Asunto(s)
Benzodiazepinas/administración & dosificación , Trastorno Bipolar/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Nordazepam/análogos & derivados , Ácido Valproico/administración & dosificación , Administración Intravenosa , Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Humanos , Nordazepam/administración & dosificación , Proyectos Piloto , Resultado del TratamientoRESUMEN
AIM: Bispectral Index Score (BIS) is an objective tool to assess sedation depth. Benzodiazepines have different pharmacological profiles and diazepam may be safer than midazolam in this setting. The aim of this study was to compare BIS values observed during anxiolysis after diazepam versus sedation after midazolam. METHODS: Thirty-six patients were randomly assigned to 3 groups: group 1 was treated with i.v. diazepam, groups 2 and 3 with iv midazolam 1 and 3 mg, respectively. Sedation was monitored clinically and by means of BIS. BIS values were evaluated as area under the curve (AUC) and compared by variance analysis. The statistical comparison of other data was performed by variance analysis or, alternatively, the χ2 according to Yates. The statistical significance was indicated by P values <0.05. RESULTS: AUC values were significantly lower after midazolam when compared to AUC values registered in diazepam treated patients; 22.6% of the group 3 patients showed BIS values <80, versus 0.4% of group 1 patients. CONCLUSION: Diazepam has a safer profile, with BIS values and clinical conditions according to the definition of minimal and/or moderate sedation. Diazepam represents the safer drug for anxiety management in dentistry, because regularly produces a state of sedation during which verbal contact with the patient is maintained and carry a margin of safety wide enough to render loss of consciousness unlikely.
Asunto(s)
Ansiolíticos/farmacología , Sedación Consciente/métodos , Monitores de Conciencia , Estado de Conciencia/efectos de los fármacos , Diazepam/farmacología , Electroencefalografía , Hipnóticos y Sedantes/farmacología , Midazolam/farmacología , Adulto , Amnesia Anterógrada/inducido químicamente , Ansiolíticos/administración & dosificación , Ansiolíticos/efectos adversos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/farmacología , Sedación Consciente/efectos adversos , Sedación Profunda/efectos adversos , Diazepam/administración & dosificación , Diazepam/efectos adversos , Relación Dosis-Respuesta a Droga , Electroencefalografía/efectos de los fármacos , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Persona de Mediana Edad , Nordazepam/administración & dosificación , Nordazepam/análogos & derivados , Nordazepam/farmacología , Procedimientos Quirúrgicos Orales , Dolor/prevención & control , Dolor/psicología , Encuestas y Cuestionarios , Inconsciencia/inducido químicamenteRESUMEN
Sixteen young (21-40 years) and nine elderly (65-78 years) volunteers received single intravenous doses of antipyrine on two occasions: once in the control state, and again while receiving therapeutic doses of cimetidine (300 mg every six hours). In the control state, antipyrine half-life was longer in elderly than in young subjects (16.4 vs 11.0 hours), and metabolic clearance lower (0.48 vs 0.72 ml/min/kg). However, coadministration of cimetidine prolonged antipyrine half-life to a similar extent in elderly and in young groups (150 and 153 per cent of control) and reduced metabolic clearance to a similar extent in both (79 vs 69 per cent of control) groups. Three young and six elderly volunteers received a single 15 mg oral dose of clorazepate, a precursor of desmethyldiazepam, with and without cimetidine. As in the case of antipyrine, cimetidine prolonged desmethyldiazepam half-life similarly in young and elderly groups (175 vs 164 per cent of control) and similarly reduced metabolic clearance (51 vs 65 per cent of control). The elderly population may already have an impaired capacity to oxidize drugs. This capacity is further impaired by coadministration of cimetidine.
