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A 34-year-old male presents to the hospital complaining of weight loss, nausea, vomiting, and lethargy. There is
no evidence of edema, orthostatic hypotension, or dehydration. Blood samples show hyponatremia, while his
urine is highly concentrated. A water-load test is performed, in which the patient is instructed to drink a large
volume of water and 5 hourly samples of urine are analyzed. All samples show concentrated urine. Which of the
following drugs could have caused this condition?
A. Baclofen
B. Carbamazepine
C. Dantrolene
D. Phenelzine
E. Phenytoin
F. Tranylcypromine
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Explanation:
The correct answer is B. The patient above is suffering from syndrome of inappropriate secretion of ADH
(SIADH). When ADH (vasopressin) is secreted in excessive amounts, or at inappropriate times, it can cause
hyponatremia as well as symptoms of nausea, vomiting, anorexia, and lethargy. Also, excessive release of
vasopressin results in the excretion of a concentrated urine (with a urinary osmolality usually over 300 mmol/kg)
despite a subnormal plasma osmolality and serum sodium concentration. SIADH can be caused by many
factors, such as ectopic ADH production and release from neoplastic tissue (small cell carcinoma of lung,
pancreatic carcinoma, lymphosarcoma, Hodgkin's disease, reticulum cell sarcoma, thymoma, and carcinoma of
duodenum or bladder) or by drugs that release or potentiate the action of ADH, such as carbamazepine,
vincristine, vinblastine, cyclophosphamide, chlorpropamide, general anesthetics, and tricyclic antidepressants.
Baclofen (choice A) is a spasmolytic agent. Baclofen has not been shown to be associated with the release of
ADH.
Dantrolene (choice C) is a spasmolytic agent and is also used to treat malignant hyperthermia. Dantrolene has
not been shown to be associated with the release of ADH.
Phenelzine (choice D) is an MAO inhibitor. MAO inhibitors have not been shown to be associated with the
release of ADH.
Phenytoin (choice E) is an antiseizure drug. Phenytoin has not been shown to be associated with the release of
ADH.
Tranylcypromine (choice F) is an MAO inhibitor. MAO inhibitors have not been shown to be associated with the
release of ADH.
