Antipsychotic agents anticholinergic effects

Antipsychotic agent Approx. equiv. dose (mg) Usual oral adult daily dose range (mg) Sedation EPS Anticholinergic effects ... 

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. 

The piperazines include fluphenazine, trifluoperazine, prochlorperazine, perazine and perphenazine. They are agents with a high antipsychotic potency with less pronounced anticholinergic effects. However their potential to produce extrapyramidal effects is more pronounced. 

Tricyclic antidepressants are notorious for their risk to be involved in drug-drug interactions. Additive anticholinergic effects can be expected in combination with antihistamines, antipsychotics and anticholinergic-type anti-Parkinson agents. Hepatic enzyme-inducing agents increase their hepatic metabolism while enzyme inhibitors may potentiate the effects of tricyclics. Concomitant use with monoamine oxidase inhibitors will produce hypertension, hyperpyrexia and convulsions. 

The case in context Clozapine is a newer antipsychotic that can, like other agents in its class, produce antimuscarinic side effects. Although Ms. Doe had not complained of anticholinergic effects prior to beginning treatment with a moderate dose of diphenhydramine, it is likely that the additive anticholinergic effects of clozapine and diphenhydramine resulted in urinary retention. 

Antipsychotic agents may have several cardiovascular effects. Medication-induced hypotension is generally more problematic with lower-potency neuroleptics than with other antipsychotics and appears to be mediated through tti-adrenergic blockade. Besides increases in heart rate that may be the result of hypotension, antipsychotics with appreciable anticholinergic effects (see Clinical Implications, below) can lead to tachycardia (Gutgesell et ah, 1999). 

Acute angle closure and difficulty with accommodation can occur from the anticholinergic effects of antipsychotic agents. In addition, pigment deposits may develop in the cornea and lens. Pigmentary retinopathy has been reported with thioridazine. Keratopathy and corneal edema may occur occasionally during pharmacotherapy with chlorpromazine and fluphenazine... 

Common pharmacodynamic interactions involve the additive anticholinergic or antidopaminergic effects of antipsychotics. Thus, concomitantly administered antiparkinsonian agents (e.g., benztropine) may increase the chances of toxicity (e.g., delirium) while dopamimetic agents (e.g., levodopa) may counteract the antipsychotic or neurotoxic effects of these agents. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Some members of the class are extremely potent antipsychotic agents and Dn and D.i receptor antagonists. BP.S are extremely marked in some members of this class, which may. in pan. be due to a potent DA block in the striatum and almost no eompen.satory striatal anticholinergic block. Mott of the compounds do not have the structural features ixsociaied with effective anticholinergic activity. 

Several dozen phenothiazine antipsychotic drugs and chemically related agents are used worldwide. Other phenothiazines are marketed primarily for their antiemetic, antihistaminic, or anticholinergic effects. 

In addition, some antipsychotics, antihistamines, antidepressants, and opioids have anticholinergic effects. Patients receiving these agents should be told that dry mouth, tachycardia and constipation are possible side effects. 

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