2- dyskinesias caused

Side effects include dyskinesias, orthostatic hypotension, dizziness, nausea, insomnia, sleep attacks, pathologic gambling, discoloration of urine/sweat, and psychiatric effects (confusion, hallucinations, nightmares, and altered behavior). Dyskinesias caused by adding other PD drugs to levodopa may be improved by decreasing the levodopa dose. Motor complications occur in about 40% of patients within 4 to 6 years of starting levodopa.1,8,24,25,37... 

When an antipsychotic is needed, we prefer using one of the newer atypical agents olanzapine, ziprasidone, risperidone, quetiapine, or aripiprazole. Each of these medications reliably reduces agitation and is well tolerated. In particular, they decrease the potential for acute dystonic reactions and tardive dyskinesia caused by the typical antipsychotics. Both ziprasidone and olanzapine are now available in an injectable form that is very rapidly acting and effective in this setting. 

Risperdal was first marketed in 1994 as an atypical neuroleptic. The clinical trials, most of which lasted a few weeks, were too short to determine the rate of tardive dyskinesia and many other adverse effects. Indeed, the brief controlled clinical trials used for the approval of both clozapine and risperidone do not provide sufficient information to determine either efficacy or safety since the drugs would be used for months and years in individual patients, rather than for a few weeks (see chapter 13). Patients taking the medications over the coming years will provide the experimental data. However, since Risperdal is a potent dopamine blocker, it should have been anticipated that it would cause similar adverse reactions as the older neuroleptics. In my own experience, I have evaluated many cases of tardive dyskinesia caused by Risperdal, Zyprexa, and Geodon. Meanwhile, the Food and Drug Administration (FDA) has required the same tardive dyskinesia and neuroleptic malignant syndrome warnings on the labels of clozapine and risperidone as on the labels of the older neuroleptics. 

SSRIs cause a wide range of neurological impairments. Spigset (1999) found the following neurological reports in order of frequency parethesias, headache, dizziness, tremor, seizures, acute dystonia, dyskinesia, muscle cramps, muscle weakness, parkinsonism, muscle stiffness, akathisia, myoclonus, extrapyramidal reactions, increased muscle tone, and migraine. There have been reports of irreversible tardive dyskinesia caused by SSRIs (see subsequent section). 

It has a mixed chemieal features of both diphenhydramine elass of antihistaminies and atropine. It has been used successfully in the treatment of parkinsonism, to arrest tremor and rigidity, oculogyric crises and pain secondary to muscular spasm. It is also employed to control extrapyramidal dyskinesia caused by tranquillizers, namely, chlorpromazine or reserpine. Its aetions and uses are similar to those of benzhexol and is preferred to that of the later due to its inherent sedative effeetive at its normal dose. 

Dyskinesias are abnormal movements, usually caused by neurological diseases or by diugs used to treat neurological (e.g., levodopa) or psychiatric diseases (e.g., neuroleptics). 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

Nevertheless it must also be expected that anything which increases DA function not only controls extrapyramidal function but also reproduces the other central effects of DA i.e. vomiting, a reduction in prolactin secretion and some psychotic manifestations. In excess it may also cause dyskinesias. Despite these problems, the therapy of PD is one of the success stories of neurology. 

Despite the fact that in quantitative studies of motor performance they often appear to produce more benefit than levodopa and are less likely to cause dyskinesia and ON-OFF fluctations, patients tend to prefer levodopa. Possibly unless DA function is... 

Since D2 (but not Di) receptors are expressed on neurons of the Ind Path, then D2 agonists will have the same effect on this pathway as levodopa and overcome the hypokinesia. Their inability to activate D] receptors could mean, however, that while they are less likely to cause dyskinesias, for the reasons given above, their ability to dampen the GPint may also not be sufficient to give the required facilitation of motor function. Conversely, the absence of Dj receptors on the Ind Path explains why their agonists carmot influence it and so appear unable to reduce hypokinesia. 

Preliminary data indicate that in the reserpinised rat or MPTP marmoset, the enkephalin agonist (SNC80) reduces PD-like symptoms without causing increased activity, i.e. no trend to dyskinesias. Enadoline, a dynorphin-like kappa opioid agonist also has similar effects in the same models. Whether it would be similar in humans remains to be seen. 

Phenothiazines may cause sedation, orthostatic hypotension, and extrapyramidal symptoms (EPS) such as dystonia (involuntary muscle contractions), tardive dyskinesia (irreversible and permanent involuntary movements), and akathisia (motor restlessness or anxiety).1,21,22 Chronic phenothiazine use has been associated with EPS, but single doses have also caused these effects.23... 

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. 

---