Phenothiazines extrapyramidal symptoms with

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... 

Metoclopramide is structurally related to orthoclopramide, a procaine derivative, and it can prolong the action of suxamethonium because of competition for cholinesterase. However, its common side effects are similar to those seen with phenothiazine derivatives. In high doses, a range of extrapyramidal symptoms may develop. The anti-emetic effects of metoclopramide are due to two main actions. Centrally, it blocks dopamine in the CTZ and peripherally, it hastens gastric emptying, abolishes irregular intestinal contractions, and increases... 

Less risk of sedation and orthostatic hypotension but greater risk of extrapyramidal symptoms than with low potency phenothiazines... 

Chlorpromazine (Thorazine) and thioridazine (Mellaril), both phenothiazine derivatives, are used for their antipsychotic effects in the control of severely disturbed or agitated behavior and in schizophrenia. Thioridazine has a higher incidence of antimuscarinic effects but a lower incidence of extrapyramidal symptoms. Pigmentary changes of the retina have been reported occasionally in association with chlorpromazine therapy, although it is recognized that only thioridazine produces retinal toxicity. 

Biperiden is an antimuscarinic agent that may be administered orally or parenterally as adjunct therapy for Parkinson s disease. This drug attenuates extrapyramidal affects produced in other disease states and may be useful in the therapy of drug-induced extrampyramidal symptoms (e.g., with phenothiazines) as well. 

Haloperidol Blockade of D2 receptors >> 5HT2A receptors Some a blockade, but minimal M receptor blockade and much less sedation than the phenothiazines Schizophrenia (alleviates positive symptoms), bipolar disorder (manic phase), Huntington s chorea, Tourette s syndrome Oral and parenteral forms with metabolism-dependent elimination Toxicity Extrapyramidal dysfunction is major adverse effect... 

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

The highest brain concentrations of DA have been shown to be in the caudate nucleus. About two-thirds of the neurons in this structure respond to DA most are depressed by the transmitter, and a minority are excited. The caudate nucleus is a component of the extrapyramidal system that controls skeletal muscle. Of course, this fact relates to Parkinson s disease. Drugs that reduce dopaminergic functions by blocking DA receptors or in some other way interfere with DA may produce Parkinson-like symptoms as side effects, irrespective of what other activities they possess. This is what occurs with many antipsychotic drugs such as the phenothiazines. 

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