Central nervous system extrapyramidal effects

Most common Sedation, restlessness, diarrhea (metoclopramide), agitation, central nervous system depression Less common Extrapyramidal effects (more frequent with higher doses), hypotension, neuroleptic syndrome, supraventricular tachycardia (with intravenous administration)... 

Pheochromocytoma is sometimes treated with metyrosine (cx-methyltyrosine), the -methyl analog of tyrosine. This agent is a competitive inhibitor of tyrosine hydroxylase, the rate-limiting step in the synthesis of dopamine, norepinephrine, and epinephrine (see Figure 6-5). Metyrosine is especially useful in symptomatic patients with inoperable or metastatic pheochromocytoma. Because it has access to the central nervous system, metyrosine can cause extrapyramidal effects due to reduced dopamine levels. 

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). 

B. Central nervous system. Centrally mediated sedation and anticholinergic effects contribute to CNS depression. Alpha-adrenergic blockade causes small pupils, despite anticholinergic effects on other systems. Extrapyramidal dys-tonic reactions are relatively common with therapeutic doses (especially of butyrophenones) and are probably caused by central dopamine receptor blockade. The seizure threshold may be lowered by unknown mechanisms. Temperature regulation is also disturbed, resulting in poikilothermia... 

Amantadine interacts with catecholamines in the central nervous system and in the periphery. This might be predicted from its prinmry amine structure. How can these interactions contribute to its effect in parkinsonism Table 1 lists five mechanisms by which amantadine and other drugs could counteract the deficit of extrapyramidal inhibition which is responsible for symptoms of parkinsonism. 

It is difficult to delineate the precise roles, if any, of noradrenaline and serotonin in the extrapyramidal motor system. Certainly, levels of these two monoamines are relatively low in the basal ganglia of the normal human brain as compared to the high levels of dopamine [38, 43] Figure 5.1). Moreover, administration of their precursors to Parkinsonian patients has no clearcut effect dihydroxyphenylserine, a non-physiological precursor of noradrenaline, has little effect [93] while 5-hydroxytryptophan occasionally ameliorates the symptoms [131]. However, there is evidence that noradrenaline and serotonin may be transmitters in other parts of the central nervous system which contribute to Parkinsonian symptomatology, particularly in the sensory system. 

Drugs affecting the autonomic nervous system or central vestibular system or causing extrapyramidal effects have been associated with ocular manifestations such as nystagmus, diplopia, extraocular muscle palsy, and oculogyric crisis. Table 35-8 fists drugs that can affect extraocular muscles. 

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