Antipsychotics extrapyramidal effects

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 effects usually diminish with a reduction in the dosage of the antipsychotic drug. The primary health care provider may also prescribe an antiparkinsonism drug, such as benztropine (see Chap. 29) to reduce the incidence of Parkinson-like symptoms. 

When administering the antipsychotic drugs, the nurse observes the patient for extrapyramidal effects , which include muscular spasms of the face and neck, the inability to steep or s t still, tremors rigidity, or involuntary rhythmic movements The nurse notifiesthe primary health care provider of the occurrence of these symptoms because they may indicate a need for dosage adjustment. 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

Typical antipsychotics may also be associated with a small increased risk of death, as well as more severe extrapyramidal effects and hypotension. 

The high potency antipsychotic haloperidol (Haldol) provides the same calming effects with minimal anticholinergic effects. Although haloperidol is very effective, dementia patients are quite sensitive to its extrapyramidal effects. These include stiffness, shuffling gait, a mask-like facial appearance, and involuntary movements. To minimize these effects, haloperidol is used in very low doses (0.5-1.0mg) when treating those with dementia. 

The side effects of conventional antipsychotics are of even greater concern when treating chronic psychosis in a patient with dementia. With sustained administration of a typical antipsychotic, these patients will be highly vulnerable to the extrapyramidal effects of the medication, which can increase the risk for falls. Thus, atypical antipsychotics have also been rapidly accepted as first-line agents when treating... 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

Chlorpromazine is the best known representative of the aliphatic phenothiazines. Although it is considered to be a low potency agent it is still frequently used. It is one of the most sedative antipsychotic agents and is therefore very effective in the treatment of agitated and violent patients. Extrapyramidal effects are seen with a rather low incidence. However it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic function, due to chlorpromazine. Alimemazine and triflupro-mazine are other representatives from this group. 

The piperazines include fluphenazine, trifluoperazine, prochlorperazine, perazine and perphenazine. They are agents with a high antipsychotic potency with less pronounced anticholinergic effects. However their potential to produce extrapyramidal effects is more pronounced. 

The heterocyclic antipsychotic agent, risperidone, is a benzisoxazole derivative with antiserotoner-gic (5-HT2) as well as antidopaminergic (D2) activity. Risperidone is also considered to be a so-called quantitatively atypical antipsychotic agent because in low doses it has few extrapyramidal effects. 

Aggravation of the extrapyramidal effects of antipsychotic agents have been described and it has been reported that the use of lithium in combination with haloperidol may result in irreversible neurological toxicity. Lithium can increase the hypothyroid effects of antithyroid agents or iodides. 

Prior to the availability of atypical antipsychotics, typical antipsychotics were used to diminish the acute agitation of mania. Onset of action is typically observed within 3 to 7 days. In a meta-analysis of chlorpromazine trials, efficacy was 54%, which was substantially less than that of lithium, but comparable to that of other mood stabilizers (range, 12%-70%). Risk of extrapyramidal effects and tardive dyskinesia limits the use of these medications beyond the acute phase. 

The answer is c. (Katzung, pp 485-486.) In addition to its antipsychotic action, olanzapine diminishes emotional bluntness and social withdrawl that are seen in schizophrenic patients, without significant anticholinergic and extrapyramidal effects. 

Many earlier reports considered extrapyramidal side effects unavoidable when treating patients with neuroleptics. There appeared to he a parallel between antipsychotic action and the incidence of unwanted neurological effects. However, the development of newer neuroleptics has changed this view. Drugs like clozapine have a high antipsychotic potency and yet produce few neurological problems. It has therefore been proposed that the DA receptors involved in the beneficial actions of neuroleptics in the treatment of psychiatric disorders are situated in mesolimbic areas, such as the nucleus accumbens, whereas the extrapyramidal effects are mediated by striatal receptors. 

Shirzadi, A. A. Ghaemi, S. N. 2006, Side effects of atypical antipsychotics extrapyramidal symptoms and the metabolic syndrome, Harv.Rev.Psychiatry, vol. 14, no. 3, pp. 152-164. 

Chlorpromazine, the first modern drug to be used in the treatment of schizophrenia and other psychotic disorders, was introduced into psychiatry in 1952 [61]. It was followed by a number of other drugs for the treatment of these conditions (e.g., haloperidol, thioridazine). These were also called neuroleptics because of their neurological side effects, such as parkinsonian syndrome and tardive dyskinesia. Tardive dyskinesia is a movement disorder characterized by involuntary movements of the face and limbs. The antipsychotic properties of these drugs were inseparable from the extrapyramidal effects. 

Ossowska K, Pietraszek M, Wardas J, Wolfarth S. 2004. Potential antipsychotic and extrapyramidal effects of (R,S)-3,4-dicarboxyphenylglycine [(R,S)-3,4-DCPG], a mixed AMPA antagonist/mGluR8 agonist. Pol j pharmacol 56 ... 

METOCLOPRAMIDE ANTIPSYCHOTICS t risk of extrapyramidal effects Additive effect Consider using an alternative antiemetic... 

Atypical drugs, particularly at high doses, can yet cause extrapyramidal effects and this strategy is not always helpful. If the classical antipsychotic is simply continued, tardive dyskinesia reiiiits spontaneously in aroimd 30% of patients within a year but since the condition is difficult to tolerate, patients may be keen to try other medications, even where evidence suggests that the success rates for remission are limited. These include vitamin E, benzodiazepines, 3-blockers, bromocriptine and... 

Atypical antipsychotics may have advantages in three areas. First, they appear to be better tolerated, in particular being less likely than classical agents to induce extrapyramidal effects and hyperprolac-... 

Antipsychotics Postural hypotension Sedation Extrapyramidal effects Falls... 

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