Narrative Review
A Review of Drug-Induced Hyponatremia

https://doi.org/10.1053/j.ajkd.2008.03.004Get rights and content

Hyponatremia (defined as a serum sodium level < 134 mmol/L) is the most common electrolyte abnormality in hospitalized patients. Certain drugs (eg, diuretics, antidepressants, and antiepileptics) have been implicated as established causes of either asymptomatic or symptomatic hyponatremia. However, hyponatremia occasionally may develop in the course of treatment with drugs used in everyday clinical practice (eg, newer antihypertensive agents, antibiotics, and proton pump inhibitors). Physicians may not always give proper attention in time to undesirable drug-induced hyponatremia. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on serum sodium levels. Here, we review clinical information about the incidence of hyponatremia associated with specific drug treatment and discuss the underlying pathophysiologic mechanisms.

Section snippets

Pathogenetic Aspects of Hyponatremia

Hyponatremia is ascribed to either water retention or (less often) loss of effective solute (sodium plus potassium) in excess of water. Because the capacity for water excretion normally is so great, retention of water resulting in hyponatremia takes place only in the presence of conditions that impair renal excretion of water. An exception to this rule is primary polydipsia, in which the excessive water intake can overwhelm even normal excretory capacity. Given that suppression of arginine

Drug-Induced Hyponatremia

Hyponatremia related to drug treatment can be caused by dozens, perhaps hundreds, of medications. Because hyponatremia can have many other causes, the diagnosis of drug-induced hyponatremia can easily be overlooked.

As shown in evidence from small studies and case reports, drugs may cause hyponatremia by affecting sodium homeostasis and water homeostasis. Clinical information about the incidence and pathophysiological process of hyponatremia of the most commonly offending agents is presented

Concluding Remarks

Hyponatremia occasionally may develop in the course of treatment with drugs used in everyday clinical practice (eg, newer antihypertensive agents, antibiotics, and PPIs). It should be noted that patients may receive complex drug regimens (eg, patients with diabetes mellitus) containing several candidates as the cause of hyponatremia. Discontinuation of treatment with these agents and avoidance of readministration is fully warranted. It is recommended that patients with acute severely

Acknowledgements

Support: None.

Financial Disclosure: None.

References (94)

  • L.L. Shepherd et al.

    Hyponatremia and seizures after intravenous administration of desmopressin acetate for surgical hemostasis

    J Pediatr

    (1989)
  • R.J. Anderson et al.

    Hyponatremia: A prospective analysis of its epidemiology and the pathogenetic role of vasopressin

    Ann Intern Med

    (1985)
  • A.I. Arieff et al.

    Neurological manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes

    Medicine (Baltimore)

    (1976)
  • P.A. Gross et al.

    The chartered unchartered waters of hyponatremia

    Kidney Int Suppl

    (1987)
  • A.I. Arieff

    Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women

    N Engl J Med

    (1986)
  • T. Berl

    Treating hyponatremia: Damned if we do and damned if we don't

    Kidney Int

    (1990)
  • S.J. Ellis

    Severe hyponatraemia: Complications and treatment

    QJM

    (1995)
  • S.M. Lauriat et al.

    The hyponatremic patient: Practical focus on therapy

    J Am Soc Nephrol

    (1997)
  • A. Spital

    Diuretic-induced hyponatremia

    Am J Nephrol

    (1999)
  • C.M. Byatt et al.

    Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions

    J R Soc Med

    (1990)
  • G. Liamis et al.

    Uric acid homeostasis in the evaluation of diuretic-induced hyponatremia

    J Investig Med

    (2007)
  • E. Friedman et al.

    Thiazide-induced hyponatremiaReproducibility by single dose rechallenge and an analysis of pathogenesis

    Ann Intern Med

    (1989)
  • O.S. Ashouri

    Severe diuretic-induced hyponatremia in the elderly

    A series of eight patients: Arch Intern Med

    (1986)
  • M. Abramow et al.

    Clinical aspects and pathophysiology of diuretic-induced hyponatremia

    Adv Nephrol Necker Hosp

    (1984)
  • B.A. Clark et al.

