A Brief Review of Drug-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone


January 24, 2002

In This Article

Treatment of Drug-Induced SIADH

Management of SIADH involves reversing excessive intakes of fluid, restoring sodium balance, and inhibiting the antidiuretic actions of ADH.[13] Treatment of drug-induced SIADH by discontinuing the suspected drug is usually effective.[9] However, patients with symptomatic hyponatremia require additional treatment, which includes fluid restriction and intravenous sodium chloride and/or furosemide.[9]

In some situations, it may be necessary to continue treatment with the drug that is causing the SIADH.[27] In such cases, treatment such as fluid restriction, sodium chloride and diuretics, or demeclocycline may be required to reduce the tendency of hyponatremia.[27]

Both demeclocycline and lithium carbonate can cause a state of nephrogenic DI by interfering with the renal action of ADH.[28] Both drugs interfere with the cellular action of ADH by preventing the formation of cyclic 3',5' adenosine monophosphate (cAMP) and the subsequent action of cAMP on the renal tubules.

In 1975, lithium carbonate was the only drug available to treat SIADH.[29] Although lithium carbonate was effective in reversing hyponatremia within 2 days, there was a gradual return of the hyponatremic state when the drug was discontinued.[30] A few months later, researchers reported the first study of the effect of prolonged treatment with demeclocycline (900 mg/day) in a patient with SIADH.[29] The results of this study suggested that the antibiotic may be of value in treating patients with chronic SIADH.

In 1978, researchers compared the effectiveness of demeclocycline vs lithium carbonate in treating 10 patients with chronic SIADH.[31] Initially, 3 of the patients who were treated with lithium carbonate (600-900 mg/day) for 3-5 days did not respond to treatment. Two of the 3 patients experienced adverse CNS symptoms (eg, confusion, disorientation, and paresthesia). When all of the patients were treated with demeclocycline (600-1200 mg/day), the drug was effective in restoring serum sodium concentration within 5-14 days without restricting water. In this study, serious adverse effects of demeclocycline were not noted. The researchers concluded that the antibiotic was superior to lithium carbonate in treating SIADH.[31]

Demeclocycline is not recommended for treatment of acute SIADH because its onset of action requires several days.[7] However, it is considered the drug of choice if pharmacologic management of SIADH is necessary.[14] The drug is administered in divided doses ranging from 600-1200 mg/day.[32] Since it takes several days to achieve maximal diuretic effects, the dose should not be increased for 3-4 days.

Renal function should be monitored if the patient is treated with demeclocycline on a regular basis.[32] Demeclocycline can cause reversible azotemia (uremia), but the drug should be stopped if there is an increase in the amount of urea and other nitrogenous wastes in the blood. Nephrotoxicity is a possible side effect, particularly in patients with cirrhosis.

Patients should be advised to avoid exposure to ultraviolet (UV) light because demeclocycline, a tetracycline, can induce photosensitivity. The drug should be administered 1 hour before or 2 hours after meals. Also, they should be advised that products containing aluminum, magnesium, iron, or calcium impair the absorption of demeclocycline.

In the future, AVP antidiuretic receptor antagonists that target specific AVP receptors in the kidney will hopefully make it easier and more effective to treat patients with chronic hyponatremia.[32]


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