Which of the following antipsychotics is a drug of choice for a patient with hepatic impairment?
B. Most antipsychotics, with the notable exception of amisulpiride, are highly lipid soluble and extensively metabolized by the liver. Amisulpiride is excreted unchanged by the kidney. Amisulpride is also considered unique in that it is a highly selective dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the mesolimbic system. It is also an ‘atypical’ antipsychotic despite, having a different receptor-affinity profile compared to the other atypical antipsychotics (i.e. absence of serotonin antagonism). At low doses (50 mg), amisulpride preferentially blocks presynaptic autoreceptors, producing an increase in dopamine release, leading to some amelioration of the dopaminergic hypoactivity seen in negative symptoms of schizophrenia and depression. At higher doses (400–1200 mg), the drug exerts its activity on postsynaptic D3/D2 receptors located in the limbic region and prefrontal areas, producing selective dopaminergic inhibition.
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Which of the following antipsychotics has the LEAST effect on weight gain?
A. Clozapine and olanzapine produce the maximum weight gain among antipsychotics. Aripiprazole is considered to be weight neutral, according to the currently available data. Ziprasidone, which is not marketed in the UK, is said to be associated with some weight loss. Average increases reported during the first year are 5.3 to 6.3 kg for clozapine and 6.8 to 11.8 kg for olanzapine, with some subgroups gaining more than 20% of their initial body weight. Moreover, Leiberman et al., found that weight gain appears to be a continuous process where no relationship exists between the dose of antipsychotics prescribed and degree of weight gain.
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Which of the following is a dibenzothiazepine in its chemical structure?
D. Quetiapine is a dibenzothiazepine. It acts similar to clozapine; both drugs having a ‘hitand-run’ profile on D2 receptors. Quetiapine does not stay at the receptor site for a long time to produce extrapyramidal effects but instead it produces a transient blockade. This has been demonstrated using 11C Raclopride PET studies.
Which of the following is true about tardive dyskinesia?
D. In tardive dyskinesia (TD) the movements can be choreiform, athetoid, dystonic, stereotypic, or a combination of these. They most commonly involve the orobuccal, lingual, and facial muscles. High risk groups includes women, elderly, patients with underlying brain damage, those with mood disorder or schizoaffective illness, learning disability, and, curiously, patients with diabetes. It is seen in up to 20% of people on long-term antipsychotic medications. The pathophysiology behind TD is considered to be receptor up-regulation (increase in postsynaptic receptor numbers due to chronic pharmacological antagonism). So, increasing the dose of the offending drugs may suppress the dyskinetic movements for a short while. Anticholinergic drugs, on the other hand, may aggravate TD. Strategies for the management of tardive dyskinesia include gradual withdrawal of antipsychotic medication, a switch to clozapine, and discontinuation of the anticholinergic medication. Tetrabenazine has been considered to be effective as it depletes dopamine from nerve endings. This makes super-sensitivity reactions less likely in spite of an increase in receptor numbers. But the risk of depression is very high with tetrabenazine (similar to reserpine). Clonazepam, diazepam, vitamin E, and melatonin are other proposed management options.
Which of the following drugs has the greatest effect on QTc interval?
B. Pimozide and thioridazine have been found to increase the QT interval. The QT interval (from the Q wave to the end of the T wave) varies with the heart rate, gender, and time of day. There are several different ways of correcting QT for heart rate (QTc), but the simplest method is using Bazett’s formula. In this method, the corrected QT interval (QTc) is calculated by the equation QTc = QT/RR. It is, however, uncertain whether QTc has any greater clinical signifi cance than the uncorrected QT interval. The normal QT interval is 340–430 ms, and irrespective of the heart rate, a QT interval >450 ms is probably risky. A prolonged QT interval can predispose to polymorphic ventricular arrhythmias (torsades de pointes).
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