Asymmetry of consequences of drug disposition mechanisms in the wall of the rabbit aorta.
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Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.
The authors assessed perceptual changes in 12 depressed patients treated wih bupropion, 12 patients given other antidepressants, and 12 drug-free controls. Bupropion was associated with vivid dreaming and changes in attention, memory, and perception. which may have contributed to its therapeutic effectiveness.
Bupropion HCl, a new nontricyclic antidepressant, produced marked improvement in 49 hospitalized patients with primary depression at doses of 300-600 mg/day. Bupropion resulted in statistically significant differences from placebo as early as day 5, and by the end of the 4-week study 79% (N = 27) of the bupropion patients and 13% (N = 2) of the placebo patients showed much to very much improvement. Bupropion and placebo had similar side effect profiles. Tremor and sweating were reported more often with bupropion and headache, nausea, and tiredness with placebo.
The authors describe the development of acute psychoses in four patients treated with bupropion, a unicyclic aminoketone antidepressant. In two of the cases the psychoses seemed to be affected by dose. The mechanism responsible for the psychotic reactions is unclear, although it may involve perturbation of dopaminergic systems. On the basis of their experience, the authors offer recommendations regarding the clinical use of bupropion.
Twelve inpatients with major depression refractory to at least two controlled antidepressant trials had tranylcypromine added to ongoing lithium treatment. Eleven patients showed reliable improvement in nurses' depression ratings compared with a prior trial of lithium added to an antidepressant that was not a monoamine oxidase inhibitor (MAOI). Eight patients were blindly judged much or very much improved, and all 12 patients improved sufficiently to be discharged. Preclinical studies of conjointly administered lithium and MAOIs suggest that central serotonergic pathways may mediate this robust clinical effect.
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The authors treated 19 adults with attention-deficit hyperactivity disorder with an open trial of bupropion. These patients had received maintenance stimulant medication or monoamine oxidase inhibitors for an average of 3.7 years. Fourteen of the patients experienced moderate to marked benefit from bupropion; ten of these patients chose to continue bupropion rather than their former medication. These results suggest that bupropion may be an alternative to stimulants in treating some adults with attention-deficit hyperactivity disorder.
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OBJECTIVE: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients. METHOD: The subjects were 36 inpatients with DSM-III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography. RESULTS: Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients. CONCLUSIONS: The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings.
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Three new antidepressants have been marketed in the United States since 1980, and about two dozen more are being evaluated. In a 1983 workshop convened by the National Institute of Mental Health, participants examined the claims made for the newer antidepressants in relation to clinical efficacy, speed of onset, cardiovascular effects, and other adverse reactions. In this summary report of the workshop, primarily covering amoxapine, maprotiline, trazodone, and the investigational drug bupropion, the authors note that none of the new antidepressants demonstrate greater effectiveness than standard tricyclics, although some produce a different profile of side effects. The main benefit of the newer drugs is that they offer new options for the treatment of patients who cannot tolerate side effects of the traditional drugs or have responded unsatisfactorily to them.
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Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment of stomatitis.