Oral Alprazolam Research Articles

Comparison of sedative effects of oral ketamine and Alprazolam in cat

Comparison of sedative effects of oral ketamine and Alprazolam in cat

Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial

The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO(2) and pulse oximetry 60-160 min after drug intake. Subjects were encouraged to keep their eyes open. Mean +/- SD minute ventilation 120 min after alprazolam and placebo was similar (6.21 +/- 0.71 vs 6.41 +/- 1.12 L/min, P = NS). End-tidal PCO(2) and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 +/- 23% vs 31 +/- 13%, P < 0.05). More encouragements to keep the eyes open were required after alprazolam than after placebo (5.2 +/- 5.7 vs 1.3 +/- 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation.

Perioperative ulnar neuropathy following shoulder surgery under combined interscalene brachial plexus block and general anaesthesia

Perioperative ulnar neuropathy following shoulder surgery under combined interscalene brachial plexus block and general anaesthesia

Oral Alprazolam Attenuates Preoperative Stress Responses to Regional Anesthesia

Background: Preoperative anxiety activates the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system, and also affects immune responses. Therefore, there is a need to reduce the anxiety. Methods: Forty-eight healthy patients scheduled for elective knee arthroscopic and reconstructive surgery under spinal anesthesia (SA) were randomly allocated into the control (CG, n = 24) and the alprazolam group (AG, n = 24). Oral 0.25 mg alprazolam in the evening before SA and 0.5 mg alprazolam 90 min before SA were administered to patients of the AG. Visual analogue scale (VAS) scores of anxiety were measured in the operating room before SA (ORSA) and operating room during operation and discharge day (DD). Serum ACTH and cortisol in the ORSA and DD, systolic and diastolic blood pressure and heart rate in the ward and ORSA, sleep time and number of night awakenings in the night before SA were measured. Results: Age (31.9 ± 10.8 yr), sex, height, weight, and sleep time were not significantly different between the two groups. The number of night awakenings in the AG were significantly lower than in the CG. VAS scores of anxiety in the ORSA were significantly higher in the CG than in the AG. ACTH and cortisol levels in the CG were significantly higher in the ORSA than in the DD. ACTH and cortisol levels in the AG were not significantly different between the ORSA and the DD. Cortisol level in the ORSA were significantly lower in the AG than in the CG. Diastolic blood pressure and heart rate in the ORSA were significantly lower in the AG than in the CG. Conclusions: These indicate that oral alprazolam attenuates preoperative stress responses to regional anesthesia. (Korean J Anesthesiol 2007; 52: 132～7)

41: Oral alprazolam attenuates stress responses to regional anesthesia and surgery

41: Oral alprazolam attenuates stress responses to regional anesthesia and surgery

Lactic Acidosis during Propofol–Remifentanil Anesthesia in an Adult

Lactic Acidosis during Propofol–Remifentanil Anesthesia in an Adult

Water Intoxication and Symptomatic Hyponatremia After Outpatient Surgery

Severe hyponatremia is associated with a mortality rate of more than 50%, primarily from cerebral edema and central nervous system dysfunction. Water intoxication is an unusual but potentially lethal cause of perioperative hyponatremia. We report a patient with severe postoperative hyponatremia resulting from excessive perioperative water consumption. Anesthesiologists should maintain an index of suspicion for hyponatremia from water intoxication in patients with neurologic symptoms during the perioperative period. Routine preoperative instructions regarding maximum perioperative water intake and inquiry into any concurrent alternative medical therapies may help to avoid this preventable complication. Water intoxication is an unusual but potentially lethal cause of perioperative hyponatremia. We report a patient with severe postoperative hyponatremia resulting from excess perioperative water consumption.

