Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Utilizing behavioral and electroencephalographic (EEG) assessments, two inbred rat strains, Lewis (LEW) and Fischer 344 (F344), were exposed to morphine (IV) over a period of 7 days to discern differences in tolerance development. Following morphine injection, the LEW group demonstrated a greater mean total amount, as well as a greater rate of reduction, of stuporous behavior across the 7 days tested. Differences in patterns of latency to onset of slow-wave sleep between the two strains were also exposed. EEG analysis of spectral parameters utilizing an analysis of variance with repeated measures revealed that peak frequency, mean frequency, and edge frequency differed as a function of inbred rat strain. All spectral parameters differed as a function of duration of morphine injection; linear trends were indicated for both strains. Naloxone was administered (IV) following the 7 days of morphine to delineate dependence differences. LEW animals reflected a greater amount of behavioral responses, for example, wet-dog shakes, diarrhea, body stretch, and sluggish behavior. However, F344 rats demonstrated a greater alteration in two spectral parameters assessed: peak frequency and total power. Genetic variability appears to play a major role in both morphine tolerance and dependence as indicated by differences in EEG and behavioral responses.
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PMID:Effects of chronic morphine administration and naloxone on EEG, EEG power spectra, and associated behavior in two inbred rat strains. 151 64

Clonidine is an antihypertensive agent with central and peripheral alpha-2 adrenergic effects. One of the postulated mechanisms of action is the release of endogenous opioids and/or the stimulation of opioid receptors in the central nervous system (CNS). Naloxone, a pure opioid antagonist, has demonstrated reversal effects from clonidine intoxication. During the past 10 y, 25 children with a mean age of 2 y were admitted for clonidine intoxication. Dosage varied widely, but as little as 0.1 mg caused significant signs and symptoms. The most common presenting findings were somnolence-lethargy (96%), miosis (56%), and respiratory depression (48%), a paradoxical hypertensive response (44%) was more common than expected. Supportive management was the mainstay of therapy. Ten patients received naloxone, 50% demonstrated clinical improvement in vital signs and CNS depression. There were no complications as a result of naloxone therapy. Children seem to be unusually sensitive to the depressant effects of clonidine. Naloxone may be an important adjunct to therapy. Expect clonidine intoxications to become more common as the market for antihypertensive drugs expands.
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PMID:Pediatric clonidine intoxications. 235 31

Opioid agonists were used to investigate the modulation of seizures mediated by mu, kappa and delta opiate receptors in the seizure-sensitive Mongolian gerbil. Morphine (1.0-25 mg/kg, s.c.) were used as prototypic agonists for mu, kappa and delta opiate receptors. Each opioid decreased the incidence and severity of the seizure as compared to control values. The anticonvulsant effects of morphine (10 mg/kg, s.c.) and ketocyclazocine (0.5 mg/kg, s.c.) were reversed by naloxone (1.0 mg/kg, s.c.), while the anticonvulsant effects of N-allylnormetazocine (2 mg/kg, s.c.) were not significantly changed by naloxone. Additionally, abnormal behavior was observed following administration of the opioids. Morphine (10 mg/kg, s.c.) produced excitation and hyperresponsiveness with intermittent cataleptic-like states. Ketocyclazocine (10 mg/kg, s.c.) predominantly produced a stuporous, immobile state, accompanied by some loss of posture. N-allylnormetazocine (10 mg/kg, s.c.) produced ataxia and stereotypic side-to-side head nodding . Naloxone was able to reverse the behavioral effects produced by morphine and ketocyclazocine but not those produced by N-allylnormetazocine. The data presented are consistent with earlier studies which demonstrated the anticonvulsant effects of beta-endorphin in the gerbil. This study further suggests that opioids have a protective role against seizure activity in the gerbil and the opioid anticonvulsant effect is not specific to one type of opioid agonist.
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PMID:Similar anticonvulsant, but unique, behavioural effects of opioid agonists in the seizure-sensitive Mongolian gerbil. 633 Jun 6

Intravenous naloxone hydrochloride (20 mg) was administered to eight normal control subjects and 12 affective disorder patients manifesting manic or hypomanic symptoms. On two consecutive days, in a counterbalanced order, naloxone and placebo were given in a double-blind crossover design. The overall effect of naloxone was to decrease pulse rate and to promote lethargy and inactivation. The normal controls manifested reduced feelings of well-being, and the manic patients noted a subjective sense of slowing. There was a variable response pattern to naloxone in the manic patients in which four of the 12 patients manifested an observable reduction in their manic symptoms and behavior after the naloxone administration. Naloxone seems to have had a nonspecific subduing effect in both normal subjects and patients and may also have had a selectively greater effect in a small subsample of the manics.
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PMID:Naloxone-induced behavioral and physiological effects in normal and manic subjects. 737 16

The incidence of clonidine overdose is increasing worldwide, possibly because of the broadening of indications to include several psychiatric conditions, yet there is a paucity of new information regarding treatment options for clonidine toxicity. We report a case in whom naloxone was used and discuss the literature on this topic. A 2-year-old male infant presented with a history of lethargy. Vital signs were notable for hypotension, pupillary constriction, and hypotonia. The Glasgow Coma score progressively worsened, precipitating intubation. Naloxone was given without response. Urine toxicology revealed high concentrations of clonidine but no opiates. Rapid boluses of isotonic crystalloids and intravenous atropine 0.02 mg/kg were administered with good response. The patient was subsequently discharged home with pediatric and community services follow-up. The use of naloxone in the treatment of clonidine intoxication is unclear, and empirical use does not seem to be justified.
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PMID:Use of naloxone for clonidine intoxication in the pediatric age group: case report and review of the literature. 2378 60

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.
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PMID:Antiepileptic Overdose. 3202 Oct 7

Background: Tianeptine is an antidepressant structurally similar to tricyclic antidepressants which is approved abroad but is currently a drug of abuse in the United States since at least 2000. In 2019, our poison center experienced an increase in calls relating to this xenobiotic. The goal of this report is to describe the characteristics of acute tianeptine intoxication and withdrawal.Methods: All calls to a statewide poison center regarding tianeptine were reviewed from January 1, 2015 to March 15, 2020. Cases were identified using the American Association of Poison Control Centers' substance code for "other types of tricyclic antidepressants." Cases were excluded if they did not involve tianeptine. Date of call, patient demographics, symptoms, cardiac intervals if available, and disposition were recorded.Results: Eighty-four cases of atypical tricyclic antidepressants were identified in the study period. Forty-eight cases involving tianeptine met inclusion criteria and were reviewed. Of these, 37 (77%) occurred from May 2019 to March 2020. Twenty-seven (56%) required medical admission including 17 cases (35%) that were managed in an intensive care unit. Seventeen of the 48 cases resulted from acute tianeptine intoxication. Lethargy was the most common presentation, but some patients also presented with agitation. Thirty-one (65%) of the cases resulted from tianeptine withdrawal, which usually exhibited agitation, anxiety, gastrointestinal distress. Naloxone was used in 4 cases (24%) of the acute intoxication cohort and benzodiazepines were frequently used both in acutely intoxicated patients and in patients experiencing tianeptine withdrawal. No patients in either cohort had cardiac conduction disturbances.Conclusion: Our center observed a dramatic rise in tianeptine toxicity, particularly in patients experiencing withdrawal symptoms, beginning in May 2019. More than half of the cases required medical admission including a third who were treated in the intensive care unit. Health care practitioners should be increasingly aware of this xenobiotic as usage may be on the rise.
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PMID:Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health. 3255 75