Urethral Syndrome Medication

  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
Updated: Jan 21, 2015

Medication Summary

The choice of medical therapy in urethral syndrome is determined by the patient's predominant symptoms and probable etiology. Determination of the optimum regimen often involves a combination of medications chosen through a process of trial and error. Even when an optimum medical therapy is determined, symptoms may wax and wane, requiring further adjustment of the medical regimen. All possible infectious etiologies should be evaluated and treated prior to initiation of additional medications.



Class Summary

Hormone replacement therapy improves mucosal quality in postmenopausal women and may improve resistance to external irritants.

Conjugated estrogens (Premarin)


Hormone replacement therapy improves mucosal quality in postmenopausal women and may improve resistance to external irritants.


Tricyclic antidepressants

Class Summary

In low doses, these agents are effective at relieving chronic pain by interfering with nerve activity. They are commonly prescribed for several chronic pain conditions, including irritable bowel syndrome (IBS) and fibromyalgia. Imipramine (Tofranil) and a host of others may be options to consider when prescribing TCAs for chronic pain. However, amitriptyline (Elavil) is the most extensively tested medication of this type for chronic pain.

Amitriptyline (Elavil)


In low doses, effective for relieving chronic pain by interfering with nerve activity. Commonly prescribed for several chronic pain conditions, including IBS and fibromyalgia.



Class Summary

Phenazopyridine hydrochloride (Pyridium) is a prescription pain reliever that works by soothing the bladder lining when excreted into urine. It is often prescribed for temporary pain relief after surgery, cystoscopy, or catheterization. It is not prescribed for long-term use to control interstitial cystitis (IC) symptoms because it can build up in the body and cause harmful effects. Pyridium colors the urine a very noticeable orange, and care must be taken to prevent staining of undergarments. Patients who wear contact lenses should be aware that lenses can also become stained. Uristat is a nonprescription version of phenazopyridine hydrochloride (Pyridium).

Urised, a blend of atropine, hyoscyamine, methenamine, methylene blue, phenyl salicylate, and benzoic acid, acts as an anesthetic and antispasmodic and inhibits bacterial growth. Tolterodine tartrate (Detrol) also acts as both an antispasmodic and anesthetic.

Topical 1-2% lidocaine jelly has been used by some patients for external urethral irritation.

Phenazopyridine (Pyridium, Urodine, Urogesic)


Azo dye excreted in urine. Exerts a topical analgesic effect on urinary tract mucosa. Compatible with antibacterial therapy and can help relieve pain and discomfort before antibacterial therapy controls infection.

Used for symptomatic relief of pain, burning, urgency, frequency, and other discomforts arising from irritation of lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of sounds or catheters. Analgesic action may reduce or eliminate need for systemic analgesics or narcotics. Uristat is a nonprescription version of phenazopyridine (Pyridium).



Class Summary

These agents decrease the contractility of bladder muscle. Multiple formulations are marketed, including flavoxate (Urispas), hyoscyamine sulfate (Anaspaz), trospium chloride (Sanctura), solifenacin succinate (Vesicare), darifenacin hydrobromide (Enablex), oxybutynin chloride (Ditropan), oxybutynin chloride ER (Ditropan XL), Urised (blend of atropine, hyoscyamine, methenamine, methylene blue, phenyl salicylate, and benzoic acid that acts as an antispasmodic and anesthetic and inhibits bacterial growth), and tolterodine tartrate (Detrol), which is also both an antispasmodic and anesthetic.

Tizanidine HCL (Zanaflex)


Centrally acting α2-adrenergic agonist that presumably reduces spasticity by increasing presynaptic inhibition of motor neurons.

A single dose of 8 mg tizanidine reduces muscle tone in patients with spasticity for a period of several hours. The effect peaks at approximately 1-2 h and dissipates between 3-6 h. Effects are dose-related.

Oxybutynin (Ditropan, Ditropan XL); oxybutynin transdermal (Oxytrol, Gelnique)


Decreases contractility of bladder muscle by anticholinergic action.

Flavoxate (Urispas)


Used for symptomatic relief of dysuria, urgency, nocturia, and incontinence as may occur in cystitis, prostatitis, urethritis, and urethrocystitis/urethrotrigonitis. Acts as anticholinergic and exerts direct effect on muscle. Counteracts smooth muscle spasms of urinary tract.

