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1.
OBJECTIVE: To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia. METHODS: Twenty-six consecutive patients with chronic orchialgia were seen in the chronic pain clinic by a multidisciplinary team. A pain questionnaire was completed prior to commencing either gabapentin or nortriptyline. They were reviewed at 3 months and a repeat questionnaire completed. A 50% improvement in pain was considered successful. RESULTS: Complete data was available for 19 patients. Overall, 61.5% of patients commenced on gabapentin and 66.6% of patients commenced on nortriptyline had a greater than 50% improvement in pain. Patients with post-vasectomy testicular pain were considered as a subgroup. None of these patients had a greater than 50% improvement in pain. However, 80% of patients in the subgroup with idiopathic chronic orchialgia had a greater than 50% improvement in pain. CONCLUSION: Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain. 相似文献
2.
Summary Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, Medicoal was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought. 相似文献
3.
Constant P. Van Schayck Janneke Kaper Edwin J. Wagena Emiel F. M. Wouters & Johannes L. Severens 《Addiction (Abingdon, England)》2009,104(12):2110-2117
Objectives In healthy smokers, antidepressants can double the odds of cessation. Because of its four times lower costs and comparable efficacy in healthy smokers, nortriptyline appears to be favourable compared to bupropion. We assessed which of both drugs was most effective and cost‐effective in stopping smoking after 1 year compared with placebo among smokers at risk or with existing chronic obstructive pulmonary disease (COPD). Methods A total of 255 participants, aged 30–70 years, received smoking cessation counselling and were assigned bupropion, nortriptyline or placebo randomly for 12 weeks. Prolonged abstinence from smoking was defined as a participant's report of no cigarettes from week 4 to week 52, validated by urinary cotinine. Costs were calculated using a societal perspective and uncertainty was assessed using the bootstrap method. Results The prolonged abstinence rate was 20.9% with bupropion, 20.0% with nortriptyline and 13.5% with placebo. The differences between bupropion and placebo [relative risk (RR) = 1.6; 95% confidence interval (CI) 0.8–3.0] and between nortriptyline and placebo (RR = 1.5; 95% CI 0.8–2.9) were not significant. Severity of airway obstruction did not influence abstinence significantly. Societal costs were €1368 (2.5th–97.5th percentile 193–5260) with bupropion, €1906 (2.5th–97.5th 120–17 761) with nortriptyline and €1212 (2.5th–97.5th 96–6602) with placebo. Were society willing to pay more than €2000 for a quitter, bupropion was most likely to be cost‐effective. Conclusions Bupropion and nortriptyline seem to be equally effective, but bupropion appears to be more cost‐effective when compared to placebo and nortriptyline. This impression holds using only health care costs. As the cost‐effectiveness analyses concern some uncertainties, the results should be interpreted with care and future studies are needed to replicate the findings. 相似文献
4.
为研究在人体内ORM1基因多态性对去甲替林游离药物浓度的影响, 首先采用测序对ORM1进行基因型分析。挑选出ORM1*F1/*F1, ORM1*F1/*S, ORM1*S/*S个体各6人, 进行临床试验。试验当日早上空腹口服去甲替林25 mg, 分别于0, 1, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96和168 h采外周静脉血5 mL, 运用HPLC-MS/MS分别测定血清中去甲替林总药物浓度、10-OH-去甲替林药物浓度及超滤液中去甲替林游离药物浓度,分析不同基因型间去甲替林各药代动力学参数的差异。结果表明不同基因型个体间总去甲替林和10-OH-去甲替林各药代动力学参数,差别无统计学意义。而对于ORM1*F1/*F1基因型个体,血浆中游离药物总量约为ORM1*F1/*S和ORM1*S/*S的2倍, 差别有统计学意义(P<0.05)。去甲替林平均血浆蛋白结合率约为(94.81±1.91)%。在服药后2, 3, 4, 6, 8和12 h, ORM1*F1/*F1基因型个体血浆蛋白结合率均低于其余两种基因型个体, 在Tmax(4 h)左右, 差异更为显著(P<0.05)。ORM1不同基因型对去甲替林血浆蛋白结合率和游离药物浓度均存在影响,表现为ORM1*S/*S基因型个体结合药物的能力强于其他两种基因型个体,从而导致血清中去甲替林游离血药浓度较低。 相似文献
5.
B. Siwers U. Freyschuss B. Hamberger D. Tuck T. Malmfors F. Sjöqvist 《European journal of clinical pharmacology》1970,3(1):12-17
Summary This report describes a phase I clinical trial of a new tricyclic imipramine analogue (Leo 640) with a hydrogen atom in one of the N-methylgroups substituted by a p-chlorobensoyl. To get an objective assessment of the effects of Leo 640 we utilized the fact that tricyclic antidepressants inhibit the uptake of tyramine (thereby blocking its indirect sympathomimetic effects) and noradrenaline into peripheral adrenergic nerves. Dose-response (systolic pressor effects) curves for tyramine (TA) were established before and during treatment with Leo 640. Adrenergic nerves from the rat iris were incubated in the patient's plasma drawn immediately before the TA tests. The inhibitory effect of the endogenous plasma level of Leo 640 (and/or its metabolites) on the uptake of3H-noradrenaline (3H-NA) in these nerves was then determined. — Leo 640 was given orally in successively increasing doses (up to 1.1–5.6 mg/kg/day) to fifteen patients with various forms of depression. The duration of treatment was usually 3–4 weeks. Leo 640 caused a blockade of TA- pressor responses. Plasma of all treated patients inhibited the uptake of3H-NA in the rat iris. The results in the two tests were reasonably well correlated (p<0.01). — The results in the TA- and rat-iris tests were compared with those obtained with nortriptyline (NT) in the same dose-range in nine other patients. In comparison with NT, Leo 640 had a more pronounced inhibitory effect on TA-responsesin vivo than of3H-NA uptake in adrenergic nervesin vitro. A possible explanation might be that Leo 640 has an -receptor blocking effect. — For both Leo 640 and NT, poor correlations were found between the doses (mg/kg) used and the objective effects, when different patients were compared, probably due to marked interindividual differences in pharmacokinetics. — It is concluded that the dose-range of Leo 640 should be similar to that of NT in terms of the effects onperipheral adrenergic neurons.A preliminary account of this paper has appeared (Siwerset al. 1969). 相似文献
6.
