Which of the following antidepressants demonstrate the highest affinity for muscarinic acetylcholine receptors of the human brain?
A. Amitriptyline has the highest affinity for central muscarinic acetylcholine receptors among various antidepressants. Its affinity is nearly one-tenth of the affinity shown by atropine. This is followed by protriptyline and clomipramine. Trazodone has very low muscarinic affinity. Anticholinergic side-effects of tricyclics include dry mouth, blurred vision, urinary retention, constipation, memory impairment, and confusion especially in elderly people.
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The number of patients who die from hypertensive crises (including fatal ‘cheese reaction’) when monoamine oxidase inhibitors such as tranylcypromine are prescribed is approximately:
D. One in every 100 000 patients treated with monoamine oxidase inhibitors such as tranylcypromine die due to fatal hypertensive reaction. The fatality rate can also be expressed as 1 in every 8000 hypertensive reactions. The so-called ‘cheese reaction’ is mainly characterized by skin flushing, tachycardia, dyspnoea, sweating, hypertension, conjunctival injection, and headache. The reaction is usually self-limiting, with signs and symptoms lasting from few minutes to a few hours. Tyramine is formed by the decarboxylation of the amino acid tyrosine; it is mainly catabolized via oxidation by monoamine oxidase-A (MAO-A) in man. Thus MAO-A acts as a protective barrier against high tyramine levels in the nervous system. Unmetabolized tyramine is transported into adrenergic nerve terminals where it displaces noradrenaline, causing hypertension.
Which of the following antidepressants has been found to be as lethal as tricyclic antidepressants (TCAs) in cases of overdose?
C. Data from the Office of National Statistics from 1993–2002 have demonstrated a significantly higher rate of fatal overdose (fatal toxicity index) with the antidepressant venlafaxine than with SSRIs. Venlafaxine has a similar lethality to TCAs in cases of overdose; most deaths are ascribed to cardiac effects of the drug. Overall, approximately 10% of venlafaxine overdoses that are reported have proven fatal. Blood pressure increases are common in therapeutic doses but severe increases do not appear to be a significant feature of overdose. Fatal toxicity indices (FTIs) are calculated using recorded deaths attributed to drug overdose obtained from prescribing data. TCAs (in particular dothiepin) have been associated with a higher FTI than venlafaxine, which in turn has been associated with a higher FTI than SSRIs.
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The lorazepam challenge test is used in the diagnosis of:
C. In the ‘lorazepam challenge test’ (coined by George Bidder), an intravenous line is established and a syringe containing 2–4 mg of lorazepam in 2 mL of solution is prepared, and 1 mg is injected. In the next 2–5 minutes if no reduction is observed in catatonic features, the second 1 mg of lorazepam is injected, and the assessment is repeated. It is noted that more than 80% of patients with catatonia have a rapid reduction in symptoms with an intravenous lorazepam challenge. Such a response to lorazepam typically results in a lorazepam treatment trial, followed by electroconvulsive therapy if substantial relief is not maintained. Fink and Taylor suggest that adhering to this algorithm achieves remission of catatonia in almost all patients. Amytal interview using intravenous barbiturates/benzodiazepines has been used in dissociative amnesia/fugue.
Which of the following laboratory abnormalities is associated with malignant catatonia?
B. The syndrome of malignant catatonia is severe form of catatonia characterized by fever, muscle rigidity and autonomic instability and can be fatal (through renal failure, pulmonary embolism or arrhythmias) if not treated promptly. It is indistinguishable from neuroleptic malignant syndrome. ECT is the treatment of choice. Laboratory studies often help to assess the overall health of a catatonic patient; they rarely help in identifying the cause or confirm the diagnosis of catatonia in isolation. Elevated levels of creatinine phosphokinase (CPK), elevated liver enzymes, and leucocytosis are some of the changes noted in patients with malignant catatonia. Low serum iron levels are associated with malignant catatonia; it is also observed in some patients with neuroleptic malignant syndrome. Serum calcium and magnesium levels are either normal or low in catatonia.