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)

A 49-year-old woman treated with cimetidine 300 mg tid for more than 18 months for Zollinger-Ellison syndrome experienced lethargy, dizziness, ataxia, and auditory and visual hallucinations after receiving triazolam 0.375 mg hs for sleep. Triazolam plasma concentrations were measured, and a triazolam elimination half-life was calculated to be approximately 8 hours (reported range 1.7-3 h). Cimetidine has been reported to decrease the apparent oral clearance of triazolam, resulting in increased triazolam plasma concentrations with the potential for exaggerated triazolam pharmacologic effects. Cimetidine may have been responsible for the unusually large elimination half-life in this patient. Until the mechanisms and clinical significance of this potential drug interaction are determined, clinicians should use the combination of triazolam and cimetidine with caution.
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PMID:Central nervous system toxicity associated with concurrent use of triazolam and cimetidine. 404 60

The adult type of neuronal ceroid lipofuscinosis (NCL) occurred in a 49-year-old man and his 51-year-old sister. They showed episodic stuporous and psychotic states, mental retardation, generalized convulsions, and ichthyosis vulgaris. At autopsy the woman had excessive accumulation of lipofuscin throughout the CNS. The degree of neuronal lipopigment accumulation was very severe in the neurons of the thalamus, substantia nigra, inferior olivary nuclei, motor nuclei of the brain stem, and cerebral cortex. Mental symptoms, such as stupor, excitement, hallucinations, and delusions, were the predominant clinical manifestations and so were misdiagnosed as schizophrenia. Though the clinical diagnosis of the adult type of NCL (Kufs' disease) is difficult because of its wide variety of manifestations, symptoms such as episodic psychotic and stuporous states accompanied by convulsive disorders with mild neurologic signs may be an indication of this disease.
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PMID:Familial occurrence of adult-type neuronal ceroid lipofuscinosis. 647 18

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.
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PMID:Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion. 687 83

Twenty-four patients, including two with aplastic anemia and 22 with malignancy, underwent marrow transplantation after preparation with mechlorethamine, 0.3 to 2.0 mg/kg body weight. Fourteen of the 21 neurologically evaluable recipients developed immediate neurotoxicity a median of 4 days after treatment (range, 0 to 34 days). Confusion and disorientation were observed in six patients, headache in six, hallucinations n four, lethargy in four, tremors in three, paraplegia in one, seizure in one, and vertigo in one. Whereas acute symptoms cleared in 11 patients, three remained symptomatic until death. Twelve evaluable patients survived more than 60 days; all six with previous acute toxicity subsequently developed delayed onset of new neurologic findings (personality change, confusion, seizure, diplopia, or dementia) a median of 169 days (range, 70 to 248 days) after treatment. Cerebrospinal fluid analysis was usually normal but cerebral computed tomographic scans showed ventricular enlargement and electroencephalograms showed diffuse slowing. Postmortem histologic examination of brain showed neuronal degenerative changes with increased vascularity, gliosis, and perivascular fibrosis. Neurotoxicity appeared to increase with age and mechlorethamine dose and was commoner in patients given additional procarbazine or cyclophosphamide.
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PMID:Immediate and delayed neurotoxicity after mechlorethamine preparation for bone marrow transplantation. 704 28

A Phase I trial of acivicin [L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid] has been performed on an escalating-dosage 24-hr continuous i.v. infusion schedule. Thirty-one patients received 77 courses of treatment, and all but one were evaluable for toxicity. Pharmacological monitoring in selected patients demonstrated that peak plasma levels correlated with dose. Postinfusion t1/2 beta was 6 to 9 hr, and urinary recovery of the administered dose was 14 to 19% as unchanged drug during the 24-hr infusion. Hematological and gastrointestinal toxicities were variable and not dose related. In contrast, neurotoxicity characterized by lethargy, fatigue, confusion, disorientation, hallucinations, nightmares, and truncal ataxia was dose limiting and related to plasma drug levels. A minimal antitumor response was observed in a patient with colorectal carcinoma, and a partial response occurred in a patient with liver metastases from gastric carcinoma. The recommended dose for Phase II trial by 24-hr infusion is 160 mg/sq m.
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PMID:Phase I and pharmacological study of acivicin by 24-hour continuous infusion. 710 49

