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C H A P T E R 2 2 Psychotherapeutic agents

are necessary. People who take either of these combina- tions should be monitored closely for adverse effects and supportive measures should be provided. People should not take ziprasidone with any other drug that is associ- ated with prolongation of the QT c interval.

Adverse effects The adverse effects associated with the antipsychotic drugs are related to their dopamine-blocking, anticho- linergic, antihistamine and alpha-adrenergic activities. The most common CNS effects are sedation, weakness, tremor, drowsiness, extrapyramidal side effects (EPS), pseudoparkinsonism, dystonia, akathisia, tardive dyskinesia and potentially irreversible neuroleptic malignant syndrome. Anticholinergic effects include dry mouth, nasal congestion, flushing, constipation, urinary retention, impotence, glaucoma, blurred vision and photophobia. Cardiovascular (CV) effects, which are probably related to the dopamine-blocking effects, include hypotension, orthostatic hypotension, cardiac arrhythmias, congestive heart failure and pulmonary oedema. Ziprasidone is associated with prolongation of the QT c interval, which could lead to serious or even fatal cardiac arrhythmias. People receiving this drug should have a baseline and periodic electrocardiogram (ECG) during therapy. In late 2003, the FDA issued a requirement that all of the atypical antipsychotics include warnings that there is a risk for the develop- ment of diabetes mellitus when these drugs are used. Consequently, when people are maintained on any of the atypical antipsychotics, they should be moni- tored regularly for the signs and symptoms of diabetes mellitus. Respiratory effects such as laryngospasm, dyspnoea and bronchospasm may also occur. The phenothiazines (chlorpromazine, fluphenazine, prochlorperazine and promethazine) often turn the urine pink to reddish-brown as a result of their excretion. Although this effect may cause great concern to the person, it has no clinical sig- nificance. In addition, bone marrow suppression is a possibility with some antipsychotic agents. Clinically important drug–drug interactions Because the combination of antipsychotics with beta-blockers may lead to an increase in the effect of both drugs, this combination should be avoided if possible. Antipsychotic–alcohol combinations result in an increased risk of CNS depression and antipsychotic–anticholinergic combinations lead to increased anticholinergic effects, so dose adjustments Evening primrose People with schizophrenia should be advised to avoid the use of evening primrose.This herb has been associated with increased symptoms and CNS hyperexcitability. Herbal and alternative therapies BOX 22.5

Prototype summary: Chlorpromazine Indications: Management of manifestations of psychotic disorders; relief of preoperative

restlessness; adjunctive treatment of tetanus; acute intermittent porphyria; severe behavioural problems in children; control of hiccups, nausea and vomiting. Actions: Blocks postsynaptic dopamine receptors in the brain; depresses those parts of the brain involved in wakefulness and emesis; anticholinergic; antihistaminic; alpha-adrenergic blocking. Pharmacokinetics: Route Onset Peak Duration Oral 30–60 mins 2–4 hours 4–6 hours Intra- muscular 10–15 mins 15–20 mins 4–6 hours T 1/2 : 2 hours, then 30 hours; metabolised in the liver, excreted in the urine. Adverse effects: Drowsiness, insomnia, vertigo, extrapyramidal symptoms, orthostatic hypotension, photophobia, blurred vision, dry mouth, nausea, vomiting, anorexia, urinary retention, photosensitivity. Prototype summary: Clozapine Indications: Management of severely ill people with schizophrenia who are unresponsive to standard drugs; reduction of risk of recurrent suicidal behaviour in people with schizophrenia or schizoaffective disorder. Actions: Blocks dopamine and serotonin receptors; depresses the RAS; anticholinergic; antihistaminic; alpha-adrenergic blocking. Pharmacokinetics: Route Onset Peak Duration Oral Varies 1–6 hours Weeks T 1/2 : 4–12 hours; metabolised in the liver, excreted in the urine and faeces. Adverse effects: Drowsiness, sedation, seizures, dizziness, syncope, headache, tachycardia, nausea, vomiting, fever, neuroleptic malignant syndrome.