Asunto(s)
Cimetidina/farmacología , Guanidinas/farmacología , Tasa de Depuración Metabólica/efectos de los fármacos , Adulto , Anciano , Antipirina/administración & dosificación , Antipirina/metabolismo , Cimetidina/administración & dosificación , Clorazepato Dipotásico/administración & dosificación , Clorazepato Dipotásico/metabolismo , Humanos , Persona de Mediana Edad , Nordazepam/administración & dosificación , Nordazepam/metabolismoRESUMEN
After single 10-mg intravenous (IV) doses of desmethyldiazepam (DMDZ) to 12 healthy human volunteers, (mean age, 62 years) blood samples were obtained over the next 14 or more days. Mean kinetic variables were volume of distribution (Vd), 90 liters; elimination half-life (t1/2), 93 hours; and clearance, 12.3 mL/min. Vd was significantly correlated with body weight (r = .73, P less than .01) and with percent ideal body weight (r = .91, P less than .001). Eleven of the same subjects also received 5- to 15-mg doses of IV diazepam (DZ). Mean kinetic variables were Vd, 180 liters; t1/2, 83 hours; and clearance, 28 mL/min. Clearances of DZ and DMDZ were significantly correlated (r = .73, P less than .02). Based on area analysis, the extent of conversion of DZ to systemic DMDZ averaged 53%. After oral administration of DMDZ in tablet form (10 mg), or of clorazepate dipotassium in capsule form (15 mg), systemic availability of DMDZ from each of the oral dosage forms was not significantly different from 100%.
Asunto(s)
Ansiolíticos/farmacocinética , Clorazepato Dipotásico/farmacocinética , Diazepam/análogos & derivados , Diazepam/farmacocinética , Nordazepam/farmacocinética , Administración Oral , Adulto , Anciano , Disponibilidad Biológica , Clorazepato Dipotásico/administración & dosificación , Diazepam/administración & dosificación , Femenino , Semivida , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Nordazepam/administración & dosificaciónRESUMEN
A double-blind, randomized protocol was used to investigate the activity of a benzodiazepine derivative, chlordesmethyldiazepam, at two different dosages, 1 mg and 2 mg (CDDZ1 and CDDZ2), on mnestic functions and information processing in normal subjects. CDDZ2 significantly impaired short-term shortage of logical and associative memory, without activity on spatial and visual memory, whereas CDDZ1 showed no difference from the placebo. Neither CDDZ1 nor CDDZ2 impaired the level of vigilance and the information processes the morning after use of the drug.
Asunto(s)
Ansiolíticos , Benzodiazepinas , Diazepam/análogos & derivados , Memoria/efectos de los fármacos , Nordazepam/análogos & derivados , Adulto , Ensayos Clínicos como Asunto , Método Doble Ciego , Humanos , Masculino , Recuerdo Mental/efectos de los fármacos , Nordazepam/administración & dosificación , Nordazepam/farmacología , Distribución AleatoriaRESUMEN
Acute administration of diazepam (2 mg/kg i.p.) to rats decreased the number of head-dips, locomotor activity and the number of rears made in the holeboard apparatus, indicating sedative effects. After daily treatment for 7 days with diazepam (2 mg/kg) tolerance developed to all these behavioural effects, despite serum concentrations of diazepam and N-desmethyldiazepam significantly higher than those following acute treatment. After 7 drug-free recovery days the rats were quite unresponsive to a probe dose of diazepam (2 mg/kg) and although there was a gradual recovery of responsiveness to diazepam, the reduction in rears still did not reach the level of the acute group even after 21 drug-free days. There was evidence for pharmacokinetic changes when probe doses of diazepam were given after 7, 14 or 21 recovery days. Lower levels of diazepam and higher levels of N-desmethyldiazepam than following an acute dose to the drug-naïve group were detected, indicating that the chronic treatment had resulted in a persistently enhanced rate of N-demethylation. It is argued that these changes do not fully account for the reduced responsiveness to the probe doses, and nor can they account for the gradual return of response over the 3-week recovery period. There were no detectable scrum concentrations of either compound 24 h after the end of the chronic treatment. However, no rebound increases in behavioural responses were detected at any time-point in withdrawal. Thus, the mechanism underlying this behavioural tolerance was not oppositional in nature. It is suggested that a situation-independent learned behavioural strategy is the most likely mechanism for the observed tolerance.
Asunto(s)
Diazepam/sangre , Diazepam/farmacología , Hipnóticos y Sedantes/farmacología , Animales , Diazepam/administración & dosificación , Tolerancia a Medicamentos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/sangre , Masculino , Actividad Motora/efectos de los fármacos , Nordazepam/administración & dosificación , Nordazepam/sangre , Nordazepam/farmacología , Concentración Osmolar , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The lymphatic bioavailability (FL) of diazepam (DZ) and its major metabolite desmethyldiazepam (DDZ) was studied. DZ was administered in intravenous and intraduodenal boluses, and in intravenous infusion in three groups of rats with different total lipid (TL) content in the central lymph. The effect of a) different lipophilicity of DZ and DDZ, b) lymphatic TL content, and c) route of DZ administration on FL was determined. It was found that a) FL values of DZ exceeded the FL values of DDZ and b) FL values of DZ increased with increasing TL content in the lymph (an opposite relation was found in DDZ), and c) the highest FL value of DZ + DDZ sum after intravenous bolus administration was attained contrary to the lowest one after intraduodenal bolus administration.
Asunto(s)
Diazepam/farmacocinética , Moduladores del GABA/farmacocinética , Sistema Linfático/metabolismo , Nordazepam/farmacocinética , Animales , Disponibilidad Biológica , Fenómenos Químicos , Química Física , Cromatografía de Gases , Diazepam/administración & dosificación , Diazepam/química , Duodeno/fisiología , Moduladores del GABA/administración & dosificación , Moduladores del GABA/química , Infusiones Intravenosas , Inyecciones , Inyecciones Intravenosas , Metabolismo de los Lípidos , Linfa/química , Linfa/metabolismo , Nordazepam/administración & dosificación , Nordazepam/química , RatasRESUMEN
The kinetics of delorazepam (chlordesmethyldiazepam; CDDZ), and its major metabolite, lorazepam (LRZ) during multiple-dose therapy have been evaluated in two groups of patients with primary or secondary anxiety. The 12 patients in group 1 were 46.8 +/- less than 13.2 years while the eight in group 2 were significantly older (69.7 +/- 7.8 years). All patients were given 0.5 mg twice daily of CDDZ for 30 days. Concentrations of CDDZ and LRZ in multiple blood samples collected during the study were determined by electron-capture gas-liquid chromatography. The degree of anxiety was evaluated from the Hamilton rating scale for anxiety (HRSA). CDDZ and LRZ accumulated in plasma but the rate of accumulation of CDDZ was slower than expected from studies in young volunteers and the half-life values were significantly related to age. Steady-state levels of glucuronated LRZ were also lower in elderly patients. Data indicate that CDDZ is more slowly eliminated and less metabolized as age increases. While pre-treatment scores of HRSA were similar in the two groups, older patients improved significantly less than those of group 1 and had also an higher incidence of side-effects. CDDZ levels positively correlated with improvement in group 1 but not in group 2.
Asunto(s)
Envejecimiento/sangre , Ansiolíticos/sangre , Trastornos de Ansiedad/sangre , Benzodiazepinas , Diazepam/análogos & derivados , Nordazepam/análogos & derivados , Adulto , Anciano , Ansiolíticos/administración & dosificación , Ansiolíticos/efectos adversos , Trastornos de Ansiedad/tratamiento farmacológico , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Nordazepam/administración & dosificación , Nordazepam/efectos adversos , Nordazepam/sangreRESUMEN
The pharmacokinetics of chlordemethyldiazepam--a pharmacologically very active new 1,4-benzodiazepine derivative--in healthy subjects after administration of a single oral dose of 2 mg, was studied. Peak concentrations were reached in 1.2 +/- 0.2 hours. Plasma levels declined with a biphasic pattern, and the elimination phase had a half-life of 82.9 +/- 14.1 hours. The concentrations of the main metabolite of chlordemethyldiazepam, lorazepam, were about 7% of those of the parent compound. In urine only conjugated lorazepam could be found its 96 hour excretion reaching about 15% of the administered dose of parent drug.
