Urethral Pain Syndrome

The etiology of urethral pain syndrome (UPS) is unknown. Historically, urethral stenosis was believed to be the cause, but a diagnosis of urethral stenosis, along with the serial urethral dilations used to treat the condition, is appropriate in only a very small minority of patients.

Unfortunately, a unified alternative etiology for UPS has not been identified; instead, it is thought that the syndrome may be the result of several complex mechanisms. Currently theorized etiologies include the following[2, 3, 4] :

• Hormonal imbalances
• Inflammation of Skene glands and the paraurethral glands (the "female prostate")
• A reaction to certain foods
• Environmental chemicals (eg, douches, bubble bath, soaps, contraceptive gels, condoms)
• Estrogen deficiency
• Low-grade infection
• Early painful bladder syndrome (interstitial cystitis)
• Urethral, spasm
• Urethral stenosis
• Hypersensitivity following urinary tract infection 
• Traumatic sexual intercourse
• Dysfunction of the pelvic floor musculature

However, there is little statistical evidence to support those postulated causes.[3, 2, 4]  Other authors hypothesize that dysfunction of the mucosal barrier layer leads to inflammatory changes in the bladder urothelium that allow solutes in the urine to seep through the epithelial layer, which results in inflammatory changes, spasm, and fibrosis.[3, 5, 6]

Regardless of the initial pain-causing event, patients with UPS have both involuntary spasms and voluntary tightening of the pelvic musculature during the painful episode, which, in addition to any residual irritant or reinjury, starts a vicious circle of worsening dysfunction of the pelvic floor musculature. In many cases, the original cause of the pain has healed, but the pelvic floor dysfunction persists and is worsened by the patient’s anxiety and frustration with the condition.

The exact incidence of urethral pain syndrome is unknown because of a lack of consensus in diagnosis and overlap with other conditions.[3]  

Urethral pain syndrome is more common in females than in males, and is more common in white women in westernized societies than in women of other races or groups.[7] Patients diagnosed with urethral syndrome are typically 13-70 years of age.

The urinary hesitancy, frequency, and dysuria that characterizes urethral pain syndrome can greatly impair quality of life. In many affected individuals, the unrelenting symptoms lead to depression, anxiety, or other secondary psychological morbidities; the coexistence of such morbidities has prompted many physicians to categorize urethral pain syndrome as a psychosomatic illness.

Symptoms of urethral pain syndrome usually improve slowly as the patient ages, but the problem may be lifelong. Many patients with urethral pain syndrome seek out multiple physicians in their quest to secure symptom relief and are at risk for polypharmacy, narcotic abuse, and antibiotic resistance.

It is important to remind patients that the treatment process for urethral pain syndrome is a trial and error of different therapies.  It may take time to find what works effectively for a particular patient.

Patients diagnosed with urethral pain syndrome are typically female and aged 13-70 years. Patients report suprapubic discomfort, dysuria, and urinary frequency. The history is important, as the diagnosis of urethral syndrome is one of exclusion. A history of smoking or gross hematuria should hasten further evaluation to rule out bladder cancer. Most patients focus on urinary symptoms, but other aspects of the patient’s history and symptoms must also be evaluated.

Urinary symptoms

Urinary symptoms in urethral pain syndrome are as follows:

• The urinary frequency is typically every 30-60 minutes during the daytime; nocturia is minimal

• The suprapubic discomfort is neither constant nor as severe as in interstitial cystitis; the pain may be relieved by voiding; at night, the pain is not severe enough to disturb sleep

• Dysuria is often described as a sensation of constant urethral irritation rather than the searing discomfort with urination that is reported by patients with an active lower urinary tract infection

The following questionnaires may be useful for evaluating urinary symptoms:

• International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS; derived from the Bristol Female Lower Urinary Tract Symptoms - Short Form Questionnaire) ^[8]
• Urogenital Distress Inventory (UDI-6)
• International Prostate Symptom Score (I-PSS) 

Other pelvic symptoms

Associated bowel symptoms, menstrual complaints, and dyspareunia may suggest pelvic floor muscle dysfunction. Irregular or excessive menstruation may indicate a gynecologic abnormality and may warrant referral for gynecologic assessment, especially in postmenopausal women. Timing of the last menstrual cycle may also suggest pregnancy as an etiology for urinary frequency.

Sexual history

Contraceptive methods (many contraceptive gels and condoms are irritative) and sexual activity (eg, rough intercourse, prolonged oral sex, intercourse in a heavily chlorinated hot tub or in a shower using bath soap as a lubricant) may result in urethral irritation. A history of sexual abuse has been linked with pelvic floor muscle dysfunction.

