Sedative agents phenothiazines

Phenothiazines are antiemetic, antianxiety and sedative agents and they may change the affective response to pain (particularly methotrimeprazine). 

Chlorpromazine is the best known representative of the aliphatic phenothiazines. Although it is considered to be a low potency agent it is still frequently used. It is one of the most sedative antipsychotic agents and is therefore very effective in the treatment of agitated and violent patients. Extrapyramidal effects are seen with a rather low incidence. However it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic function, due to chlorpromazine. Alimemazine and triflupro-mazine are other representatives from this group. 

Huphenazine is a short acting agent. Eor the management of agitated and potentially violent patients its hydrochloride formulation is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot preparation. Although its principal pharmacological activities are similar to those of the other phenothiazines fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive effect. 

Phenothiazines are antipsychotic agents that can be used for their potent antiemetic and sedative properties (see Chapter 29). The antiemetic properties of phenothiazines are mediated through inhibition of dopamine and muscarinic receptors. Sedative properties are due to their antihistamine activity. The agents most commonly used as antiemetics are prochlorperazine, promethazine, and thiethylperazine. 

Incorporation of the aromatic rings of the ethyienediamines into the tricyciic phenothiazine structure produced compounds (e.g., promethazine) with good antihistaminic action and relatively strong sedative properties (see Chapter 37). At first, these compounds were found to be useful as antihistamines, but their very strong sedative properties aiso iead to their use as potentiating agents for anesthesia (25). Further deveiopment to increase the sedative properties of the phenothiazines resulted in the development of chlorpromazine in 1950 (26). 

Tramadol ER should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, antidepressants, or sedative hypnotics. Tramadol ER increases the risk of CNS and respiratory depression in these patients. 

The two phenothiazine drugs that have been used in veterinary medicine are chlorpromazine and acepromazine (Figure 13.9). Both have been used as tranquilizing agents and sedatives in large and small animals. Their use now is restricted to companion animals because of concerns over residues when administered to food animals. 

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