December 2017
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Urinary incontinence is a common presenting complaint primarily affecting dogs and occasionally cats. The most common cause of urinary incontinence is urethral sphincter mechanism incompetence (USMI), which typically affects spayed female dogs and occasionally male dogs. Other causes include disorders such as urine retention and bladder outflow obstruction, which are more common in male dogs.

Therapeutic objectives include treating signs of incontinence-related disorders such as storage disorders (eg, USMI, ectopic ureter, overactive bladder) and emptying disorders (eg, detrusor-urethral dyssynergia, functional obstruction, urethrospasm, detrusor atony, neurogenic upper motor neuron bladder). Goals for treating storage disorders include increasing urethral sphincter smooth and striated muscle tone, increasing bladder compliance, and decreasing intravesicular pressures during filling and storage. Goals for treating emptying disorders include decreasing urethral sphincter smooth and striated muscle tone, increasing detrusor contraction, and reducing postvoid residual volume.

Following are therapeutic targets for the various causes of incontinence.

DRUGS TO MANAGE STORAGE DISORDERS

α-Adrenergic Drug

Phenylpropanolamine

Phenylpropanolamine is a nonselective α-agonist that also has some β-agonist effects. It indirectly increases urethral smooth muscle tone and may also induce relaxation of the detrusor muscle via β-adrenergic effects. Its nonselectivity may lead to stimulation of vasoconstriction and overall sympathetic activation. 

Formulation → Oral

Dose (dogs, cats) → 1-2 mg/kg PO q8-12h1

Key Points

  • Dose escalation or increased frequency over time may be necessary.
  • Adverse effects include hypertension, restlessness, decreased appetite, and aggression.2
  • Should be used with caution in patients that are predisposed to hypertension because of comorbid conditions (eg, kidney disease, hyperadrenocorticism, hyperthyroidism)3 
  • May increase agitation in patients with anxiety disorders
Estrogens

Estriol

Estriol is a naturally occurring estrogen with affinity for both types of estrogen receptors. It can improve continence by increasing the number and sensitivity of α-receptors in the urethral smooth muscle, and it has a trophic effect on periurethral tissues and vasculature.4

Formulation → Oral

Dose (dogs only) → 2 mg/dog PO q24h for 14 days, then reduce in 0.5-mg increments q7d to lowest effective dose1

Key Points

  • Efficacy in female dogs reported as 82% to 92% improved or complete continence5 
  • Although estrogens can lead to bone marrow suppression, this effect has not been reported when this drug is used at the recommended doses.
  • Adverse effects include vulvar or mammary swelling, attractiveness to males, lethargy, vomiting, and diarrhea. 
    • Most patients respond to dose reduction.
  • Should not be used in intact females 
  • Use in males may lead to prostatic metaplasia. 
  • Overdose can lead to bone marrow suppression.
  • Should not be used in cats

Diethylstilbestrol

Diethylstilbestrol is a potent, synthetic, nonsteroidal estrogen that improves continence by increasing the number and sensitivity of α-receptors in the urethral smooth muscle. It has a trophic effect on periurethral tissues and vasculature.

Formulation → Not commercially available; must be compounded

Dose (dogs only) → 0.5-1.0 mg/dog PO q24h for 3 to 5 days, then q7d1

Administration interval should be titrated to effect.1

Key Points

  • Reported efficacy of approximately 65% complete and 23% improved continence in female dogs6 
  • Although estrogens can lead to bone marrow suppression, this has not been reported at recommended doses.7 
  • Adverse effects include vulvar or mammary swelling, attractiveness to males, lethargy, vomiting, and diarrhea. 
    • Most patients respond to dose reduction.
  • Should not be used in intact females
  • Use in males may lead to prostatic metaplasia. 
  • Overdose can lead to bone marrow suppression.
  • Should not be used in cats
Tricyclic Antidepressant

Imipramine

Imipramine is a norepinephrine reuptake inhibitor and potential anticholinergic that indirectly increases α-receptor stimulation in the urethral smooth muscle. This drug may increase bladder relaxation.

