Control - Lorazepam

The utilization of prepackaged diazepam for intramuscular use is a poor parenteral therapeutic delivery technique for this anticonvulsant. The diazepam is dissolved in propylene glycol and is poorly and erratically absorbed following intramuscular use. Although the intramuscular route is considered to be the least effective route for seizure control, lorazepam can be used intramuscularly and could be preferred to diazepam for EMS and Hazmat use. Lorazepam, however, has several disadvantages. From a financial perspective it is more expensive than diazepam. Lorazepam is not stable at high temperatures and therefore cannot be as easily stored as diazepam. Finally, without preloaded syringes or... 

The benzodiazepine, lorazepam, acts allosterically on GABAa receptors to facilitate the actions of GABA. Lorazepam has some antiemetic activity in cancer chemotherapy. When used in combination therapy, it does not appear to add to antiemetic control but may contribute to a reduction in anxiety. 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

The first-line treatment for status epilepticus is intravenous benzodiazepines. Diazepam, lorazepam, or midazolam may be used to rapidly control clinical signs of seizures. Lorazepam is currently considered the first-line agent by most clinicians. 

Intramuscular (IM) lorazepam, 2 mg, as needed in combination with the maintenance antipsychotic may actually be more effective in controlling agitation than using additional doses of the antipsychotic. 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

Delle Chiaie, R., Pancheri, P., Casacchia, M., Stratta, P., Kotzalidis, G.D. and Zibellini, M. (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam a placebo-controlled, doubleblind study. Journal of Clinical Psychopharmacology, 15,... 

Hanks GW, O Neill WM, Simpson P, Wesnes K. (1995). The cognitive and psychomotor effects of opioid analgesics II. A randomized controlled trial of single doses of morphine, lorazepam, and placebo in healthy subjects. EurJ Clin Pharmacol. 48(6) 455-60. 

In the presence of cirrhosis or other liver impairment, lorazepam or oxazepam should be utilized for detoxification. These two benzodiazepines have no active hepatic metabolites and are generally considered safer choices for patients with liver damage. Once the starting point for the taper is determined, the dose is decreased by 10-20% per day. It is important to note that this rate of taper is much faster than that used for patients treated chronically with benzodiazepines who are discontinuing their anxiolytic in order to determine if it is still needed for control of symptoms. In that case, the rate of decrease is 10-20% per week. Should the patient display... 

Lorazepam (Ativan, Others) [C-IV] [Anxiolytic, Sedative/ Hypnotic/Benzodiazepine] Uses Anxiety preprocedure sedation control Szs Action Benzodiazepine Dose Adults. Preprocedure sedation 2.0-4.0 mg... 

Ceulemans DLS, Floppenbrouwers MLJA, Gelders YG, et al The influence of ritanserin, a serotonergic antagonist, in anxiety disorders a double-blind placebo-controlled study versus lorazepam. Pharmacopsychiatry 8 303-305, 1985... 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

Knowing the differential pharmacokinetics for a class of drugs allows the clinician to choose specific members to either achieve a faster onset or a delayed offset of action (13, 14, 17, 18). For example, lorazepam is rapidly absorbed from the gastrointestinal tract into the systemic circulation and from there distributed into the brain. In contrast, oxazepam, the most polar BZD, is slowly absorbed from the gastrointestinal tract. Even after oxazepam is in the systemic circulation, it slowly enters tissue compartments, including the brain, during the distribution phase. Unlike lorazepam, oxazepam is not available in either the intramuscular or intravenous formulations. Thus, lorazepam would be preferable to achieve acute control of alcohol withdrawal (e.g., delirium tremens), whereas oxazepam would better stabilize a dependency-prone patient on sedative-hypnotics, because it does not cause the euphoria seen with the more rapidly absorbed members of this class. 

Lorazepam. Lorazepam has been increasingly studied for control of psychotic aggressivity ( 157,158, 159,160, 161,162, 163,164, 165,166 and 167). One reason is that, of all the BZDs available in parenteral form, lorazepam has a pharmacokinetic profile (quick, reliable absorption) that makes it particularly suitable for this type of use. Open, retrospective, and controlled studies indicate that oral or parenteral lorazepam added to an antipsychotic controls disruptive behavior safely and effectively for most patients. The combination may also permit an overall reduction of the antipsychotic dose, although this assumption requires further study ( 162, 164, 166). 

Saizman C, Solomon D, Miyawaki E, et al. Parenteral lorazepam versus parenteral haloperidol forthe control of psychotic disruptive behavior. J Clin Psychiatry 1991 52 177-180. 

Fontaine R, Mercier P, Beaudry P, et al. Bromazepam and lorazepam in generalized anxiety a placebo-controlled study with measurement of drug plasma concentrations. Acta Psychiatr Scand 1986 74 451-458. 

Valproate Versus Lithium. The previously discussed Bowden et al. (135) study found the DVPX formulation to be comparable with lithium, which was used as a positive comparator in this placebo-controlled study. Freeman et al. (99) conducted a 3-week, double-blind, parallel-group comparison of VPA and lithium for acute mania. Both drugs demonstrated clinically significant efficacy (i.e., 9 of 14 responded to DVPX and 12 of 13 to lithium), and there was no difference in the need for rescue medications (i.e., lorazepam or chloral hydrate) between the two treatment groups. Response to VPA was associated with high pretreatment depression scores. 

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