Antipsychotic drugs parkinsonism caused

There is an increased risk of sedation and delirium with increased age. There is also an increased risk of antidopaminergic effects such as parkinsonism due to antipsychotic drugs. Many other drugs that pass the blood-brain barrier may cause adverse effects in the elderly. The response of opioids may be increased in the elderly, resulting in oversedation (Turnheim 1998). 

Amoxapine is a metabolite of the antipsychotic drug loxapine and retains some of its antipsychotic action and dopamine receptor antagonism. A combination of antidepressant and antipsychotic actions might make it a suitable drug for depression in psychotic patients. However, the dopamine antagonism may cause akathisia, parkinsonism, amenorrhea-galactorrhea syndrome, and perhaps tardive dyskinesia. 

In 1967 after 6 years of studies, trials of L-dopa in patients with Parkinson s disease showed dramatic improvements in aU motor deficits. The hypothesis that dopamine is involved in the pathogenesis of psychosis, in particular schizophrenia, rests on the finding that most antipsychotic drugs are dopamine-receptor antagonists and that agents which cause excessive release of dopamine mimic schizophrenia-like states. In 1979, John Kebabian and Donald Caine (NIH, Bethesda, USA) found that dopamine exerts its effects by binding to two subtypes of receptors. 

Clozapine, which is associated with higher risk of agranulocytosis and seizures, is indicated (25 mg once or twice daily) only in the management of schizophrenic patients who fail to respond adequately to standard antipsychotic drug treatment. On the other hand, it is relatively free from extrapyramidal side effects such as parkinsonism. Approximately 50% of the administered dose is excreted in the urine and 30% in the feces as inactive demethylated, hydroxylated, and N-oxide derivatives. Clozapine has anticholinergic properties and causes tachycardia, and hence poses a serious risk for a patient with compromised cardiovascular function (see also Table 23). 

The belladonna alkaloids and related muscarinic receptor antagonists have long been used in parkinsonism. These agents can be effective adjuncts to treatment with levodopa see Chapter 20). Muscarinic receptor antagonists also are used to treat the extrapyramidal symptoms that commonly occur as side effects of conventional antipsychotic drug therapy see Chapter 18). Certain antipsychotic drugs are relatively potent muscarinic receptor antagonists, and these cause fewer extrapyramidal side effects. 

Pharmacologic effects Drugs such as benztropine or trihexj henidyl may improve the tremor and rigidity of parkinsonism but bave little effect on bradykinesia. They are used ad-junctively in parkinsonism and also alleviate the reversible extrapyramidal sjmtiptoms caused by antipsychotic drugs. 

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. 

On the other hand, the effects of two medications can counteract one another. The result is usually that both medications are rendered less effective. A common example is the patient with Parkinson s disease. On occasion, the L-DOPA that is the mainstay of treatment causes hallucinations. The treatment for hallucinations is an antipsychotic, which blocks the activity of dopamine. The problem is that using a typical antipsychotic to treat L-DOPA-induced hallucinations will interfere with the therapeutic effect of the L-DOPA, thereby worsening the symptoms of the Parkinson s disease. Fortunately, the advent of the newer atypical antipsychotics has provided a remedy to this particular Catch-22 drug interaction dilemma. 

One common denominator of all antipsychotics is the biockade of centrai dopamine (DA) receptors. As a result, extrapyramidal reactions, particularly parkinsonian symptoms, are a major adverse effect of many of these drugs, as well as an important clue to their mechanism of action. True Parkinson s disease is caused by a DA deficiency in the nigrostriatal system. Further, crystallographic data have demonstrated that CPZ s molecular configuration is similar to that of DA, which could explain its ability to block this neurotransmitter s receptors. Drugs with similar structures that do not block DA receptors (e.g., promethazine, imipramine) do not have antipsychotic activity. Another example is the isomer of flupenthixol, which blocks DA receptors is an effective antipsychotic, but the isomer that does not is ineffective (7). The other family of dopamine receptors, D and Dg, have not yet been implicated in psychosis. 

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