Formulation → Oral

Dose (dogs) → 5-15 mg/dog PO q12h1

Dose (cats) → 2.5-5 mg/cat PO q12h1

Key Points

  • Imipramine has complex mechanisms of action and appears to act through both stimulation of the sympathetic nervous system and inhibition of the parasympathetic nervous system. 
  • Evidence of efficacy in the treatment of urinary storage disorders in dogs and cats is lacking. 
    • Rationale for use is extrapolated from in vitro studies and clinical evidence of the drug’s effect in humans and healthy dogs.
  • Adverse effects include vomiting, diarrhea, hyperexcitability, seizure, and sedation.
  • May lower seizure threshold in epileptic patients 
  • Should not be coadministered with monoamine oxidase inhibitors
Testosterone Analog

Testosterone Cypionate

Testosterone is thought to improve urethral smooth muscle tone; however, evidence of the mechanism and its efficacy in the treatment of urinary tract disorders in dogs and cats is lacking.

Formulation → Parenteral for IM injection

Dose (dogs only) → 2.2 mg/kg IM q30-60d1

Key Points

  • Anecdotally considered to be less effective than phenylpropanolamine in male dogs with USMI
  • Adverse effects include perianal adenoma and prostate enlargement in male patients and clitoral hypertrophy, masculinization, and aggression in female patients.
  • Should not be used in patients with prostatic carcinoma and should be used with caution in patients with renal, cardiac, or hepatic disease
  • May decrease insulin needs in diabetic patients1
Gonadotropin-Releasing Hormone (GnRH) Analog

Leuprolide Acetate

Leuprolide acetate is a GnRH analog that suppresses both follicle-stimulating hormone and luteinizing hormone increases after ovariohysterectomy in dogs. Some evidence shows that the alteration of these hormones may play a larger role in USMI development as compared with a change in estrogen levels.8 This drug does not appear to affect urethral pressures but can improve bladder relaxation and compliance.9,10 

Formulation → Depot injection

Immediate-release form should be avoided.

Dose (dogs) → 20-30 mg/dog IM q3mo10 

Doses are extrapolated from the literature.10 No standard dose regimen has been established.

Key Points

  • Effects may last longer than 3 months. 
    • Treatment should be repeated as needed when clinical signs return.
  • Most commonly used to treat endocrine diseases in ferrets and suppress egg formation in birds
  • Little is known about adverse effects in dogs and cats.
Antimuscarinic & Spasmolytic Drugs

Oxybutynin

Oxybutynin has direct antimuscarinic effects on the smooth muscle of the bladder without affecting the smooth muscle of the vasculature.

Formulation → Oral

Dose (dogs) → 0.2 mg/kg PO q8-12h or 1.25-3.75 mg/dog PO q8-12h1

Dose (cats; extra-label) → 0.5-1.25 mg/cat PO q8-12h1

Key Points

  • Primarily used in cases of suspected overactive bladder or detrusor instability
  • Also acts as an antispasmodic and reduces maximum filling and emptying bladder pressures11 
  • Adverse effects include diarrhea, constipation, hypersalivation, urine retention, and sedation.
  • Use with other sedatives may increase effect.
  • Should be used with caution in patients with hypotension

Propantheline

Propantheline is an antimuscarinic agent that has effects on the smooth muscle of the bladder and may reduce spasm related to detrusor hyperreflexia and associated urinary incontinence.

Formulation → Oral; injectable form available in Australia

Dose (dogs) → 7.5-30 mg/dog PO q8-24h1

Dose (cats) → 5-7.5 mg/cat PO q8-72h; lowest effective dose should be used1

Key Points

  • Variable absorption of the oral formulation in small animals; dose must be adjusted for each patient.
  • Should not be used if urinary obstruction or urine retention is suspected
  • Adverse effects include dry mouth, tachycardia, ileus, and constipation; vomiting and hypersalivation may be seen in cats.1

DRUGS TO MANAGE EMPTYING DISORDERS

α-Adrenergic Blocking Drugs & Smooth Muscle Relaxants

Prazosin

Prazosin is a nonselective α1-inhibitor used to block α-receptors in the urethral smooth muscle and treat functional urethral obstruction.12

Formulation → Oral

Dose (dogs) → 1 mg/dog PO q8-12h for dogs weighing <15 kg; 2 mg/dog PO q8-12h for dogs weighing >15 kg1 

Dose (cats) → 0.25-1 mg/cat PO q8-12h1

Key Points

  • The nonselective nature of prazosin also leads to vasodilation and decreased vascular resistance.
  • Hypotension is the primary adverse effect. 
    • Patients should be monitored with each dose increase.
    • Caution should be used when administering with β-blocking agents and calcium channel blockers, as prazosin may induce significant hypotension.
  • Has been found to be more effective than phenoxybenzamine at decreasing urethral pressures13 
  • Rates of urethral reobstruction in cats treated with prazosin were lower than in those treated with phenoxybenzamine.14 
  • Prazosin may also be effective in treating ureterospasm in cases of ureteral obstruction or ureteritis.15

Tamsulosin

Tamsulosin is a selective α1a-adrenergic blocker that is more selective to the urinary tract (ie, prostatic urethra, bladder neck) and thus has more limited cardiovascular side effects.

