoking and maintain long-term abstinence. Nicotine replacement therapy, available in a variety of forms, is most effective when it is used as part of a smoking cessation program for the nicotine-dependent patient.

Humans↗

PubMed1997

An unusual complication of immunosuppressive therapy in inflammatory bowel disease.

A 68-yr-old man with steroid refractory distal ulcerative colitis was treated with low-dose 6-mercaptopurine, and corticosteroids were successfully discontinued. He later presented with dyspnea and fever, was diagnosed with Pneumocystis carinii pneumonia by bronchoalveolar lavage, and died despite aggressive therapy. Serological tests for HIV were negative, and his white blood cell count was normal. This is the first report of P. carinii pneumonia complicating therapy of inflammatory bowel disease with 6-mercaptopurine. Although the mechanism is not entirely clear, 6-mercaptopurine appears to decrease cell-mediated immunity. Opportunistic infections such as P. carinii pneumonia should be added to the list of potential bronchopulmonary complications of antimetabolite immunosuppressive therapy of inflammatory bowel disease.

Aged↗

PubMed1997

Carvedilol following AMI.

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Adrenergic beta-Antagonists↗

PubMed1996

Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies.

Consistent with expectations based on human in vitro microsomal experiments, administration of fluconazole (400 mg/day) for 6 days to six human volunteers significantly reduced the cytochrome P450 (P450)-dependent metabolic clearance of the warfarin enantiomers. In particular, P4502C9 catalyzed 6- and 7-hydroxylation of (S)-warfarin, the pathway primarily responsible for termination of warfarin's anticoagulant effect, was inhibited by approximately 70%. The change in (S)-warfarin pharmacokinetics caused by fluconazole dramatically increased the magnitude and duration of warfarin's hypoprothrombinemic effect. These observations indicate that co-administration of fluconazole and warfarin will result in a clinically significant metabolically based interaction The major P450-dependent, in vivo pathways of (R)-warfarin clearance were also strongly inhibited by fluconazole. 10-Hydroxylation, a metabolic pathway catalyzed exclusively by P4503A4, was inhibited by 45% whereas 6-, 7-, and 8-hydroxylations were inhibited by 61, 73, and 88%, respectively. The potent inhibition of the phenolic metabolites suggests that enzymes other than P4501A2 (weakly inhibited by fluconazole in vitro) are primarily responsible for the formation of these metabolites in vivo as predicted from in vitro kinetic studies. These data suggest that fluconazole can be expected to interact with any drug whose clearance is dominated by P450s 2C9, 3A4, and other as yet undefined isoforms. Overall, the results strongly support the hypothesis that metabolically based in vivo drug interactions may be predicted from human in vitro microsomal data.

Adult↗

PubMed1993

Evaluation of the effect of fluoxetine on the formation of carbamazepine epoxide.

Fluoxetine has been reported to increase carbamazepine (CBZ) plasma concentrations and cause adverse effects. CBZ-10, 11 epoxide (CBZE), the major metabolite of CBZ, contributes to the clinical effect and toxicity of CBZ. The objective of the present study was to investigate the effect of fluoxetine and its major metabolite, norfluoxetine, on CBZE formation in isolated perfused rat liver, in vitro human liver (n = 5) microsomes, and patients (n = 14), after either CBZ monotherapy or polytherapy with fluoxetine. In isolated perfused rat liver, there was no effect of fluoxetine (n = 8) or norfluoxetine (n = 6) on the formation clearance of CBZE (12.8 +/- 5.3 and 11.7 +/- 3.8 ml/min, respectively) or the intrinsic metabolic clearance of CBZ (6.6 +/- 2.7 and 6.3 +/- 1.8 ml/min, respectively). Studies on human liver microsomes confirmed that neither fluoxetine or norfluoxetine inhibited formation of CBZE until concentrations were > 20 times those found clinically. In support of this, there was no difference in the ratio of CBZE to CBZ plasma concentrations in patients also receiving fluoxetine when compared to patients on CBZ monotherapy; however, there was a trend toward a decrease in the apparent plasma clearance of CBZ. In conclusion, increased plasma concentrations of CBZ found when fluoxetine is added are not due to decreased formation of CBZE. Clinically, if fluoxetine causes an increase in CBZ levels, CBZE plasma concentrations will increase proportionately and contribute to the toxicity.

Animals↗

PubMed1990

Possible potentiation of warfarin by fluconazole.

Fluconazole, a new triazole antifungal agent, interacts with a number of drugs. Only one study to date has examined the potentiation of warfarin's anticoagulant effect by fluconazole. To our knowledge, this is the first published case report of this interaction in the clinical setting. The patient had received a stable dosage regimen of warfarin for a number of months. Fluconazole 100 mg bid was added for a candidal wound infection. The prothrombin time increased from 19 to 65 seconds eight days later and the patient experienced a gastrointestinal bleeding episode. Fresh-frozen plasma was administered and warfarin was discontinued while the patient completed a planned 21-day course of fluconazole. The patient eventually resumed the original warfarin dosage with stable coagulation parameters. Until the influence of fluconazole on the anticoagulant effect of warfarin is studied in further detail, careful monitoring of coagulation parameters is recommended for all patients receiving the combination.

Administration, Oral↗

PubMedDate not supplied

Combined ipratropium and beta2--adrenergic receptor agonist in acute asthma.

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Administration, Inhalation↗

PubMedDate not supplied

Troglitazone in type II diabetes mellitus.

Troglitazone, a new antihyperglycemic agent, is approved for use alone, with oral sulfonylureas, or with insulin in the treatment of type II diabetes mellitus. Rather than stimulating insulin secretion, it enhances insulin sensitivity. Potential advantages of troglitazone over oral sulfonylureas include decreased endogenous insulin concentrations, decreased exogenous insulin requirements, reduced hypoglycemic risk, and convenient once/day administration. The effect on morbidity and mortality from lowering endogenous and exogenous insulin concentrations remains to be determined. Troglitazone also has potential disadvantages. It induces cytochrome P450 isoenzyme 3A4, although few drug interactions have been identified to date. Serum transaminases must be monitored routinely because of rarely reported cases of idiosyncratic hepatocellular injury. In addition, the cost of troglitazone is much higher than that of other oral antihyperglycemic agents or insulin. Given the available information, troglitazone has limited benefit over oral sulfonylureas or metformin as monotherapy or in combination with oral sulfonylureas. Until additional combination and comparative studies have been done, the agent should be reserved for patients with poor glycemic control receiving high daily doses of insulin.

Chromans↗