No abstract available in English.
Flunitrazepam*

It has recently been reported that chemical evaluations of a new benzodiazepine derivative, flunitrazepam (Ro 5-4200) revealed promising effects as premedicant. We studied on effects of premedication by double blind technique comparing flunitrazepam (Ro 5-4200) 0.03mg/kg I.M. and meperidine HCI 1mg/kg I.M. in 300 cases of preoperative patient by random selection. The questionaire on drowsiness, sleepiness and awareness during transport to the operation theatre, as well as nausea and vomiting were checked by anesthetists who were ignorant of the given premedicant. Following results were obtained; 1) Flunitrazepam has excellent calming effects in preanesthetic period, inducing drowsiness and adequate rest. 2) Flunitrazepam produces good sleep the night before operation. 3) Flunitrazepam has lower incidence of nausea and vomiting than that cf meperidine HCI.
Benzodiazepines ; Flunitrazepam* ; Humans ; Incidence ; Meperidine* ; Nausea ; Premedication ; Sleep Stages ; Vomiting

To assess the effect of premedication for pediatric cases, flunitrazepam (Rohypnol) was given to small children under 6 years of age. 70 patients were divided into 4 groups to which the drug was given intramuscularly, 0. 06 mg, 0.1 mg, 0.15 mg and 0. 2 mg per kilogram of body weight, of the drug respectively. The dose was given 30 minutes before anesthesia and the maximum dose was limited to 2.0 mg for each patient if the calculated dose of the drug exceeded this amount. 1) The shortest time of onset of sleep was 5 minutes. The group which fell asleep between 5 and 10 minutes did not respond to needle stimulation. The group which fell asleep between 11 and 15 minutes moved upon needle stimuli but an intravennous needle was inserted without difficulty. 2) The group which fell between 16 and 20 minutes and became sedated after 20 minutes. without asleep was induced by anesthesia with an inhalational agent but aroused by needle stick. The last group was sedated in presence of their guardian only and became uncooperative when they were separated from the latter. 3) The patients were not affected at all with the dose of 0.06mg/kg of flunitrazepam. 4) With the dose of 0. 1 mg/kg, the group under 6 months of age did not sleep and in the; group between 4 and 6 years of age, half did sleep. ) With the dose of 0.15 mg/kg, in the group under the age of one year, 50% of the cases slept and in the group between 2 and 6 years of age, 30% of the cases slept. 6) With the dose of 0. 2 mg/kg, the sleep group was 25% under 1 year of age, 30. 8% between one and 3 years of age and 33% between 4 and 5 years of age, but the maximum. dose given was limited to 2 mg for each case. A tendency to increased effect according to the increase of age was noticed. 7) The optimum dose of the drug was suggested to be 0. 15 mg/kg and if a dose was used of more than 2. 0 mg, it was not needed to increase above this amount for the purpose of sedation. 8) Optimal time for premedication was suggested to be 30 minutes before the induction of anesthesia. 9) Respiratory and circulatory depression were not noticed with the above doses. 10) Endotracheal intuhation was faeilitated without the aid of muscle relaxant in about 30% of cases when 0.15mg)kg Of the drug was given. (Acknowledgement: We are grateful to Roche Far East Research Foundation for supplies of flu- nitrazepam for this study and to Dr. R. Lassere for advice.)
Anesthesia ; Body Weight ; Child* ; Depression ; Equipment and Supplies ; Far East ; Flunitrazepam* ; Humans ; Needles ; Nitrazepam ; Premedication

Pregnolone[5beta-pregnan-3alpha-ol-one(5beta3alpha)] and allopregnanolone [(5alpha-pregnan-3alpha-ol-20-one(5alpha3alpha))] are neuroactive steroids that are reduced metabolites of progesterone. It was reported that Neuroactive steroids may have anxiolytic and anticonvulsant action similar to benzodiazepines and barbiturates. Therefore, the present study was designed to assess the interaction of steroids with GABAA-benzodiazepine receptor complex. The effect of steroids on the ligands binding to GABAA receptor complex was investigated using rat cortices. 5beta3alpha and 5alpha3alpha enhanced the binding of [3H] flunitrazepam to GABAA receptor, but testosterone, progesterone and dexamethasone did not. GABA also showed the enhancement of [3H] flunitrazepam binding, but did not show the additive effect. Unlike to GABA, 5beta3alpha and 5alpha3alpha did not affect on the [3H] muscimol binding to rat cortices. From these findings, it can be concluded that Neuroactive steroids are potent positive modulators of the GABA A receptor, and do not act at GABA binding site.
Animals ; Barbiturates ; Benzodiazepines ; Binding Sites ; Dexamethasone ; Flunitrazepam ; gamma-Aminobutyric Acid ; Ligands ; Muscimol ; Pregnanolone ; Progesterone ; Rats ; Receptors, GABA-A ; Steroids* ; Testosterone