Hyoscyamine (Anaspaz)


Anticholinergic agents with antispasmodic properties used for the treatment of urge incontinence. Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which in turn has antispasmodic effects. Absorbed well by the GI tract. Food does not affect absorption. Available in sublingual form (Levsin SL), conventional tablets (Levsin), extended-release capsules (Levsinex Timecaps, Cystospaz-M), and extended-release tablets (Levbid).

Trospium (Sanctura, Sanctura XR)


Quaternary ammonium compound that elicits antispasmodic and antimuscarinic effects. Antagonizes acetylcholine effect on muscarinic receptors. Parasympathetic effect reduces smooth muscle tone in the bladder. Indicated to treat symptoms of overactive bladder (eg, urinary incontinence, urgency, frequency).

Solifenacin succinate (Vesicare)


Elicits competitive muscarinic receptor antagonist activity, which results in anticholinergic effect and inhibition of bladder smooth muscle contraction. Indicated for overactive bladder with symptoms of urgency, frequency, and urge incontinence.

Darifenacin (Enablex)


Extended-release product eliciting competitive muscarinic receptor antagonistic activity. Reduces bladder smooth muscle contractions. Has high affinity for M3 receptors involved in bladder and GI smooth muscle contraction, saliva production, and iris sphincter function. Indicated for overactive bladder with symptoms of urge incontinence, urgency and frequency. Swallow whole; do not chew, divide, or crush.

Tolterodine tartrate (Detrol)


Competitive muscarinic receptor antagonist for overactive bladder. Differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands. Exhibits high specificity for muscarinic receptors. Has minimal activity or affinity for other neurotransmitter receptors and other potential targets such as calcium channels. In clinical studies, mean decrease in urge incontinence episodes was 50% and the mean decrease in urinary frequency was 17%.

Fesoterodine (Toviaz)


Competitive muscarinic receptor antagonist. Antagonistic effect results in decreased bladder smooth muscle contractions. Indicated for symptoms of overactive bladder (eg, urinary urge incontinence, urgency, and frequency). Available as 4- or 8-mg extended-release tab.


Alpha-adrenergic blocking Agents

Class Summary

Alpha blockade can help relieve increased muscle tone at the bladder neck and proximal urethra in men and women and provide relief of symptoms in some. Include prazosin (Minipress) and the more specific alpha-1 blockers doxazosin (Cardura), tamsulosin (Flomax), alfuzosin hydrochloride (Uroxatral), and terazosin (Hytrin).

Terazosin (Hytrin)


Reduces muscle tone at bladder neck and proximal urethra by blocking alpha receptors.

Prazosin (Minipress)


Decreases internal sphincter tone and can improve flow of urine, improving emptying of bladder. If need to increase dose, give first dose of each increment at bedtime to reduce syncopal episodes. Although doses greater than 20 mg/d usually do not increase efficacy, a few patients may benefit from dose as high as 40 mg/d.

Doxazosin (Cardura)


Selective inhibitor of alpha1-adrenergic receptors. Blockade of alpha1-adrenergic receptors in the bladder neck decreases outflow resistance.

Tamsulosin (Flomax)


Selective alpha1-antagonist for treatment of BPH.

Alfuzosin (Uroxatral)


Alpha I-blocker of adrenoceptors in prostate. Blockade of adrenoceptors may cause smooth muscles in bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.



Class Summary

Increased tone of pelvic floor may respond to pharmacological therapy with sedative effects.

Diazepam (Valium, Diazepam Intensol)


Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

Contributor Information and Disclosures

Martha K Terris, MD, FACS Professor, Department of Surgery, Section of Urology, Director, Urology Residency Training Program, Medical College of Georgia at Augusta University; Professor, Department of Physician Assistants, Medical College of Georgia School of Allied Health; Chief, Section of Urology, Augusta Veterans Affairs Medical Center

Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, Society of Women in Urology

Disclosure: Nothing to disclose.


Christopher A Hathaway, MD, PhD Urologist, Yankton Medical Clinic

Christopher A Hathaway, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Urological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Mark Jeffrey Noble, MD Consulting Staff, Urologic Institute, Cleveland Clinic Foundation

Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, SWOG

Disclosure: Nothing to disclose.

