Side effects of antipsychotic drugs

Changes in dopamine receptor density may be involved in the side effects of antipsychotic drugs 222... 

Extrapyramidal symptoms may occur as a side-effect of antipsychotic drugs. 

Many side effects of antipsychotic drugs can be understood in terms of the drugs receptor-blocking properties. When antipsychotics reduce dopamine activity in the nigrostriatal pathway (via dopamine... 

Tertiary-amine muscarinic receptor antagonists gain access to the central nervous system and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal side effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine mesylate (Cogentin) and trihexyphenidyl hydrochloride (Artane, others). 

Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic drug treatment scope of problem and impact and outcome. Ann Clin Psychiatry 2002 14 123-129. 

Drugs that are successful in treating the disease act as dopamine receptor blockers and are known as antipsychot-ics or neuroleptics (e.g. chlorpromazine, haloperidol). Antipsychotic drags reduce some of the symptoms, especially the delusions and hallucinations. A side-effect of the drugs is that they can result in symptoms similar to those seen in patients with Parkinson s disease. This is not surprising, since the hypothesis to explain Parkinson s disease is too low a concentration of dopamine in a specific area of the brain (see below). 

Antipsychotics also have been used in the treatment of anorexia nervosa. The apparent role of dopamine in feeding and satiety involves increased receptor activity, producing symptoms similar to those found in anorexia nervosa. Thus, it seems reasonable to use dopamine antagonists to alter these behaviors. It also seems appropriate to use the sedative side effects of these drugs to decrease anxiety associated with eating. 

ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL, PERPHENAZINE, RISPERIDONE, SERTINDOLE SSRIs Possible t plasma concentrations of these antipsychotics Inhibition of CYP2D6-mediated metabolism of these drugs. The clinical significance of this depends upon whether alternative pathways of metabolism of these substrates are also inhibited by co-adminis-tered drugs. The risk is theoretically greater with clozapine, haloperidol and olanzapine because their CYPl A2-mediated metabolism Is also Inhibited by SSRIs Warn patients to report T side-effects of these drugs, and consider reducing the dose of the antipsychotic... 

As a consequence, several drugs have been developed by enhancing the side effect of another drug. For example, the mood-improving effect of iproniazid was discovered when it was tested as an antituberculous drug antidepressant inhibitors of neurotransmitter reuptake, like imipramine and desipramine, stem from the antipsychotic dopamine antagonist chlorpromazine, which itself was derived from Hi antihistaminics [35,36,51]. 

The side effects of these drugs are well known and have been summarized earlier (SED VIII, p. 313). Drugs with selective activity may be classified as antidepressants, antipsychotics, antihistamines, antispasmod-ics or antiparkinsonism agents and yet have anticholinergic actions as side effects. When two or more are given together the unwanted effects are more likely to arise. 

Many antihistamines, antipsychotics and antidepressants have stmctural similarities with muscarinic receptor antagonists and, predictably, show antimuscarinic effects which are considered in many cases the major side effects of these drug categories. Imipramine (Fig. 16.19) is a... 

Tardive dyskinesia A chronic disorder of the nervous system characterized by involuntary jerky or writhing movements of the face, tongue, jaws, trunk, and limbs, usually developing as a late side effect of prolonged treatment with antipsychotic drugs. 

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