Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Dig Liver Dis ; 37(11): 832-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16169302

RESUMO

BACKGROUND: Smoking increases plasma fibrinogen and cardiovascular risk whereas transdermal nicotine may not. Fibrinogen is an acute phase protein and may reflect disease activity in ulcerative colitis. AIMS: To examine the effect of topical nicotine on plasma fibrinogen and any relationship between fibrinogen and ulcerative colitis disease activity. PATIENTS: Forty-eight non-smokers with moderately active ulcerative colitis. METHODS: Patients were randomised to 6 mg nicotine enema or placebo for 6 weeks, followed by open nicotine therapy for 4 weeks. Plasma fibrinogen was measured at baseline and after 6 and 10 weeks; at each assessment sigmoidoscopy with a rectal biopsy was performed. RESULTS.: At 6 weeks median plasma fibrinogen was 3.30 g/l on nicotine compared to 3.05 g/l on placebo, P = 0.90 when adjusted for baseline values. There was a correlation between fibrinogen and the UC disease activity index (UCDAI) at weeks 0 and 10, P = 0.036 and 0.033, respectively, and between fibrinogen and sigmoidoscopic grade at each assessment, P = 0.014, 0.021 and 0.034. Changes in fibrinogen did not correlate with changes in disease severity. CONCLUSIONS: There was no significant effect of nicotine enemas, in either direction, on plasma fibrinogen-this was raised in moderately active UC and correlated with the sigmoidoscopic grade of colitis and the UCDAI; however, fibrinogen was not sufficiently sensitive to be of practical clinical value.


Assuntos
Colite Ulcerativa/sangue , Fibrinogênio/análise , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Enema , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Sensibilidade e Especificidade , Sigmoidoscopia
2.
Postgrad Med J ; 81(959): 594-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16143691

RESUMO

BACKGROUND: Therapeutic enemas are often used to treat active colitis but their retention may be limited because of urgency to defecate. Some preparations may be better retained and tolerated than others because of their physical properties. AIM: To compare patient preference and retention of four therapeutic enemas, including a nicotine enema, in patients with ulcerative colitis (UC). METHODS: Twenty four patients with active UC received the four trial enemas-corticosteroid, 5-amino salicylate (5-ASA), and nicotine liquid enemas and a corticosteroid foam, in a randomised order, taking one enema on each of four successive nights. Patients scored them 1 to 4 for ease of administration and retention, degree of abdominal bloating, and for their overall preference. RESULTS: Fifteen patients rated nicotine their overall favourite or second favourite, compared with 14 for corticosteroid foam and 11 for 5-ASA and corticosteroid liquids, but this was not significant (p = 0.302). Overall, there was no significant difference in overnight retention. However, the nicotine enema tended to be less well retained in patients with milder urgency but a higher proportion retained it overnight with more severe urgency (p = 0.031 compared with 5-ASA enema). CONCLUSION: There was no significant difference in patient preference or overall duration of retention for the four enemas.


Assuntos
Colite Ulcerativa/terapia , Enema/métodos , Fármacos Gastrointestinais/uso terapêutico , Satisfação do Paciente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Enema/psicologia , Enema/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/uso terapêutico
3.
Aliment Pharmacol Ther ; 20(8): 859-65, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15479357

RESUMO

BACKGROUND: Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events. AIM: To assess the pharmacokinetics of nicotine enemas in three doses. METHODS: Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine. RESULTS: Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'--30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the tmax. 'Early' adverse events occurred in eight subjects--six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema. CONCLUSION: The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Enema/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Nicotina/farmacocinética , Agonistas Nicotínicos/efeitos adversos , Agonistas Nicotínicos/farmacocinética
4.
Eur J Gastroenterol Hepatol ; 11(11): 1299-304, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10563544

RESUMO

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.


Assuntos
Colo/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Tono Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Nicotina/farmacologia , Adulto , Idoso , Colite Ulcerativa/fisiopatologia , Colo/fisiologia , Cotinina/análise , Relação Dose-Resposta a Droga , Enema , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Nicotina/administração & dosagem , Saliva/química , Sigmoidoscopia
5.
Ital J Gastroenterol Hepatol ; 30(3): 260-5, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9759592

RESUMO

AIMS: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine has therapeutic benefit but causes frequent side-effects. We have previously developed a topical enema combining nicotine with a polyacrylic carbomer; pharmacokinetic parameters were similar in healthy volunteers and patients with active ulcerative colitis. This enema was reformulated to reduce and delay nicotine absorption, thereby improving tolerance. METHOD: Pharmacokinetic observations and side-effects with both formulations are compared in the same 8 healthy volunteers--all non-smokers, 3 male, mean age 33 years. Six milligrams of nicotine were complexed with 400 mg of carbomer in a 100 ml liquid enema. The original formulation was buffered with potassium/phosphate to pH 5.5, kinematic viscosity was 3 mNm; the revised preparation incorporated trometamol 1% solution to buffer to pH 4.2, viscosity 5 mNm. All subjects had the two formulations on separate occasions at least a month apart, with serial blood measurements and side-effect profile recorded for 8 hours. RESULTS: The revised enema formulation significantly reduced Cmax for nicotine from 8.3 +/- 2.7 to 6.6 +/- 2.1, p = 0.03 with some reduction in nicotine absorption and improved tolerance. Although there was considerable intersubject variation in profiles for nicotine and cotinine, they were similar for each subject on both occasions. CONCLUSIONS: The lower pH and greater viscosity reduced the amount of free nicotine in its unionised form available for absorption, but made it possible to expose colonic mucosa to the same nicotine dose. In other drug formulations where side-effects are a limiting factor these modifications may also be relevant.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Nicotina/administração & dosagem , Nicotina/farmacocinética , Polivinil , Resinas Acrílicas , Adulto , Química Farmacêutica , Cotinina/sangue , Portadores de Fármacos , Enema , Feminino , Humanos , Absorção Intestinal , Masculino , Nicotina/uso terapêutico
6.
Aliment Pharmacol Ther ; 11(5): 859-63, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9354193

RESUMO

BACKGROUND: Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side-effects, an alternative in the form of topical therapy with nicotine enemas has been developed. METHODS: In an open study, 22 patients with active colitis, all non-smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre-trial treatment using mesalazine (n = 16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks. RESULTS: Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3-94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side-effects. CONCLUSION: Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Adulto , Idoso , Colite Ulcerativa/patologia , Enema , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sigmoidoscopia
7.
Clin Pharmacol Ther ; 61(3): 340-8, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9084459

RESUMO

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.


Assuntos
Colite Ulcerativa/sangue , Nicotina/administração & dosagem , Nicotina/farmacocinética , Resinas Acrílicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos de Casos e Controles , Colite Ulcerativa/tratamento farmacológico , Cotinina/sangue , Portadores de Fármacos , Enema , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/sangue , Nicotina/química , Polivinil , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA