Mg Of Diazepam Research Articles

Benzodiazepines and the risk of falls in nursing home residents.

For nursing home residents who require a benzodiazepine, short-acting agents are recommended, primarily to avoid increased risk of falls and other injuries associated with the long-acting agents. However, much of the data for the clinical outcomes of falls and injuries comes from community-dwelling older people. To quantify the rate of falls among nursing home residents taking benzodiazepines and how this varies with drug elimination half-life. Historical cohort study. A total of 2510 residents of 53 Tennessee nursing homes, classified according to benzodiazepine use on each day of follow-up. Falls occurring during study follow-up. After adjustment for differences in resident characteristics, benzodiazepine users had a 44% increased rate of falls (adjusted rate ratio 1.44 [95% confidence interval, 1.33-1.56]). The adjusted rate ratio increased from 1.30 (1.12-1.52) for a dose equivalent to < or = 2 mg of diazepam, to 2.21 (1.89-2.60, P < .001) for a dose of > 8 mg. The rate of falls was greatest in the 7 days after the benzodiazepine was started (rate ratio of 2.96 [2.33-3.75]) but remained elevated (1.30 [1.17-1.44]) after the first 30 days of therapy. Drugs with elimination half-lives of <12, 12-23, and > or = 24 hours had adjusted rate ratios of 1.15 (0.94-1.40), 1.45 (1.33-1.59), and 1.73 (1.40-2.14), respectively. Users of hypnotics with elimination half-lives <12 hours had an increased rate of falls occurring during the night (adjusted rate ratio 2.82 [2.02-3.94]). Although the risk of falls among nursing home residents receiving short-acting benzodiazepines is less than that for the long-acting agents, these drugs are associated with a materially increased risk of nocturnal falls.

Epileptological emergencies in Accident and Emergency: a survey at St James’s University Hospital, Leeds

Many patients attending an Accident and Emergency (A&E) department with seizures never come into contact with a neurological service. This survey was designed to find out how many patients with epileptological emergencies come to A&E and how they are managed. Cases were identified using the computerized A&E database. The A&E records of all adult patients attending the casualty department at St James’s University Hospital with emergencies related to epilepsy between 1 April and 30 September 1998 were reviewed retrospectively. Out of a total of 36 024 adults attending A&E, 190 were related to epileptological emergencies. A problem relating to a previously recognized seizure disorder was the commonest reason for attendance. Patient management was highly variable and often suboptimal. Descriptions of seizure semiology and examination findings were frequently deficient. Up to 37.5 mg of diazepam, in up to five boluses, was given. Twenty per cent of patients with a diagnosis of status epilepticus were discharged home after diazepam treatment. Neurologists only became involved in 24.2% of cases. Epileptological emergencies only make up a small proportion of cases seen in adult A&E departments. Treatment and referral guidelines should be agreed between A&E staff and neurologists. The communication between general, specialist and acute services needs to be improved.

Detection of diazepam in horse hair samples by mass spectrometric methods.

A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the neck, coat on the back, mane and tail were collected from two thoroughbreds which had received several dosages of diazepam corresponding to a total dose of 750 mg and 200 mg of diazepam respectively. In the first experiment, by low resolution GC-MS using single ion monitoring, diazepam was detected in the mane for at least 85 d after the last administration. In the second one, using the same method, diazepam was detected in the coat on the neck up to 25 d following the last administration. Low resolution GC-MS data were confirmed by the two other techniques. Furthermore, GC-HRMS even made possible the detection of diazepam up to 38 d after the administration of 200 mg of diazepam.

Severe gamma-hydroxybutyrate withdrawal: a case report and literature review

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient’s symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated.

Hanging-induced status epilepticus

Survival from hanging is associated with a variety of neuropsychiatric consequences, including amnesia, localized muscle spasms, transient hemiplegia, central cord syndrome, and multiple transient neurologic findings. This report describes a near-hanging episode in a patient who subsequently had status epilepticus requiring 40 mg of diazepam and 1,200 mg of phenytoin for control in the prehospital and emergency department stabilization period. This is the first well-documented report of hanging with subsequent status epilepticus in an adult. The patient survived with an abnormal electroencephalogram consistent with anoxic injury and was discharged on anticonvulsant therapy, although the rationale for medication in such patients is unclear and requires further study.

The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia

Study Objective: To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. Design: Randomized double-blinded study. Setting: Operating room ASA physical status I and II room and recovery room of the cancer center. Patients: 80 breast cancer patients scheduled for surgery. Interventions: Patients were randomized to one of four treatment groups (placebo, clonidine 75 μg, or 150 μg of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O 2): nitrous oxide (N 2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. Measurements and Main Results: Preanesthetic oral clonidine (150 μg) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 μg, clonidine 150 μg, and 10 mg of diazepam groups were 841 ± 70 (9.0 ± 0.3), 720 ± 63 (7.1 ± 0.4), 491 ± 39 (5.6 ± 0.2), and 829 ± 77 mg (7.9 ± 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 ± 3.8, $45.5 ± 3.2, $33.5 ± 2.3, and $50.5 ± 4.4, respectively. Conclusions: Preanesthetic oral clonidine (150 μg) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 μg of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.

Diazepam-Treated Female Rats: Flumazenil- and PK 11195-Induced Withdrawal in the Hippocampus CA1

Six female rats had a loading dose of 180 mg of diazepam (DZ) contained in two Silastic capsules implanted in their backs. Thereafter, a single 90-mg capsule was implanted weekly for 4 weeks prior to weekly microinjections of 1 μl of flumazenil (6.25, 12.5, or 25 μg) and PK 11195 (3.125, 6.25, or 12.5 μg) or vehicle into the CA1. Three control rats had empty capsules implanted but received only the high dose of flumazenil after 5 weeks. The time of DZ exposure spanned 8 weeks. Mean steady-state plasma levels of DZ were 1.06 ± 0.11, and the mean total (DZ + metabolites) was 2.46 μg/ml ± 0.37. Flumazenil elicited a dose-related precipitated withdrawal score (PAS) in DZ-treated rats (but not in controls) characterized by dose-related increases in convulsive (twitches and jerks), motor and autonomic signs, dose-related increases in the percent of total power in the low frequency (1–4 Hz), and decreases in the high-frequency (18–26 Hz) bands of the EEG recorded from the dentate and the amygdala. PK 11195 produced a dose-related increase in the 4–12 Hz band of the EEG recorded from the CA1, whereas the PAS was mild and not dose-related. However, the 6.25 and 12.5-μg doses elicited a significant PAS that tended to increase with dose. These data indicate that chronic DZ produces dependence, and that in the CA1 it involves the participation of central and possibly peripheral benzodiazepine (BZ) receptors located within this structure.

Evaluation of Anxiolysis and Pain Associated with Combined Peri- and Retrobulbar Eye Block for Cataract Surgery

Study Objectives: To evaluate five different preoperative anxiolytic regimens in cataract surgery performed under regional anesthesia; to quantify the pain associated with combined peri- and retrobulbar injection (PRBI) of local anesthetic drugs; and to describe a technique of painless eye block. Design: Randomized, double blind, placebo-controlled study. Setting: Private clinic. Patients: 376 ASA I and II patients presenting for cataract surgery. Interventions: Patients were extensively briefed by the nursing staff on the various procedures. Of the 376 study patients, 136 preferred to have no anxiolytic drug. The remaining 240 patients were randomly allocated to one of six groups to receive either 3 mg of bromazepam, 6 mg of bromazepam, 0.5 mg of alprazolam, 1 mg of alprazolam, 5 mg of diazepam, or a placebo on a double-blind protocol. All patients received a standard combined peri- and retrobulbar eye block (PRBB) before surgery. Measurements and Main Results: Anxiety at various stages of the procedure and PRBB were measured on visual analog scale (0–10). PRBB pain was compared with pain of intravenous (IV) cannula placement. On admission, anxiety of the 136 patients who preferred no anxiolytic premedication was significantly less than that of the 240 patients assigned to one of the six treatment groups (p <0.05). There was no difference between the six treatment groups in reported anxiety before surgery (p >0.05) except for Group 1 (3 mg bromazepam), where anxiety increased before and during PRBB administration (p <0.05). In all six treatment groups, anxiety decreased significantly 30 minutes after medication was administered (p <0.05). For the total group, 61.18% of patients reported more or equal pain associated with the placement of the 20-gauge IV cannula than by the PRBB. Of the patients who received medication, 94% stated that, should they require another eye operation, they would like the same anxiolytic treatment. No patient requested general anesthesia for their next operation or to be rendered unconscious for PRBB. Conclusions: 1. There was interpersonal variation in the level of preoperative anxiety. 2. In patients who were anxious, the anxiolytic drugs and placebo decreased anxiety although the level of anxiety did not differ between the anxiolytic drugs or between placebo and the anxiolytic drugs. The only difference was in Group 1 patients (3 mg promazepam), who reported slightly increased anxiety before and during PRBB administration (p <0.05). 3. Placement of the PRBB is less painful than the insertion of a 20 g IV cannula.

Modifications of Oxygen Saturation During Transesophageal Echocardiography.

The present study was designed: (1) to establish the effects of transesophageal echocardiography (TEE) on arterial oxygen saturation (SAO(2)%); (2) to verify the possible clinical consequences of this phenomenon; and (3) to study the possibility of predicting modifications of SAO(2)% by clinical or hemodynamic variables or by specific factors related to the TEE procedure. We prospectively studied 116 unselected patients, aged 61 +/- 12 years, who underwent diagnostic TEE for various clinical indications. Thirty-seven patients had mitral valve disease, 19 aortic valve disease, 14 combined mitroaortic disease, 8 congenital heart disease, and 38 other cardiovascular diseases. Eight patients were affected by chronic obstructive pulmonary disease. Ninety-seven patients were sedated by 4 +/- 2 mg of diazepam IV SAO(2)% (5-min average) (Ohmeda Biox 3700 pulse oxymeter finger probe), heart rate (HR), and blood pressure (BP) were considered during baseline transthoracic examination, after pharmacological sedation but before the introduction of the probe, and finally during TEE. Neither clinical complications nor major arrhythmias were observed. Baseline SAO(2)%, HR and BP were, respectively, 93.6 +/- 3.3%, 76 +/- 14 beats/min, and 129 +/- 20/75 +/- 10 mmHg. Pharmacological sedation did not modify SAO(2)%, HR, and BP (P > 0.1). During TEE a small but significant reduction in SAO(2)% by an average of 1.2 +/- 3.2% was observed (P < 0.005), as well as a small and significant increase in HR by an average of 3 +/- 10 beats/min (P < 0.01). BP did not change significantly (P > 0.1 for both systolic and diastolic). The changes of SAO(2)% and HR were not interrelated and were not related to the duration of the procedure and to any of the clinical and hemodynamic variables taken into consideration. TEE can induce a small but significant drop in SAO(2)% and a small increase in HR even without any clinical relevance. No clinical or hemodynamic variable or specific factors related to the TEE procedure were related to these changes.

閉塞型睡眠時無呼吸症における閉塞部位診断 薬物睡眠下内視鏡検査を用いて

Objective: 55 patients diagnosed as having obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The effects of surgery were studied based on the findings of endoscopic examination under drug-induced sleep and AHI measurements performed before and after the operation. Changes in airway form during sleep were observed, and the usefulness of upper airway endoscopy in the diagnosis and surgical treatment of OSAS was studied.Methods: The site of airway obstruction during sleep induced by intravenous injection of 10mg of diazepam was classified into five types, and changes in AHI and the site of airway obstruction were compared before and after surgery.Results: The postoperative improvement rate was 73.5% in the soft palate type of obstruction, 75.6% in the tonsillar type, 52.3% in the full-circumference palatal type and 32.3% in the mixed type. Surgical treatment by UPPP had an excellent or good effect on the soft palate and tonsillar types. However, many patients with the ful1-circumference palatal type and the mixed type showed less improvement compared with the soft palate and tonsillar type.Conclusion: In the full-circumference palatal type and the mixed type, improvement can be expected following operations which include surgical treatment of the posterior pharyngeal wall or the lateral funiculus, or midline laser glossectomy.

The effect of the antimycotic itraconazole on the pharmacokinetics and pharmacodynamics of diazepam

The azole antimycotic itraconazole is a potent and relatively unspecific inhibitor of cytochrome P450 enzymes and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between itraconazole and diazepam was investigated in a double-blind, randomized, cross-over study. Ten healthy volunteers were given orally placebo or itraconazole 200 mg a day for 4 days. The challenge dose of 5 mg of diazepam was ingested on the fourth day, after which plasma samples were collected and psychomotor performance tests were carried out for 42 h. Despite a statistically significant small increase in the area under the plasma diazepam concentration-time curve and the elimination half-life of diazepam, there was no clinically significant interaction as determined by the psychomotor performance tests. The lack of significant first-pass metabolism and the different metabolic pathways of diazepam explain the smaller interaction potential of diazepam compared with midazolam and triazolam. Diazepam, unlike midazolam and triazolam, can be prescribed in usual doses for patients receiving itraconazole and probably other inhibitors of P4503A4, at least when diazepam is used as single doses.

