Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diphenhydramine and other antihistamines produce biphasic effects on drug disposition and lower seizure threshold, thereby potentially diminishing the efficacy of anticonvulsants such as mephobarbital. Accordingly, the influence of diphenhydramine (50 mg/kg, IP) pretreatment on the anticonvulsant activity of mephobarbital (50 mg/kg, IP) was determined in adult female Swiss-Webster mice given pentylenetetrazol (SC). Diphenhydramine lowered the pentylenetetrazol convulsive dose (CD50) by 60%. Administration of diphenhydramine in combination with mephobarbital produced a 65% decrease in the CD50 of pentylenetetrazol in comparison with that of animals given mephobarbital plus pentylenetetrazol. Pharmacokinetic evaluation of mephobarbital blood level data indicates that the mechanism responsible for the observed interaction between diphenhydramine and mephobarbital involves a decrease in mephobarbital uptake from the administration site.
 ...
PMID:Diminished mephobarbital anticonvulsant action following diphenhydramine pretreatment. 145 71

In West Germany, the antihistaminic diphenhydramine is marketed as a non-prescription hypnotic. Results of toxicological screening in cases of drug overdose indicate that poisoning with diphenhydramine represents a substantial part (4.5%) of the total number of intoxications. A total of 136 cases of diphenhydramine poisoning in 1982-1985 were evaluated with respect to age, ingested dose, plasma level, and clinical symptomatology. All patients had taken diphenhydramine with suicidal intent. Two-thirds of the patients were aged 14-30 years. In about 50% of the cases, between 6 and 40 times a therapeutic dose was ingested. Diphenhydramine plasma levels showed a wide range (0.1-4.7/micrograms/ml) due to differences in ingested dose and time between ingestion and admission to hospital. Impaired consciousness was the most common symptom. Psychotic behavior similar to catatonic stupor--often combined with anxiety--was highly specific for diphenhydramine poisoning. Further symptoms included hallucinations, mydriasis, tachycardia, and less frequently diplopia, respiratory insufficiency, and seizures. Primary treatment included gastric lavage, administration of activated charcoal and sodium sulfate. In one case, hemodialysis and ultrafiltration were performed which had only limited effect on diphenhydramine plasma elimination kinetics. This patient died of diphenhydramine overdose and extreme hypothermia. All intoxications except the one mentioned before had an uncomplicated clinical course. In vitro experiments indicate that diphenhydramine may be almost completely removed from the plasma compartment by hemoperfusion. Routine analysis of urine samples in diphenhydramine overdose led to the identification of 4 previously unknown metabolites and artifacts of diphenhydramine.
 ...
PMID:Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. 358 86

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.
 ...
PMID:Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats. 1022 31

Diphenhydramine (DPH) is a commonly reported overdose that shares similar toxicities with other agents. such as tricyclic antidepressants, that interact with the fast sodium channels. Although physostigmine is considered an acceptable antidote for severe DPH toxicity, adverse effects such as seizures and cholinergic crisis may occur. We hypothesized that hypertonic saline or bicarbonate is equivalent or are better antidotes in an animal model of DPH toxicity. In a preliminary study. Sprague-Dawley rats were given toxic doses of DPH while continuous ECG, EEG, and blood pressure monitoring was performed. Seizures were the common toxic effect observed and was chosen. Four groups of 10 rats each were established as control physostigmine, hypertonic sodium bicarbonate, and hypertonic saline(3%) treatment. Control had initial "drop-off" seizure burst rates over time; seizure bursts in the treatment groups were compared to these rates. Hypertonic sodium bicarbonate was the most effective treatment, followed closely by hypertonic saline. Hypertonic sodium bicarbonate may interact with DPH neuronal sodium channels and may be considered adjuvant therapy in humans with DPH-induced seizures.
 ...
PMID:Physostigmine, sodium bicarbonate, or hypertonic saline to treat diphenhydramine toxicity. 1182 63

