versed adj : thoroughly acquainted with and skilled in something through study or experience; "well versed in classical languages" [syn: knowledgeable] [ant: unversed] n : an injectable form of benzodiazepine (trade name Versed) useful for sedation and for reducing pain during uncomfortable medical procedures [syn: midazolam]
- Rhymes: -ɜː(r)st
Midazolam (marketed under brand names Dormicum, Flormidal, Versed, Hypnovel and Dormonid, pronounced mɪˈdæzəlæm) is a drug which is a benzodiazepine derivative. It has powerful anxiolytic, amnestic, hypnotic, anticonvulsant, skeletal muscle relaxant and sedative properties. It is considered a short-acting benzodiazepine, with a short elimination half-life. It is therefore a very useful drug to use for short minor procedures such as dental extraction.
Midazolam was first synthesized in 1976 by Fryer and Walser.
Mechanism of action
Like other benzodiazepines, midazolam acts on the benzodiazepine binding site of GABAA receptors. When bound it enhances the binding of GABA to the GABAA receptor which results in inhibitory effects on the central nervous system.
Midazolam is indicated for the short term treatment of insomnia in patients who did not adequately react to other (benzodiazepines) hypnotics, and who have persistent trouble in falling asleep. Because of midazolam's extremely short duration, midazolam is not used for patients who have trouble staying asleep through the night, moderate to long acting benzodiazepines like temazepam, nitrazepam, flunitrazepam and lormetazepam are used for those purposes. Like other benzodiazepines, midazolam produces a decrease in delta activity, though the effect of benzodiazepines on delta may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; it is thought to reflect sleep quality, with lower levels of delta sleep reflecting poorer sleep. Thus midazolam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to nitrazepam in the treatment of insomnia as it enhances sleep quality based on EEG studies.
Midazolam is also indicated for the acute management of aggressive or delirious patients and also is sometimes used for the acute management of seizures such as status epilepticus. Long term use for the management of epilepsy is not recommended however, due to the significant risk of tolerance which renders midazolam and other benzodiazepines ineffective and as well the significant side effect of sedation. In mice given chronic midazolam a slowly evolving tolerance developed to the anticonvulsant properties of midazolam over 15 days, although some anticonvulsant effects were still apparent after 15 days of continued administration.
InteractionsMidazolam is metabolized almost completely by cytochrome P450-3A4. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations, which could result in overdose.
ContraindicationsHypersensitivity, acute narrow angle glaucoma, shock, hypotension, head injury, and drug or alcohol use. Most are relative contraindications.
Side EffectsResidual 'hangover' effects after nighttime administration of midazolam such as sleepiness, impaired psychomotor and cognitive functions may persist into the next day which may impair the ability of users to drive safely and increase risks of falls and hip fractures.
PregnancyMidazolam (as with other central nervous system depressants), if taken regularly in pregnancy, may result in reduced IQ, developmental problems, physical malformations - however this data is inconclusive. Midazolam when taken during the third trimester of pregnancy may cause severe risk to the neonate, including benzodiazepine withdrawal syndrome with possible symptoms including hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.
OverdoseSymptoms of midazolam overdose include:
In animal models, the oral LD50 of midazolam is 825 mg/kg.
Midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of midazolam (or any other benzodiazepine) is flumazenil (Anexate). The risk of midazolam overdose is increased significantly if midazolam is abused in conjunction with opiates as was highlighted in a review of deaths of users of the opiate buprenorphine in Singapore.
AvailabilityDormicum brand midazolam is marketed by Roche as white, oval 7.5mg tablets in boxes of 2 or 3 blisterstrips of 10 tablets, and as blue, oval 15mg tablets in boxes of 2 blisterstrips of 10 tablets. The tablets are imprinted with "Roche" on one side and the dose of the tablet on the other side. Dormicum is also available as 1ml, 3ml and 10ml ampoules at a concentration of 5mg/ml.
Legal statusIn the Netherlands, midazolam is a List II drug of the Opium Law. Midazolam is a Schedule IV drug under the Convention on Psychotropic Substances.
Popular CultureMidazolam is offered to death row inmates before execution in the United States, according to the film The Missouri Protocol (1990). A Missouri prison doctor interviewed in the film said virtually no prisoners turned down the drug when it was offered a few hours prior to execution.
Prolonged after-effects of midazolam dosing after dental surgery inspired Duran Duran vocalist Simon Le Bon to entitle the group's 1997 album Medazzaland, likely in reference to psychotropic effects he experienced.
- EMEA Summary of Product Characteristics: Hypnovel and associated names.
- Clinical Use of Midazolam by John Shou.
- Prediction of the disposition of midazolam in surgical patients by a physiologically based pharmacokinetic model, Bjorkman, S et al, J Pharm Sci 2001:90(9)1226-1241.
versed in German: Midazolam
versed in Spanish: Midazolam
versed in French: Midazolam
versed in Italian: Midazolam
versed in Dutch: Midazolam
versed in Norwegian: Midazolam
versed in Polish: Midazolam
versed in Portuguese: Midazolam
versed in Finnish: Midatsolaami
versed in Swedish: Midazolam