Flumazenil-precipitated panic and dysphoria in patients dependent on benzodiazepines: a possible aid to abstinence

Ten long-term users of benzodiazepines (average daily dose, 20 mg of diazepam or equivalent) who had experienced problems in withdrawing from the drugs were given an i.v. challenge with either the benzodiazepine antagonist flumazenil (1 mg injected over 30 s) or placebo (vehicle solution) in a randomized double-blind design. There were no 'pseudo withdrawal' responses to either single-blind or double-blind placebo injections, whereas flumazenil produced dramatic panic reactions in all four subjects tested, followed by characteristic benzodiazepine withdrawal symptoms. There were also small but significant rises in pulse rate and blood pressure, but no change in serum cortisol. Flumazenil-induced panic could not be entirely accounted for by a past or present diagnosis of panic disorder, and did not seem to be related to previous withdrawal problems, present benzodiazepine dosage, or to the severity of withdrawal symptoms precipitated by flumazenil in the same challenge test. Attempts to reduce benzodiazepine intake over the next 3 weeks tended to be more successful in the flumazenil group. The results are discussed with reference to possible changes in the GABA-benzodiazepine system in long-term benzodiazepine users.

Anesthetic Implications in Stiff-Person Syndrome

A 46-yr-old female presented to the operating room for repair of an intrathecal baclofen pump. Her diagnosis of SPS was based on clinical presentation and the presence of an autoantibody against the central nervous system enzyme glutamic acid decarboxylase (GAD). The syndrome began as muscle stiffness in her lower extremities and insidiously progressed to a state of constant stiffness resulting in permanent contractures of her lower extremities and moderate rigidity of her upper extremities. The patient’s facial, cervical, and extraocular muscles were spared. When startled by a loud noise, the patient experienced a painful brisk spasm resulting in opisthotonic posturing. These acute exacerbations were treated with a 50-mg dose of diazepam administered intramuscular. Other pharmacologic therapies included intrathecal baclofen and 100 mg of diazepam orally per day. Past surgical history was significant for a 2-day history of prolonged postoperative weakness after the baclofen pump was inserted, and an overdose of baclofen was suggested as the cause. A review of the previous anesthetic record revealed that propofol and succinylcholine followed by desflurane was used for induction of anesthesia, tracheal intubation, and maintenance of anesthesia, respectively. Anesthesia was induced with sufentanil 10 pg, thiopental 375 mg (5.8 mg/kg), and vecuronium 8 mg (0.12 mg/kg) administered intravenously (IV). It was inferred from the slow and inadequate induction of anesthesia that the IV catheter had infiltrated subcutaneously although visual inspection was equivocal. A facial nerve train-of-four twitch monitor indicated an absence of all four twitches 10 min after induction of anesthesia. Inhalation anesthesia via a

Anesthetic Implications in Stiff-Person Syndrome

Anesthetic Implications in Stiff-Person Syndrome

Progesterone co-administration in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and taper outcome

Since recent research has suggested that the major metabolites of progesterone are barbiturate-like modulators of GABAergic function, we undertook a pilot study of the efficacy of micronized progesterone in attenuating withdrawal and facilitating discontinuation in benzodiazepine-dependent patients with a minimum of 1 year of continuous daily use. Forty-three patients taking a mean daily dose of 16.2 mg of diazepam (or its equivalent) were assigned, doubleblind, to treatment with either placebo (n = 13) or progesterone (n = 30). Progesterone was titrated to a mean daily dose of 1983 mg, and was co-administered for 3 weeks, after which the benzodiazepine was tapered by 25% per week. Progesterone (or placebo) was then continued for 4 weeks before being discontinued. There was no progesterone versus placebo difference in the severity of taper withdrawal. Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo (F 0.63; df 2.31; n.s.), and the Hamilton rating scale for anxiety change scores were 7.8 for progesterone and 6.3 for placebo (F 0.22; df 2.30; n.s.). There was no difference in ability to remain drug-free at 12 weeks post-taper, with 57% of progesterone-treated patients, and 58% of placebo-treated patients having a successful outcome.

Individualized treatment of alcohol withdrawal

<h3>To the Editor.</h3> —The recent article entitled "Individualized Treatment for Alcohol Withdrawal" by Dr Saitz and colleagues¹compared "fixed-schedule therapy" (substitution) with "symptom-triggered therapy" (suppression). The conclusions are open to misinterpretation for the following reasons. The dosage chosen for the fixed schedule (400 mg of chlordiazepoxide) may be high for groups of subjects with little evidence of alcohol withdrawal (selection bias). A Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) median score of 9 is barely recognizable as alcohol withdrawal (and some subjects had scores of 0). No entry criterion for alcohol withdrawal was used (presumably it was the expectation of withdrawal). Previous studies using a predominantly white male veteran population have demonstrated that only 13% of these subjects required drug treatment.²Other general hospital studies have revealed that a median dose of 50 mg of diazepam (200 mg of chlordiazepoxide) was required using similar criteria for treatment

