Which of the following statements is true about plasma levels of clozapine?
B. Clozapine plasma level monitoring is indicated in patients who are not responding to standard doses of clozapine. A plasma level of 350 µg/l is reasonable for most patients. A full blood count is done initially weekly while starting clozapine, in accordance with the clozapine patient monitoring service guidelines. Smoking induces the enzymes that metabolize clozapine. Hence, stopping smoking can increase the levels of clozapine. Fluoxetine is an inhibitor of CYP1A2, which metabolizes clozapine and may increase the levels of clozapine. This may also be therapeutic at times, in patients who do not respond to a maximum dose of clozapine.
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A ‘therapeutic window’ is well established in which one of the following?
C. A therapeutic window is a range of concentrations of a drug measured in the blood that are associated with a good therapeutic response. Plasma concentrations outside this range are either too low to ensure a therapeutic response or so high that they induce toxic side-effects. There is no evidence to say that there is an established therapeutic window for neuroleptics. Lithium has a therapeutic window. Nortriptyline is the only medication in the list that appears to have an established therapeutic window, in the range of 50 to 150 ng/ml. This level is usually reached by doses ranging from 50 to 100 mg/day.
A 30-year-old man is started on amitriptyline. He develops dry mouth, constipation, and blurred vision.
Action on which of the following receptors could explain the side-effects described?
C. The side-effects mentioned in the question are features suggestive of the action of the tricyclic antidepressant on muscarinic cholinergic receptors. This includes dry mouth, urinary retention, blurred vision, and constipation. Dry mouth may lead to caries teeth in the long term. In the case of overdose with TCA, the anticholinergic action can lead to confusion, coma, and death due to respiratory failure. Action on α-adrenoceptors, may result in postural hypotension, causing falls and injuries. Therapeutic action of TCAs is thought to be due to its inhibitor action on serotonin and norepinephrine reuptake pumps. Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, which has a dopamine receptor blocking effect. Amoxapine may be useful in cases of psychotic depression due to its dopamine blocking properties.
Which of the following is an example of a pharmacodynamic drug interaction?
D. There are two main types of drug interactions, pharmacodynamic and pharmacokinetic. Pharmacodynamic interactions arise when one drug increases or decreases the pharmacological effect of a second drug that is given at the same time, for example the depressant action of alcohol is augmented by benzodiazepines. When one drug alters a pharmacokinetic component of another drug, thus causing a change in the concentration of the other drug, this is called a pharmacokinetic interaction, for example inhibition of CYP450 enzyme, displacement of a drug from protein binding, reduced renal excretion of a drug, etc.
Considering psychopharmacology in perinatal psychiatry, which one of the following is true?
A. Most psychotropic medications are best avoided in the first trimester. Caution should also be exercised at the time of delivery and early neonatal period. Most medications, including lithium, are secreted in breast milk and should be used with caution. TCAs and fluoxetine have the best evidence for safety in pregnancy. Lithium can cause Ebstein’s anomaly (cardiac valvular deformity) and floppy baby syndrome in newborns. SSRI withdrawal may be seen in newborns, especially if the mother was on short-acting SSRIs immediately prior to delivery. With respect to antipsychotics, high potency drugs are preferred to low potency ones in pregnancy. Anticonvulsant mood stabilizers have a high risk of neural tube defects. Benzodiazepines have a high risk of cleft lip.
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