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Katzung & Trevor's Pharmacology: Examination & Board Review, 12e

Chapter 29: Antipsychotic Agents & Lithium

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Which statement about the pathophysiologic basis of schizophrenia is most accurate?

(A) All clinically effective antipsychotic drugs have high affinity for dopamine D₂ receptors

(B) Dopamine receptor-blocking drugs are used to alleviate psychotic symptoms in parkinsonism

(C) Drug-induced psychosis can occur without activation of brain dopamine receptors

(D) Serotonin receptors are present at lower than normal levels in the brains of untreated schizophrenics

(E) The clinical potency of olanzapine correlates well with its dopamine receptor-blocking activity

Although most first generation antipsychotic drugs block D₂ receptors, this action is not a requirement for antipsychotic action. Aripiprazole, clozapine, and most newer second-generation drugs have a very low affinity for such receptors, but a high affinity for serotonin 5-HT₂ receptors. There are no reports of decreased serotonin receptors in the brains of schizophrenics. The CNS effects of phencyclidine (PCP) closely parallel an acute schizophrenic episode, but PCP has no actions on brain dopamine receptors. Dopamine receptor blockers cause extrapyramidal dysfunction. The answer is C.

Trifluoperazine was prescribed for a young male patient diagnosed as suffering from schizophrenia. He complains about the side effects of his medication. Which of the following is not likely to be one of his complaints?

(A) Constipation

(B) Decreased libido

(C) Excessive salivation

(D) Postural hypotension

Phenothiazines such as trifluoperazine cause sedation and are antagonists at muscarinic and α adrenoceptors. Postural hypotension, blurring of vision, and dry mouth are common autonomic adverse effects, as is constipation. Effects on the male libido may result from increased prolactin or from increased peripheral conversion of androgens to estrogens. The answer is C.

Which statement concerning the adverse effects of antipsychotic drugs is most accurate?

(A) Acute dystonic reactions occur commonly with olanzapine

(B) Akathisias due to antipsychotic drugs are managed by increasing the drug dose

(C) Blurring of vision and urinary retention are common adverse effects of haloperidol

(D) Retinal pigmentation is a dose-dependent toxic effect of thioridazine

(E) The late-occurring choreoathetoid movements caused by conventional antipsychotic drugs may be alleviated by atropine

Olanzapine has minimal dopamine receptor–blocking action and is unlikely to cause acute dystonias. Muscarinic blockers such as atropine exacerbate tardive dyskinesias. Akathisias (uncontrollable restlessness) resulting from antipsychotic drugs may be relieved by a reduction in dosage. Retinal pigmentation may occur from treatment with thioridazine. The answer is D.

Haloperidol is not an appropriate drug for management of

(A) Acute mania

(B) Amenorrhea-galactorrhea syndrome

(C) Phencyclidine intoxication

(D) Schizoaffective disorders

(E) Tourette syndrome

In addition to its use in schizophrenia and acute mania, haloperidol has been used in the management of intoxication due to phencyclidine (PCP) and in Tourette syndrome. Hyperprolactinemia and the amenorrhea-galactorrhea syndrome may occur as adverse effects during treatment with antipsychotic drugs, especially those like haloperidol that strongly antagonize dopamine receptors in the tuberoinfundibular tract. The answer is B.

Which statement concerning the use of lithium in the treatment of bipolar affective disorder is most accurate?

(A) Ingestion of foods with high salt content enhances the toxicity of lithium

(B) Lithium usually alleviates the manic phase of bipolar disorder within 12 h

(C) Lithium dosage may need to be decreased in patients taking thiazides

(D) Since lithium does not cross the placental barrier, it is safe in pregnancy

(E) The elimination rate of lithium is equivalent to that of creatinine

Clinical effects of lithium are slow in onset and may not be apparent before 1 or 2 weeks of daily treatment. High urinary levels of sodium inhibit renal tubular reabsorption of lithium, thus decreasing its plasma levels. Lithium clearance is decreased by distal tubule diuretics (eg, thiazides) because natriuresis stimulates a reflex increase in the proximal tubule reabsorption of both lithium and sodium. Any drug that can cross the blood-brain barrier can cross the placental barrier! Teratogenic risk is low, but use of lithium during pregnancy may contribute to low Apgar score in the neonate. The answer is C.

