Extrapyramidal disturbances

Zotepine is a dibenzothiepine neuroleptic drug, an antagonist at Di dopamine receptors and at 5-HTi and 5-HT2 receptors (1). It rarely causes extrapyramidal disturbances, and when they do occur they are usually mild. 

Aceruloplasminaemia is a very rare, autosomal recessive disease with diffuse iron overload. It is caused by a mutation of the ceruloplasmin gene. This leads to excessive iron storage, mainly in the brain, liver and pancreas. The principal symptoms are increased serum ferritin, decreased serum iron and transferrin saturation as well as extrapyramidal disturbances, retinal degeneration, cerebellar ataxia and diabetes mellitus. (486-488) (s. tab. 31.17)... 

Messing B (1991). Extrapyramidal disturbances after cyanide poisoning (first MRI-investigation of the brain).J Neural Transm, 33, 141-147. 

Metoclopramide is a dopamine antagonist that can cause extrapyramidal disturbances (parkinsonian symptoms), especially in children and young... 

Primitive reflexes and a non-paralytic squint, with failure of abduction of one or both eyes on lateral gaze, were present in many patients (see Table 4). Half the patients were deaf to a greater or lesser extent. We found no signs of cerebellar dysfunction or of a peripheral neuropathy. The only evidence of an extrapyramidal disturbance was mildly abnormal posturing of the hands and a... 

Among the most significant adverse reactions associated with the antipsychotic dm are the extrapyramidal effects. The term extrapyramidal effects refers to a group of adverse reactions occurring on the extrapyramidal portion of the nervous system as a result of antipsychotic drains. This part of the nervous system affects body posture and promotes smooth and uninterrupted movement of various muscle groups. Antipsychotics disturb the function of the extrapyramidal portion of the nervous system, causing abnormal muscle movement. Extrapyramidal effects include Parkinson-like symptoms (see Chap. 29), akathisia, and dystonia (see Display 32-1). 

Extrapyramidal side effects These are caused by antipsychotic drugs. They are characterised by motor and postural disturbances, of which the most serious is late-onset tardive dyskinesia. 

Drags that exhibit central anticholinergic properties are used in treating Parkinsonism. It is believed that they do not affect the synthesis, release, or hydrolysis of acetylcholine. Their medicinal efficacy is manifest by the rednction or removal of motor disturbances cansed by damage to the extrapyramidal system. They reduce rigidity, and to a somewhat lesser degree, akinesia, and they have little effect on tremors. 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

The butyrophenones (prototype haloper-idol) were introduced after the phenothiazines. With these agents, blockade of D2 receptors predominates entirely (p. 235B). Antimuscarinic and antiadrenergic effects are attenuated. The extrapyramidal motor disturbances that result from D2 receptor blockade are, however, preserved and constitute the clinically most important adverse reactions that often limit therapy. 

Heck AH, Haffmans PM, de Groot IW, Hoencamp E. Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms a double-blind, multi-center trial. Schizophr Res 2000 46(2-3) 97-105. 

Risperidone has also been used in combination with topiramate in a Spanish multicenter study in 58 patients (28 men and 30 women mean age 41 years) with bipolar I disorder, with manic but not mixed episodes (20). Risperidone (mean dose 2.7 mg/day) and topiramate (mean dose 236 mg/day) were started with a maximum 48-hour time difference risperidone was used for acute manic symptoms and topiramate for longer-term stabilization and prevention of relapse. The incidence of any adverse event was 64%, mostly somnolence, paresthesia, dizziness, tremor, weight loss (n = 27 mean change -1.1 kg), extrapyramidal disorders, gastrointestinal effects, and cognitive disturbances. One patient developed tardive dyskinesia during the study and there were five dropouts because of adverse effects adverse effects that required withdrawal of risperidone but not topiramate were amenorrhea (n = 3) and sexual dysfunction (n = 1). 

In a 9-week open study of risperidone for agitated behavior in 15 patients with dementia (modal dose 0.5 mg/day), extrapyramidal symptoms developed at some point during the trial in 8 patients, and cognitive skills were impaired in 3 patients (70). Similarly, in 22 patients with dementia and behavioral disturbances, treated with risperidone 1.5 mg/ day (range 0.5 mg qds to 3 mg bd), 50% had significant improvement, but 50% had some extrapyramidal symptoms (71). A further case of a severe extrapyramidal reaction in an old patient with dementia further illustrated these susceptibility factors (72). 

Hypersalivation or sialorrhea has been reported with all neuroleptic drugs, and has been associated with risperidone as one of the most frequently mentioned adverse effects in patients with disturbing extrapyramidal symptoms during previous neuroleptic drug treatment (SEDA-25, 68). Hypersalivation is a troublesome adverse effect that can contribute to non-adherence to therapy, but it can be treated with clonidine. 

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