Which of the following antidepressants is used by urologists for patients with incontinence?
D. In the UK, duloxetine is marketed to treat stress urinary incontinence (SUI) in women under the name Yentreve® (Eli Lilly and Company). The female urethra has a rhabdosphincter of circularly arranged striated muscles. Generally, relaxation of this sphincter allows micturition. The sphincter is innervated by neurones from the sacral spinal cord (S2–S4). Duloxetine blocks the reuptake of serotonin and norepinephrine at this site to stimulate contraction of the rhabdosphincter, leading to an increase in the tone of the urethral sphincter. The increased muscle tone inhibits involuntary urine loss. To treat stress incontinence, a dose of 40 mg twice daily (80 mg/day) is recommended. In depression a dose of 60 mg/day given once daily is often used. Duloxetine can also help neuropathic pain, where a higher dose of up to 120 mg has been used.
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Which one of the following can increase plasma levels of lamotrigine?
C. Lamotrigine is mainly metabolized via glucuronidation and does not have much effect on other prescribed medications, but valproate has been observed to double the plasma levels of lamotrigine. The elimination half-life of lamotrigine in healthy young adults is approximately 25 to 30 hours. In patients taking valproate this is prolonged to 60 hours. As a result, when lamotrigine is initiated for patients who are taking valproate, the starting dose should be approximately 50% of the normal starting dose of lamotrigine. Some suggest that if valproate is started for a patient who is already on lamotrigine, one must consider obtaining a baseline lamotrigine plasma concentration. The lamotrigine dose may have to be reduced during the valproate dose titration. As a result of this interaction, the incidence of lamotrigine-induced rash seems to be more common in those taking the combination. Phenytoin, carbamazepine, and oral contraceptives may reduce the half-life of lamotrigine.
One of your regular out-patients with recurrent depression was recently started on a medication but comes back with aggravated psoriatic skin lesions.
The most probable offending agent is:
A. Lithium can aggravate psoriasis. The induction of psoriasis without pre-existing disease is less common than exacerbation of existing disease. Not all patients with pre-existing psoriasis have a flare when starting lithium and psoriasis is not considered to be a contraindication to taking lithium for mania or depression. Similarly, other drugs such as β-blockers, antimalarials, and indomethacin can aggravate psoriasis. Psoriasis that has flared with lithium appears to be more resistant to standard treatment modalities. Some preliminary evidence suggests that supplemental inositol or omega-3-fatty acids may improve symptoms in patients with psoriasis during lithium treatment. Histological studies on the skin lesions induced or aggravated by lithium are equivocal; some support the lesions to be consistent with psoriasis, although others have claimed the features as non-specific and refer to as psoriasiform dermatitis.
A 34-year-old man taking lithium twice daily experiences side-effects. Your consultant has advised him to take it once daily to reduce the side-effect.
Which one of the following side-effects may respond to this intervention?
C. Ployuria, one of the most common side-effects of lithium, is related to tubular concentrating defect that is resistant to vasopressin. This results in nephrogenic diabetes insipidus. Vasopressin receptor expression is reduced by lithium, leading to a failure of facilitation of water movement. It is thought that taking lithium in a single dose prevents, or at least limits, renal tubular impairment. The most likely reason for the reduction of thirst and polyuria is the less frequent stimulation of the thirst centre by the lithium salts in once-a-day doses. However, some studies have shown that the beneficial effect of single dosage is seen only in those who received multiple doses for a short time. It is possible that long-term, multiple-dose administration results in irreversible changes in tubular mechanisms. Patient adherence can be improved by a single-dosing schedule of lithium; however, once-a-day schedules have not been shown to be conclusively superior with respect to glomerular damage or renal failure.
An intoxicated patient needs prescription for alcohol withdrawal. He is known to have cirrhosis with ascites. The benzodiazepine of choice is:
E. On pharmacokinetic grounds, oxazepam may be preferable to chlordiazepoxide in cirrhotic patients since the elimination of oxazepam is not greatly altered in cirrhosis. In general, longer-acting benzodiazepines, such as chlordiazepoxide or diazepam, are preferred as they produce a smoother withdrawal course with less breakthrough or rebound symptoms, but they may lead to excess sedation for patients with hepatic dysfunction/cirrhosis. Shorter-acting benzodiazepines, such as oxazepam, may result in greater discomfort and more discharges against medical advice, because alcohol withdrawal symptoms tend to recur when the plasma drug levels drop. Shorter-acting agents, such as lorazepam or oxazepam, require more frequent dosing. They may be more useful for symptom-triggered regimens than fixed-dose regimens of alcohol detoxification.
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