Habits

Prolonged driving in vehicles with limited shock-absorbing mechanisms (eg, buses, trucks), horseback riding, and long-distance biking can result in urethral irritation. These are more commonly the etiology in men with urethral pain syndrome than in women. Women may acquire symptoms from wearing tight thong underwear or blue jeans (especially when worn without underwear).

Medications and past medical history

Diuretics can cause urinary frequency, as can lithium if secondary diabetes insipidus develops. Cholinergic cold and sinus preparations increase the tone of the bladder neck and proximal urethra and can cause symptoms in some individuals.

Prior medical conditions are also important, especially if they were treated with pelvic surgery or radiation therapy.

Neurologic symptoms

Frequent falls, limping, or other neurologic symptoms may suggest a central nervous system abnormality. Multiple sclerosis has a propensity to affect women at the same age as urethral pain syndrome, and vague bladder symptoms are often the initial presenting symptom of this disease.

A diagnosis of urethral pain syndrome is made after exclusion of infection and local vaginal conditions such as genital herpes and variants of vaginitis. Physical examination findings are usually unremarkable; however, genital examination may reveal a cystocele or atrophic urethritis.

Pelvic examination

Initially, the inner thighs and outer labia should be inspected for sensation (sharp vs dull end of a broken cotton-tipped swab works well). Localized hypersensitivity may indicate shingles (herpes zoster), even in the absence of cutaneous manifestations. Global hypersensitivity or hyposensitivity may suggest a neurologic condition.

An initial inspection should be performed to evaluate for ulcers or inflammation caused by herpes, yeast, or other infectious agents. Standard culture swabs and specialized swabs for viral, gonococcal, and chlamydia cultures should be available so that specimens can be obtained at the time of the examination, if indicated.

The labia and other external genitalia should be carefully inspected for erythematous patches or white, heaped-up epithelium, which may indicate condyloma or squamous cell carcinoma. Careful examination of the urethra for any lesions is important to exclude urethral prolapse, urethral caruncle, or transitional cell carcinoma. The health of the mucosal tissues should be noted; dry, thin, pale mucosa suggests atrophy, which is usually hormonal in origin.

The wall shared by the anterior vagina and the posterior urethra should be carefully palpated to exclude masses or stones. Expressed purulent material or a compressible mass detected during this maneuver suggests a urethral diverticulum.

The patient should be asked to perform a Valsalva maneuver or cough to assess for urethrocele, cystocele, or rectocele.

A speculum examination should be performed to rule out foreign bodies (eg, retained tampons), cervicitis, or other lesions. A Papanicolaou test (Pap smear) should be performed if the patient has not had one in the past year. Many patients have generalized pelvic floor dysfunction and tight pelvic musculature, causing them to experience difficulty with a speculum examination. A pediatric speculum should be available for such situations.

The presence of an intact anal wink should be confirmed as part of the pelvic/neurologic examination, and a rectal examination should be performed to assess rectal tone and the presence of any lesions that might be contributing to the patient's symptoms, such as masses, rectal/perianal fissures, ulcers, or hemorrhoids.

Abdominal examination

The presence of any masses or tenderness should be noted. Patients with urethral pain syndrome may experience mild-to-moderate suprapubic discomfort, but the pain is not as dramatic as that observed in patients with interstitial cystitis. Uterine enlargement may indicate pregnancy, fibroids, or malignancy and should prompt a pregnancy test, if appropriate, and referral to a gynecologist.

Tenderness localized to the pubic symphysis may indicate osteitis pubis, particularly in patients receiving systemic steroid therapy or those with a history of radiation therapy.

Neurologic examination

Reflexes, symmetry of strength and sensation, and balance should all be assessed to evaluate for intracranial or spinal cord lesions, lumbar stenosis or disc herniation, or neurodegenerative diseases. For example, multiple sclerosis has a propensity to strike women at the same age as urethral syndrome, and vague bladder symptoms are often the initial presenting feature of this disease.

A urine sample should be collected for urinalysis and urine culture. Urinalysis may show up to three red blood cells (RBCs) per high-power field. More pronounced microhematuria or any history of gross hematuria should prompt (1) cystoscopy to evaluate the bladder and (2)  computed tomography (CT) scanning to assess the upper urinary tract. Urine cytology may be considered if cystoscopy results are abnormal or for suspicion of bladder cancer. Elevated glucose levels on urinalysis results may suggest uncontrolled diabetes as an etiology of the urinary frequency.