Formulation → Oral

Dose (dogs) → 0.1-0.2 mg/10 kg (up to 0.4-mg total dose) PO q12-24h1  

Dose (cats) → 0.004-0.006 mg/kg PO q12-24h1

Key Points

  • Effectively inhibits hypogastric nerve-induced urethral pressure rise in dogs without clinically significant vasodilation and hypotension16 
  • May be useful in treating ureterospasm associated with ureteritis or ureteroliths15
  • Oral bioavailability in dogs is about one-third of that in humans.17 
    • Bioavailability may be increased when administered on an empty stomach. 
  • May take several days for effect
  • High doses may lead to hypotension. 
  • Sustained-release formulations should not be crushed.

Phenoxybenzamine

Phenoxybenzamine is a pure α-adrenergic blocker used to reduce urethral pressures and treat hypertension.

Formulation → Oral

Dose (dogs) → 0.25 mg/kg PO q12h or 5-20 mg/dog PO q12h1 

Dose (cats) → 2.5-7.5 mg/cat PO q12-24h1

Key Points

  • Cost is significantly higher as compared with other α-adrenergic blockers.
  • Often used to reduce pheochromocytoma-induced hypertension
  • Blood pressure should be monitored.
  • Adverse effects include hypotension, weakness, nausea, miosis, and sodium retention.
  • Should be used with caution in patients with cardiac disease or other conditions predisposed to hypotension
Skeletal Muscle Relaxants

Benzodiazepines

Diazepam

Diazepam is a benzodiazepine used for relaxation of primarily skeletal muscle in the urethra in dogs with functional urethral obstruction. 

Formulation → Oral, injectable

Dose (dogs) → 2-10 mg/dog PO 30 minutes before voiding (≤3 times a day)1

Key Points

  • Serum half-life in dogs and cats is significantly shorter than in humans.1 
  • Adverse effects include CNS depression, appetite stimulation, and sedation. 
  • May cause disinhibition in aggressive patients
  • Oral form should not be used in cats, as there is significant potential for hepatotoxicity.
  • Should be used carefully in debilitated patients or those with liver dysfunction 

Alprazolam

Alprazolam is a benzodiazepine that produces sedation, anxiolysis, and skeletal muscle relaxation. It may be used to relax the skeletal muscle of the urethra in patients with urethrospasm; however, no data on its use in this manner in either dogs or cats has been published.

Formulation → Oral

Dose (dogs) → 0.02-0.05 mg/kg PO q6-12h1

Dose (cats) → 0.125-0.25 mg/cat PO q8-24h1

Doses extrapolated from anxiolytic use

Acepromazine

Acepromazine is a phenothiazine that has antispasmodic and α-adrenergic blocking effects. It is used in dogs and cats with functional urethral obstruction.

Formulation → Oral, injectable

Dose (dogs, cats) → 0.55-2.2 mg/kg PO q6-12h or to effect1

Key Points

  • Has been shown to significantly decrease preprostatic and prostatic urethral pressures in intact male cats18
  • Adverse effects include hypotension and prolapse of the nictitans.
  • Should not be used in patients with hypotension, volume depletion, or shock 
  • Should be used carefully in patients with cardiac disease or hepatic dysfunction
  • Caution: Dose should be reduced in patients with possible breed-related MDR1 mutations (eg, collies, Shetland sheepdogs, Australian shepherds).1,19

Baclofen

Baclofen is a skeletal muscle relaxant that appears to act at the level of the spinal cord. It has been shown to reduce urethral striated (skeletal) muscle sphincter tone in dogs.20

Formulation → Oral

Dose (dogs only) → 1-2 mg/kg PO q8h

Key Points

  • Should be gradually discontinued to reduce risk for psychomotor effects (eg, seizures, hallucinations)
  • Adverse effects include sedation, weakness, or GI cramping.
  • Narrow margin of safety in dogs and should not be used in cats 
    • Should be used with caution in patients with seizure disorders

Dantrolene

Dantrolene is a direct-acting muscle relaxant that has been used to treat patients that have functional urethral obstruction. Because of the availability of more effective and safer muscle relaxants, dantrolene is not recommended as a first-line treatment for detrusor-urethral dyssynergia.

