Combined paracetamol and amitriptyline adsorption to activated charcoal

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q_m) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC?:?drug ratios were 10?:?1, 5?:?1, 3?:?1, 2?:?1, and 1?:?1. The mixed-drug adsorption vials contained the same AC?:?paracetamol ratios, but amitriptyline was added as fixed dose (0.080 g) to all samples. Drug concentrations in the liquid phase were analyzed using high-performance liquid chromatography (HPLC)/UV-detection. Results. Q_m, amitriptyline, were 0.49 g/g Carbomix® and 0.70 g/g Norit Ready-To-Use, and Q_m, paracetamol, were 0.63 g/g Carbomix® and 0.72 g/g Norit Ready-To-Use. The tested pH differences had minor effect on the adsorption. The mixed-drug adsorption showed about 40% Q_m reduction of each drug with increasing amounts of drug/g AC, but the total gram of drug adsorbed to AC was increased compared to one-drug conditions. Conclusion. The adsorption of the two compounds to AC seems to compete resulting in lower maximum adsorption capacity for both drugs when mixed. However, a great adsorptive capacity was noted and might be explained by adsorption of the drugs to different AC surface sites. Furthermore, the Norit Ready-To-Use preparation, with less volume and total weight for the same AC dose as Carbomix®, showed a higher Q_m. This might be clinically significant in terms of preventing nausea, vomiting, and subsequent aspiration.     

Acetaminophen/diphenhydramine overdose in profound hypothermia

Background. There are few reports of acetaminophen overdose in hypothermic patients and even fewer reports describing profound hypothermia. The kinetics, risk of hepatotoxicity, and the possible dose adjustments to N-acetylcysteine (NAC) therapy are not known in this setting. Case report. A 37-year-old female was found unconscious outside in December and was brought by ambulance to a tertiary care Emergency Department (ED) following a presumed overdose of acetaminophen and diphenhydramine. She later confirmed the ingestion and reported the ingestion had occurred approximately 18 hours prior to being found. On arrival, she was profoundly hypothermic, with a core rectal temperature of 17°C. Her initial serum acetaminophen concentration was 232 mcg/mL 19 hours post ingestion of a reported dose of approximately 50 grams of acetaminophen and 2.5 grams of diphenhydramine. Active rewarming was started immediately and IV NAC was initiated using the standard treatment protocol. The patient did not develop serious signs of hepatic injury or NAC toxicity. The patient's AST and ALT peaked 12 hours after admission at 84 IU/L (ref 10–37 U/L) and 104 IU/L (ref 12–78 U/L), respectively. Her INR peaked 2 hours after admission at 1.46 (ref < 1.2). Discussion. Despite the significant ingestion of acetaminophen, delayed presentation, prolonged period of decreased responsiveness, and profound hypothermia, the patient did not develop any signs/symptoms of liver injury. NAC was administered in a standard dose during her rewarming period without apparent toxicity. The patient's absorption and/or metabolism of acetaminophen were likely slowed by her hypothermia and possibly by the anticholinergic coingestant. Initiation of IV NAC at a standard dose was apparently safe and effective in preventing hepatotoxicity as the patient was rewarmed. Conclusions. Profound hypothermia may be protective of hepatic injury in acetaminophen overdose. Delayed absorption from the coingestant, diphenhydramine, may also have played a role. IV NAC was given in a standard dose without apparent toxicity in the setting of profound hypothermia. Lastly, IV NAC, in standard dosing, appeared to be effective in preventing hepatotoxicity during rewarming in a patient with a potentially hepatotoxic concentration of acetaminophen with a coingestion of the anticholinergic agent, diphenhydramine.     

Diazabicyclononanones,a potent class of kappa opioid analgesics

The 1,5-dimethyl 3,7-diaza-3,7-dimethyl-9-oxo-2,4-di-2-pyridine-bicyclo[3.3.1]nonane-1,5-dicarboxylate, HZ2, has a high and selective affinity for the kappa opioid receptor and an antinociceptive activity comparable to morphine. In addition, it is characterized by a long duration of action and a high oral bioavailability. QSAR studies within series of kappa agonists revealed a chair-boat conformation of a double protonated HZ2 characterized by an almost parallel orientation of the C9 carbonyl group and the N7-H group and at least one aromatic ring to be the pharmacophoric arrangement. Structural variations showed that the pyridine rings in 2 and 4 position can be replaced with p-methoxy-, m-hydroxy- and m-fluoro-substituted phenyl rings. However, all other substituents have to be kept the same for a high affinity to the kappa receptor.     