Asunto(s)
Ansiolíticos , Benzodiazepinas , Diazepam/análogos & derivados , Nordazepam/análogos & derivados , Administración Oral , Adulto , Semivida , Humanos , Cinética , Lorazepam/metabolismo , Masculino , Matemática , Nordazepam/administración & dosificación , Nordazepam/metabolismoRESUMEN
AIM: This study was performed to evaluate the effects on the cardiocirculatory system, on perioperative anxiety and compliance of sedation with 2 benzodiazepines, chlordemethyldiazepam (CDDZ) a long acting oral drug for presedation and midazolam, a short acting drug, administered by nasal route to induce intraoperative sedation. METHODS: Fifty randomized patients undergoing third molar extraction at the Dental Clinic, University of Padua, were preoperatively evaluated. Anxiety was evaluated through a visual, analogue, scale (VAS) of 10 cm, a questionnaire of adjectives called interval scale of anxiety response (ISAR) and the Newman test was applied to evaluate the changes in psychomotor functions. All patients were treated with 1 ml of oral CDDZ for presedation and midazolam by the nasal route for intraoperative sedation at doses of 1 mg in Group 1 (25 patients) and 2 mg in Group 2 (25 patients). In all patients preoperative cardiocirculatory parameters were evaluated and in the first 20 min after the beginning of intervention. At the end of intervention the Newman test was reapplied, anxiety and postoperative cardiocirculatory data were reevaluated and the quality of the intervention judged in an interview made 1 week after the intervention (quality of the sedation technique, perioperative pain intensity, assumption of analgesic drugs, swelling, amnesia etc. after intervention). RESULTS: The treatment with 1 mg CDDZ + 2 mg midazolam by nasal route is the best association to slightly attenuate intra- and postoperative cardiocirculatory response, anxiety and to improve the quality of the treatment without interfering on the psychomotor response of patients at the time of the discharge. CONCLUSION: To conclude, the sedative technique employed is easily applied by the dentist, and is safe, efficacious and well tolerated by patients.
Asunto(s)
Benzodiazepinas/administración & dosificación , Sedación Consciente/métodos , Hipnóticos y Sedantes/administración & dosificación , Midazolam/administración & dosificación , Tercer Molar , Nordazepam/análogos & derivados , Nordazepam/administración & dosificación , Extracción Dental , Administración por Inhalación , Administración Oral , Adulto , Femenino , Humanos , MasculinoRESUMEN
26 patients with generalized anxiety disorder have been treated with diazepam (20 mg/24h) for 3 weeks. Blood samples were taken on the days of clinical assessment (before treatment and on the 7th, 14th, 21st day). Determination of drug level was performed parallelly by RRA and GC. The results obtained by both methods agreed well. The intra- and interindividual variations were high. We conclude that diazepam can adequately be measured by both techniques.
Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Diazepam/administración & dosificación , Nordazepam/administración & dosificación , Trastornos de Ansiedad/sangre , Cromatografía de Gases/métodos , Diazepam/sangre , Esquema de Medicación , Monitoreo de Drogas/métodos , Flumazenil , Humanos , Nordazepam/sangre , Ensayo de Unión Radioligante/métodos , TritioRESUMEN
OBJECTIVE: To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). ANIMALS: 6 healthy mixed-breed dogs. PROCEDURES: Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. RESULTS: Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.
Asunto(s)
Anticonvulsivantes/sangre , Diazepam/sangre , Perros/sangre , Nordazepam/sangre , Administración Rectal , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacocinética , Área Bajo la Curva , Estudios Cruzados , Diazepam/administración & dosificación , Diazepam/metabolismo , Diazepam/farmacocinética , Femenino , Semivida , Inyecciones Intravenosas , Masculino , Nordazepam/administración & dosificación , Nordazepam/farmacocinética , SupositoriosRESUMEN
BACKGROUND: Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks. METHODS: We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years. RESULTS: The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up. CONCLUSIONS: Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.
