Side effects extrapyramidal

It has been suggested that high affinity for certain 5-HT receptors is a possible method for reducing extrapyramidal side effects observed with antipsychotics. LiabiUty for extrapyramidal side effects has been hypothesi2ed to be related to the ratio of the affinity between dopamine receptor... 

Extrapyramidal Side Effects Extrasynaptic Receptors F-actin... 

Antipsychotics are not indicated for the treatment of withdrawal, except when hallucinations or severe agitation are present (Naranjo and Sellers 1986), in which case they should be added to a benzodiazepine. In addition to their potential to produce extrapyramidal side effects, antipsychotics lower the threshold for seizures, which is particularly problematic during alcohol withdrawal. 

Trihexyphenidyl (Artane) and benztropine (Cogentin) are prescription drugs used in the treatment both of Parkinson s disease and the extrapyramidal side effects produced by neuroleptic medication. They are occasionally abused for their mind-altering properties, which occur at toxic doses (Perry et al. 1978). Abusers often try to obtain these drugs by false representation of extrapyramidal symptoms, which are claimed to result from the use of phenothi-azines or other neuroleptics (Rubinstein 1978). 

The drug was subsequently reintroduced for treatment-resistant or treatment-intolerant patients in the UK and USA in 1990. The drug is completely free of extrapyramidal side effects but has to be monitored for the development of neutropenia and agranulocytosis. Other problems include sialorrhoea, sedation, reduction in seizure... 

Importantly, they achieve this without inducing extrapyramidal side-effects or increasing prolactin secretion, which are real problems with neuroleptics. These results have been borne out by preliminary clinical trials of buspirone, used in combination with neuroleptics, and several novel S-HTja agonists (e.g. BSF 190555) are currently under development for this clinical application (Meltzer 1999). 

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. 

What forms of extrapyramidal side-effects occur and how they might arise ... 

THE EXTRAPYRAMIDAL SIDE-EFFECTS (EPSs) OF NEUROLEPTIC DRUGS... 

Monitor for QT-interval prolongation and extrapyramidal side effects... 

EPS, extrapyramidal side effects X, very low XX, low XXX, moderate XXXX, high. 

D2-receptors correlates with the severity of EPSE. PET (using 3-N-nC-methylspiper-one or nC-raclopride) and SPECT (123I-iodobenzamide) studies show that an occupancy of 70-80% is likely to cause extrapyramidal side effects, while above 80% most patients will experience them (Kasper et al., 2002). 

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. 

Lane RM. SSRI-induced extrapyramidal side-effects and akathisia implications for treatment. J Psychopharmacol 1998 12 192-214. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

Extrapyramidal side-effects generally appear with blockade of dopamine D2 receptors in excess of 80%, whereas clinical efficacy in treating psychosis is associated with 60-70% D2 receptor blockade [12]. Recently, a partial agonist for the D2 receptor known as aripiprazole has been developed, which results in approximately 70% antagonism/30% agonism at the D2 receptor. It is an effective antipsychotic, has low risk for extrapyramidal symptoms, and does not cause elevated levels of prolactin as do the full antagonists at D2 receptors. 

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