市售西咪替丁和双嘧达莫抗森林脑炎病毒作用的研究

目的　探讨西咪替丁与双嘧达莫对感染森林脑炎病毒的小鼠的死亡保护作用。方法　将不同浓度的西咪替丁和双嘧达莫经腹腔注射给已感染森林脑炎病毒的小鼠 ,同时设立对照组。结果　西咪替丁与双嘧达莫均可延长感染病毒鼠的平均存活天数 (P均小于 0 .0 5) ,西咪替丁还可降低小鼠的死亡率 (P <0 .0 5) ,但未观察到随西咪替丁浓度的增加有降低死亡率的特点。结论　西咪替丁与双嘧达莫均有抗森林脑炎病毒的作用     

Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats

Summary— The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (ip) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected ip with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 ± 18 to 164 ± 13 ng/mL) and a parallel increase in lidocaine levels (from 73 ± 22 to 172 ± 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produced a significant decrease in MEGX levels (151 ± 16 and 139 ± 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with Cimetidine produced a marked decrease in lidocaine levels (37 ± 27 and 63 ± 28 ng/mL, respectively) and no modification of MEGX levels (155 ± 12 and 165 ± 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of Cimetidine.     

The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats

The role of vagus in the actions of different acid inhibitors on ethanol-induced gastric damage and mucosal blood flow (GMBF) changes was studied in anaesthetized rats, using an ex vivo stomach chamber preparation. Subdiaphragmatic bilateral vagotomy decreased the basal gastric acid secretion and GMBF; it also intensified ethanol-evoked lesions in the glandular mucosa. Misoprostol, omeprazole and cimetidine produced a similar degree of reduction in acid output. Misoprostol given subcutaneously (s.c.) (50 micrograms/kg), or added to the incubation solution (12.5 micrograms) for 15 min, markedly prevented ethanol-induced lesion formation and reduction in GMBF. The reversing effect of s.c. injection of misoprostol on either lesion formation or on GMBF reduction was attenuated by vagotomy. Omeprazole protected against lesion formation only when present in the incubation solution (12.5 mg) of ex vivo chamber preparations of both vagus-intact and vagotomized animals, but the effect was significantly less in the latter group. The drug also prevented the depressive action of ethanol in vagus-intact animals. Cimetidine pretreatment (50 mg s.c. or 12.5 mg in incubation solution), however, did not modify the effects of ethanol on lesion formation and the GMBF. The findings indicate that the three different types of acid inhibitors exert different actions on ethanol-induced gastric mucosal damage, although they produced similar inhibition of acid output. Vagotomy lowers the GMBF and attenuates the antiulcer action of misoprostol and omeprazole, especially when the drugs are given by the parenteral route.     

甲氰咪胍与硫糖铝对老年食管癌术后院内感染性肺炎的观察

目的观察甲氰咪胍与硫糖铝对老年食管癌术后院内感染性肺炎的影响.方法将60岁以上食管癌病人分为甲氰咪胍组、硫糖铝组、对照组,术后观察院内感染性肺炎情况.结果院内感染性肺炎发生率:甲氰咪胍组30.6%,硫糖铝组8.6%,对照组10.7%,甲氰咪胍组分别与硫糖铝组、对照组相比,差别有统计学意义.硫糖铝组与对照组相比,差別无统计学意义.结论甲氰咪胍组与硫糖铝组相比,可引起较高的院内感染肺炎的发生率,硫糖铝在老年食管癌病人术后可替代甲氰咪胍应用.     

甲氰咪胍与硫糖铝对呼吸机相关性肺炎发病的影响

对６１例急性呼吸衰竭进行气管插管机械通气患者，分别用硫糖铝和甲氰咪胍预防应激相关性上消化道出血，观察防治效果及对呼吸机相关性肺炎（ＶＡＰ）发病率的影响，结果显示，两组患者消化道出血发生率无差异（Ｐ〉０．０５），ＶＡＰ总发生率亦无显著性差别（Ｐ〉０．０５），而晚发性ＶＡＰ发生率硫糖铝组显著低于甲氰咪胍组（Ｐ〈０．０５）。建议机械通气患者用药物预防应激相关性上消化道出血时，优先选用硫糖铝，以降低晚发生     

Single dose oral H2-antagonists do not affect plasma lidocaine levels in the parturient

We studied whether a single oral dose of either cimetidine or ranitidine affects the disposition of epidurally administered lidocaine in the parturient. Patients given epidural analgesia for elective caesarean section were randomly pretreated with either cimetidine 400 mg (n = 5), ranitidine 150 mg (n = 7) or no H2 receptor antagonist (n = 5). Following the administration of 400 mg of lidocaine 2% with adrenaline 1:200,000 no difference was found in peak plasma lidocaine levels or area under the plasma concentration/time curve (AUC) between the three groups. A single oral dose of cimetidine or ranitidine does not affect lidocaine disposition in the obstetric patient.     

Do nizatidine and cimetidine interact with ibuprofen?

Summary The potential for interaction between ibuprofen and two histamine H₂-receptor blocking drugs — nizatidine and cimetidine — was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration.There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects.It is concluded that neither H₂-blocker affects the kinetics of ibuprofen in man.     

THE INFLUENCE OF SMOKING ON THE HEALING OF DUODENAL ULCER TREATED WITH OXMETIDINE OR CIMETIDINE

The influence of smoking on duodenal ulcer healing was examined during a double blind study of 83 patients randomly allocated to oxmetidine or cimetidine treatment. Smoking habits were recorded but patients were not advised to change these. Smokers and nonsmokers were similar clinically and did not differ in compliance with medication. Both H₂-receptor antagonists were equally effective and after four weeks of treatment ulcers were healed in 76% of patients. Ulcer healing occurred significantly less frequently in smokers (69%) than nonsmokers (89%). Smokers with healed ulcers consumed fewer cigarettes per day (mean ± SE: 15.8±1.4) than those whose ulcers did not heal (22.2±2.7). When smokers were grouped according to daily cigarette consumption, a direct relationship was found between increasing cigarette consumption and decreasing frequency of ulcer healing. No reduction in ulcer healing was apparent in patients who smoked nine cigarettes a day, or less. (Aust NZ J Med 1983; 13:687-590.)     

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2-receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P < 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P < 0.002), SP (943 ± 183 vs 1072 ± 187 msec P < 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P < 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P < 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P < 0.05), SP (686 ± 114 vs 717 ± 109 msec P < 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P < 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2-receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.     

Effect of cimetidine and ranitidine on plasma theophylline in patients with chronic obstructive airways disease treated with theophylline and corticosteroids

Summary Thirty adults with chronic obstructive airways disease, who were stabilised on theophylline and corticosteroids, took part in a single blind study of the effects of cimetidine and ranitidine on plasma theophylline concentrations. The patients were randomised to receive either 150 mg ranitidine b. d. or 400 mg cimetidine b. d. for one week and serial plasma theophylline measurements were made over a 12-hour period on two consecutive days before, during and after treatment with the H₂-antagonist.There was a significant increase in plasma theophylline during treatment with cimetidine; two patients had levels > 20 mg·1^–1. The average increase in the theophylline concentration due to cimetidine was 32%. There was no significant change in plasma theophylline during ranitidine administration. No adverse effect occurred in any patient during the study.