Although some urologists feel that a bacterial colony count of 100/mL may be significant, especially when accompanied by symptoms, colony counts of 100,000/mL in a voided urine specimen (10,000/mL in men) confirms urinary tract infection in the presence of symptoms and should prompt treatment with antibiotics. Repeat urine cultures may be warranted for intermediate results.

Presence of the same bacteria on multiple urine cultures, even at low colony counts, may merit therapy. Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, and Lactobacillus species may be present at low colony counts in urine cultures, and although that usually represents vaginal colonization with these organisms, treatment is recommended to rule out urethral colonization, especially with Ureaplasma species.

Pap smear results may reveal cervical malignancy, and this test should be performed if the patient has not had one in the past year. Usually, this has been performed by the gynecologist who referred the patient to the urologist. If the patient has not seen a gynecologist, a referral should be made to rule out gynecologic causes of the discomfort.

A pregnancy test may be indicated in women in the appropriate age group with an enlarged uterus or history of irregular menstrual cycles. This is particularly true if radiographic evaluation is planned.

Vaginal swabs for routine and viral, chlamydial, and gonococcal culture may be indicated. Again, usually these studies have been performed by the gynecologist. Potassium hydroxide preparation of vaginal secretions helps assess for fungal infection and, as with other tests, has usually been performed by the gynecologist.

Kidney/bladder ultrasound may be considered to help rule out other urological causes if associated symptoms and history suggest them. Pelvic ultrasonography is used to visualize the bladder and bladder neck–trigone and to evaluate the reproductive organs for masses in women and evaluate for a prostatic abscess in men.

Further radiologic studies may be indicated in select patients. Magnetic resonance imaging (MRI) is emerging as possibly superior to cystography in the identification of urethral diverticula. In addition, MRI may be useful in the identification of pelvic floor hypertonicity (manifested as shortened levator, increased posterior puborectalis angles, and decreased puborectal distances), which may be suggestive of interstitial cystitis/bladder pain syndrome.[9, 10]

 

For suspicion of urethral diverticulum, cystography with a double-balloon catheter to occlude both the urethral opening and bladder neck may be performed. Urodynamic evaluation, including a cystometrogram and electromyelography of the urinary sphincter, uroflow, and determination of postvoid residual are performed to eliminate the possibility of a neurogenic unstable bladder, detrusor sphincter dyssynergia, or hyperactive pelvic floor musculature.

For suspicion of painful bladder syndrome (interstitial cystitis), cystourethroscopy with hydrodistention of the bladder under general anesthesia is diagnostic, revealing ulcerations or glomerulations and decreased bladder capacity in patients with interstitial cystitis. It also may be therapeutic in some patients with interstitial cystitis.

For suspicion of bladder pathology, cystoscopy under anesthesia also allows an assessment for bladder masses, stones, or chronic inflammation.

Bladder biopsy is used to rule out carcinoma in situ. Eosinophilia and mast cells in bladder biopsy samples support the diagnosis of interstitial cystitis.

The goal of treatment in urethral pain syndrome is to relieve the discomfort and urinary frequency. This often involves a trial-and-error approach that uses behavioral, dietary, and medical therapy. The urologist must gain the confidence of these patients and should provide assurance and encouragement throughout therapy.  

Medications include the following:

• Hormone replacement
• Anesthetics
• Antispasmodics
• Tricyclic antidepressants (TCAs)
• Muscle relaxants
• Alpha blockers
• Mucosa-protecting agents such as oral elmiron
• Local corticosteroids
• Antibiotics

Behavioral therapy, including biofeedback, meditation, and hypnosis has been used with some success. Biofeedback has the most promise in individuals whose symptoms are due to a failure to relax the pelvic musculature during voiding. Attempts at relaxation while undergoing electromyelography monitoring can help the patient retrain their muscles to allow them to void normally.

Dietary therapy is geared primarily at increasing urinary pH. Increased fluid intake has been suggested to decrease the potassium concentration in the urine.