Formulation → Oral; injectable is available but not practical for veterinary use

Dose (dogs) → 1-5 mg/kg PO q8-12h1 

Dose (cats) → 0.5-2 mg/kg PO q12h1 

Key Points

  • May be less effective than baclofen
    • Several studies have indicated its effect on striated muscle is poor.21 
  • Adverse effects include hepatotoxicity, weakness, and sedation.
  • Should not be used in patients with hepatic dysfunction
  • Should be used with caution in patients with cardiac disease
Cholinergic Agent

Bethanechol

Bethanechol is a cholinergic that directly stimulates muscarinic receptors in the detrusor smooth muscle of the bladder.

Formulation → Oral 

Only the oral formulation is commercially available in the United States; injectable formulations may be available outside the United States or through compounding pharmacies. 

Dose (dogs) → 2.5-25 mg/dog PO q8h1

Dose (cats) → 1.25-7.5 mg/cat PO q8h1

Key Points

  • May not be effective in patients with chronic bladder over-distension resulting from loss of smooth muscle tight junctions
  • Vomiting, diarrhea, decreased appetite, hypersalivation, and other SLUD (salivation, lacrimation, urination, defecation)-like effects may be seen at recommended doses. 
  • Overdose can lead to bradycardia, hypotension, and/or increased respiratory secretions.
  • Should not be used in patients with untreated urethral obstruction or questionable bladder wall integrity
Prokinetic Agent

Cisapride

Cisapride is a 5-HT4-receptor agonist that indirectly leads to acetylcholine release and smooth muscle (eg, GI, detrusor) contraction.

Formulation → Must be compounded; no commercial products are available in the United States, Europe, or India.

Dose (dogs) → 0.1-0.5 mg/kg PO q8-12h1 

Dose (cats) → 2.5-7.5 mg/cat PO q8-12h1 

Key Points

  • May help increase bladder contraction and reduce residual urine volume22 
  • Commonly used to treat cats with megacolon
  • Removed from commercial manufacture in 2002 because of arrhythmias seen in humans23 
    • These effects are not well demonstrated in dogs and cats.
  • Adverse effects include diarrhea, vomiting, and ataxia. 
    • Administration should start at low end of dose range and titrate up to avoid these effects.
  • Cisapride is metabolized by the cytochrome P450 CYP3A and should be used with caution in patients receiving CYP3A-inhibitors (eg, azole antifungals, cimetidine, diltiazem, chloramphenicol).
  • Dose reduction may be necessary in patients that have hepatic dysfunction. 

  • Use should be avoided in patients with GI obstruction.