Amnestic and anxiolytic effects of alprazolam in oral surgery patients

Purpose This study was designed to identify a dose of alprazolam that would reduce anxiety associated with oral surgery without causing accompanying memory impairment. Patients and Methods Thirty-six subjects in experiment 1 and 48 subjects in experiment 2, were pretested on a computerized memory battery to establish baseline performance. Subjects were then randomly assigned to receive placebo, 0.25 mg, or 0.75 mg oral alprazolam (experiment 1) or placebo, 0.25 mg, 0.50 mg, or 0.75 mg oral alprazolam (experiment 2). Forty-five minutes after the double-blind administration of alprazolam, subjects were given a second memory battery. The memory batteries tested story recall and recognition and word recall and recognition. Subjects in experiment 2 subsequently underwent oral surgery for the removal of one to four molars. The subjects completed anxiety questionnaires both before and after surgery. Results The 0.75-mg and 0.50-mg doses, but not the 0.25-mg dose, impaired word recall. The 0.75-mg dose also impaired story recall and recognition. The proportion of subjects reporting moderate to high anxiety during oral surgery decreased with increasing doses of alprazolam. Multiple regression indicated that the 0.75-mg alprazolam dose significantly decreased anxiety during oral surgery. The 0.25-mg and 0.50-mg doses also tended to reduce anxiety, but beta values for these doses did not reach significance. Conclusions These findings indicate that alprazolam produces memory impairment at the dosages necessary to produce clinically significant anxiolysis during oral surgery.

Effects of genetically determined S-mephenytoin 4-hydroxylation status and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam

This study examines the effects of genetically determined S-mephenytoin 4-hydroxylation capacity and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam in 12 healthy male volunteers. Six subjects each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Seven subjects were smokers (> 10 cigarettes/day), and five were nonsmokers, according to their self-reports. Each subject took a single oral dose of 0.8 mg of alprazolam, and blood samples were collected up to 48 hours postdose. Psychomotor function was assessed at times of blood samplings using the Digit Symbol Substitution Test (DSST), Visual Analog Scale (VAS), and UKU Side Effect Rating Scale. Plasma alprazolam concentrations were measured by a high-performance liquid chromatography assay. None of the mean pharmacokinetic parameters was significantly different between the EM and PM phenotype groups. Although the mean elimination half-life was significantly shorter in the smoker group (p < .01) than in the nonsmoker group (13.1 +/- 2.9 vs. 20.0 +/- 2.7 hours, mean +/- SD), other pharmacokinetic parameters did not differ significantly between the two groups. Psychomotor function parameters did not differ significantly either between the EM and PM groups or between the nonsmoker and smoker groups. The present study thus suggests that neither S-mephenytoin 4-hydroxylation status nor self-reports of extensive cigarette smoking has a major impact on the metabolism of alprazolam in humans.

A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: In vivo evidence for the involvement of CYP3A4 in alprazolam metabolism*

To assess the possible involvement of CYP3A4 in the metabolism of alprazolam in vivo. Twelve healthy male volunteers were randomly allocated to one of the two different treatment sequences, placebo-erythromycin or erythromycin-placebo, with an at least 6-week washout period between the two trial phases. Each volunteer received 400 mg erythromycin or matched placebo given orally three times a day for 10 days and an oral dose (0.8 mg) of alprazolam on the posttreatment day 8. Plasma concentration of alprazolam was measured up to 48 hours after the administration, and psychomotor function was assessed at each time of blood samplings with use of the Digit Symbol Substitution Test, visual analog scale, and Udvalg for kliniske undersøgelser side effect rating scale. Erythromycin significantly (p < 0.001) increased the area under the plasma concentration-time curves (200 +/- 43 versus 322 +/- 49 ng . hr/ml from 0 to 48 hours and 229 +/- 52 versus 566 +/- 161 ng . hr/ml from 0 hour to infinity), decreased the apparent oral clearance (1.02 +/- 0.31 versus 0.41 +/- 0.12 ml/min/kg), and prolonged the elimination half-life (16.0 +/- 4.5 versus 40.3 +/- 14.4 hours) of alprazolam. However, any psychomotor function variables did not differ significantly between the erythromycin and placebo trial phases. This study suggests that erythromycin, an inhibitor of CYP3A4, inhibits the metabolism of alprazolam, providing an in vivo evidence for the involvement of CYP3A4 in its metabolism. However, the kinetic change of alprazolam by erythromycin does not result in the pharmacodynamic change of this triazolobenzodiazepine, at least after single dosing.

Clinical pharmacokinetics of alprazolam. Therapeutic implications.

Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by hepatic microsomal oxidation, yielding alpha-hydroxy- and 4-hydroxy-alprazolam as principal initial metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma concentrations of the 4-hydroxy metabolite exceed those of the alpha-hydroxy derivative, but urinary recovery of alpha-hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be explained by chemical instability of 4-hydroxy-alprazolam in vitro. After single 1 mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a peak plasma concentration 12 to 22 micrograms/L occurring 0.7 to 1.8h postdose, a volume of distribution of 0.8 to 1.3 L/kg, elimination half-life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg. Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-independent and are unchanged during multiple-dose treatment. On average, mean steady-state plasma alprazolam concentrations change by 10 to 12 micrograms/L for each daily dosage change of 1 mg/day. Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender. Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced by the phase of the menstrual cycle in women. Coadministration of cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs alprazolam clearance. However, alprazolam clearance is not altered by coadministration of propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance may be impaired if alprazolam is coadministered. Alprazolam does not alter the pharmacokinetics of digoxin. Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 micrograms/L. Concentrations higher than this may be needed for suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness, sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in frequency with higher steady-state plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of acute and chronic alprazolam treatment on cerebral blood flow, memory, sedation, and plasma catecholamines.

The effects of 0.014 mg/kg intravenous alprazolam administration on cerebral blood flow (CBF), memory, sedation, and plasma norepinephrine and epinephrine were determined in eight healthy males at baseline levels and following 1 week of daily oral alprazolam treatment. At baseline, intravenous alprazolam administration caused acute reductions in whole-brain CBF (25% to 30% decrease), memory, plasma epinephrine, and self-rated alertness. Following 1 week of alprazolam treatment, tolerance developed to the acute effects of intravenous alprazolam on CBF, memory, and plasma epinephrine. There were no consistent regional neuroanatomic differences in the CBF effects of acute alprazolam, or in the development of tolerance to these effects, and no correlations between the various measures of acute alprazolam effects on either test day.

Antiemetic activity of high-dose methylprednisolone associated with continuous-infusion metoclopramide and oral alprazolam during multiple-day chemotherapy

The addition of high-dose methylprednisolone (120 mg given i.v. and repeated after a 4-h interval) to a conventional antiemetic regimen consisting of metoclopramide (0.5 mg/kg given as an i.v. bolus over 30 min followed by 1 mg/kg given as a continuous infusion over 24 h) and alprazolam (0.5 mg given p.o.) was evaluated in a randomized study of leukemic patients undergoing anthracycline-containing multiple-day chemotherapy. Double-blind analysis was done in 30 patients who completed a total of 40 treatment courses. Cumulative 3-day results revealed complete control of nausea in 66% of patients and complete control of emesis in 77% of cases. The addition of methylprednisolone significantly reduced the occurrence of nausea (p = 0.003) and emesis (P = 0.06). Moreover, antiemetic rescue with chlorpromazine was less frequently necessary in patients receiving corticosteroids (P = 0.02). No harmful side effect was observed, and the incidence of severe infectious episodes was similar in both arms. We conclude that high-dose methylprednisolone can improve the efficacy of metoclopramide and alprazolam in controlling nausea and emesis induced by anthracycline-containing multiple-day chemotherapy in patients with acute myeloblastic leukemia.

Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety ratings in healthy human subjects

In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO 2-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO 2-induced increase in ratings of anxiety. Neither drug altered CO 2-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO 2 induces anxiety-like effects involve neural systems regulated by benzodiazepine receptors and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.

The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam.

12 obese patients, pair-matched with 12 normal subjects, received a single 1 mg oral dose of alprazolam. Nine similar subject pairs received a single 0.5 mg oral dose of triazolam. Oral volume of distribution (Vd) was much greater in obese than control subjects for alprazolam (mean 114 vs 73L, p less than 0.001), but there was no difference between the 2 groups for triazolam (117 vs 116L). Apparent oral clearance (not corrected for body weight) of alprazolam was lower, although not significantly so, in obesity (66 vs 88 ml/min), but for triazolam it was much lower in the obese (340 vs 531 ml/min, p less than 0.005). Elimination half-life, which is dependent on both Vd and clearance, was prolonged in obesity for alprazolam (22 vs 11h, p less than 0.001) due to the increase in Vd, and also for triazolam (4.1 vs 2.6 h, p less than 0.025) because of the decreased clearance. Plasma protein binding was unchanged in obese compared with control subjects for both alprazolam and triazolam. During long term administration alprazolam should therefore take longer to reach steady-state concentrations in obese patients but the final levels achieved should be no different than for patients of normal bodyweight, provided dosage is adjusted for ideal rather than total bodyweight. In contrast, triazolam has impaired clearance in obesity. However, if given once-daily it still would not accumulate with long term dosing due to its short half-life relative to the interval between doses.