The use of physostigmine for the treatment of jimsonweed ingestion remains controversial. We have reviewed the records of 29 cases reported to the Kentucky Regional Poison Center (KRPC) over a 7-y period during which time physostigmine was not recommended by the Center to assess the results of conservative therapy. 28/29 cases represented intentional abuse; 26/29 were males and the mean age for the group was 18.9 y (range 16 mo to 39 y). The reported ingested amounts ranged from a few to 1/2-cup of seeds. Typical mild anticholinergic symptoms including mydriasis, tachycardia, flushing, hallucinations, and both agitated behavior and lethargy were observed. No patient had life-threatening symptoms. All cases were referred to the Emergency Department, although only 20 complied. Of these, 17 were admitted for stays of 1-3 d (mean 1.8). Seventeen patients received activated charcoal on recommendation of the KRPC. Three patients with hallucinations received 1 or more doses of valium or haloperidol for sedation. All patients recovered uneventfully. We conclude that conservative treatment of jimsonweed ingestion is safe and adequate.
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PMID:Conservative treatment of jimsonweed ingestion. 843 47

The therapeutic use of methylphenidate for the management of attention-deficit hyperactivity disorder in children is increasing. As therapeutic use increases, the risk increases of unintentional overdoses, medication errors, and intentional overdoses caused by abuse, misuse, or suicide gestures and attempts. Side effects during therapy, which include nervousness, headache, insomnia, anorexia, and tachycardia, increase linearly with dose. Clinical manifestations of overdoses include agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia. Methylphenidate tablets can be abused orally, or they can be crushed and the powder injected or snorted. Despite its abuse potential, there is disagreement regarding the extent to which methylphenidate is being diverted from legitimate use to abuse in preteens and adolescents.
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PMID:Abuse and toxicity of methylphenidate. 1198 Dec 94

Pellagra is a systemic disturbance caused by a cellular deficiency of niacin, resulting from inadequate dietary nicotinic acid and/or its precursors, the essential amino-acid tryptophan. In Europe and North America cases of pellagra are rarely encountered, but in some developing countries this disease is frequent, and is the most frequent clinical feature of nutritional deficiency of adult. The principal causes of pellagra are: nutritional niacin deficiency; chronic alcoholism; gastro-intestinal malabsorption; some medications (5-fluoro-uracil, isoniazid, pyrazinamide ehtionamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol). The diagnosis of pellagra is based on the patient's history and the presence of "3 D syndrome": dermatitis, diarrhea, and dementia. The dermatitis caused by pellagra is a bilaterally symmetrical erythema at the sites of solar exposure. The dermatitis begins in the form of an erythema with acute or intermittent onset gradually changing to an exsudative eruption on the dorsa of the hand, face, neck, and chest with pruritus and burning. Acute dermatitis of pellagra resembles sunburn in the first stages, sometimes with vesicles and bullae. The gastro-intestinal disturbances are: anorexia, nausea, epigastric discomfort and chronic or recurrent diarrhea. Anorexia and malabsorbative diarrhea lead to a state of malnutrition and cachexia. Stools are typically watery, but occasionally can be bloody and mucoid. Neuropsychologic manifestation included photophobia, asthenia, depression, hallucinations, confusions, memory loss and psychosis. As pellagra advances, patient become disoriented, confused and delirious; then stuporous and finally die. Pathological changes in the skin is non-specific, there are no chemical tests available to definitively diagnose pellagra. However low levels of urinary excretion of N-methylnicotinamide and pyridone indicates niacin deficiency. The treatment of pellagra consisted to exogenous administration of niacin or nicotinamide cures. Topical management of skin lesions with emollients may reduce discomfort. The therapy should also include other B vitamins, zinc and magnesium as well as a diet rich in calories. The prevention is based in the nutritional education (food sources of niacin: eggs, bran, peanuts, meat, poultry, fish, red meat, legumes and seeds), and the eviction of alcohol.
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PMID:[Pellagra]. 1620 85

Butamirate citrate is a central-acting antitussive drug and is widely used in clinical practice in childhood. It is thought that to be centrally active antitussive drugs act through receptors in the brainstem to inhibit cough, and these findings were based on the evidence of animal models. Central nervous system adverse effects of cough suppressants are rare and include irritability, lethargy, hallucinations, and dystonic reactions. In this report, we present the first patient who developed cervical dystonia shortly after the first dose of butamirate citrate, and the patient's symptoms improved immediately after a single intramuscular dosage of biperiden.
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PMID:Acute cervical dystonia after the first dose of butamirate citrate. 2328 72

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.
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PMID:Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. 2375 86


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