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)

Nineteen patients with senile brain disease (including 2 with parkinsonian symptoms) were treated with amantadine in an oral dosage of 200--300 mg daily. Seven showed definite clinical benefits such as increased alertness and decreased agitation, and 2 others showed slight benefits. However, in only one instance was the benefit maintained without complications. Toxic effects such as overactivity, anxiety and visual hallucinations were observed in 8 patients. Withdrawal effects (e.g., lethargy and staggering) occurred when amantadine was discontinued. The electroencephalograms (EEGs) of all 19 patients showed a frequency increase, chiefly of occipital alpha activity, and sometimes a return to normal, irrespective of clinical changes. Toxic side effects were associated with particularly prominent EEG acceleration. In 10 of the 19 patients, the clinical changes were further validated by by additional psychologic assessments. Although the value of amantadine is limited when given in this way to patients with senile brain disease, it seems important to observe its effects in drug combinations aimed at correction of neurotransmitter imbalances.
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PMID:Amantadine in senile dementia: electroencephalographic and clinical effects. 75 72

Clinical experience seems to indicate two separate types of entry to coma. Some patients follow a pathway characterized by confusion, hallucinations, mumbling delirium, myoclonic jerks, and seizures. The author has called this sequence of symptoms the high road to coma and hypothesized that its basic underlying pathophysiology involves increased neuronal firing rates. Other patients develop somnolence, lethargy, obtundation, and unresponsiveness without seizures or muscle twitches. This low road to coma involves either anatomical compression of the midbrain reticular formation or a metabolic or toxic disorder characterized by membrane stabilization and decreased neuronal excitability.
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PMID:Two roads to coma: the Scottish hypothesis. 94 May 9

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
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PMID:Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial. 164 69

While all delirious patients have clouding of consciousness (alteration of attention) and cognitive dysfunction, the level of alertness of different patients may range from stuporous to hyperalert. We, therefore, developed an analog scale to rate the alertness of delirious patients, and a separate scale to rate the severity of their clouding of consciousness. Based on these scales, patients were categorized overall as relatively "activated" (relatively alert despite clouding of consciousness), or "somnolent" (relatively stuporous along with clouding of consciousness). Cognitive function was estimated using the Mini-Mental Status Exam. Separate ratings were made of hallucinations, delusions, illusions, and agitated behavior. Activated and somnolent patients had similar ages, overall severity of delirium, and Mini-Mental Status Exam scores. Activated patients, however, were more likely to have hallucinations, delusions, and illusions than somnolent patients, and were more likely to have agitated behavior. Patients with hepatic encephalopathy were more likely to have somnolent delirium, while patients with alcohol withdrawal appeared more likely to have activated delirium. These data indicate that phenomenologic subtypes of delirium can be defined on the basis of level of alertness. These subtypes are validated in part by their differing associations with symptoms unrelated to alertness. These subtypes may have different pathophysiology, and thus, potentially different treatments.
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PMID:Delirium: phenomenologic and etiologic subtypes. 181 69

Transient recurrent confusional and stuporous states of nonepileptic origin are clearly less frequent than epileptic ones. They are relatively common in diseases of disturbed vigilance, like narcolepsy, idiopathic hypersomnolence, and sleep apnea. These patients often suffer from attacks of hypovigilance, characterized by altered awareness, automatic behaviour and partial or complete amnesia for the attack. Because of the memory 'black outs' and the frequently associated hypnagogic hallucinations, the patients behave inappropriately and often appear confused. Confusional states also typically arise during basilar artery migraine attacks. This special form of complicated migraine predominantly affects young females and is characterized by symptoms and signs of brain stem dysfunction such as vertigo, ataxia, paresthesia, limb weakness, dysarthria; in 75% of the cases, disorders of consciousness dominate. Transient ischemic attacks are sometimes recurrent and, when involving the cranial basilar territory, may result in confusional states without significant motor dysfunction. Attacks of transient global amnesia are possibly also ischemic in nature and are assumed to arise from transient bilateral limbic failure. Affecting only memory functions, they are strictly spoken not confusional, but must nevertheless be taken into consideration when proper observation during the attack was not possible.
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PMID:[Non-epileptic impaired consciousness in neurologic diseases]. 267 60

beta-Adrenoreceptor antagonists are liable to produce behavioural side-effects such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depressive moods, and hallucinations. These undesirable actions indicate that beta-blockers affect not only peripheral autonomic activity but also some central nervous mechanisms. In experimental animals beta-blockers have been found to reduce spontaneous motor activity, to counteract isolation-, lesion-, stimulation- and amphetamine-induced hyperactivity, and to produce slow-wave and paradoxical sleep disturbances. Furthermore, central effects such as tranquilizing influences are used for the treatment of conditions such as anxiety. Several different mechanisms of action could be responsible for these CNS effects: Centrally mediated specific actions on centrally located beta-adrenergic receptors, known to exist downstream from, and at the terminals of, 'vigilance-enhancing' central noradrenergic pathways. Centrally mediated specific actions on centrally located receptors of the non-adrenergic type; an affinity of some beta-blockers towards 5-HT-receptors is well documented. Centrally mediated non-specific actions on centrally located neurones, owing to the membrane-stabilizing effects of beta-blockers. Peripherally mediated actions whereby beta-blockers induce changes in the autonomic activity in the periphery, which are relayed to the CNS to induce changes in activity of a variety of central systems. It can be assumed that with any one of the beta-blockers all these mechanisms come into play, yet with varying degrees depending on characteristics of the drugs such as lipophilicity and hydrophilicity, the ratio of antagonist versus (partial) agonist properties, affinity to 'alien' receptor sites, strength of membrane-stabilizing activity, stereospecific affinity, and potency.
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PMID:CNS-related (side-)effects of beta-blockers with special reference to mechanisms of action. 286 51