USMI = urethral sphincter mechanism incompetence

References and author information Show
References
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  2. Byron JK, March PA, Chew DJ, DiBartola SP. Effect of phenylpropanolamine and pseudoephedrine on the urethral pressure profile and continence scores of incontinent female dogs. J Vet Intern Med. 2007;21(1):47-53.
  3. Segev G, Westropp JL, Kulik C, Lavy E. Changes in blood pressure following escalating doses of phenylpropanolamine and a suggested protocol for monitoring. Can Vet J. 2015;56(1):39-43.
  4. Skala CE, Petry IB, Albrich SB, Puhl A, Naumann G, Koelbl H. The effect of hormonal status on the expression of estrogen and proges-terone receptor in vaginal wall and periurethral tissue in urogynecological patients. Eur J Obstet Gynecol Reprod Biol. 2010;153(1):99-103.
  5. Mandigers RJ, Nell T. Treatment of bitches with acquired urinary incontinence with oestriol. Vet Rec. 2001;149(25):764-767.
  6. Nendick PA, Clark WT. Medical therapy of urinary incontinence in ovariectomised bitches: a comparison of the effectiveness of diethylstilboestrol and pseudoephedrine. Aust Vet J. 1987;64(4):117-118.
  7. Sontas HB, Dokuzeylu B, Turna O, Ekici H. Estrogen-induced myelotoxicity in dogs: a review. Can Vet J. 2009;50(10):1054-1058.
  8. Reichler IM, Pfeiffer E, Piché CA, et al. Changes in plasma gonadotropin concentrations and urethral closure pressure in the bitch during the 12 months following ovariectomy. Theriogenology. 2004;62(8):1391-1402.
  9. Reichler IM, Barth A, Piché CA, et al. Urodynamic parameters and plasma LH/FSH in spayed beagle bitches before and 8 weeks after GnRH depot analogue treatment. Theriogenology. 2006;66(9):2127-2136.
  10. Reichler IM, Jöchle W, Piché CA, Roos M, Arnold S. Effect of a long acting GnRH analogue or placebo on plasma LH/FSH, urethral pressure profiles and clinical signs of urinary incontinence due to sphincter mechanism incompetence in bitches. Theriogenology. 2006;66(5):1227-1236.
  11. Yamamoto T, Koibuchi Y, Miura S, et al. Effects of vamicamide on urinary bladder functions in conscious dog and rat models of urinary frequency. J Urol. 1995;154(6):2174-2178.
  12. Haagsman AN, Kummeling A, Moes ME, Mesu SJ, Kirpensteijn J. Comparison of terazosin and prazosin for treatment of vesico-urethral reflex dyssynergia in dogs. Vet Rec. 2013;173(2):41. 
  13. Fischer JR, Lane IF, Cribb AE. Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs. Can J Vet Res. 2003;67(1):30-38.
  14. Hetrick PF, Davidow EB. Initial treatment factors associated with feline urethral obstruction recurrence rate: 192 cases (2004-2010). J Am Vet Med Assoc. 2013;243(4):512-519.
  15. Kobayashi S, Tomiyama Y, Hoyano Y, et al. Mechanical and gene expression of alpha(1)-adrenoceptor subtypes in dog intravesical ureter. Urology. 2009;74(2):458-462.
  16. Ohtake A, Sato S, Saitoh C, Yuyama H, Sasamata M, Miyata K. Effects of tamsulosin on hypogastric nerve stimulation-induced intraurethral pressure elevation in male and female dogs under anesthesia. Eur J Pharmacol. 2004;497(3):327-334.
  17. Matsushima H, Kamimura H, Soeishi Y, Watanabe T, Higuchi S, Tsunoo M. Pharmacokinetics and plasma protein binding of tamsulosin hydrochloride in rats, dogs, and humans. Drug Metab Dispos. 1998;26(3):240-245.
  18. Marks SL, Straeter-Knowlen IM, Moore M, Speth R, Rishniw M, Knowlen GG. Effects of acepromazine maleate and phenoxybenzamine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats. Am J Vet Res. 1996;57(10):1497-1500.
  19. Deshpande D, Hill KE, Mealey KL, Chambers JP, Gieseg MA. The effect of the canine ABCB1-1∆ mutation on sedation after intravenous administration of acepromazine. J Vet Intern Med. 2016;30(2):636-641. 
  20. Teague CT, Merrill DC. Effect of baclofen and dantrolene on bladder stimulator-induced detrusor-sphincter dyssynergia in dogs. Urology. 1978;11(5):531-535.
  21. Harris JD, Benson GS. Effect of dantrolene sodium on canine bladder contractility. Urology. 1980;16(2):229-231.
  22. Madeiro AP, Rufino AC, Sartori MGF, Baracat EC, De Lima GR, Girão MJBC. The effects of bethanechol and cisapride on urodynamic parameters in patients undergoing radical hysterectomy for cervical cancer. A randomized, double-blind, placebo-controlled study. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17(3):248-252.
  23. Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35(7):745-767. 
Author

Julie Kathleen Byron

DVM, MS, DACVIM The Ohio State University

Julie Kathleen Byron, DVM, MS, DACVIM, is an associate professor at The Ohio State University, where she also earned her DVM. She completed a rotating small animal internship at VCA West Los Angeles Animal Hospital and an internal medicine residency at The Ohio State University. She earned two master’s degrees, one in biology from Stanford University and one in veterinary medicine from The Ohio State University. Her practice and research interests are in lower urinary tract disease and kidney disease. Dr. Byron enjoys developing and working with new ways to teach students, from case-based simulations to novel-technique lessons.

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