Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009676 (confusion)
 21,692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since most of the toxicity associated with class 1B antiarrhythmic drugs is dose-related, this review examines adverse effects seen in both therapeutic practice and accidental or premeditated overdose. Toxicity is very common with these agents and can be life-threatening. A high percentage of patients must discontinue therapy because of adverse effects. Mexiletine and tocainide are structural analogues of lignocaine (lidocaine) and toxicity is similar with all 3 drugs. With gradual intoxication (the most common form) central nervous system effects such as lightheadedness, dizziness, drowsiness and confusion are seen first. Seizures and respiratory arrest can occur. Cardiovascular toxicity is manifested by progressive heart block, reduced cardiac contraction, hypotension and asystole. Both mexiletine and tocainide may have proarrhythmic effects. Gastrointestinal toxicity is also common. Shock, hypotension, cardiac failure and beta-blocker therapy reduce lignocaine clearance and enhance the risk of intoxication during routine therapy. Both lignocaine and mexiletine elimination is impaired in severe liver disease while tocainide clearance is reduced in renal failure. Management of toxicity is largely supportive and symptomatic. Lignocaine infusion must be discontinued and decontamination of the gut in the case of oral preparations is recommended. Serious intoxication requires intensive care unit admission. Haemodialysis or haemoperfusion may be helpful in serious lignocaine and tocainide poisoning. In institutions where extracorporeal circulatory assistance is available, massive lignocaine poisoning has been successfully treated with this intervention. In the therapeutic setting serious toxicity can be prevented by close clinical surveillance and appropriate dose reduction in patients with reduced drug clearance. Because of the large interindividual variation in lignocaine pharmacokinetic parameters, therapeutic drug monitoring is recommended if results can be reported quickly. Mexiletine and tocainide have stereoselective metabolism and assays do not distinguish the more active isomers. Therapeutic drug monitoring is less useful in this situation.
 ...
PMID:Poisoning due to class 1B antiarrhythmic drugs. Lignocaine, mexiletine and tocainide. 251 64

Practically all drugs administered in large amounts can give rise to neurologic symptoms such as drowsiness, insomnia, confusion, seizures or coma and extrapyramidal disorders. In this study, five classes of agents are reviewed: antipsychotic drugs, drugs for Parkinson's disease, antiepileptic drugs, calcium antagonists and salts of bismuth.
 ...
PMID:[Various encephalopathies caused by drugs]. 256 72

An acute confusional state was observed to follow heavy exposure to polyurethane gloss paint fumes in a previously healthy 60 year old man. This state remitted over a 3-day period, but was followed by transient bone marrow suppression and evidence of liver cell damage. The corroborated absence of other toxins and the temporal association of exposure to paint fumes suggest that a volatile paint component was responsible. White spirit is the major volatile solvent in polyurethane gloss paint. Ingestion of related aliphatic hydrocarbons has been reported to cause nausea, drowsiness and hepatotoxicity, but these symptoms have not previously been documented following excessive inadvertent inhalation of paint fumes.
 ...
PMID:Toxic reaction to inhaled paint fumes. 260 52

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.
 ...
PMID:Intrathecal baclofen for severe spinal spasticity. 265 24

Wernicke encephalopathy is a disorder caused by a deficiency of thiamine which is a cofactor of several metabolic enzymes. The symptoms include mental confusion, ataxia, and ocular signs in adults, infants, and children. Patients often have somnolence and weakness combined with ophthalmoplegia. Alcoholics are the best known risk group; however, Wernicke encephalopathy occurs in poorly nourished patients of all ages. We present 2 children with malignant disease in whom Wernicke encephalopathy--an underdiagnosed and potentially fatal, but preventable and treatable disease--was diagnosed postmortem.
 ...
PMID:Wernicke encephalopathy--a preventable cause of death: report of 2 children with malignant disease. 267 84