    Increased susceptibility to thiazide-induced hyponatremia in the elderly

    J Am Soc Nephrol

    (1994)
  • C.A. Pinnock

    Hyponatraemia associated with hydrochrorothiazide treatment

    Br Med J

    (1978)
  • M. Chapman et al.

    Hyponatremia and hypokalemia due to indapamide

    MJA

    (2002)
  • M.H. Luzecky et al.

    The syndrome of inappropriate secretion of antidiuretic hormone associated with amitriptyline administration

    South Med J

    (1974)
  • W.L. ten Holt et al.

    Severe hyponatremia during therapy with fluoxetine

    Arch Intern Med

    (1996)
  • C. Jackson et al.

    SIADH associated with fluoxetine and sertraline therapy

    Am J Psychiatry

    (1995)
  • B.A. Liu et al.

    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

    (1996)
  • S. Jacob et al.

    Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults

    Ann Pharmacother

    (2006)
  • K.L. Movig et al.

    Association between antidepressant drugs and hyponatremia: A case-control study

    Br J Clin Pharmacol

    (2002)
  • J.C. Peterson et al.

    Inappropriate antidiuretic hormone secondary to a monamine oxidase inhibitor

    JAMA

    (1978)
  • F.M. Vincent et al.

    Antidiuretic hormone syndrome and thioridazine

    Ann Intern Med

    (1978)
  • K.J. Rao et al.

    Water intoxication and thioridazine (Mellaril)

    Ann Intern Med

    (1975)
  • V. Peck et al.

    Haloperidol-induced syndrome of inappropriate secretion of antidiuretic hormone

    Clin Pharmacol Ther

    (1979)
  • A.E. Meinders et al.

    The antidiuretic action of carbamazepine in man

    Clin Sci Mol Med

    (1974)
  • P.W. Gold et al.

    Carbamazepine diminishes the sensitivity of the plasma arginine vasopressin response to osmotic stimulation

    J Clin Endocrinol Metab

    (1983)
  • K.M. Flegel et al.

    Inappropriate antidiuresis during carbamazepine treatment

    Ann Intern Med

    (1977)
  • T. Van Amelsvoort et al.

    Hyponatremia associated with carbamazepine and oxcarbazepine therapy: A review

    Epilepsia

    (1994)
  • G.M. Kuz et al.

    Carbamazepine-induced hyponatremia: Assessment of risk factors

    Ann Pharmacother

    (2005)
  • B. Holtschmidt-Taschner et al.

    Hyponatremia-induced seizure during carbamazepine treatment

    World J Biol Psychiatry

    (2007)
  • X. Dong et al.

    Hyponatremia from oxcarbazepine and carbamazepine

    Neurology

    (2005)
  • K. Ikeda et al.

    Valproate related syndrome of inappropriate secretion of antidiuretic hormone (SIADH)—A case report

    Rinsho Shinkeigaku

    (1994)
  • G.L. Robertson et al.

    Vincristine neurotoxicity and abnormal secretion of antidiuretic hormone

    Arch Intern Med

    (1973)
  • T.S. RaviKumar et al.

    The syndrome of inappropriate antidiuretic hormone secretion secondary to vinblastine-bleomycin therapy

    J Surg Oncol

    (1983)

    • Cited by (343)

    • Disorders of Sodium

      2023, Emergency Medicine Clinics of North America

    • Age-Associated Abnormalities of Water Homeostasis

      2023, Endocrinology and Metabolism Clinics of North America

    • An adolescent with adnexal torsion presenting with severe hyponatremia

      2023, Journal of Pediatric Surgery Case Reports

    • Hyponatremia is associated with unfavorable outcomes after reperfusion treatment in acute ischemic stroke

      2024, European Journal of Neurology

    • Endocrine changes, endocrine diseases in the elderly

      2024, Orvosi Hetilap

    • The psychedelic future of post-traumatic stress disorder treatment

      2024, Current Neuropharmacology
    View all citing articles on Scopus

    Originally published online as doi:10.1053/j.ajkd.2008.03.004 on May 8, 2008.

    View full text
    Copyright © 2008 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.