How does hydroxyzine affect bladder function?

How Hydroxyzine Affects Bladder Function

Hydroxyzine impairs bladder emptying through its anticholinergic properties, which can cause urinary retention, inhibition of micturition, and increased post-void residuals, particularly in elderly patients and those with pre-existing voiding dysfunction. 1

Anticholinergic Effects on the Bladder

Hydroxyzine, as a first-generation antihistamine, exerts significant anticholinergic activity that directly impacts bladder function through multiple mechanisms:

Direct Bladder Effects

• Urinary retention and inhibition of micturition are well-documented anticholinergic effects of hydroxyzine, occurring through blockade of muscarinic receptors in the detrusor muscle. 1

• The anticholinergic properties of agents like hydroxyzine are important for bladder control in certain contexts (such as overactive bladder), but these same properties cause impaired bladder emptying when not desired. 2

• Hydroxyzine should have its dose halved in moderate renal impairment and should be avoided entirely in severe renal or hepatic impairment due to accumulation and enhanced anticholinergic burden. 1

Cumulative Anticholinergic Burden

• While moderate anticholinergic loads (anticholinergic risk scale scores 0-4) may not significantly affect post-void residual volumes, very high anticholinergic burdens (scores ≥5) significantly increase post-void residuals (127.5 ml vs. 68.3 ml, p<0.01) and maximum cystometric capacity. 3

• Combining hydroxyzine with other anticholinergic medications substantially increases the risk of urinary retention, constipation, dry mouth, and cognitive impairment. 4

High-Risk Populations

Elderly Patients

• Older adults are particularly vulnerable to hydroxyzine's anticholinergic effects on the bladder, with increased risk of urinary retention, falls (potentially triggered by urgency or nocturia), and cognitive impairment. 1, 4

• The American College of Physicians specifically lists hydroxyzine in deprescribing tables for older adults due to broad muscarinic receptor blockade. 4

• Hydroxyzine has an elimination half-life of approximately 29 hours in elderly patients, with its active metabolite cetirizine having a similar half-life of 25 hours, leading to prolonged anticholinergic effects. 5

Patients with Pre-existing Voiding Dysfunction

• Patients with benign prostatic hyperplasia, neurogenic bladder, or baseline elevated post-void residuals are at substantially higher risk for acute urinary retention when taking hydroxyzine. 1

• In children with dysfunctional voiding (incomplete bladder emptying), anticholinergic agents that relax the detrusor muscle can worsen emptying efficiency. 1

Paradoxical Therapeutic Use in Interstitial Cystitis

Despite its anticholinergic effects that impair normal voiding, hydroxyzine has a specific role in interstitial cystitis/bladder pain syndrome (IC/BPS):

• Hydroxyzine improves IC/BPS symptoms through mechanisms beyond simple antihistamine activity, including inhibition of neurogenic bladder mast cell activation. 1, 6

• The 2022 American Urological Association guidelines rate hydroxyzine as Grade C evidence for IC/BPS treatment, noting that patients with systemic allergies may be more likely to respond. 1

• Hydroxyzine reduces carbachol-induced bladder mast cell activation by 25-34%, an effect not seen with other antihistamines like diphenhydramine, suggesting a unique mechanism independent of H1-receptor blockade. 6

• In clinical practice, hydroxyzine and pentosan polysulfate are the preferred IC/BPS medications, with 40% of IC/BPS patients receiving hydroxyzine prescriptions. 7

Critical Clinical Caveats

• Avoid hydroxyzine in patients with narrow-angle glaucoma unless specifically approved by an ophthalmologist, as anticholinergic effects can precipitate acute angle closure. 1

• Hydroxyzine is contraindicated in early pregnancy and should be avoided in severe hepatic impairment where sedation may precipitate coma. 1

• The combination of sedation, anticholinergic effects, and prolonged half-life creates particular risk for nighttime falls in elderly patients attempting to void. 1, 4

• When hydroxyzine is used at bedtime (10-50 mg) for conditions like urticaria, anticholinergic effects persist well into the following day due to the 29-hour half-life, potentially affecting daytime voiding function. 1, 5