Medications that cause water retention
Pro Research Analysisby 
Searched over 200M research papers
Medications That Cause Water Retention
Water retention, also known as fluid retention or edema, can be a side effect of various medications. This article explores the different classes of drugs that are known to cause water retention, the mechanisms behind this side effect, and the clinical implications.
Antidiabetic Medications and Water Retention
Sulfonylureas
Sulfonylureas, such as chlorpropamide, are known to potentiate the antidiuretic action of arginine vasopressin (AVP), leading to water retention and hyponatremia. Chlorpropamide increases the density of AVP V2 receptors in the kidneys, impairing water excretion2 5. Other sulfonylureas like methanesulfonamide and tolbutamide also exhibit water-retaining properties, whereas glipizide, glibenclamide, acetohexamide, and tolazamide do not5.
Thiazolidinediones
Thiazolidinediones (TZDs), such as pioglitazone, are another class of antidiabetic drugs associated with fluid retention. These drugs activate peroxisome proliferator-activated receptor gamma (PPARγ), which has salt-retaining effects on the nephron, leading to edema and potentially exacerbating congestive heart failure (CHF)4 9. Pioglitazone has been shown to increase the expression of sodium and water channels in the kidney, further contributing to fluid retention9.
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
While SGLT2 inhibitors generally cause osmotic diuresis and natriuresis, they can also lead to elevated serum potassium and magnesium concentrations. However, they are less likely to cause fluid retention compared to other antidiabetic drugs5 9.
Psychotropic Medications
Antipsychotics and Antidepressants
Several psychotropic drugs, including antipsychotics like olanzapine and antidepressants such as sertraline, can cause water retention by decreasing renal clearance. This is often due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH)3 6 10. Olanzapine, for instance, has been associated with water retention, hypertension, and preterm preeclampsia in pregnant women6.
Lithium
Lithium, commonly used for bipolar disorder, can interfere with renal water resorption, leading to nephrogenic diabetes insipidus and subsequent water retention10.
Other Medications
Desmopressin
Desmopressin, a synthetic vasopressin receptor agonist, is used to treat conditions like diabetes insipidus. However, it can lead to significant water retention and hyponatremia if fluid intake is not properly managed3 7.
Chemotherapeutic Agents
Certain chemotherapeutic agents, such as vincristine and ifosfamide, are known to cause SIADH, leading to water retention and hyponatremia3.
Thiazide Diuretics
Although primarily used to treat hypertension and edema, thiazide diuretics can paradoxically cause water retention and hyponatremia through mechanisms involving aquaporin-2 upregulation in the kidneys3.
Conclusion
Various medications, particularly antidiabetic and psychotropic drugs, can cause water retention through different mechanisms, including the potentiation of antidiuretic hormone action and the upregulation of water and sodium channels in the kidneys. Understanding these mechanisms is crucial for managing and mitigating the side effects associated with these medications. Clinicians should be vigilant in monitoring patients on these drugs for signs of water retention and adjust treatment protocols accordingly.
Sources and full results
Most relevant research papers on this topic
Drug-induced dilutional hyponatremia.
Water-retaining drugs can cause serious water retention and dilutional hyponatremia, affecting the maintenance of water balance in humans.
Highly CitedWater retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors.
Oral chlorpropamide increases the density of renal papillary arginine vasopressin receptors, leading to impaired water excretion without altering plasma arginine vasopressin levels.
RCT
Animal StudyPathophysiology of Drug-Induced Hyponatremia
Drug-induced hyponatremia is mainly caused by nephrogenic antidiuresis, with psychotropic agents, anticancer chemotherapeutic agents, and thiazide diuretics being the major causes.
Rigorous JournalDoes Thiazolidinedione therapy exacerbate fluid retention in congestive heart failure?
Thiazolidinedione therapy may not worsen fluid retention in congestive heart failure patients, as recent studies challenge the common belief that it does.
Literature ReviewEffects of water-sodium balance and regulation of electrolytes associated with antidiabetic drugs.
Antidiabetic drugs can affect water-sodium balance and electrolyte regulation, with some causing water retention, others reducing serum magnesium, and others affecting blood pressure and plasma volume.
Case report: Olanzapine-associated water retention, high blood pressure, and subsequent preterm preeclampsia
Olanzapine use during pregnancy can lead to water retention, hypertension, and preterm preeclampsia, making it the first case of its association in literature.
Case ReportUse of Desmopressin in Hyponatremia: Foe and Friend
Desmopressin should not be withheld in patients with neurologic symptoms, as it can help minimize water excretion during hyponatremia correction and prevent overly rapid "autocorrection" of serum sodium levels.
Rigorous JournalSalicylate poisoning complicated by fluid retention.
Mannitol is an effective diuretic for treating acute symptoms of fluid retention in salicylate poisoning, but strict fluid restriction is necessary for prompt diuresis.
Case ReportEffects of SGLT2 inhibitor ipragliflozin alone and combined with pioglitazone on fluid retention in type 2 diabetic mice with NASH.
Ipragliflozin alone or combined with pioglitazone may be a potential treatment option for type 2 diabetes with NASH without fluid retention as a side effect.
Non-RCTAnimal StudyRigorous Journal