Buspirone is an anxiolytic with no immediate effect on acute administration, unlike diazepam. This is due to:
E. Buspirone is an azapirone which, by partial agonistic action on the 5-HT1A receptor, suppresses activity in presynaptic serotonergic neurons. This in turn reduces the serotonin activity, leading to down-regulation of various 5-HT receptors. This is related to anxiolytic activity but with no hypnotic effect. Though buspirone is equi-effective to diazepam, patients taking buspirone improve more slowly. This is related to the inherent mode of action, which depends on receptor down-regulation rather than producing a direct receptor action. Patients who are switched from benzodiazepines to buspirone do not do as well as those without previous exposure to benzodiazepines.
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Most diuretics interact with lithium to produce significant changes in plasma lithium levels.
Which one of the following diuretics is useful in treating polyuria, a common side-effect of lithium?
A. Amiloride is useful in some cases of lithium-induced polyuria. Polyuria is the most common adverse effect of lithium, occurring in 25% of patients. This polyuria is related to the antagonistic effects of lithium on antidiuretic hormone, leading to diuresis. Conservative management includes fluid replacement, decreasing the dosage of lithium, and single daily dosing of lithium. Potassium-sparing diuretics, such as triamterene and amiloride, or thiazide diuretics are also useful. Unlike thiazides and frusemide, amiloride does not reduce lithium clearance; instead it may increase lithium excretion.
A 30-year-old woman was diagnosed with paranoid schizophrenia. She has been hospitalized and is prescribed antipsychotics.
Which one of the following treatment-emergent conditions is known to be associated with the risk of suicide?
A. Akathisia is the commonest movement disorder associated with antipsychotic prescription. It is more commonly acute, with onset within 48 to 96 hours of administration of the antipsychotics. It is unclear whether akathisia results from dopamine antagonism or dysfunction of other neurotransmitters such as serotonin, acetyl choline, and norepinephrine. Akathisia is often mistaken for anxiety or worsening of psychotic agitation. Akathisia can vary in severity over time, making assessment difficult. Akathisia is associated with suicidality, absconsion, aggression, and non-compliance. Tardive dyskinesia develops late in the course of antipsychotic treatment and as such is not associated with absconsion from in-patient units, as more often than not the patients do not recognize having troublesome movement disorders. Neuroleptic malignant syndrome and laryngeal dystonia are life-threatening syndromes, often requiring immediate medical attention.
For typical neuroleptics, the antipsychotic effect on positive psychotic symptoms is strongly correlated with:
A. D2 occupancy in typical antipsychotics correlates with their antipsychotic efficacy and propensity to cause extrapyramidal side-effects. This was demonstrated in a landmark positron emission tomography (PET) study by Kapur et al., where haloperidol produced therapeutic effect at around 65% occupancy; extrapyramidal side-effects occurred when the occupancy was around 78%. For atypicals, both 5-HT2A blockade and D2 occupancy are correlated with clinical efficacy. Clozapine and quetiapine occupy less than half of D2 receptors but still are efficacious as antipsychotics.
Memantine is an antidementia drug licensed for moderately severe Alzheimer’s dementia. The mechanism by which memantine acts is:
A. Memantine has moderate affinity for the NMDA receptor and acts as a voltage-dependent and non-competitive antagonist. Calcium-mediated excito-toxicity could be due to overstimulation of NMDA receptors by glutamate. Memantine may protect cells against excess glutamate by partially blocking NMDA receptors associated with abnormal transmission of glutamate, while physiological transmission remains unaffected.
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