A 30-year-old male patient is on drug therapy for a psychiatric problem. He complains that he feels “flat” and that he gets confused at times. He has been gaining weight and has lost his sex drive. As he moves his hands, you notice a slight tremor. He tells you that since he has been on medication he is always thirsty and frequently has to urinate. The drug he is most likely to be taking is

(A) Carbamazepine

(B) Clozapine

(C) Lithium

(D) Risperidone

(E) Valproic acid

Confusion, mood changes, decreased sexual interest, and weight gain are symptoms that may be unrelated to drug administration. On the other hand, psychiatric drugs are often responsible for such symptoms. Tremor and symptoms of nephrogenic diabetes insipidus are characteristic adverse effects of lithium that may occur at blood levels within the therapeutic range. The answer is C.

A young woman recently diagnosed as schizophrenic develops severe muscle cramps with torticollis a short time after drug therapy is initiated with haloperidol. The best course of action would be to

(A) Add risperidone to the drug regimen

(B) Discontinue haloperidol and observe the patient

(C) Give oral diphenhydramine

(D) Inject benztropine

(E) Switch the patient to fluphenazine

Acute dystonic reactions are usually very painful and should be treated immediately with parenteral administration of a drug that blocks muscarinic receptors such as benztropine. Adding risperidone is not protective, and fluphenazine is as likely as haloperidol to cause acute dystonia. Oral administration of diphenhydramine is a possibility, but the patient may find it difficult to swallow and it would take a longer time to act. The answer is D.

Which of the following drugs is established to be both effective and safe to use in a pregnant patient suffering from bipolar disorder?

(A) Carbamazepine

(B) Fluphenazine

(C) Lithium

(D) Olanzapine

(E) Valproic acid

Carbamazepine and valproic acid are effective in bipolar disorder but are contraindicated in the pregnant patient because of possible teratogenic effects. Although the potential for dysmorphogenesis due to lithium is probably low, the most conservative approach would be to treat the patient with quetiapine or olanzapine. Fluphenazine has no proven efficacy in bipolar disorder. The answer is D.

In comparing the characteristics of thioridazine with other first generation antipsychotic drugs, which of the following statements is most accurate?

(A) Most likely to cause extrapyramidal dysfunction

(B) Least likely to cause urinary retention

(C) Most likely to be safe in patients with history of cardiac arrhythmias

(D) Most likely to cause ocular dysfunction

(E) The safest antipsychotic drug in overdose

Atropine-like side effects are more prominent with thioridazine than with other phenothiazines, but the drug is less likely to cause extrapyramidal dysfunction. The drug has quinidine-like actions on the heart and, in overdose, may cause arrhythmias and cardiac conduction block with fatality. At high doses, thioridazine causes retinal deposits, which in advanced cases resemble retinitis pigmentosa. The patient may complain of browning of vision. The answer is D.

Which of the following drugs has a high affinity for 5-HT₂ receptors in the brain, does not cause extrapyramidal dysfunction or hematotoxicity, but is reported to increase the risk of significant QT prolongation?

(A) Clozapine

(B) Haloperidol

(C) Olanzapine

(D) Valproic acid

(E) Ziprasidone

Many of the newer antipsychotic drugs have a greater affinity for 5-HT₂ receptors than dopamine receptors. However, because clozapine is hematotoxic, the choice comes down to olanzapine and ziprasidone, both of which block 5-HT receptors. Of the currently available atypical antipsychotic drugs, ziprasidone carries the greatest risk of QT prolongation. The answer is E.

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Chapter 29: Antipsychotic Agents & Lithium

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