Syndrome of inappropriate secretion

While the dose-limiting toxicity for vinblastine usually is leukopenia, that for vincristine is most commonly neurotoxicity (58). Prominent manifestations of neurotoxicity are loss of the Achilles tendon reflex, paresthesias, loss of muscle strength (e.g., in the foot and wrist), and ataxia. Constipation and abdominal pain may occur and are thought to result, at least in part, from actions on the autonomic nervous system. Leukopenia and stomatitis are possible effects of vincristine treatment, but they occur relatively infrequently. Alopecia occurs with vincristine at a frequency comparable to that observed with vinblastine, and vincristine also is a potent tissue irritant. Vincristine may produce a syndrome of inappropriate secretion of antidiuretic hormone, and some manifestations of neurotoxicity, such as seizures, have been considered to be due to electrolyte disturbances associated with the relative excess of the antidiuretic hormone (58). 

Loss of blood glucose control When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue the drug and give insulin. Disulfiram-like syncframe. A sulfonylurea-induced facial flushing or breathlessness reaction may occur when some sulfonylureas are administered with alcohol. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Water retention and dilutional hyponatremia have occurred after administration of sulfonylureas to type 2 diabetes patients, especially those with CHF or hepatic cirrhosis. 

Liu, B.A., Mittmann, N., Knowles, S.R., and Shear, N.H. (1996) Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors a review of spontaneous reports. CMAJ 155 519-527. 

BUN, blood urea nitrogen CBC, complete blood cell count CBZ, carbamazepine DVP, divalproex sodium EKG, electrocardiogram SIADH, syndrome of inappropriate secretion of antidiuretic hormone TSH, thyroid-stimulating hormone. 

Case reports have indicated an association between SSRIs and the syndrome of inappropriate secretion of antidiuretic hormone. Symptoms include lethargy, headache, hyponatremia, increased urinary sodium excretion, and hyperosmotic urine. Acute treatment of this syndrome should consist of discontinuation of the drug as well as restriction of fluid intake. Patients experiencing severe confusion, convulsions, or coma should receive intravenous sodium chloride. Elderly persons may he at a higher risk for developing this syndrome. 

Note. SIADH=syndrome of inappropriate secretion of antidiuretic hormone CBC=complete blood count TSH=thyroid-stimulating hormone ECG=electrocardiogram AST=aspartate aminotransaminase ALT=alanine aminolransaminase. 

The main dose-limiting toxicity is neurotoxicity, usually expressed as a peripheral sensory neuropathy, although autonomic nervous system dysfunction with orthostatic hypotension, urinary retention, paralytic ileus, or constipation, cranial nerve palsies, ataxia, seizures, and coma have been observed. While myelosuppression occurs, it is generally milder and much less significant than with vinblastine. The other potential adverse effect that can develop is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 

Amiodarone-induced hyponatremia, due to the syndrome of inappropriate secretion of antidiuretic hormone, is rare (SEDA-21, 199 25). The mechanism is unknown. Unlike other adverse effects of amiodarone, it seems to occur rapidly and to resolve rapidly after withdrawal. 

The syndrome of inappropriate secretion of antidiuretic hormone has been reported with enalapril (377, 378). 

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (728) may be the mechanism of action underlying cases of peripheral edema that have been described (SEDA-2, 12 SEDA-6, 28). Diuretics are not helpful, but dosage reduction produces relief (729). 

A rare but well-known adverse effect of vinca alkaloids, including vinorelbine, is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (1195-1197). The diagnosis is usually based on clinical and laboratory... 

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a possible adverse effect of the SSRIs (SEDA-14, 14) (SEDA-18, 20) (SEDA 21, 11) (40). The mechanism is not known. Several of the affected patients have been elderly, and old people may be at greater risk. 

Nako Y, Tachibana A, Harigaya A, Tomomasa T, Morikawa A. Syndrome of inappropriate secretion of antidiuretic hormone complicating neonatal diazepam withdrawal. Acta Paediatr 2000 89(4) 488-9. 

Hanagiri T, Muranaka H, Hashimoto M, Nagashima A. A syndrome of inappropriate secretion of antidinretic hormone associated with pleuritis caused by OK-432. Respiration 1998 65(4) 310-12. 

Forrest JN Jr., Cox M, Hong C, Morrison G, Bia M, Singer I. Superiority of demeclocycUne over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 1978 298(4) 173-7. 

SIADH syndrome of inappropriate secretion of ADH TSH thyroid-stimulating hormone... 

The sulphonylureas, particularly chlorpropamide, may infrequently induce a syndrome of inappropriate secretion of antidiuretic hormone (augmenting hypothalamic-pituitary release of this hormone) characterized by water retention, hyponatraemia, low serum osmolality and high urine osmolality, and central nervous system signs. Water retention and dilutional hyponatraemia have occurred after administration of chlorpropamide and tolbutamide to NIDDM patients, especially those with congestive heart failure or hepatic cirrhosis. Glipizide, acetohexamide (Moses et al., 1973), tolazamide, glibenclamide are mildly diuretic. 

In patients with the syndrome of inappropriate secretion of antidiuretic hormone and symptomatic hypotonic hyponatremia, the most efficient means of correcting the hyponatremia involves the administration of 3% saline in conjunction with a loop diuretic. 

FIGURE 49-2. Diagnostic algorithm for the evaluation of hyponatremia. CHF, congestive heart failure SIADH, syndrome of Inappropriate secretion of antidluretic hormone Una, urine sodium concentration Uosm, urine osmolality. 

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