Hexamethylene bisacetamide (HMBA), a potent differentiating agent, was administered to patients with refractory malignant tumors. Thirteen patients received 30 evaluable courses. HMBA was given by continuous i.v. infusion for 5 days. Therapy was repeated every 28 days, if patients had recovered from toxicity. The starting dose was 24 g/m2/day. Because our previous trial had shown wide interpatient variability in HMBA pharmacokinetics and excess toxicity at HMBA plasma concentrations greater than 2 mM (HMBA doses between 24 and 33.6 g/m2/day), we attempted to individualize each patient's dose based on a dosing scheme using an adaptive (feedback) control algorithm, which assumed linear clearance for HMBA. In all courses, a plasma sample was assayed daily and infusion rates were adjusted to achieve an HMBA plasma concentration of 1.5-2.0 mM (300-400 mg/liter). The patients included 12 men and 1 woman with a median age of 56 years (range, 34-76) and median Karnofsky performance status of 90% (range, 60-100). All patients had received prior chemotherapy and 9 patients had also received radiation therapy. The linear adaptive control algorithm was reasonably precise, with a mean absolute error of 0.28 (SE 0.04) mM. However, adjustments in infusion rate systematically overshot the desired change in steady state concentration, probably due to nonlinear clearance of HMBA. For levels within 24 h of a change in infusion rate, this resulted in significant bias, with a mean error of 0.24 (SE 0.09) mM. The mean absolute error was 0.40 (SE 0.06) mM. A second adaptive control algorithm, using a pharmacokinetic model with parallel first-order (renal) clearance and Michaelis-Menten (nonrenal) clearance and using Bayesian parameter estimation with a priori estimates based on our previous phase I trial, proved to be much more precise than the linear method and was unbiased when applied retrospectively to the same observations, with a mean error (within 24 h of a change in infusion rate) of 0.02 (SE 0.06) mM and a mean absolute error of 0.22 (SE 0.03) mM. Toxicity was reversible in all cases. Neurotoxicity, consisting of hallucinations, agitation, somnolence, or confusion, was seen in 2 patients. Four patients complained of insomnia or anxiety. Mild asymptomatic acidosis was seen in 3 patients. Other toxicity included grade 1-2 nausea and vomiting (10 patients), grade 2 diarrhea (2 patients), grade 3 thrombocytopenia (3 patients), grade 1-3 leukopenia (3 patients), and oral herpes simplex infection (4 patients). Mild reversible renal insufficiency (measured by creatinine clearance) was seen in 8 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Phase I trial using adaptive control dosing of hexamethylene bisacetamide (NSC 95580). 272 Jun 96

Benzodiazepines are used as hypnotics to reduce anxiety and give a good night's sleep on the night prior to surgery. In a double-blind procedure, patients were given either lorazepam (2 mg or 4 mg), lormetazepam (1 mg or 2 mg), nitrazepam 10 mg or placebo. Measures were taken of sleep, anxiety, memory and after-effects. There was no evidence that the drugs reduced anxiety, nor evidence of amnesia. Quality and length of sleep was shown to be better for nitrazepam (P less than 0.05), lorazepam 2 mg (P less than 0.05) and lorazepam 4 mg (P less than 0.01), compared with placebo. However, significantly higher ratings of clumsiness and confusion as after-effects were found with nitrazepam (P less than 0.05), and clumsiness (P less than 0.005), slurred speech and blurred vision (P less than 0.01), sleepiness, nausea, weakness and confusion (P less than 0.05) with lorazepam 4 mg. It was concluded that lorazepam 2 mg produced the greatest net benefit.
 ...
PMID:A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives. 290 15

A study is presented, of adjacent cerebral abscesses secondary to otorhinolaryngological infections. A total of 386 patients were included. According to frequency, and in relation to the adjacent septic focus the cerebral abscesses were classified as: otogenic--334 cases (86.5%); rhinogenic--47 cases (12.2%); tonsillary--5 cases (1.3%). These abscesses had similar characteristics: they occurred with the highest frequency in the second and the third decade of life, had a higher incidence in males, the otorhinolaryngologic infection had a chronic course with frequent recidives, propagation of the infection from the original focus occurred by continuity or through the venous system, and the clinical picture was marked by symptoms of local and general infection, by meningeal manifestation, and frequently by altered consciousness (somnolence, confusion). Surgical treatment, next to other therapeutic measures (administration of antibiotics, anti-inflammatory drugs, and intensive care) was aimed at improving the vital prognosis. The postoperative mortality was 23.8%. It was also aimed at increasing the functional recovery rate. Neuropsychical sequellae were noted in 54.9% of all cases. After surgery for the cerebral abscess attempts were made at removing the septic focus, preventing any additional risk of cerebral seeding.
 ...
PMID:Cerebral abscesses secondary to otorhinolaryngological infections. A study of 386 cases. 304 85

Terguride is an ergoline derivative with mixed agonistic/antagonistic dopaminergic activity. This led to a paradoxical suggestion that it is effective in the treatment of both schizophrenia and parkinsonism. A total of 65 in- or outpatients with parkinsonism mostly of vascular or idiopathic etiology were included in a 4-week, open, multicenter trial. Terguride was administered under an increasing dose schedule which was leveled off according to the clinical response. Mostly because of nausea, vomiting, and lack of improvement 25% of inpatients and 61% of outpatients were removed from the study. The average daily dose at the end of the trial was 4.2 mg, ranging from 1.0 to 5.5 mg. The average Simpson and Angus scale total score and performance in the Spiral Drawing Task improved significantly during the trial by 20% and 38% respectively. The following adverse effects were noted most frequently throughout the study (including those who withdrew): constipation (occurred in 42% of all ratings performed during the trial) drowsiness and nausea (16% each). Adverse circulatory effects were negligible. Psychotic symptoms, including depression, confusion, hallucinations, and paranoid syndrome, each occurred in 1 patient, i.e., at a lower rate than with other dopaminergic drugs. Scotopic electroretinograms in a subsample of 7 patients showed a significant transitory decrease in the B-wave amplitude at the end of the 1st week and a subsequent return to pretreatment values.
 ...
PMID:Terguride in parkinsonism. A multicenter trial. 304 1

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.
 ...
PMID:Phase II trial of ifosfamide in children with malignant solid tumors. 310 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>