P D Hrdina 《Psychiatry research》1984,11(4):271-278
Specific binding of 3H-imipramine to membrane preparations from the cerebral cortex and hippocampus was measured in rats given nortriptyline (10 mg/kg/day), mianserin (10 mg/kg/day), haloperidol (1 mg/kg/day), or saline for 21 days and killed 48 hours after the last injection. Chronic treatment with nortriptyline resulted in a significant decrease in density (Bmax) of 3H-imipramine binding sites in the hippocampus but not in cerebral cortex without significant changes in binding affinity (Kd). Mianserin treatment failed to alter Bmax and Kd of specific 3H-imipramine binding in either of the two brain regions. Repeated administration of haloperidol also produced a lowering in the number of 3H-imipramine binding sites (Bmax) in the hippocampus. The results indicate that the ability of tricyclic antidepressants to down-regulate 3H-imipramine recognition sites in the brain is not shared by nontricylic antidepressants such as mianserin. The observation that down-regulation of binding can also be produced by a typical antipsychotic drug, haloperidol, suggests that this phenomenon may not be related to the mode of therapeutic effect of antidepressants. 相似文献
7.
The polymorphic enzyme cytochrome P450 CYP2D6 is involved in the metabolism of many antidepressants, including nortriptyline and fluoxetine. Some 7%-10% Caucasians have inactivating mutations in both alleles of the CYP2D6 gene, and are referred to as poor metabolizers (PMs). Several case reports and clinical studies suggest that CYP2D6 PMs are at a greater risk of developing adverse drug reactions (ADRs) on antidepressant medication than extensive metabolizers (EMs). However, few clinical trials have investigated whether CYP2D6 PM genotype is predictive of ADRs during antidepressant treatment. This paper explores the link between CYP2D6 genotype and antidepressant-associated ADRs in outpatients being treated for major depression with either nortriptyline or fluoxetine. Patients were randomized to fluoxetine (n=65) or nortriptyline (n=60) for the 6 week trial. CYP2D6 genotypes predicted that of these patients 115 were EM and the remaining 10 were PMs. ADRs attributed to antidepressant usage were recorded over the 6-week trial. Although the type of ADR was, as expected, different between drugs, the frequency of ADRs experienced did not differ significantly between the two antidepressants or between CYP2D6 PMs and EMs. In addition, the frequency at which PMs discontinued antidepressant medication was not noticeably different from EMs, although with only 10 PMs the study is under powered to detect moderate or small differences. These findings suggest that inability to efficiently metabolize antidepressants that are CYP2D6 substrates does not necessarily lead to increased occurrence of antidepressant-associated ADRs. Thus, for clinicians prescribing antidepressant monotherapy, CYP2D6 polymorphisms are probably not of relevance to antidepressant side effects and therapy. 相似文献
8.
José M. Vila Pascual Medina Gloria Segarra Paloma Lluch Federico Pallardó Blas Flor & Salvador Lluch 《British journal of clinical pharmacology》1999,48(2):223-229
AIMS: The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. METHODS: Arterial segments (lumen diameter 0.8-1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operations (22 men and 19 women), and rings 3 mm long were mounted in organ baths for isometric recording of tension. In some artery rings the endothelium was removed mechanically. RESULTS: In precontracted artery rings amitriptyline, nortriptyline and sertraline (3x10(-7)-10(-4) m ) produced concentration-dependent relaxation that was independent of the presence or absence of vascular endothelium. Incubation with indomethacin (3x10(-6) m ) reduced the pD2 values thus indicating the participation of dilating prostanoid substances in this response. Amitriptyline and nortriptyline inhibited both the neurogenic-and noradrenaline-induced contractions. In contrast, only the highest concentration of sertraline reduced the adrenergic responses. Amitriptyline, nortriptyline and sertraline inhibited contractions elicited by KCl and produced rightward shifts of the concentration-response curve to CaCl2 following incubation in calcium-free solution. CONCLUSIONS: These results indicate that amitriptyline and nortriptyline could act as adrenoceptor antagonists and direct inhibitors of smooth muscle contraction of human mesenteric arteries, whereas sertraline might principally exert its action only as direct inhibitor of smooth muscle contraction. This relaxant mechanism involves an interference with the entry of calcium. 相似文献
9.
10.
DeterminationofamitriptylineandnortriptylineinhumanlivermicrosomeswithreversedphaseHPLCinvitro1SHUYan,ZHURongHua2,XUZhenHu... 相似文献