Corticosteroids have endowed the organism with the capacity to resist many types of noxious stimuli, and enviromental changes. Although many anesthetic agents and surgical stress have been shown to have some influence on adrenocortical function in man, there is no report on the effect of flunitrazepam-morphine-nitrous oxide anesthesia on endocrine activity. The present investigation was undertaken to study to what extent flunitrazepam-morphine-nitrousoxide anesthesia nfluences adrenocortical function by judging its effect on plasma cortisol levels in peripheral venous blood in man. Fifteen patients, ranging in age from 17 to 48 years (average 33 years) and in weight from 46kg to 73kg(average 58kg) who underwent various surgical operations, were free from endocrine, neurological, hepatic, renal and cardiopulmonary disease. Each patient was premedicated with atropine sulfate(0.01mg/kg) and Valium(0.15mg/kg) i.m. one hour before the induction of anesthesia. Anesthesia was induced at 9:00 a.m. with flunitreazepam(0.05+/-0.01mg/kg) and morphine(0.29+/-0.04mg/kg) was given by intreavenous injection. Pancuronium bromide(0.09+/-0.013 mg/kg) was given intreavenously for endotracheal intubation. General anesthesia was maintained with nitrous oxide 2L/min. and oxygen 1L/min. controlled ventilaration was carried on throughout the procedure. A moderate depth of anesthesia was maintained by clinical judgment based on signs including blood pressure and pulse rate. Blood samples were obtainesd at the following times: 1) the control group at 9:00 a.m. just prior to induction. 2) 30 min after anesthesia only. 3) 30 min. after the start of operation. Venous blood(5ml) was drawn into an aseptic syringe previously rinsed with heparin. The plasma was separated within 30 min. in a refrigerated centrifuge, then frozen at -40 degrees C. for storage. the cortisol levels in plasma were determined by a Gamma coat I 125 cortisol radiommunoassay kit. The plama cortisl level at 9:00 a.m. just prior to induction in the control group was 12.64+/-3.77 ug/ml. It decreased slightly (about 20%) but no significantly(p>0.01) to 10.11+/-2.47 ug/100ml at 30 min. after the anesthesia alone. At 30 min. after the start of operation it was elevated slightly (about 24%) but not significantly(p>0.1) to 15.42+/-6.88 ug/100ml. This finding indicated that flunitrazepam-nitrous oxide anesthesia has a depressing effect on adrenal cortical function, but did not block the influence on adrenal cortical function of surgical stress.
Adrenal Cortex Hormones ; Anesthesia ; Anesthesia, General ; Anesthetics ; Atropine ; Blood Pressure ; Flunitrazepam* ; Heart Rate ; Heparin ; Humans ; Hydrocortisone ; Intubation, Intratracheal ; Judgment ; Morphine* ; Nitrous Oxide* ; Oxygen ; Pancuronium ; Plasma ; Syringes

