Clinical Pharmacokinetics of Lorazepam II. Intramuscular Injection

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Lorazepam (LZP) may be a more useful anticonvulsant to stop convulsions in children with severe malaria (SM) than diazepam, since it has a longer duration of action and can be given by other routes, such as intramuscular (i.m. WHAT THIS STUDY ADDS• Administration of LZP (i.v. or i.m.) at the currently recommended dose (0.1 mg kg -1 ) resulted in rapid achievement of plasma LZP concentrations within the reported effective therapeutic range without clinically significant cardiorespiratory effects.• A single dose of LZP was effective in the rapid termination of convulsions in all children, and prevention of seizure recurrence for >72 h in 11 of 15 (73%) children and 10 of 11 (91%) children after i.v. and i.m. administration, respectively. AIMTo investigate the pharmacokinetics and clinical efficacy of intravenous (i.v.) and intramuscular (i.m.) lorazepam (LZP) in children with severe malaria and convulsions. METHODSTwenty-six children with severe malaria and convulsions lasting Ն5 min were studied. Fifteen children were given a single dose (0.1 mg kg -1 ) of i.v. LZP and 11 received a similar i.m. dose. Blood samples were collected over 72 h for determination of plasma LZP concentrations. Plasma LZP concentration-time data were fitted using compartmental models. ) resulted in rapid achievement of plasma LZP concentrations within the reported effective therapeutic range without significant cardiorespiratory effects. I.m administration of LZP may be more practical in rural healthcare facilities in Africa, where venous access may not be feasible. RESULTS Median

Section: Discussionsupporting

confidence: 91%

Pharmacokinetics and clinical efficacy of lorazepam in children with severe malaria and convulsions

Muchohi

Kokwaro

Ogutu

et al. 2007

“…It is reasonable to start with 1-2 mg doses of midazolam (or 5-10 mg doses of diazepam) intravenously with repeat dosing every 3-5 min until sedation occurs. When intravenous access has not yet been achieved either midazolam (5-10 mg) or lorazepam (2-4 mg) intramuscularly may be acceptable [52][53][54]. Diazepam should not be given intramuscularly because of erratic absorption [54][55][56].…”

Section: Treatment Of Arrhythmias Resulting From Cocaine-associated Cmentioning

confidence: 99%

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Hoffman

2010

Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with significant cocaine toxicity. The likely aetiologies; catecholamine excess, sodium channel blockade, potassium channel blockade, calcium channel effects, or ischaemia may act alone or in concert to produce a vast array of clinical findings that are modulated by hyperthermia, acidosis, hypoxia and electrolyte abnormalities. The initial paper in the series by Wood & Dargan providing the epidemiological framework of cocaine use and abuse is followed by a detailed review of the electrophysiological effects of cocaine by O'Leary & Hancox. This review is designed to complement the previous papers and focuses on the diagnosis and treatment of patients with cocaine‐associated arrhythmias.

“…The most important compounds in this group are, nevertheless, structurally similar to diazepam, although they are without active, long-acting metabolites. The hydroxylated metabolites of diazepam, temazepam (3-hydroxydiazepam) and oxazepam (3-hydroxy-N-desmethyldiazepam) have elimination half-lives of4-10 h and 6-24 h respectively (Fucella, Bolcioni, Tamassia, Ferrario & Tognoni, 1977;Sjoqvist & Sundwall, 1977) and their chlorinated derivatives, lorazepam and lormetazepam, have elimination half-lives of 9-22 h (Greenblatt, Joyce, Comar, Knowles, Schader, ©Macmillan Publishers Ltd 1981 Kyriakopoulos, MacLaughlin & Ruelius, 1977) and 11-15 h (Schering AG, internal report) respectively, whereas triazolam, a triazolo-1,4-benzodiazepine with an orthochlorophenyl group, has an elimination half-life of 3-5 h (Eberts, Ko & Thomas, 1979).…”

Section: Introductionmentioning

confidence: 99%

The use of short‐ and long‐acting hypnotics in clinical medicine.

Nicholson¹

1981

1 Activity of short‐ and long‐acting benzodiazepines is reviewed with reference to pharmacokinetics and residual sequelae, and to efficacy and adverse effects. 2 Some benzodiazepines may not lead to obvious effects on performance, such as nordiazepam and clobazam, and the persistence of residual sequelae may not relate obviously to elimination half‐lives (as with diazepam and possibly flunitrazepam). However, benzodiazepines with mean half‐lives less than 8 h may have residual sequelae, whereas hypnotics with mean half‐lives greater than 16 h are likely to lead to impared performance and/or anxiolytic effects the next day. 3 Potassium chlorazepate 15 mg, with its long‐ acting metabolite nordiazepam, would seem to be the drug of choice for insomnia secondary to anxiety. For the insomniac without significant psychopathology, temazepam 10‐20 mg, triazolam 0.125‐0.25 mg and for occasional use, diazepam 5‐10 mg, provide the initial approach. Flurazepam hydrochloride 15‐30 mg, nitrazepam 5‐10 mg and flunitrazepam 1 mg and above, have persistent residual effects and should be reserved for refractory patients, and for those in whom some impairment of performance the next day would be acceptable. 4 There is little or no evidence to suggest that the proper use of the short‐acting hypnotics, triazolam and temazepam, leads to a worsening of sleep on withdrawal. However, some benzodiazepines may lead to disturbances of sleep and/or rebound insomnia, and nitrazepam and flunitrazepam may be implicated.