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Benzodiazepines have been used for the management of acute seizures and epilepsy since the 1960s and are, at present, the drugs of first choice for status epilepticus and prolonged seizures in both adults and children.8 The benzodiazepines share a common set of neuropharmacological effects, including anxiolysis, sedation, muscle relaxation, and anticonvulsant action. The differing affinity of each of the benzodiazepines for their receptor subtypes account for the extent to which they exert each of these effects. In general, the benzodiazepines, diazepam, lorazepam, and midazolam, have been the most studied and are therefore preferred for the acute management of seizures.
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Midazolam is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. This enzyme is expressed primarily in the liver, but is also active in the intestinal mucosa. As a result, the oral bioavailability of midazolam is only approximately 40%. The unconjugated metabolite, α-hydroxymidazolam, is also pharmacologically active and contributes about 10% of the pharmacological effect of midazolam. The glucuroconjugated α-hydroxymidazolam is excreted in urine, with a terminal elimination half-life of about one hour. Due to the almost exclusive metabolism mediated by the CYP3A4 isoenzyme, coadministration of CYP3A4 inhibitors and inducers may result in pharmacokinetic interactions. CYP3A4 is only expressed at low levels in the liver in the neonatal period, increasing to adult levels over the first year of life. Consequently, young infants may experience more prolonged effects, both desirable and undesirable, and repeated dosing may lead to accumulation.3
The characteristic undesirable effects of benzodiazepines are reported also for midazolam. Sedation, amnesia, impaired attention, and impaired muscular function may adversely affect the ability to drive or use machines. Paradoxical reaction such as agitation, involuntary movements, hyperactivity, hostility, rage reactions, aggressiveness, excitement, and assault have been reported. These reactions occur mainly with high doses and/or when the injection is given rapidly. The highest risk for paradoxical reaction has been reported for children and elderly patients, as well as patients with actual or amnestic psychiatric diseases and patients with alcohol addiction. Furthermore paradoxical reaction is often related to high midazolam doses.13
As a result, there have been suggestions that a test dose of buccal midazolam should be given to children in hospital prior to its use in the community.27 However, a dose given to a conscious, nonconvulsing child does not mimic its use during a seizure, and most clinicians do not follow this practice.28
In a prospective, double-blind, randomised, placebo-controlled trial, we have compared the effects of midazolam co-induction with propofol predosing on the induction dose requirements of propofol in elderly patients. We enrolled 60 patients aged > 70 years, attending for urological surgery. The patients were allocated randomly to one of three groups, to receive either midazolam 0.02 mg.kg(-1), propofol 0.25 mg.kg(-1), or normal saline 2 ml (placebo) 2 min prior to induction of anaesthesia using propofol 1% infusion at 300 ml.h(-1). The propofol dose requirements for induction were recorded for two end-points (loss of verbal contact and insertion of an oropharyngeal airway). Cardiovascular parameters were recorded at 1-min intervals for each patient until induction was complete. The midazolam group showed a significant reduction in propofol dose requirements for induction (p = 0.05) compared to the placebo group. The propofol group did not show a significant dose reduction compared to placebo. There were no demonstrable differences in terms of improved cardiovascular stability between groups. We conclude that propofol predosing does not significantly reduce the induction dose of propofol required in the elderly, and there were no cardiovascular benefits to either midazolam co-induction or propofol predosing in the elderly.
Methods: After i.v. detomidine (20 μg/kg) thirty-eight ponies undergoing field castration received either 0.06 mg/kg (0.6 mL/50 kg) midazolam (group M) or 0.6 mL/50 kg placebo (group P) with 2.2 mg/kg ketamine i.v. for anaesthetic induction. Quality of anaesthetic induction, endotracheal intubation, surgical relaxation and recovery were scored using combinations of simple descriptive and visual analogue scales. Time of sedation, induction, start of endotracheal intubation, first movement, sternal recumbency and standing were recorded, as were time, number and total quantity of additional i.v. detomidine and ketamine injections. Cardiorespiratory variables were assessed every 5 min. Adverse effects were documented. Data were tested for normality and analysed with a mixed model ANOVA, Fisher's exact test, unpaired Students' t test and Wilcoxon Rank-sum as appropriate; P
Midazolam injection is used in medical procedures to create drowsiness before surgery to reduces anxiety and prevent any recollection of the event. It is sometimes given as part of anesthesia during surgery to cause loss of consciousness. Midazolam injections are also using in intensive care units (ICUs). That reduces the awareness of critically ill people who breathe with the machine. Many people buy midazolam online. Moreover, Midazolam for injection belongs to the benzodiazepine class. It works by reducing mental activity, which allows you to relax and lower your senses.
