Intravenous or rectal administration of sedatives in outpatient oral surgery

A number of cross-over studies on sedation in outpatient oral surgery investigated the quality of sedation produced by intravenous or rectal administration of diazepam. The sedation methods were equally efficient with a mean dose of 0.24 mg/kg (range 0.1–0.4) for i.v. administration and 0.53 mg/kg (range 0.5–0.6) for rectal administration. Eighty-five percent of the patients preferred surgery under sedation and local anaesthesia to local anaesthesia alone. The patients preferred the session in which they experienced stronger sedation, regardless of the route of administration.     

Gastric contents and pH after oral premedication

Forty women, aged 26-40 years, were investigated with regard to gastric contents and pH before general anaesthesia. The patients were divided into two groups (20 in each). Group 100 received 0.3 mg kg-1 diazepam orally with 100 ml of water 2 h before surgery. Group 50 received 0.3 mg kg-1 diazepam with 50 ml of water 2 h before surgery. The amount of gastric content was significantly greater in Group 100 than in Group 50 (P less than 0.05). There was no statistical difference in pH values between the groups. The number of patients with both gastric pH less than 2.5 and gastric volume greater than 25 ml was significantly higher in Group 100 compared to Group 50 (P less than 0.05). We cannot recommend the use of oral premedication using these amounts of water, considering the increased risk of aspiration of gastric contents.     

Cases of buprenorphine abuse in India.

Buprenorphine was introduced as a potent analgesic with low abuse potential. Reports of buprenorphine abuse by opiate abusers have accumulated over the years, highlighting its use as a cheap alternative to heroin. The lower potency compared with heroin is being compensated by using a cocktail of buprenorphine with benzodiazepines or cyclizine. This study of 18 cases seen over 3 years broadly confirms these findings. Four cases reported haematemesis during acute withdrawal, a symptom not reported in earlier studies.     

Dissimilarities between benzodiazepine-binding sites and adenosine uptake sites in astrocytes and neurons in primary cultures

The question whether the benzodiazepine receptor site in astrocytes or in neurons might be identical to the adenosine uptake site was studied by determining pharmacological profiles, inhibition types, and the effects of benzodiazepine antagonsts in primary cultures of either astrocytes or neurons. Fourteen different benzodiazepines and five different adenosine uptake inhibitors displaced [³H] diazepam and inhibited adenosine uptake in both astrocytes and neurons. However, the rank orders (determined as IC₅₀ values) with which these two parameters were affected were profoundly different, indicating dissimilarities between these two sites. For several of the compounds a difference in inhibition type (competitive vs. noncompetitive) was observed between the benzodiazepine-binding site and the adenosine uptake site in astrocytes and/or neurons, which further corroborated the conclusion of a difference between the benzodiazepine-binding site and the adenosine uptake site. Finally, the neuronal benzodiazepine antagonists RO 15-1788 and CGS-8216 and the astrocytic benzodiazepine antagonist PK 11195, which reverse the action of benzodiazepines, were not able to reverse inhibition of adenosine uptake by diazepam but exerted an inhibitory effect of their own.     

Simple reaction time event-related potentials: Effects of alcohol and diazepam

1. 1. Acute effects of alcohol and diazepam on reaction time (RT) and event-related potential (ERP) measures were examined in 108 healthy male volunteers.

2. 2. The subjects engaged in a simple RT task at two levels of stimulus intensity during baseline and treatment sessions.

3. 3. Lower stimulus intensity produced increased RTs, increased ERP peak latencies, and suppression of peak amplitudes.

4. 4. Moderate and high doses of alcohol, and high doses of diazepam produced increased RTs. Alcohol suppressed P100 and N100 amplitudes, while diazepam suppressed P100 amplitudes only. P100 amplitudes were correlated to RTs under baseline and treatment conditions.

5. 5. These results were taken as evidence for impaired stimulus detection during alcohol and diazepam intoxication, with both drugs influencing sensory-perceptual processes and alcohol alone influencing the degree of attentiveness.

MK-801 induced stereotypies in rats are decreased by haloperidol and increased by diazepam

Summary The effects of haloperidol and diazepam were investigated on stereotypies (wall contacts and turn rounds) induced by the non-competitive NMDA antagonist MK-801 in rats. Haloperidol (0.03, 0.10, 0.25 and 0.40mg/kg body weight) caused a dose-dependent antagonism whereas diazepam (3.0 and 5.0 mg/ kg) caused a dose-dependent agonism of the stereotypies induced by 0.30 mg/ kg MK-801 (all drugs given intraperitoneal). Conversely, diazepam (5.0 mg/kg) given alone reduced significantly the number of spontaneous wall contacts and turn rounds. The paradoxial stimulation of MK-801 induced stereotypies by diazepam could be explained by a shift between positive and negative corticostriatothalamic feedback loops envolving GABAergic neurons in favour of the former.     

Effect of Omeprazole on Diazepam Disposition in the Rat: in Vitro and in Vivo Studies

Purpose. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat. Methods. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500µM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/ L) and to study the diazepam-omeprazole interaction in vivo. Results. The 3-hydroxlation pathway was more prone to inhibition (K_Is 108 ± 30 and 28 ± 11 µM in microsomes and hepatocytes, respectively) than the demethylation pathway (K_Is of 226 ± 76 and 59 ± 27 µM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/K_I ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a K_I of 57µM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole. Conclusions. The in vivo K_I for the omeprazole: diazepam inhibition interaction shows closer agreement with the K_I values obtained in hepatocytes than with those observed in microsomes.     

安定东莨菪碱在产程中的联合应用（附176例分析）

产程延长传统处理方法是应用催产素静脉点滴，根据安定能选择性使宫颈肌纤维松驰；东莨菪碱能扩张血管，改善微循环，解除平滑肌痉挛，使宫颈水肿消失或减轻，我院妇产科自1988年5月至1989年4月，对176例在产程延长或宫颈水肿的产妇，联合应用安定、东莨菪碱，取得良好的效果，本文介绍了应用方法，并对二药的药理作用进行了讨论。     

Dixyrazine premedication for cataract surgery. A comparison with diazepam

Peroral dixyrazine (15–30 mg, n = 50) and diazepam (4–10 mg, n = 50) were used as premedicants for geriatric patients having cataract surgery under regional block. Compared to the diazepam patients, a larger number of the dixyrazine medicated patients appeared anxious, and there was a statistically significant difference between the groups, when summing up changes in anxiety throughout the study period. The dixyrazine patients needed more frequent supplementation with intravenous sedative drugs, compared with their diazepam counterparts. Peroral dixyrazine is an applicable choice for calm patients, when only slight sedation, or avoidance of somnolence are required.