Remifentanil-sevoflurane anaesthesia for laparoscopic cholecystectomy: comparison of three dose regimens

The objective of this study was to determine a dosing regimen for remifentanil-sevoflurane anaesthesia that achieves an optimal balance between quality of anaesthesia and time to recovery. Patients undergoing elective laparoscopic cholecystectomy were randomly allocated to receive 0.4, 0.8 or 1.2 MAC (minimal alveolar concentration) of sevoflurane combined with remifentanil as required to maintain stable anaesthesia. For induction of anaesthesia, the remifentanil dose was 25 microg x kg(-1) x h(-1) and the mean propofol dose which was required to obtain loss of consciousness was 1.59 mg x kg(-1). During the maintenance phase, the mean remifentanil dose was 16.0, 14.1 and 13.0 microg x kg(-1) x h(-1) for the 0.4, 0.8 and 1.2 MAC groups, respectively. The mean sevoflurane maintenance dose was 0.91, 1.24 and 2.1% end-tidal for the 0.4, 0.8 and 1.2 MAC groups, respectively. The incidence of somatic responses was significantly higher in the 0.4 MAC sevoflurane group. Recovery times were significantly faster in the 0.4 compared to the 0.8 and 1.2 MAC groups and in the 0.8 compared to the 1.2 MAC group. The combination of 14 microg x kg(-1) x h(-1) remifentanil and 1.24% end-tidal sevoflurane achieved the optimal balance between the quality, and recovery from anaesthesia.     

消炎宁痔疮栓药效学研究

目的观察消炎宁痔疮栓的药效学作用。方法以小鼠耳肿胀和大鼠足跖肿胀法实验,观察其抗炎作用;应用热板法考察其镇痛作用;用小鼠断尾法观察出血时间。结果消炎宁痔疮栓有明显的抑制小鼠耳肿胀和大鼠足跖肿胀作用(P<0.01);热板法验证消炎宁痔疮栓能明显提高痛阈;小鼠断尾显示其能缩短小鼠尾出血时间。结论消炎宁痔疮栓具有明显的抗炎、镇痛及止血作用。     

Role of the double-contrast barium enema in rectal stenosis due to suppositories containing paracetamol and acetylsalicylic acid

Self-treatment of chronic headache with suppositories containing paracetamol and acetylsalaicylic acid may lead to serious complications. We report the radiological features of five cases of rectal stenosis following the use of such suppositories. The role of the double-contrast barium enema in suggesting the diagnosis of this complication of a chronic and often unrecognized self-treatment is emphasized. Received: 1 August 1997; Accepted: 27 October 1997     

Controlled-release morphine in cancer pain

Nineteen patients with pain from advanced cancer stabilised on oral 4-hourly aqueous morphine who were to be converted to twice daily controlled-release morphine tablets (MST Continus) completed this study. Patients were randomised to receive either their usual 4-hourly morphine dose or placebo with the first dose of MST tablets. There were no significant differences between the treatment groups in ratings of pain intensity, pain relief or side effects, or in any of the measured pharmacokinetic parameters. No patients in the placebo group experienced any breakthrough pain, and nursing staff were unable to identify which patients had received the active dose of morphine elixir. We conclude that there is no need for a loading dose when aqueous morphine is changed to MST tablets.     

Patterns of regular drug use in Spanish childbearing women: changes elicited by pregnancy

Objective: To determine drug use in Spanish women before pregnancy and from conception to the awareness of pregnancy (early period of pregnancy, EPP), as well as to analyse attitudinal changes when pregnancy was planned or known. Methods: Trained gynaecologists used a structured questionnaire to collect demographic and obstetric characteristics, histories of regular drug taking before pregnancy, attitudes towards drug taking during pregnancy and current drug use in the EPP. Women were interviewed at their first antenatal visit during the first trimester. Results: Two hundred and seventy-two women were included (mean age 29.3 years and 66.3 days of gestation). Before pregnancy, 24% regularly took drugs, 70% of them more than twice a week; a significantly higher frequency was found in those receiving public antenatal care and in those who had had less education. In 39% of women, awareness of pregnancy did not change their attitudes towards regular drug use. Among those who decided to suppress their regular drug intake, 58% did so when their pregnancy was confirmed and 42% when they planned it. In women who planned their pregnancy, 30.1% stopped when they tried to become pregnant. However, 62% of all women took drugs during the EPP. In private antenatal care significantly more drugs were taken per patient. By the 168 women 278 compounds were consumed during the EPP: 40% were analgesics (mainly paracetamol and acetylsalicylic acid) and 25% were digestive and metabolic drugs (mainly antacids and laxatives). Drugs were often used more than twice a week, particularly in women receiving public antenatal care and in those who had had less education. Conclusion: Drug taking is common in Spanish women of childbearing age, and many of those in our study did not decide to stop during the EPP. Few women avoid drugs when planning a pregnancy. Therefore, gynaecologists must advise against drug taking in patients who wish to become pregnant and suggest that unnecessary drug use be avoided when the pregnancy is already diagnosed. Received: 17 February 1998 / Accepted in revised form: 20 May 1998