The midazolam is a mediated by gamma-aminobutyric acid (GABA), a nervous system. If you Buy Midazolam Online it can important neurotransmitter in the central nervous system. That inhibits the action of various benzodiazepines such as midazolam. Benzodiazepines increase the activity of GABA, thus creating a ridiculous effect, relaxing skeletal muscles and inducing drowsiness, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors. Providing the effects of GABA by increasing the frequency of chloride channel opening.
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Not everyone with epilepsy will be prescribed buccal bidazolam as emergency medication for their seizures. If someone with epilepsy is known to be at increased risk of status epilepticus, their doctor may prescribe them buccal midazolam or an alternative emergency medication.
NAYZILAM (midazolam) nasal spray, CIV is a prescription medicine used for the short-term treatment of seizure clusters (also known as acute repetitive seizures) in patients 12 years of age and older.
For conscious sedation prior to diagnostic or surgical intervention, midazolam is administered IV The dose must be individualised and titrated, and should not be administered by rapid or single bolus injection. The onset of sedation may vary individually depending on the physical status of the patient and the detailed circumstances of dosing (e.g. speed of administration, amount of dose). If necessary, subsequent doses may be administered according to the individual need. The onset of action is about 2 minutes after the injection. Maximum effect is obtained in about 5 to 10 minutes.
In adults over 60 years of age, debilitated or chronically ill patients, the initial dose must be reduced to 0.5-1.0mg and given 5-10 minutes before the beginning of the procedure. Further doses of 0.5 to 1mg may be given as necessary. Since in these patients the peak effect may be reached less rapidly, additional midazolam should be titrated very slowly and carefully. A total dose greater than 3.5mg is usually not necessary.
IV administration: midazolam should be titrated slowly to the desired clinical effect. The initial dose of midazolam should be administered over 2 to 3 minutes. One must wait an additional 2 to 5 minutes to fully evaluate the sedative effect before initiating a procedure or repeating a dose. If further sedation is necessary, continue to titrate with small increments until the appropriate level of sedation is achieved. Infants and young children less than 5 years of age may require substantially higher doses (mg/kg) than older children and adolescents.
Rectal administration: the total dose of midazolam usually ranges from 0.3 to 0.5mg/kg. Rectal administration of the ampoule/vial solution is performed by means of a plastic applicator fixed on the end of the syringe. If the volume to be administered is too small, water may be added up to a total volume of 10ml. Total dose should be administered at once and repeated rectal administration avoided. The use in children less than 6 months of age is not recommended, as available data in this population are limited.
Premedication with midazolam given shortly before a procedure produces sedation (induction of sleepiness or drowsiness and relief of apprehension) and preoperative impairment of memory. Midazolam can also be administered in combination with anticholinergics. For this indication midazolam should be administered IV or IM, deep into a large muscle mass 20 to 60 minutes before induction of anaesthesia), or preferably via the rectal route in children (see below). Close and continuous monitoring of the patients after administration of premedication is mandatory as interindividual sensitivity varies and symptoms of overdose may occur.
For preoperative sedation and to impair memory of preoperative events, the recommended dose for adults of ASA Physical Status I & II and below 60 years is 1-2mg IV repeated as needed, or 0.07 to 0.1mg/kg administered IM The dose must be reduced and individualised when midazolam is administered to adults over 60 years of age, debilitated, or chronically ill patients. The recommended initial IV dose is 0.5mg and should be slowly uptitrated as needed. A dose of 0.025 to 0.05mg/kg administered IM is recommended. In case of concomitant administration of narcotics the midazolam dose should be reduced. The usual dose is 2 to 3mg. 041b061a72