Lorazepam toxicity

Refractory GCSE has also been treated with large-dose continuous infusion lorazepam or diazepam. Lorazepam contains propylene glycol, which can accumulate and cause marked osmolar gap, metabolic acidosis, and renal toxicity. 

Though not used clinically, the therapeutic serum level for lorazepam is 50-240 ng/ml the toxic serum level is unknown... 

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... 

Cawley MJ. Short-term lorazepam infusion and concern for propylene glycol toxicity case report and review. Pharmacotherapy 2001 21(9) 1140-4. 

Benzodiazepine and azapirone derivatives are widely used drugs in this class, and most are metabolized extensively by enzymes of the CYP3A family, except oxazepam, lorazepam, and temazepam, which are mostly glucuronidated (52). Again, several studies have shown that inducers and inhibitors of CYP3A can markedly alter plasma concentrations of many of these drugs, but in only a few cases have toxic effects, such as deep unconsciousness, been reported (19,52,53). Nonetheless, patients on these drugs should probably be monitored carefully, particularly the elderly, who may suffer severe physical injury as a result of falls from impairment of psychomotor function. 

The other toxicities of carboplatin are generally milder and better tolerated than those of cisplatin. Nausea and vomiting, though frequent, is less severe, shorter in duration, and more easily controlled with standard antiemetics (for example compazine, dexamethasone, lorazepam) than that following cisplatin treatment. Renal impairment is infrequent, though alopecia is common, especially with the paclitaxel-containing combinations. Neu-... 

Although the shorter-acting BZs such as Xanax (alprazolam) and Halcion (triazolam) seem to be the most toxic and most prone to cause dependence, any BZ can cause these untoward effects, including the commonly used Klonopin (clonazepam) and Ativan (lorazepam). Overall, the BZs and many related medications used to treat anxiety and insomnia are potentially very brain disabling and spellbinding, and entail much graver risks than commonly recognized by health care providers and their patients. 

Suriclone, a cyclopyrrolone analogue of zopiclone, has similar pharmacology to the benzodiazepines, binding close to the same site of the GABA receptor-chloride channel complex. It is effective as an anxiolytic and has the notable advantages of minimal sedation and cognitive toxicity, and milder withdrawal effects than those of diazepam or lorazepam (1). Its withdrawal from further development is a mystery. 

Plasma concentrations of 0.3 to 0.6 pg/ml were reported in 3 subjects suffering toxic effects after the ingestion of overdoses of lorazepam the estimated amounts ingested were 100 and 120 mg in 2 of the cases. The subjects recovered within 24 to 30 hours (M. D. Allen et al.. Am. J. Psychiat., 1980,137, 1414-1415). 

Yaucher NE, Fish JT, Smith HW, Wells JA. Propylene glycol-associated renal toxicity from lorazepam infusion. Pharmacotherapy 2003 23(9) 1094-9. 

A combination of paracetamol (acetaminophen) plus codeine is especially well suited to post-peel pain, but should not be used in the hours following a phenol peel, as paracetamol (a phenol derivative) goes through the same detoxification pathways as phenol, which could create metabolic competition and the risks of toxicity associated with phenol might be increased. Preventive administration of benzodiazepines (lorazepam 2.5 mg before the peel and on the night of the peel before going to bed) relieves the anxiety caused by these unpleasant sensations and reduces the need for analgesics after the peel. In case of very severe, localized pain (extremely rare), a nerve block could be used. 

All narcotics are expected to have this problem. The most common side effects demonstrated with narcotics include decreased gastrointestinal motility and risk of hypotension. Lorazepam is the preferred sedative agent in the absence of pain owing to its fast onset of action, its lack of hemodynamic toxicities, and its low risk of metabolite accumulation in comparison with diazepam. Midazolam continuous infusion is a reasonable altemative, although more costly and requiring additional fluid, which may be detrimental in a patient predisposed to PDA. Muscle paralysis has been used to reduce ventilator fighting and the consequent comphcations. However, its role in RDS has diminished owing to adverse effects (e.g., edema and hypoventilation). If paralysis is induced, assessment of sedation and seizures is confounded. Consequently, concurrent phenobarbital serum concentrations of 40 mg/L are recommended. Independent of... 

Absence status epilepticus is a condition of impaired consciousness, perhaps including mild motor symptoms, that lasts from 30 minutes to 12 hours. It can be distinguished from ongoing seizures because of organic or toxic causes by the spike-and-wave EEC pattern that is characteristic of absence seizures. The usual pharmacological treatment of absence status employs diazepam or lorazepam, followed by ethosuximide. 

Animal studies suggest that the benzodiazepines may possibly increase the metabolic activation and the toxicity of high doses of cyclophosphamide and ifosfamide. However, diazepam did not alter the pharmacokinetics of high-dose cyclophosphamide in a clinical study. Note also that lorazepam is widely used for chemotherapy-induced nausea and vomiting. 

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