Intravenous succinylcholine is often associated with adverse effects, including muscle fasciculation, postoperative myalgia, increased intraocular and intragastric pressure, along with potassium and creatinine phosphokinase, myoglobinuria, and disturbances in cardiac rate and rhythm. Several methods have been used to modify these side effects, the most popular of which has been the of subparalyzing doses of nondepolarizining relaxants prior to injection of succinylcholine. With such pretreatment however satisfactory muscular relaxation is often not achieve, necessitaing use of larger doses of succinylcholine becauses pretreatment renders the endplateless sensitive to succinylcholine; hence large doses of succinylcholine are necessary to ensure adquate degress of relaxation. The present investigation was undertaken to determine the effects of flunitrazepam on the adverse effects of succinylcholine. This paper covers the period from March, 1981 to March, 1982 in the Department of Anesthesiology, Hanyang University Hospital. The 45 subjects were divided into 3 groups: 1) propanidid (8mg/kg) with succinylcholine 2) flunitrazepam(0.03mg/kg) with succinylcholine 3) flunitrazepam(0.06mg/kg) with succinylcholine. None had existing neuromuscular disease nor were any patients receiving diazepam or any drug known to influence myoneural blocking agent. Patients with burns, muscle injury of muscle atrophy were excluded. In each group, the plasma concentration of potassium and creatinie phosphokinase was observed before and 10 minutes after use of succinylcholine. Also succinylcholine in duced myalgia, fasciculation, onset of loss of eyelid reflex and relaxation were observed and compared. The conclusions are as follows: 1) There were no significant changes of plasma concentration of potassium and creatinine phosphokinase in presuccinylcholine and 10 minutes postsuccinylcholine. Also any statistically significant changes were not observed in the comparison of the propanidid group and the flunitrazepam groups. 2) Flunitrazepam significantly diminished the incidence of postoperative muscle pain and it was shown that the degree of fasciculation has no relationship with succinylcholine induced muscle pain. 3) In the propanidid group, the onset of loss of eyelid reflex was most rapid(22+/-13 second). In the flunitrasepam 0.03mg/kg group, the onset of loss of eyelid reflex was statistically significant (p<0.05), as compared with the 0.06mg/kg group(42+/-27 second). 4) In all groups, excellent conditions of intubation were observed. Propanidid and flunitrazepam did not affect the magnitude nor duration of the succinylcholine neuromuscular block.
Anesthesiology ; Burns ; Creatinine ; Diazepam ; Eyelids ; Fasciculation ; Flunitrazepam* ; Humans ; Incidence ; Intubation ; Muscular Atrophy ; Myalgia ; Myoglobinuria ; Neuromuscular Blockade ; Neuromuscular Diseases ; Plasma ; Potassium ; Propanidid ; Reflex ; Relaxation ; Succinylcholine*

Benzodiazepine derivatives, chlordiazepoxide(Librium), diazepam(Valium), nitrazepam(Mogadon) and oxazepam(Serenid-D) are mainly used as hypnotics at present. Diazepam has been used mainly for premedication in anesthesia and as an intravenous anesthetic agent. The pharmacological actions of these drugs are tranquilizing effects for central nervous system, slight depression on the cardiovascular and respiratory system, anticonvulsant, anxiolytic and antidepressant effects. A new benzodiazepine derivative, Flunitrazepam(Ro 5-4200) has strong hypnotic action, is anticonvulsant and antidepressant in spite of slight depression of the cardiovascular and respiratory systems. Furthermore the onset and duration of this drug are shorter than the others. In our clinical study, flunitrazepam in the dosage of 0.005mg/kg was administered intravenously, as an intravenous anesthetic induction agent, for 22 surgical adult patients. In each patient, the blood pressure, pulse rate, respiratory rate, minutes volume and arterial gas study were done, before and after administration of the Ro 5-4200. The results are as follows; 1. Dosage of this flunitrazepam is not constant as other benzodiazepines. 2. The effects of flunitrazepam on the cardiovascular system showed slight depression but no effect by one hour post-operation. 3. In respiratory system, the minute volume was depressed slightly and the respiratory rate was increased but negligibly. 4. Undesirable side effects attributed to this drug were not found, except the developing of cough (one case).
Adult ; Anesthesia ; Benzodiazepines ; Blood Pressure ; Cardiovascular System ; Central Nervous System ; Clinical Study* ; Cough ; Depression ; Diazepam ; Flunitrazepam ; Heart Rate ; Humans ; Hypnotics and Sedatives ; Premedication ; Respiratory Rate ; Respiratory System ; Tranquilizing Agents

A new benzodiazepine derivative, Rohypnol (Ro 5-4200), was used for management of general anesthesia with nitrous oxide, narcotics and muscle relaxants to evaluate the effect on the cardiovascular and respiratory system in 35 surgical patients. In each patient, we observed the blood pressure, pulse rate, minute volume and arterial blood gas analysis and also local effects, postoperative recovery state and amnesia. The results are as follows; 1) Induction dosage of Rohypnol was not constant as other benzodiazepines. 2) Rohypnol showed a little effect an the cardiovascular system. 3) The effects of Rohypnol on the respiratory system were negligible but slight depression was seen. 4) If respiration became shallower or apnea occured during induction with Rohypnol, it was preferred to use assisted or controlled ventilation with 100% oxygen. 5) It was thought better to give oxygen through a nasal catheter for prevention of decreased PaO2 in recovery room. 6) When we used the non-depolarizing muscular relaxants instead of S.C.C. for intubation, we observed that a significantly decreased amount of relaxant was needed for maintenance of general anesthesia.
Amnesia ; Anesthesia, General ; Apnea ; Balanced Anesthesia* ; Benzodiazepines ; Blood Gas Analysis ; Blood Pressure ; Cardiovascular System ; Catheters ; Depression ; Flunitrazepam* ; Heart Rate ; Humans ; Intubation ; Narcotics ; Nitrous Oxide ; Oxygen ; Recovery Room ; Respiration ; Respiratory System ; Ventilation