Chief Editor

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, Tennessee Medical Association, Sexual Medicine Society of North America, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Repros.


Subbarao V Cherukuri, MD Consulting Staff, Department of Urology, St Joseph Regional Health Center

Subbarao V Cherukuri, MD is a member of the following medical societies: American Urological Association and Ohio State Medical Association

Disclosure: Nothing to disclose.

  1. Bogart LM, Suttorp MJ, Elliott MN, Clemens JQ, Berry SH. Validation of a quality-of-life scale for women with bladder pain syndrome/interstitial cystitis. Qual Life Res. 2011 Dec 7. [Medline].

  2. Ichim G, Fufezan O, Farcau M, Asavoaie C, Pop D, Staticescu S, et al. Clinical, imaging and cystometric findings of voiding dysfunction in children. Med Ultrason. 2011 Dec. 13(4):277-82. [Medline].

  3. Palleschi G, Carbone A, Ripoli A, Silvestri L, Petrozza V, Zanello PP, et al. A prospective study to evaluate the efficacy of cistiquer in improving lower urinary tract symptoms in females with urethral syndrome. Minerva Urol Nefrol. 2014 Jul 18. [Medline].

  4. Costantini E, Zucchi A, Del Zingaro M, Mearini L. Treatment of urethral syndrome: a prospective randomized study with Nd:YAG laser. Urol Int. 2006. 76(2):134-8. [Medline].

  5. Chen YL, Ha LF, Cen J, et al. [Comparative observation on therapeutic effects of electroacupuncture and manual acupuncture on female urethral syndrome]. Zhongguo Zhen Jiu. 2005 Jun. 25(6):425-6. [Medline].

  6. Cruz F, Silva C. Botulinum toxin in the management of lower urinary tract dysfunction: contemporary update. Curr Opin Urol. 2004 Nov. 14(6):329-34. [Medline].

  7. Allen TD. Commentary on dysfunctional abnormalities of the urinary tract. Urol Clin North Am. 1980 Jun. 7(2):357-9. [Medline].

  8. Barrett DM, Wein AJ, Barrett DM, Wein AJ. Voiding dysfunction: Diagnosis, classification, and management. Gillenwater JY, Grayhack JT, Howards SS, eds. Adult and Pediatric Urology. 2nd ed. St. Louis, Mo: Mosby-Year Book; Vol 1: 1073-5.

  9. Bogart LM. Berry SH. Clemens JQ. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. J. Urol. Feb. 2007. 177(2):450-6. [Medline].

  10. Gerstenberg TC, Lykkegaard Nielsen M, Lindenberg J. Spastic striated external sphincter syndrome imitating recurrent urinary tract infection in females. Effect of long-term alpha- adrenergic blockade with phenoxybenzamine. Eur Urol. 1983. 9(2):87-92. [Medline].

  11. Kaur H, Arunkalaivanan AS. Urethral pain syndrome and its management. Obstet Gynecol Surv. May 2007. 62(5):348-51. [Medline].

  12. Lemack GE, Foster B, Zimmern PE. Urethral dilation in women: a questionnaire-based analysis of practice patterns. Urology. 1999 Jul. 54(1):37-43. [Medline].

  13. Schmidt RA. The urethral syndrome. Urol Clin North Am. 1985 May. 12(2):349-54. [Medline].

  14. Sugaya K, Nishijima S, Oda M, et al. Transabdominal vesical sonography of urethral syndrome and stress incontinence. Int J Urol. 2003 Jan. 10(1):36-42. [Medline].

  15. Voelzke BB, Breyer BN, McAninch JW. Blunt pediatric anterior and posterior urethral trauma: 32-year experience and outcomes. J Pediatr Urol. 2011 Jun 9. [Medline].

  16. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome. J Urol. 2001 Dec. 166(6):2226-31. [Medline].

  17. Wesselmann U, Burnett AL, Heinberg LJ. The urogenital and rectal pain syndromes. Pain. 1997 Dec. 73(3):269-94. [Medline].

  18. Zhang D, Xu Z. [Female prostatitis]. Zhonghua Nan Ke Xue. 2004 Jul. 10(7):547-8, 550. [Medline].

Medscape Consult