Medical Management of Urinary Incontinence and Retention Disorders

Chapter 201

Medical Management of Urinary Incontinence and Retention Disorders

Micturition disorders can be divided into urinary incontinence and urinary retention. Urinary incontinence is defined as an involuntary escape of urine during the storage phase of the urinary cycle, whereas urinary retention is defined as a failure of the urine voiding phase of micturition, ultimately resulting in signs of overflow incontinence. An accurate characterization of the incontinence is warranted so that the appropriate pharmacologic treatment regimen can be chosen. This chapter reviews the mode of action of the pharmacologic agents available in veterinary medicine and gives an update on new agents and therapeutic approaches.

Urinary Incontinence

So that the most appropriate treatment can be provided, an accurate diagnosis of the cause of urinary incontinence should be made. Although urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in dogs, incontinence can be associated with low bladder capacity or detrusor instability. The goal of therapy in cases of urinary incontinence is improvement of urethral resistance, bladder capacity, or both. Two classes of drugs commonly are used to increase urethral resistance: sympathomimetic agents and estrogenic compounds. The use of additional agents with potential effects on both urethral and bladder functions can be contemplated in refractory cases. Recommended dosages are given in Table 201-1.

TABLE 201-1

Therapeutic Options for the Management of Urinary Incontinence

Agent Recommended Dosage Possible Adverse Effects
Phenylpropanolamine Dog and cat: 1-1.5 mg/kg q8-12h PO or
1.5 mg/kg q24h PO
Restlessness, hypertension, tachycardia, anxiety
Ephedrine Dog: 1-4 mg/kg q8-12h PO
Cat: 2-4 mg per cat q8h or 2-4 mg/kg q6-12h
Restlessness, hypertension, tachycardia, anxiety, excitability
Pseudoephedrine Dog: 0.2-0.4 mg/kg q8-12h PO Restlessness, hypertension, tachycardia, anxiety, excitability
Estriol* Dog: 0.5-2 mg per dog q24h PO Vulvar swelling, attraction to males, metrorrhagia
Depot leuprolide Dog: 1 mg/kg or 11-25 mg per dog  
Depot deslorelin Dog: 5-10 mg per dog or
 Dog <30 kg: one 4.7-mg implant
 Dog >30 kg: one 9.4-mg implant
Oxybutynin Dog: 0.2 mg/kg q8-12h PO or
 Small dog: 0.75-1.25 mg per dog q8-12h PO
 Larger dog: 2.5-5 mg per dog q8-12h PO
Cat: 0.5-1.25 mg per cat q8-12h
Diarrhea, constipation, urinary retention, hypersalivation, sedation, dry mouth, dry eyes, tachycardia, anorexia, vomiting, weakness, mydriasis
Propantheline bromide Dog: 7.5-15 mg per dog q12h PO up to 30 mg per dog q8h or 0.2 mg/kg q6-8h PO
Cat: 0.25-0.5 mg/kg q12-24h or 5-7.5 mg per cat every 3 days or 5-7.5 mg per cat q8h every 3 days
Dry mouth, dry eyes, urinary hesitancy, tachycardia, constipation
Imipramine Dog: 5-20 mg per dog q12h PO
Cat: 2.5-5 mg per cat q12h
Sedation, dry mouth, urinary retention, vomiting, constipation
Duloxetine Dog: 1 mg/kg q12h PO  

PO, Orally.

*Recommended dosages for other estrogenic compounds can be found in the previous edition of Current Veterinary Therapy, Chapter 207.

Dosage is extrapolated from experimental studies in rabbits and cats and has not yet been investigated in dogs.

Sympathomimetic Agents

Phenylpropanolamine (PPA) is an indirect α-agonist amine producing a contraction of the bladder neck and proximal urethra by acting on the α-adrenergic receptors. PPA is very effective in the treatment of USMI, resulting in continence in 75% to 90% of the patients. PPA traditionally has been administered two or three times daily. However, recurrence of incontinence can be observed after prolonged administration. Urodynamic studies in beagle dogs have shown lack of modification of urethral resistance after 1 week of three-times-daily administrations of PPA, whereas significant increase in urethral resistance was observed clearly after 1 week of once-daily administration. In the author’s experience, the administration of a single daily dose of PPA (1.5 mg/kg) in dogs affected with USMI can achieve long-term continence in 90% of cases (Claeys et al, 2011). This administration regimen obviously is more convenient and less expensive for owners. Adverse effects of PPA include hypertension, restlessness, anxiety, and tachycardia. Therefore PPA should be administered cautiously to dogs with concurrent cardiovascular diseases or hypertension.

Ephedrine is a mixed-action sympathomimetic drug whose efficacy is slightly less predictable than that of PPA, with a complete response to treatment observed in about 75% of treated bitches. Adverse effects are those of sympathomimetic drugs. Experimental studies have shown that both PPA and ephedrine improved urethral function; however, bladder storage function also was improved after administration of ephedrine (Noël et al, 2012). This latter effect can be explained by stimulation of the β3-adrenoreceptors present in the bladder dome. Therefore ephedrine potentially could be a useful drug in the treatment of refractory urinary incontinence with concurrent bladder dysfunction, but this hypothesis still needs to be confirmed in clinical cases.

Treatment with either ephedrine or PPA should be initiated at the recommended starting dosage, and then the dosage should be decreased progressively once the incontinence is controlled.

Pseudoephedrine is a stereoisomer of ephedrine that was shown to produce a lower increase in urethral resistance, a lower continence score, and more adverse effects in bitches with USMI compared with PPA (Byron et al, 2007). Pseudoephedrine generally is not recommended for the management of urinary incontinence.

Estrogenic Compounds

High-affinity estradiol receptors are located at the level of the proximal urethra, and estrogens are known to increase the number and the responsiveness of α-adrenergic receptors to sympathetic stimulation. Additional potential effects of estrogenic compounds include improvement of urethral vascularization, stimulation of collagen synthesis, and cellular proliferation leading to an increase in urethral wall thickness. Long-acting synthetic estrogen preparations are associated with bone marrow depletion and should no longer be used. Estriol is a short-acting natural estrogen compound with few adverse effects. It recently has received U.S. Food and Drug Administration approval for use in veterinary medicine. Long-term administration is associated in rare cases with adverse effects such as pyometra or bone marrow suppression. Minor associated adverse effects include swelling of the vulva, attraction to males, and metrorrhagia. Success rate is lower with estrogen administration than with administration of sympathomimetic compounds, and complete continence is achieved in 65% of treated bitches (Mandigers and Nell, 2001). Estrogen administration can be chosen when the use of sympathomimetic agents is contraindicated, such as in dogs with concurrent cardiovascular disease or hypertension. Estrogen use is contraindicated in immature bitches with congenital USMI because of adverse effects associated with the negative feedback on the hypophysis. Estrogen administration also should be avoided in intact bitches and in male dogs.

Although the combination of estrogens and sympathomimetic agents has been advocated in cases of refractory incontinence to achieve a theoretical synergetic effect, the superiority of this combination still remains to be documented. Indeed, experimental urodynamic studies have failed to demonstrate a superior effect of this combination on urethral function compared with the effect of either estrogens or α-agonists alone (Hamaide et al, 2006). However, the combination still may be useful in individual dogs. If the drugs are used in combination, the dosage of each drug is identical to that used when the drug is given alone, and dosages of both medications also can be tapered over time.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Medical Management of Urinary Incontinence and Retention Disorders

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