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.
 ...
PMID:Fatal diphenhydramine intoxication in infants. 1266 5

Diphenhydramine overdose in one of the frequent reported causes of acute poisoning. Patients with diphenhydramine overdose can present with central nervous system manifestations, anticholinergic manifestations and cardiovascular symptoms. The cardiovascular symptoms of diphenhydramine overdose include myocardial depression and refractory hypotension. Massive ingestions have been reported to cause myocardial depressant effect with widening of QRS complex and prolonged QT interval on electrocardiogram. We report an adolescent male with moderate diphenhydramine ingestion, who was found unresponsive with seizure like activity. Electrocardiogram on presentation showed wide complex tachycardia with right bundle branch block pattern and QT interval prolongation. These changes reverted to normal with treatment. Diphenhydramine overdose may occasionally result in prolongation of QT interval.
 ...
PMID:QT interval prolongation in diphenhydramine toxicity. 1568 90

As an antihistamine, diphenhydramine (DPH) is well known for its use in allergy treatment. Since its introduction in 1946, it has been marketed under various trade names, the most popular being Benadryl. Three years after its introduction, the first fatality due to DPH toxicity was reported in 1949. To better understand the incidence of fatalities due to DPH monointoxication, we reviewed deaths that were reported from 2 data sources: (1) the English-language literature using PubMed, from 1946 through 2003; and (2) the Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System (ARAAPCCTESS), from 1983 through 2002. The results were then tabulated using age, gender, clinicopathologic findings, and toxicology results. Combined results from both data sets show the following mean (and range) for age and DPH levels: Adult, 35.6 years (18-84) and 19.53 mg/L (0.087-48.5); pediatric, 8.6 years (1.25-17) and 7.4 mg/L (1.3-13.7); infant, 31 weeks (6 weeks-11 months) and 1.53 mg/L (1.1-2.2), respectively. Most deaths were certified as accident or suicide; however, 6 infant homicides were reported. The most common symptoms for all cases were cardiac dysrhythmias, seizure activity, and/or sympathetic pupil responses. The most common autopsy finding was pulmonary congestion.
 ...
PMID:Fatality from diphenhydramine monointoxication: a case report and review of the infant, pediatric, and adult literature. 1991 60

The influences of histamine H1 receptor antagonists on maximal electroshock seizure were studied using infant rats. In this study, electroconvulsion was induced by stimulating rats using ear-clip electrodes, and the durations of electroencephalogram (EEG) seizure, tonic extensor (TE) seizure and clonic (CL) seizure induced by maximal electroshock were measured. Diphenhydramine, chlorpheniramine, cyproheptadine and ketotifen caused a dose-dependent and significant prolongation of both EEG seizure and TE seizure induced by maximal electroshock. On the other hand, epinastine and fexofenadine caused no such effects, even at a dose of 50 mg/kg. All drugs used in this study showed no significant effect on CL seizure induced by maximal electroshock. From these findings, it is suggested that epinastine and fexofenadine may cause no harmful influence on epilepsy, even when used in a little child.
 ...
PMID:Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats. 1732 41

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of IFE after a confirmed sole ingestion of diphenhydramine is not previously reported. We present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after IFE administration.
...
PMID:Life-threatening diphenhydramine toxicity presenting with seizures and a wide complex tachycardia improved with intravenous fat emulsion. 2409 6

Diphenhydramine toxicity commonly manifests with antimuscarinic features, including dry mucous membranes, tachycardia, urinary retention, mydriasis, tachycardia, and encephalopathy. Severe toxicity can include seizures and intraventricular conduction delay. We present here a case of a 23-year-old male presenting with recurrent seizures, hypotension and wide complex tachycardia who had worsening toxicity despite treatment with sodium bicarbonate. The patient was ultimately treated with intravenous lipid emulsion therapy that was temporally associated with improvement in the QRS duration. We also review the current literature that supports lipid use in refractory diphenhydramine toxicity.
...
PMID:Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. 2549 35


1 2 Next >>