Individualized Treatment of Alcohol Withdrawal

To the Editor. —The recent article entitled Individualized Treatment for Alcohol by Dr Saitz and colleagues 1 compared fixed-schedule therapy (substitution) with symptom-triggered therapy (suppression). The conclusions are open to misinterpretation for the following reasons. The dosage chosen for the fixed schedule (400 mg of chlordiazepoxide) may be high for groups of subjects with little evidence of alcohol withdrawal (selection bias). A Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) median score of 9 is barely recognizable as alcohol withdrawal (and some subjects had scores of 0). No entry criterion for alcohol withdrawal was used (presumably it was the expectation of withdrawal). Previous studies using a predominantly white male veteran population have demonstrated that only 13% of these subjects required drug treatment. 2 Other general hospital studies have revealed that a median dose of 50 mg of diazepam (200 mg of chlordiazepoxide) was required using similar criteria for treatment

Drug and Ethanol Effects on the Clinical Test for Drunkenness: Single Doses of Ethanol, Hypnotic Drugs and Antidepressant Drugs

The clinical test for drunkenness has been used in Finland to detect alcohol-induced impairment of driving fitness. Since the data about the effects of psychotropic drugs on the clinical test for drunkenness are limited, this test was administered in two randomized double-blind cross-over trials with 12 subjects in each. The clinical tests were done at 2 hr and 5 hr after drug intake. For comparison, the representative laboratory tests used were digit symbol substitution, simulated driving (tracking+reaction time) and "global psychomotor performance". In Trial I, 15 mg of diazepam, 50 mg of amitriptyline and 15 mg of mirtazepine, each drug administered alone, had minor effects on the clinical tests. Compared to the placebo, mirtazepine, and diazepam, diazepam+mirtazepine impaired performance on the motor subtests at 2 hr. The tracking error percentage was increased by amitriptyline, diazepam+amitriptyline, and diazepam+mirtazepine up to 4.5 hr. In Trial II with 7.5 mg of zopiclone, 0.25 mg of triazolam and 0.8 g/kg of ethanol, ethanol alone and hypnotic-ethanol combinations impaired performance on the motor and vestibular subtests, whereas single drug intake had minor effects. Tracking was more sensitive to drugs than to ethanol. In conclusion, the clinical test for drunkenness detected impaired performance following single doses of ethanol or drug-ethanol combinations better than it detected impaired performance following moderate doses of drugs or drug-drug combinations, respectively.

Changes in plasma cortisol, corticotropin, and α-melanocyte-stimulating hormone concentrations in cats before and after physical restraint and intradermal testing

SUMMARY In 6 cats, mean ± sem baseline plasma concentrations of cortisol, corticotropin, and α-melanocyte-stimulating hormone (α-msh) were 87 ± 16 nmol/ L, 73 ± 14 ng/L, and 129 ± 12 ng/L, respectively. The cats were subjected to: handling and subsequent skin testing without anesthesia; anesthesia with 50 mg of ketamine HCl and 2.5 mg of diazepam given IV, immediately followed by handling and skin testing; and anesthesia and handling as previously described, but without skin testing. Significant (P &lt;0.05; multivariate analysis for repeated measures) increase in plasma cortisol, corticotropin, and α-msh concentrations was observed until 20 minutes after the start of the experiments in cats undergoing physical restraint and subsequent skin testing with or without preceding anesthesia. These responses were largely abolished when anesthesia with ketamine and diazepam was only followed by handling. We conclude that, during stress in cats (in contrast to dogs), the pituitary intermediate lobe is activated to secrete α-msh. In addition, the cortisol response after skin testing of cats under anesthesia may be a reasonable explanation for the reported weak skin test reactivity in cats.

Simultaneous Determination of Otilonium Bromide and Diazepam by First-Derivative Spectroscopy

A rapid, simple assay procedure was developed for simultaneous analysis of otilonium bromide, a smooth‐muscle relaxant, and diazepam in tablets containing 20mg of otilonium bromide and 2mg of diazepam (20:2 tablets) or 40mg of otilonium bromide and 2mg of diazepam (40:2 tablets) by “zero‐crossing” first‐derivative spectroscopy. The tablets were dissolved in 0.01N HCl, mixtures were centrifuged at 3500rpm (2472 × g) for 5 min, and first‐derivative spectra were recorded. The absolute values of the derivative were measured at 264nm for determination of otilonium bromide and between 406 and 408nm (380nm for analysis of 40:2 tablets) for determination of diazepam. The method is linear, quantitative, and reproducible and can also be used for the tablet dissolution test. Ten tablets of the same batch were analyzed by the described method and by a high‐performance liquid chromatographic method, and the results were in good agreement.