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Journal of Avian Medicine and Surgery May 2022Currently, drug-induced stimulation of appetite is not commonly performed in hyporexic or anorexic companion psittacine birds. Instead, to prevent a catabolic state and...
Currently, drug-induced stimulation of appetite is not commonly performed in hyporexic or anorexic companion psittacine birds. Instead, to prevent a catabolic state and weight loss, supplemental feedings are routinely performed by crop gavage. However, crop gavage is not without complications and is stressful to the patient and labor intensive. The objective of this study was to evaluate the effect of midazolam on food intake in healthy budgerigars. In a randomized, blinded, controlled study, change in food intake after intramuscular administration of midazolam (1 mg/kg) or a placebo-control treatment (0.9% saline) was evaluated in 12 healthy adult budgerigars (). Food intake was quantified for 1 hour before and after drug administration. Birds were monitored for feeding behavior as well as signs of sedation. After midazolam administration, a median 6-fold (1.1-28) increase in food intake was recorded. In 3 of 6 (50%) birds, the food intake increase after midazolam administration was >10-fold (median 17-fold [10-28]), whereas in the remaining 3 birds, food intake increased by only 1.7-fold (1.1-1.8). The median amount of food ingested (16.7 g/kg [3.2-43.2 g/kg]) was significantly higher after midazolam administration compared with the control group (1.9 g/kg [0.0-19.7 g/kg], = .015). The median time birds spent displaying feeding behavior after the midazolam injection was 18% (0-43%), compared with 1% (0-20%) in the control group after saline injection. Five of 6 (83%) birds showed signs consistent with mild sedation after midazolam administration. This study demonstrates that midazolam is an appetite stimulant in budgerigars. Future studies are needed to evaluate whether midazolam's effects on food intake are dose dependent and whether the duration of effect exceeds 1 hour.
Topics: Animals; Eating; Melopsittacus; Midazolam; Parrots
PubMed: 35526164
DOI: 10.1647/20-00096 -
Expert Review of Neurotherapeutics Jul 2014Midazolam is a short-acting benzodiazepine that has clearly demonstrated to be an effective option for the acute management of epileptic seizures. It has the advantage... (Review)
Review
Midazolam is a short-acting benzodiazepine that has clearly demonstrated to be an effective option for the acute management of epileptic seizures. It has the advantage of being water-soluble, with a rapid onset of action and it can be administered orally or intranasally, implementing an early intervention at the pre-hospital setting. This article aims to provide an overview of intranasal midazolam in the acute management of epileptic seizures. Available data suggest that midazolam 0.2 mg/kg is as effective as diazepam 0.5 mg/kg, especially in children with febrile or afebrile seizures. Local mucosal irritation seems to occur in less than one-third of cases while serious side effects such as respiratory depression in about 1%. Future studies need to be focused on adults and optimized technologies for intranasal delivery. Moreover, comparisons with buccal midazolam are warranted.
Topics: Administration, Intranasal; Anticonvulsants; Epilepsy; Humans; Midazolam
PubMed: 24910118
DOI: 10.1586/14737175.2014.925398 -
DICP : the Annals of Pharmacotherapy May 1991
Comparative Study Review
Topics: Administration, Intranasal; Administration, Rectal; Child; Child, Preschool; Humans; Infant; Injections, Intramuscular; Midazolam
PubMed: 2068833
DOI: No ID Found -
Pediatric Dentistry 1993
Review
Topics: Anesthesia, Dental; Child; Child, Preschool; Conscious Sedation; Humans; Midazolam
PubMed: 8247896
DOI: No ID Found -
Acta Anaesthesiologica Scandinavica.... 1990Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.)... (Review)
Review
Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.) administration, both drugs are rapidly distributed into similar distribution volumes, from which they are cleared with a comparable short elimination half-life (t1/2 beta) in the range of 1 h (flumazenil) to 3 h (midazolam). Both drugs undergo hepatic metabolisation with a relatively high hepatic extraction ratio of around 0.3 for midazolam and 0.6 for flumazenil. The metabolisation of midazolam and flumazenil may equally be affected by considerable loss of active liver cells or by temporarily reduced hepatic blood flow. In such a case, elimination of both drugs may be prolonged in the same way. Flumazenil has only an inactive metabolite. The main active alpha-hydroxy-metabolite of midazolam does not contribute much to the activity of midazolam after parenteral administration. Its potency is lower than that of midazolam and its shorter elimination half-life (0.8 h) does not prolong the activity of the parent drug. As indicated by the therapeutic index, both drugs have a very high safety margin, which is considerably higher than that of thiopentone or propofol. Only low doses of both drugs are necessary to produce initial effects. Increasing doses intensify the drug activity and a ceiling effect is observed after maximal doses of midazolam and flumazenil. The onset of effect immediately follows the diffusion of the substances into the CNS and can be observed within the first minutes following flumazenil or midazolam administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Chemical Phenomena; Chemistry; Flumazenil; Humans; Infusions, Intravenous; Mice; Midazolam; Rats
PubMed: 2109472
DOI: No ID Found -
Biomolecules Jun 2022Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions...
Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of the possible involvement of new drug candidates in CYP3A4-mediated DDI, we evaluated the application of midazolam (MDZ) as a probe substrate. MDZ is hydroxylated by CYP3A4 in two positions: 1-hydroxy MDZ formed at lower substrate concentrations, and up to 35% of 4-hydroxy MDZ at high concentrations. The ratio of the formation rates of these two products (the site of metabolism ratio, SOM) was used as a measure of allosteric heterotropic interactions caused by effector molecules using CYP3A4 incorporated in lipid nanodiscs. The extent of the changes in the SOM in the presence of effectors is determined by chemical structure and is concentration-dependent. MD simulations of CYP3A4 in the lipid bilayer suggest that experimental results can be explained by the movement of the F-F' loop and concomitant changes in the shape and volume of the substrate-binding pocket. As a result of PGS binding at the allosteric site, several residues directly contacting MDZ move away from the substrate molecule, enabling the repositioning of the latter for minor product formation.
Topics: Allosteric Site; Cytochrome P-450 CYP3A; Drug Interactions; Humans; Lipid Bilayers; Midazolam
PubMed: 35740978
DOI: 10.3390/biom12060853 -
Lancet (London, England) Aug 1988
Topics: Aged; Drug Combinations; Flumazenil; Gastroscopy; Humans; Midazolam
PubMed: 2899787
DOI: No ID Found -
Acta Anaesthesiologica Scandinavica.... 1990Midazolam is useful as an intravenous supplement to local anaesthesia techniques in producing sedation, amnesia and anxiolysis, and has about five times the sedative... (Review)
Review
Midazolam is useful as an intravenous supplement to local anaesthesia techniques in producing sedation, amnesia and anxiolysis, and has about five times the sedative potency of diazepam. Considerable interpatient variability exists in dose requirements, especially in elderly patients. The combined effects of local anaesthetics and midazolam may contribute to enhanced haemodynamic effects and changes in the respiratory pattern, impairing ventilation and oxygenation. Flumazenil can be titrated in incremental doses to reverse the residual sedative effects of midazolam, without intrinsic haemodynamic or respiratory effects, but may not fully antagonise the decrease in chemoreceptor sensitivity nor the changes in breathing pattern induced by midazolam. Patients treated with epidural or spinal anaesthesia supplemented with midazolam should be monitored to avoid hypoxaemia risks even after the administration of flumazenil.
Topics: Anesthesia, Conduction; Anesthesia, Local; Flumazenil; Hemodynamics; Humans; Midazolam; Respiration
PubMed: 2109468
DOI: 10.1111/j.1399-6576.1990.tb03181.x -
Drug Intelligence & Clinical Pharmacy Sep 1988
Topics: Adult; Humans; Injections, Intravenous; Male; Midazolam
PubMed: 3215120
DOI: 10.1177/106002808802200924 -
Clinical Therapeutics 1998Status epilepticus is an epileptic seizure that lasts at least 30 minutes or is repeated at sufficiently brief intervals to produce a continued epileptic condition... (Review)
Review
Status epilepticus is an epileptic seizure that lasts at least 30 minutes or is repeated at sufficiently brief intervals to produce a continued epileptic condition lasting a total of 30 minutes without the patient fully regaining consciousness. Various combinations of anticonvulsant agents, including benzodiazepines, phenytoin, and phenobarbital, have been used to manage this condition. However, at least 9% of patients with generalized convulsive status epilepticus do not respond to conventional first-line agents, and additional intervention is required. Refractory status epilepticus refers to sustained seizures that do not respond to initial drug therapy and persist longer than 60 minutes. Reports on the response to first- and second-line agents suggest that the incidence of refractory status epilepticus is between 2000 and 6000 cases per year in the United States. Refractory status epilepticus is a major medical and neurologic emergency that requires immediate treatment to avoid significant morbidity and mortality. The anticonvulsive agent midazolam has proved to be effective, well tolerated, and fast acting when used to treat refractory status epilepticus in both adults and children. Its pharmacodynamic effects can be seen within 1 to 5 minutes of administration, and its anticonvulsive effects are apparent as early as 5 to 15 minutes after administration. This article reviews the pharmacology of midazolam and recent clinical reports on the drug's tolerability and effectiveness in the treatment of patients with refractory status epilepticus.
Topics: Animals; Drug Resistance; GABA Modulators; Humans; Midazolam; Status Epilepticus
PubMed: 9916604
DOI: 10.1016/s0149-2918(98)80106-9