The effect of flunitrazepam on circulation and respiration as an anesthetic induction agent was studied in 28 patiens(11women, 17men) undergoing open heart surgery and sortocoronary bypass graft surgery. The body weight varied between 30~69kg and the age ranged from 10~79yrs. They patients were premedicated with diasepam, triflupromasine, hydroxysine, pethidine and atropine in 19 cases, and morphine, hydroxysine and morphine, hydroxysine and atropine in 9 cases. Before the induction of anesthesia, Hartmann's solution was injected to maintaman adequated preload(CVP). Anesthesia was induced with flunitrazepam 0.03mg/kg and pressure pulse and respiratory rate were continuously monitored for 3 mintues. There after morphine 0.3mg/kg and pancuronium 0.1~1.15mg/kg were injected for endotracheal intubation. AFter the injection of flunitrazepam, spontaneous breathing in room ari was maintained in 19 cases even though the respiratory rate was somewhat decreased. The remaining cases were assisted in this respiration with oxygen because of severe respiratory depression or for prophylaxis of hypoxia in angina cases. Arterial blood gas tension showed normal ranges in all cases 3 min after flunitrazepam injection. Pulse rate, systolic and diastolic blood pressure were decreased 8.66%, 16.32%, and 15.9% respectively: however these are still within normal range. And those parameters were increased transiently following intubation as when other induction agents are used. From the above results, it can be concluded that flunitrasepam can be used safely as an induction agent in cardiac anesthesia with adequate preload and ventilation maintenance.
Anesthesia ; Anoxia ; Atropine ; Blood Pressure ; Body Weight ; Flunitrazepam* ; Heart Rate ; Humans ; Intubation ; Intubation, Intratracheal ; Meperidine ; Morphine ; Oxygen ; Pancuronium ; Reference Values ; Respiration ; Respiratory Insufficiency ; Respiratory Rate ; Thoracic Surgery* ; Transplants ; Ventilation

Acute pulmonary thromboembolism (PTE) is a major medical problem in many hospitalized patients with medical and surgical conditions, and venous thromboembolism is responsible for up to 15% of all in-hospital deaths. However, PTE complicating acute intoxication has been reported only rarely, and prophylaxis for venous thromboembolism is not routinely incorporated into the management of acute poisoning in emergency departments or general wards. We describe here a case of pulmonary thromboembolism that developed within 48 h of acute benzodiazepine overdose. A 47-year-old female patient was brought to the emergency department by ambulance. She had been found unconscious, and empty packages of medications prescribed by her psychiatrist and an empty bottle of liquor were found. The estimated drugs and amounts were alprazolam 22.5 mg, diazepam 150 mg, flunitrazepam 7.5 mg, fluoxetine 150 mg, and propranolol 600 mg. Approximately 40 hours after initial presentation, she complained of dyspnea and pulse oxymetry indicated 84%. Her arterial pH was 7.41, pCO2 41.6 mmHg, pO2 46.8 mmHg, and oxyhemoglobin saturation was 83.4%. The serum D-dimer concentration was 2.78 mcg/dL, and computed tomography of the chest showed acute PTE in the right upper lobar and segmental pulmonary arteries and both lower segmental pulmonary arteries. When caring for patients with sedative drug overdose, a high level of suspicion of PTE is required, and appropriate diagnostic and therapeutic measures might be undertaken when PTE is suspected. In addition, appropriate prophylaxis for venous thrombosis should be considered.
Alprazolam ; Ambulances ; Benzodiazepines* ; Diazepam ; Drug Overdose ; Dyspnea ; Emergency Service, Hospital ; Female ; Flunitrazepam ; Fluoxetine ; Humans ; Hydrogen-Ion Concentration ; Middle Aged ; Oxyhemoglobins ; Patients' Rooms ; Poisoning ; Propranolol ; Psychiatry ; Pulmonary Artery ; Pulmonary Embolism* ; Thorax ; Venous Thromboembolism ; Venous Thrombosis