We carried out a phase I trial with chlorambucil. Thirty patients with advanced cancer were entered in six dose levels: 36, 48, 60, 84, 108, and 144 mg/m2. The drug was given in six divided oral doses every 6 hours and the regimen was repeated every 3 weeks. The median age was 62 years (31-84), median Karnofsky performance status (KPS) 60 (40-90). All patients but one had received prior radiation therapy, chemotherapy, or both. Central nervous system toxicity was dose limiting, occurring in 5 of 6 patients at 144 mg/m2. It was characterized by transient seizures, hallucinations, lethargy, stupor, and coma. Metoclopramide was successful in controlling nausea and vomiting, which was severe if the antiemetic was not used. Leukopenia (3 patients) and thrombocytopenia (2 patients) were mild. One patient with colorectal carcinoma had a minor response, and two patients with non-small cell lung cancer had stable disease. A safe dose for phase II trials is 108 mg/m2 in six 6-hourly oral doses.
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PMID:A phase I trial of chlorambucil administered in short pulses in patients with advanced malignancies. 317 70

Spirohydantoin mustard (spiromustine, NSC 172112) is a classical bifunctional alkylating agent synthesized in an effort to develop antitumor agents effective against CNS tumors. The rationale was to combine the reactive moiety of an active antitumor agent with the hydantoin part of the molecule, which might serve as a carrier to cross the blood brain barrier. Thirty-eight patients with refractory solid tumors received spiromustine as part of a phase I trial at the Johns Hopkins Oncology Center. Three schedules were investigated: intravenously (IV) daily for three consecutive days, IV every other day for 3 days, and IV on a weekly basis for three doses, all cycled every 28 days. Hematologic toxicity was infrequently seen. Mild to moderate nausea and vomiting occurred on all schedules. The dose limiting toxicity was CNS toxicity characterized by mydriasis, xerostomia, lethargy, confusion, and hallucinations. This CNS toxicity was dose related, cumulative, and reversible. IV physostigmine appeared to diminish the neurotoxicity if administered before spiromustine and at frequent intervals following the drug. The maximum tolerated dose of spiromustine (without concomitant physostigmine) on the three times a week schedule is 6 mg/m2. With physostigmine pretreatment, 8 mg/m2 can be administered. The three times daily and every other day for three days schedules are not recommended for further study due to the severity of neurotoxicity. It is recommended that 6 mg/m2 be used as the starting dose for any phase II studies using the three times weekly schedule, and that physostigmine be used as needed to minimize neurotoxicity. Dose escalation above this level can be considered when individual tolerance has been established. Phase II trials to investigate the activity of this agent against primary and metastatic CNS malignancies appear indicated on the basis of three transient radiographic responses in refractory malignancies metastatic to the CNS.
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PMID:A phase I trial of spirohydantoin mustard (NSC 172112) in patients with advanced cancer. 352 70

Alzheimer's disease is a slowly progressive disorder involving deterioration of both intellect and personality. The neuropathological features of Alzheimer's disease include abundant neurocortical senile plaques and neurofibrillary tangles. Drug therapies of Alzheimer's disease have been based on empirical observations of the signs and symptoms of the disease and have included the use of hypnotics to reverse insomnia or inverse sleep rhythms; anxiolytics to relieve anxiety, tension and restlessness antipsychotics to "tranquilize" or control psychotic symptoms, such as delusions and hallucinations; stimulants to overcome withdrawn behavior or lethargy; and lastly, antidepressants to control depression. Our growing knowledge of neuropathological and neurochemical changes associated with normal aging and Alzheimer's disease has made it possible to explore and develop pharmacologically-based therapies in Alzheimer's disease. Recent research has revealed behavioral symptoms associated with underlying biochemical changes in either the cholinergic, dopaminergic/ GABAergic (gama-aminobutyric acid) noradrenergic, serotoninergic, neurochemical and/or neuropeptidergic systems. Pharmacological strategies involving manipulation of these systems as a means of relieving Alzheimer's disease symptoms will be reviewed from several perspectives, e.g., those involving transmitter substitution, enzyme inhibition and direct specific receptor stimulation.
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PMID:Pharmacotherapy in Alzheimer's disease: basis and rationale. 354 Oct 49

Five cases of poisoning by indigenous mushroom Hikageshibiretake (Psilocybe argentipes) are reported. As this mushroom contains psilocybin, in general, clinical features were similar to those seen by pure psilocybin. Acute toxic stuporous state with complete amnesia in the culminating period occurred in one case, psychedelic state with dreamy consciousness in one case and psychotic adverse reactions with vivid visual hallucinations with consciousness in three cases. There were accompanied with anxiety and panic reactions to subjective experiences. Though these toxic effects were usually short-lived, for management of such patients it is important to recognize that horrible emotional reactions and other harmful behavioral problems can also occur.
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PMID:Poisoning by hallucinogenic mushroom hikageshibiretake (Psilocybe argentipes K. Yokoyama) indigenous to Japan. 370 65


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