Which of the following antidementia drugs is/are prescribed for administration once daily?
B. Donepezil is administered once daily. This is possible because of the extended half-life of donepezil compared to other antidementia drugs. Gallantamine and rivastigmine are administered twice daily. An extended release form of gallantamine is now available and this can be administered once daily.
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The effect of paroxetine on sleep is mainly due to its action on:
B. Unlike tricyclic antidepressants, most SSRIs have a disruptive effect on sleep, hence administered in the morning. Stimulation of serotonin 5HT2A receptors in the brainstem sleep centres may cause rapid muscle movements called myoclonus during the night; it may also disrupt slow-wave sleep and cause nocturnal awakenings. 5 HT2A and 5HT2C are also responsible for the panic attacks and anxiety associated with SSRIs. 5HT3 receptors are involved in the gastrointestinal side-effects like nausea and vomiting, mediated through their location at the chemoreceptor trigger zone. SSRIs generally have very much less or absent antihistamine or anticholinergic action, except paroxetine which has signifi cant anticholinergic activity. The antidepressant action of SSRIs is thought to be mediated through the down-regulation of 5HT1A autoreceptors.
Which one of the following is NOT an idiosyncratic reaction?
B. Side-effects are generally divided into two types. Dose-dependent side-effects can be predicted, for example postural hypotension or parkinsonian side-effects with antipsychotics. Dose-independent side-effects are either idiosyncratic or immune-mediated side-effects that cannot be predicted in a patient beforehand, for example anaphylactic reactions. Lamotrigineinduced rash is dose independent and often occurs during the early phase of treatment. Hepatotoxicity due to valproate and Steven Johnson syndrome related to carbamazepine are potentially life-threatening, idiosyncratic effects.
Which of the following is a dose-dependent side-effect?
A. Agranulocytosis can occur at any given dose of clozapine. It is not a dose-dependent effect. The risk of agranulocytosis is higher in the first year of clozapine therapy and gradually reduces over the course of treatment. Similarly, neuroleptic malignant syndrome is an idiosyncratic reaction which cannot be predicted in an individual patient. The most important clinical implication to remember is the fact that if a patient has an idiosyncratic side-effect, then this can reoccur at even small doses if rechallenged. Stopping the drug rather than lowering its dose is the appropriate management strategy in such cases. Naltrexone produces hepatocellular damage in proportion to the dose administered, especially in patients with pre-existing liver damage.
Which one of the following affects blood levels of lithium?
E. The clearance of lithium is delayed by most non-steroidal anti-infl ammatory drugs including cyclo-oxygenase 2 (COX-2) inhibitors. Thiazide diuretics increase the plasma concentration of lithium. Other drugs which increase the concentration of lithium include ACE inhibitors. SSRIs increase the risk of serotonin syndrome with lithium, while haloperidol and carbamazepine increase the risk of neurotoxicity without altering plasma levels.
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