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C H A P T E R 2 2 Psychotherapeutic agents

TABLE 22.1

DRUGS IN FOCUS Antipsychotic/neuroleptic drugs (continued)

Common side effects

Drug name

Potency

Usual dosage

Sedation Anticholinergic Hypotension Extrapyramidal

ziprasidone (Zeldox)

Medium +++

++

+

+

Adult: 20–80 mg PO b.d.; rapid control of as-stated behaviour: 10–20 mg IM, maximum dose 40 mg/day IM; monitor QTc intervals

Each plus sign indicates increased incidence of the given adverse effect. b.d., twice daily; IM, intramuscularly; PO, orally; PR, rectally; q.i.d., four times daily; q 4–6 hours, every 4–6 hours; q 4–8 hours, every 4–8 hours; q 6 hours, every 6 hours; t.d.s., three times daily; XR, extended release.

surgery and chemotherapy. It has the advantage of being available in oral, rectal and parenteral forms. Aripipra- zole, one of the newer atypical antipsychotics, has been found to be effective in treating schizophrenia, major depressive disorder and bipolar disorders and has been used parenterally for the treatment of acute agitation associated with these disorders. Olanzapine and ziprasi- done are also used for bipolar disorders and parenterally to treat acute agitation. Quetiapine is also approved for short-term treatment of acute manic episodes associated with bipolar disease. Risperidone is used frequently to treat irritability and aggression associated with autistic disorders in children and adolescents, as well as for acute manic episodes of bipolar disease. Any of these drugs may be effective in a particular person; the selec- tion of a specific drug depends on the desired potency and tolerance of the associated adverse effects. A person who does not respond to one drug may react success- fully to another agent. (Responses may also vary because of cultural issues [Box 22.3].) To determine the best therapeutic regimen for a particular person, it may be necessary to try more than one drug. Pharmacokinetics The antipsychotics are erratically absorbed from the gastrointestinal (GI) tract, depending on the drug and the preparation of the drug. Intramuscular doses provide four to five times the active dose as oral doses and caution is required if one is switching between routes. The antipsychotics are widely distributed in the tissues and are often stored there, being released for up to 6 months after the drug is stopped. They are metabo- lised in the liver and excreted through the bile and urine. Children tend to metabolise these drugs faster than do adults and elderly people tend to metabolise them more slowly, making it necessary to carefully monitor these people and adjust doses as needed. Clinical effects may not be seen for several weeks and people should be encouraged to continue taking the drugs even if they see no immediate effectiveness. The antipsychotics cross the placenta and enter breast milk (see Contraindications and cautions).

■■ BOX 22.2  Neuroleptic malignant syndrome

Therapeutic actions and indications The typical antipsychotic drugs block dopamine recep- tors, preventing the stimulation of the postsynaptic neurons by dopamine. They also depress the RAS, limiting the stimuli coming into the brain. They also have anticholinergic, antihistamine and alpha-adrenergic blocking effects, all related to the blocking of the dopamine-receptor sites. Newer atypical antipsychotics block both dopamine and serotonin receptors. This dual action may help to alleviate some of the unpleasant neurological effects and depression associated with the typical antipsychotics (see Table 22.1). The antipsychotics are indicated for schizophrenia and for manifestations of other psychotic disorders, including hyperactivity, combative behaviour and severe behavioural problems in children (short-term control); some of them are also approved for the treatment of bipolar disorder. Chlorpromazine, one of the older antipsychotics, is also used to decrease preoperative restlessness and apprehension, to treat intermittent por- phyria, as an adjunct in the treatment of tetanus and to control nausea, vomiting and intractable hiccups. Haloperidol is frequently used to treat acute psychiat- ric situations and is available for intravenous (IV) use when prolonged parenteral therapy is required because of swallowing difficulties or the acuity of the behav- ioural problems. Prochlorperazine is also frequently used to control severe nausea and vomiting associated with Neuroleptic malignant syndrome is a rare but potentially fatal adverse effect of all antipsychotic drugs. This includes symptoms such as hyperthermia, fluctuating level of consciousness, muscle rigidity, autonomic dysfunction with pallor, tachycardia, labile blood pressure, sweating and urinary incontinence. People who presents with neuroleptic malignant syndrome should seek specialist medical assessment immediately as admission to a medical intensive care facility may be necessary. Symptoms usually last for 5–7 days after the drug is discontinued.