A nationwide survey of Swedish clinics identified 19 methods in use for treatment of urethral pain syndrome, with local corticosteroids and local estrogens being the most common; in addition, more than half the clinics used antibiotics. The survey included public gynecology, urology, gynecologic oncology, and venereology clinics and one public general practice in every county in Sweden.[11]

Topical estrogen has been demonstrated to produce symptom improvement in postmenopausal women with urethral pain syndrome.[12]

Phillip et al propose that high concentrations of potassium in the urine have toxic effects on the muscles and nerves, providing an ideal environment for the growth of microbes; consequently, they advocate for the use of bactericidal broad-spectrum antibiotics.[3]  These authors also note that alpha blockers have been used with variable success in urethral pain syndrome, and postulate that these agents may work by decreasing urethral spasticity, which eliminates turbulence during voiding and allows the urethral mucosa to heal and regenerate the mucosal barrier.[3]

Palleschi and colleagues reported significant and comparable symptom improvement with the oral phytotherapeutic product CistiQuer versus intravesical gentamicin plus betamethasone in a randomized study of 60 women with urethral syndrome and trigonitis. The dropout rate and the incidence of infection were higher in the intravesical treatment group.[13]

Successful treatment of urethral pain syndrome with neuropathic medicines has been reported. The 31 study patients were given 300 mg/day gabapentin, titrated to 600 mg/day. In addition, sertraline was administered at 50 mg/day, titrated to 100 mg/day in four patients and increased to 200 mg/day in three patients. Significant improvement in symptoms and symptom-related anxiety was observed. Sertraline may also have had a positive impact by decreasing pain-related anxiety with its anxiolytic effect.[14]

Acupuncture and electroacupuncture have been used in China with some short-term benefits.[15]  However, the lack of adequate scientific data and expertise by Western physicians in the practice of acupuncture significantly hinder its widespread practice.

Botulinum toxin (OnabotulinumtoxinA) injections have shown some promise in treating urethral symptoms that occur with other dysfunctional voiding conditions.[16] However, studies have yet to be performed for its use in urethral pain syndrome.

Historically, the primary surgical procedure used to treat urethral pain syndrome has been urethral dilation. Previously a commonly used technique for practically all female urinary tract pain syndromes, urethral dilation is rarely performed in current practice. However, women with true urethral stenosis as the etiology of their symptoms experience significant improvement after urethral dilation.

The implantable InterStim system (Medtronic, Minneapolis, MN) uses mild electrical stimulation of the sacral nerve (near the sacrum). These nerves provide the most distal common autonomic and somatic nerve supply to the pelvic floor, detrusor muscle, and lower gastrointestinal tract. In properly selected patients, InterStim therapy can dramatically reduce or eliminate symptoms. Interstim is approved by the US Food and Drug Administration (FDA) for the treatement of urinary retention and symptoms of overactive bladder, including urgency urinary incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatment. 

Nd:YAG laser ablation of squamous metaplasia at the bladder neck–trigone has shown some promise in patients with urethral pain syndrome refractory to medical management and with findings of trigonitis. Success appears to depend on necrotic coagulation followed by reconstitution of normal functional epithelium.[17]

Most women with urethral pain syndrome–type symptoms initially present to a gynecologist; thus, most gynecologic abnormalities have been excluded as diagnostic possibilities before the patient reaches the urologist. However, if a female patient has not seen a gynecologist and concern exists that she may have a gynecologic abnormality as an etiology of her symptoms or as a separate disease entity, referral to a gynecologist is recommended.

The secondary psychological impact of chronic pain syndromes can be substantial. Consultation with a psychiatrist or pain-control specialist may help in management.

Any question of a previously undiagnosed neurologic condition (eg, multiple sclerosis, Parkinson disease) should prompt a consultation with a neurologist.

A physical therapist experienced in biofeedback or pelvic floor therapy can provide support and relief to some patients with urethral pain syndrome.

Intake of foods and liquids that are excreted as irritants in the urine may worsen symptoms. Oral hydration is important as concentrated urine may act as a bladder irritant.

Patients should avoid highly acidic foods. These typically include spicy foods, but a more complete, although not comprehensive, list is provided below. Food reactions can be extremely individualized. Patients may find that some of these foods worsen their symptoms, while others do not. The most recommended approach is to initiate a bland diet, excluding all of the suspect foods; then, gradually reintroduce individual foods, one per week, while noting symptoms. If symptoms worsen upon introduction of a particular food, that food should be eliminated from the diet on a long-term basis.

