Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic malignant syndrome, parkinsonian reactions such as postural abnormality, tremor, akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the complications of neuroleptic chemotherapy, the most serious and potentially fatal complication is malignant syndrome, which is characterized by extreme hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia, and rhabdomyolysis, autonomic instability, fluctuating consciousness, leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant syndrome should be differentiated from malignant hyperthermia, lethal catatonia, and other pathological states producing some of these same symptoms. 4. In addition to neuroleptics, malignant syndrome has been caused by thymoleptics (antidepressants), metoclopramide (antiemetic), metoclopramide combined with cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the emergence of neuroleptic malignant syndromes are reportedly organic brain syndrome, dehydration, exhaustion, external heat load, excessive sympathetic discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism agents, and concurrent lithium therapy. 6. Although, the pathogenesis of neuroleptic malignant syndrome is not understood completely, a blockade of dopaminergic receptors in the hypothalamus, spinal cord and striatum, an alteration of dopaminergic-serotonergic transmission in the body, an enhanced synthesis and action of prostaglandin E1 and E2, and a modification of calcium-mediated signal transduction in the body have been suggested. 7. The treatment of malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v. infusion of dantrolene, and oral administration of bromocriptine; or alternatively i.v. infusion of dantrolene and the combination of levodopa-carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the aforementioned regimens are to include the use of anticholinergic drugs such as benztropine to enhance the effectiveness of bromocriptine, of lorazepam if catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic symptoms persist. 9. These treatments, however, must be "active" rather than "passive", in order to avert fatalities and/or unfortunate sequelae from this iatrogenic and incompletely understood disease.
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PMID:Pathogenesis and treatment of neuroleptic malignant syndrome. 197 19

Tardive dyskinesia is a disorder secondary to prolonged treatment (from 18 months to 3 years) with antipsychotic agents, affecting approximately 15% to 20% of patients. Tardive dyskinesia is characterized by difficulty controlling involuntary movements of the small muscle groups, producing tic-like reactions, muscle rigidity, and difficulty maintaining muscle tone. It is a chronic and unrelenting disorder which may be permanent if not successfully treated. The mechanism of action is thought to be secondary to dopamine hypersensitivity resulting from prolonged deprivation of dopamine on the part of dopamine-sensitive receptors. Theoretically, these receptors have been deprived of the neurotransmitter by chronic treatment with antipsychotic drugs, which are recognized as dopamine-blocking agents. We present a case in which alprazolam was successfully used in treating tardive dyskinesia.
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PMID:Tardive dyskinesia successfully treated with alprazolam. 221 17

In a double-blind crossover placebo controlled trial the effectivity of piracetam in neuroleptic-induced extrapyramidal side effects was confirmed. 40 psychotic patients treated with neuroleptics in an average daily dose equal to 600 mg of chlorpromazine were included in this study. Akathisia, tremor, muscle rigidity and dyskinesia were evaluated on a 4-point scale. The patients were randomly divided into two subgroups--40 g of piracetam or placebo from identic ampoules were given i.v. with a crossover readministration after 60 min. The intensity of the extrapyramidal side effects was evaluated at 30-min intervals during 2 h. Piracetam was proved to be significantly effective in both subgroups, the onset of its action being between 30 and 60 min after i.v. administration. Possible interpretations of the observed piracetam effectivity are considered. Further trials with piracetam in neurologic complications during neuroleptic treatment, tardive dyskinesia included, are suggested.
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PMID:Effect of piracetam on extrapyramidal side effects induced by neuroleptic drugs. 612 31

Perospirone is a novel serotonin-2 and dopamine-2 receptor antagonist (SDA) developed in Japan. Premarketing trials suggested that this agent was effective in reducing positive and negative symptoms of schizophrenia and had a favorable side-effect profile. However, these trials included only a few elderly patients, so the usefulness of perospirone in this population remains unknown. In this report we describe the treatment of 2 elderly patients with schizophrenia for whom perospirone therapy was efficacious. Case 1 was a patient with acute exacerbation of schizophrenic symptoms after discontinuance of medication. He was treated with 12 mg of perospirone daily and his symptoms reduced markedly from the 4th day of perospirone therapy. Efficacy was assessed by the positive and negative symptom scale (PANSS); all subscales of PANSS (positive symptom, negative symptom, and general psychopathology) reduced and the total score reduced from 78 to 38 by the end of the 6th week of treatment. No side effects such as extrapyramidal symptoms were noted. Thus, perospirone may be a useful antipsychotic for elderly patients with acute schizophrenia. Case 2 was a patient who had severe negative symptoms and extrapyramidal symptoms such as tardive dyskinesia, tardive dystonia, and sialorrhea. She had been hospitalized for more than 7 years. In this patient 12 mg of perospirone was administered daily after 3 mg of risperidone had been tapered off. The negative symptom subscale and general psychopathology subscale in PANSS were gradually reduced after perospirone therapy was started. Extrapyramidal symptoms were assessed by the drug-induced extrapyramidal symptoms scale (DIEPSS), which consists of eight individual parameters and one global assessment, and each parameter is graded on a 5-point (0 = none to 4 = severe) scale. Sialorrhea, muscle rigidity, tremor, dystonia and overall sererity were improved more than 2 points by the end of the 6th week. The clinical course of this patient suggests that the clinical characteristics of perospirone and risperidone may be different, even though these agents are categorized into the same class of antipsychotics, SDA. Because this is a case report, evaluations are limited the clinical properties of perospirone. Further examination is necessary to evaluate the efficacy and safety of perospirone for elderly patients with schizophrenia, who are more vulnerable to the side effect of antipsychotics than the younger population.
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PMID:[Perospirone therapy in elderly patients with schizophrenia]. 1467 81

This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders.
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PMID:Neurological complications of psychiatric drugs: clinical features and management. 1809 17