Asunto(s)
Trastorno Paranoide Compartido , Suicidio , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Benzodiazepinas/administración & dosificación , Benzodiazepinas/uso terapéutico , Clozapina/administración & dosificación , Clozapina/uso terapéutico , Terapia Combinada , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Resultado Fatal , Femenino , Haloperidol/administración & dosificación , Haloperidol/análogos & derivados , Haloperidol/uso terapéutico , Humanos , Nordazepam/administración & dosificación , Nordazepam/uso terapéutico , Olanzapina , Cooperación del Paciente , Psicoterapia , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/genética , Trastornos Psicóticos/terapia , Esquizofrenia Paranoide/diagnóstico , Esquizofrenia Paranoide/tratamiento farmacológico , Esquizofrenia Paranoide/terapia , Trastorno Paranoide Compartido/complicaciones , Trastorno Paranoide Compartido/tratamiento farmacológico , Trastorno Paranoide Compartido/terapia , Relaciones entre Hermanos , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéuticoAsunto(s)
Ansiolíticos/administración & dosificación , Benzodiazepinas , Implantación Dental/psicología , Diazepam/uso terapéutico , Nordazepam/análogos & derivados , Medicación Preanestésica , Adulto , Anestesia Dental/métodos , Distribución de Chi-Cuadrado , Ansiedad al Tratamiento Odontológico/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nordazepam/administración & dosificaciónRESUMEN
Desmethyldiazepam (Vegesan) was administered in the form of 5-mg and 10-mg tablets and of 10-mg drops to 4 male and 4 female young healthy volunteers. The plasma levels of desmethyldiazepam were measured over 168 h. The time courses could be fitted to the one- or to the two-compartment model. The mean half-lives of elimination came to 75.3 +/- 32.0 (SD) h (5-mg tablets), 66.5 +/- 21.0 (SD) h (10-mg tablets) and 78.4 +/- 33.2 (SD) h (10-mg drops). The bioavailability of desmethyldiazepam from tablets and from drops was practically the same. The bioavailability appeared to be independent of dose in this range. A significantly higher total plasma clearance was calculated for the male than for the female volunteers after all three dosage forms (p less than 0.05). The total plasma clearance lay between 4.8 and 13.0 ml/min for the female and 12.4 and 24.3 ml/min for the male volunteers. Ingestion of the contraceptive pill is suggested as a possible cause of the sex differences.
Asunto(s)
Diazepam/análogos & derivados , Nordazepam/sangre , Adulto , Femenino , Humanos , Cinética , Masculino , Nordazepam/administración & dosificación , Factores Sexuales , Soluciones , Comprimidos , Factores de TiempoRESUMEN
A rapid method was developed for the determination of diazepam and nordiazepam (N-desmethyldiazepam) in human plasma using electron capture gas--liquid chromatography (GLC--ECE). The concentration of diazepam and nordiazepam is determined using 0.5 ml of plasma extracted with 1.0 ml of benzene containing 25 ng/ml of methylnitrazepam as the internal standard. The benzene extract is removed and an aliquot is subjected to automated GLC-ECD analysis. The method has a sensitivity limit of 5 ng diazepam and 10ng nordiazepam per milliliter of plasma. The method was used to determine the plasma levels in man following the first 5-mg diazepam dose, as well as during chronic oral administration of 5 mg diazepam three times daily and 15 mg diazepam once a day.
Asunto(s)
Diazepam/análogos & derivados , Diazepam/sangre , Nordazepam/sangre , Autoanálisis , Cromatografía de Gases , Cromatografía Liquida , Diazepam/administración & dosificación , Humanos , Nordazepam/administración & dosificaciónRESUMEN
Chlorodesmethyldiazepam (I) concentrations were followed for 72 h in the plasma of four volunteers given 2 mg of the drug orally. The drug appears to be well absorbed, reaching peak plasma levels of 20--30 ng ml-1 1--2 h after administration; 72 h after administration, plasma concentrations are still measurable (5 ng ml-1). The analytical method involved a single extraction of I from the plasma into benzene followed by centrifugation, evaporation, and gas-chromatographic analysis of the samples.
Asunto(s)
Ansiolíticos , Benzodiazepinas , Diazepam/análogos & derivados , Nordazepam/análogos & derivados , Administración Oral , Adulto , Biotransformación , Humanos , Masculino , Nordazepam/administración & dosificación , Nordazepam/sangre , Factores de TiempoRESUMEN
The pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The kinetics was also examined after a single 2 mg oral dose in 6 of the 11 renal failure patients. After intravenous administration the kinetics of total chlordesmethyldiazepam in renal patients and controls were the same. The unbound fraction of the drug in renal patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed a reduced apparent volume of distribution (47 vs. 140 l.kg-1) and a reduced clearance (5.0 vs. 10.5 ml.min-1.kg-1) in the patients. The systemic availability of oral chlordesmethyldiazepam was good (82%) despite a relatively slow absorption rate.