Alcohol and other beverages that may worsen syndromes include the following:

• Beer
• Champagne
• Liquor
• Wine
• Coffee (decaffeinated, regular)
• Soft drinks (eg, cola)
• Carbonated beverages
• Tea (decaffeinated, regular, iced)

Condiments and foods that may worsen syndromes include the following:

• Barbecue sauce
• Capers
• Chutney
• Cocktail sauce
• Corn relish
• Cranberry sauce
• Horseradish
• Hot pepper sauce
• Ketchup
• Mustard
• Pickles
• Relishes
• Roasted peppers
• Salsa
• Sauerkraut
• Sweet and sour sauce
• Tartar sauce
• Vinegar
• Worcestershire sauce

Fruits that may worsen syndromes include the following:

• Apples
• Bananas
• Cantaloupe
• Grapefruit
• Grapes
• Kiwi
• Lemon
• Lime
• Mango
• Nectarines
• Oranges
• Peaches
• Pears
• Pineapple
• Plums
• Star fruit
• Strawberries
• Tomatoes (all varieties)

Juices that may worsen syndromes include the following:

• Apple juice or cider
• Cranberry-apple or cranberry-grape
• Cranberry
• Mixed fruit
• Grape
• Grapefruit
• Guava
• Lemon (eg, lemonade)
• Mango
• Papaya
• Peach
• Pear
• Pineapple
• Prune
• Tamarind
• Tomato

Salad dressings that may worsen syndromes include the following:

• Bleu cheese
• Caesar
• French
• Honey mustard
• Italian
• Poppy seed
• Ranch
• Thousand Island
• Vinaigrette

Snacks that may worsen syndromes include the following:

• Applesauce
• Chocolate
• Gelatin (eg, Jell-O)
• Any spicy snacks

Vegetables that may worsen syndromes include the following:

• Beets
• Cabbage
• Canned or jarred artichokes
• Peppers (green, red)
• Hot peppers (eg, jalapeño)

Miscellaneous foods that may worsen syndromes include the following:

• Olive oil
• Chili
• Pizza sauce
• Marinara sauce
• Tomato sauce
• Tomato soup

A diet high in vegetables, fruits, and dairy products reduces the acidity of urine. The Interstitial Cystitis (IC) Network has developed low-acid recipes specifically for patients with IC and urethral pain syndrome (see The IC Chef). Calcium glycerophosphate, marketed as Prelief, can be sprinkled over foods to reduce acidity. Dietary supplementation with sodium bicarbonate or potassium bicarbonate can provide relief for some patients.

Increased fluid intake is advisable. Because many drinks increase acidity, patients may be prone to dehydration. In addition, patients may attempt to decrease urinary frequency by decreasing urine output. In fact, more concentrated urine is more acidic and contains a higher concentration of irritants. Patients should be encouraged to drink plenty of fluid, specifically water.

Exercise and massage programs that put patients in better control of their muscles can be very helpful.

Yoga and t'ai chi both emphasize balance, posture, and integrated movement that diminish tightness of the muscles. Through these activities, patients learn to better control and relax muscle groups and learn which muscle groups contribute to or improve their chronic pain. 

To center the mind, t'ai chi uses a physical location in the lower abdomen/pelvis, close to the area of problems in urethral pain syndrome patients, called the Tan T'ien. From this state of attention develops the possibility to change, correct, and heal. According to t'ai chi principles, the Tan T'ien, located approximately 2 inches below the navel and in the center of the pelvic area, is a body location that expresses the multifaceted principle that is referred to in t'ai chi as "center." The Tan T'ien is understood to be the true body center in a sense of balance, integration, and strength. T'ai chi emphasizes the ability to place the focus of the mind in the Tan T'ien in order to improve movement skills by eliminating the poor movement habit of excessive upper-body emphasis (ie, head, shoulders, arms).

Myofascial therapy represents a philosophy of care in which the therapist facilitates the patient's own inherent ability to correct soft-tissue dysfunction. Myofascial models were described in the osteopathic literature of the 1950s. Many other contemporary treatment approaches such as connective-tissue massage, Rolfing, strain and counterstrain, and soft-tissue mobilization use the same principles. This is a highly interactive stretching technique that requires feedback from the patient's body to determine the direction, force, and duration of the stretch and to facilitate maximum relaxation of the tight or restricted tissues.

Walking has a less direct effect on the pelvic musculature but is a potent antidepressant. Walking regularly for 3 months has been shown to yield improvements in depression similar to those of antidepressant medications.

Emotional support and encouragement of patient with urethral pain syndrome are essential. Reevaluation for possible urinary tract infection and malignancy is also imperative whenever symptoms worsen.

The choice of medical therapy in urethral pain syndrome is determined by the patient's predominant symptoms and their probable etiology. Determination of the optimal regimen often involves a combination of medications chosen through a process of trial and error. Even when an optimal 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.

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.

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.

Class Summary

Myrbetriq (mirabegron) is a FDA approved treatment for overactive bladder (OAB) with symptoms of urgency, frequency, and urgency urinary incontinence. It facilitates relaxation of the bladder muscle.