Allergic reaction as above see 9.
Reactions have been attributed to the vehicle used for some parenteral diazepam formulations Huttel et al. There is also a report of a type I hypersensitivity reaction to a lipid emulsion of diazepam Deardon, Martin, ; Hojer et al.
Adverse effects may persist in the neonate for several days after birth because of immature drug metabolising enzymes. Competition between diazepam and bilirubin for protein binding sites could result in hyperbilirubinemia in the neonate Notarianni, The abuse of benzodiazepines by pregnant women can first aid for acute urinary retention withdrawal syndrome in the neonate.
The administration of benzodiazepines during childbirth can produce hypotonia, hyporeflexia, hypothermia and respiratory depression in the newborn. Benzodiazepines have been used in pregnant patients and early reports associated diazepam and chlordiazepoxide with some fetal malformations, but these were not supported by later studies Laegreid et al.
Breast feeding Benzodiazepines are excreted in breast milk in significant amounts and may result in lethargy and poor feeding in neonates. Benzodiazepines should be avoided in nursing mothers Brodie, ; Reynolds, Abrupt cessation after prolonged use causes a withdrawal syndrome Ashton, The mechanism of dependence is probably related to functional deficiency of GABA activity.
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Withdrawal symptoms include anxiety, insomnia, headache, dizziness, tinnitus, anorexia, vomiting, nausea, tremor, weakness, perspiration, irritability, hypersensitivity to visual and auditory stimuli, palpitations, tachycardia and postural hypotension.
In severe and rare cases of withdrawal from high doses, patients may develop affective disorders or motor dysfunction: seizures, psychosis, agitation, confusion, and hallucinations Einarson, ; Hindmarch et al, ; Reynolds, The time of onset of the withdrawal syndrome depends on the half-life of the drug and its active metabolites; the symptoms occur tratament pt cancer la prostata and may be more severe with short- acting benzodiazepines.
Others risk factors for withdrawal syndrome include prolonged use of the drug, higher dosage and abrupt cessation of the drug.
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Abuse Benzodiazepines, particularly temazepam, have been abused both orally and intravenously Stark et al. It should be remembered that benzodiazepine ingestions by adults commonly include other drugs and other CNS depressants. Activated charcoal normally provides adequate gastrointestinal decontamination.
Gastric lavage is not routinely indicated.
Emesis is contraindicated. The use of flumazenil is reserved for cases with severe respiratory or cardiovascular complications and should not replace the basic management of the airway and respiration. Renal and extracorporeal elimination methods are not effective. Continue clinical observation until evidence of toxicity has resolved.
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Intravenous access should be available for administration of fluid. Endotracheal intubation, assisted ventilation and supplemental oxygen may be required on rare occasions, more commonly when benzodiazepines are ingested in large amounts or with other CNS depressants.
Emesis is contraindicated because of the potential for CNS depression. Activated charcoal can be given orally.
Number 2, 2020
Although it effectively reverses the CNS effects of benzodiazepine overdose, its use in clinical practice is rarely indicated. Use of Flumazenil is specifically contraindicated when there is history of co-ingestion of tricyclic antidepressants or other drugs capable of producing seizures including aminophylline and cocainebenzodiazepine dependence, or in patients taking benzodiazepines as an anticonvulsant agent.
In such situations, administration of Flumazenil may precipitate seizures Lopez, ; Mordel et al.
Adverse effects associated with Flumazenil include hypertension, tachycardia, anxiety, nausea, vomiting and benzodiazepine withdrawal syndrome. The initial intravenous dose of 0. The absence of clinical response to 2 mg of flumazenil within 5 to 10 minutes indicates that benzodiazepine poisoning is not the major cause of CNS depression or coma.
The patient regains consciousness within 15 to 30 seconds after injection of flumazenil, but since it is metabolised more rapidly than the benzodiazepines, recurrence of toxicity and CNS depression can occur and the patient should be carefully monitored after initial response to flumazenil therapy. If toxicity recurs, further bolus doses may be administered or an infusion commenced at a dose of 0.
Continuous intravenous infusion should be administered at a rate of 0. Flumazenil is the specific antagonist of the effects of benzodiazepines, but the routine use for the treatment of benzodiazepine overdosage is not recommended.
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The use of Flumazenil should only be considered where severe CNS depression is observed. This situation rarely occurs, except in cases of mixed ingestion. The administration of flumazenil may improve respiratory and cardiovascular function enough to decrease the need for intubation and mechanical ventilation, but should never replace basic management principles. Flumazenil is an imidazobenzodiazepine and has been shown to reverse the sedative, anti-convulsant and muscle-relaxant effects of benzodiazepines.
In controlled clinical trials, flumazenil significantly antagonizes benzodiazepine-induced coma arising from anaesthesia or acute overdose. However, the use of flumazenil has not been shown to reduce mortality or sequelae in such cases. The administration of flumazenil is more effective in reversing the effects of benzodiazepines when they are the only drugs producing CNS toxicity.
Flumazenil does not reverse the CNS depressant effects of non-benzodiazepine drugs, including first aid for acute urinary retention. The diagnostic use of flumazenil in patients presenting with coma of unknown origin can be justified by its high therapeutic index and the fact that this may limit the use of other diagnostic procedures CT scan, lumbar puncture, etc.
Flumazenil is a relatively expensive drug and this may also influence its use, especially in areas with limited resources. Additional information Lancet, ii: Ashton CH Drug-induced stupor and coma: some physical signs and their pharmacological basis.
Adverse drug React Acute Poisoning Rev, 8: Lancet, Brigby M. JAMA, Biopharm Drug Dispos, 2: J Urol, Deardon DJ. Br J Anaesth, Einarson TR Oxazepam withdrawal convulsions.
Drug Intell Clin Pharm, Ellenhorn, M. Oxford University Press, Oxford. Lancet, 2: Drug Alcohol Depend, Clin Pharm Ther, cum să tratezi rapid prostatita Guilleminault C.
J Intern Med, Am J Psychiatry, N Eng J Med Br J Clin Pharmacol, Crit Care Med, Martin SM The effect of diazepam on body temperature change in humans during cold exposure.
J Clin Pharmacol, J Clin Psychiatr, McElhatton PR. Reprod Toxicol, 8: Cambridge University Press, Cambridge. Minder EI Toxicity in a case of acute and massive overdose of chlordiazepoxide and its correlation to blood concentration. Clin Toxicol, Lancet, i: Notarianni LJ. Clin Pharnacokinet, Pau Braune H [Eyes effect of diazepam. A study of cases based on a physiologic system of classification of the severity of intoxication.
Ann Intern Med, The Pharmaceutical Press, London, Ridley CM Bullous lesions in nitrazepan overdosage.
Br Med J, 3: Sandyk R Orofacial diskynesias associated with lorazepam therapy. Clin Pharm, 5: Sullivan RJ Jr Respiratory depression requiring ventilatory support following 0. J Am Geriatr, Soc Dig Dis Sci Ferner, L. Murray ChairpersonM-O. Rambourg, A. Nantel, N. Ben Salah, M. Mathieu- Nolf, A.