Asunto(s)
Ansiolíticos , Benzodiazepinas , Nordazepam/análogos & derivados , Diálisis Renal , Administración Oral , Femenino , Humanos , Inyecciones Intravenosas , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Nordazepam/administración & dosificación , Nordazepam/sangre , Nordazepam/farmacocinética , Unión ProteicaRESUMEN
Clorazepate dipotassium (Tranxilium) is one of the benzodiazepines which is widely used for oral premedication. After oral administration it is decarboxylated to its active metabolite nordiazepam (desmethyldiazepam). Nordiazepam is also commercially available in the form of drops (Tranxilium N). The aim of the present study was to compare the effect of these drugs on preoperative anxiety. One hundred and eight patients scheduled for orthopaedic surgery (ASA I-II) were studied. Medication was administered at 10 p.m. the evening before surgery (E) and at 7 a.m. on the morning of surgery (M). There were four groups: 1) E no medication; M clorazepate dipotassium; 2) E no medication; M nordiazepam; 3) E clorazepate dipotassium; M clorazepate dipotassium, 4) E clorazepate dipotassium; M nordiazepam. Dosages were: clorazepate dipotassium: body weight < 55 kg: 10 mg; body weight > 55 kg: 20 mg; nordiazepam: 1 gtt/kg; 5 mg = 24 gtt). Anxiety was measured by using the self-evaluating Erlangen anxiety scales, which measure both background and situational anxiety. Background anxiety (EAS-H) was evaluated during the evening before surgery; situational anxiety (EAS-S) was evaluated at the same time and also on the day of surgery before premedication and immediately before surgery. Pulse rate was measured each time the test was administered. There were no differences between the groups in sex, age, weight or the intervals between premedication and anaesthesia induction (p > 0.05). There were no statistically significant differences between the groups with respect to background anxiety. Situational anxiety did not significantly increase or decrease at any of the testing times, nor were there any differences between the groups (p > 0.05). Heart rate did not vary between the groups or with time (p > 0.05). In this group of patients undergoing elective orthopaedic procedures, clorazepate prevented a rise in anxiety in the immediate preoperative period. Since clorazepate is rapidly metabolized to nordiazepam when administered orally it might be predicted that the two drugs have similar properties. This hypothesis is confirmed by the results of the present study. We conclude that orally administered clorazepate dipotassium and nordiazepam have a similar effect on preoperative anxiety.
Asunto(s)
Ansiolíticos/administración & dosificación , Ansiedad/tratamiento farmacológico , Clorazepato Dipotásico/administración & dosificación , Nordazepam/administración & dosificación , Medicación Preanestésica , Procedimientos Quirúrgicos Operativos/psicología , Administración Oral , Adulto , Anciano , Ansiolíticos/efectos adversos , Clorazepato Dipotásico/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nordazepam/efectos adversos , Ortopedia , Inventario de Personalidad , Estudios ProspectivosRESUMEN
Six healthy, fasting volunteers were given single doses of chlordesmethyldiazepam by 1 mg i.v., or as drops or tablets. Chlordesmethyldiazepam and its metabolite, lorazepam, in multiple plasma samples and in urine collected for 120 h after each dose were determined by electron-capture GLC. Mean kinetic variables for intravenous chlordesmethyldiazepam were: volume of distribution, 1.71 l.kg-1; elimination half-life, 113 h; total clearance, 0.21 ml.min-1.kg-1; cumulative excretion of lorazepam glucuronide 24.2% of the dose. Following a lag time of 15.5 min (tablets) and 4.2 min (drops), which were significantly different, the absorption of oral chlordesmethyldiazepam was a first order process, with apparent absorption half-life values averaging 1.5 h (tablets) and 1.1 h (drops). Bioavailability was 77% for tablets and 79% for drops.