Urinary incontinence is a common presentation that affects dogs (primarily) and cats (occasionally). The most common cause is urethral sphincter mechanism incompetence (USMI), which typically affects female dogs that have been spayed and occasionally affects male dogs. Other causes include disorders like urine retention and bladder outflow obstruction, which are more common in intact and neutered male dogs.
Therapeutic objectives include treating signs of incontinence-related disorders (eg, storage disorders [eg, USMI, ectopic ureter, overactive bladder], emptying disorders [eg, functional outflow 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.
Drugs Used to Manage Storage Disorders in Dogs & Cats
Alpha-Adrenergic Drugs
Phenylpropanolamine
Phenylpropanolamine is a nonselective alpha-agonist with some beta-agonist effects. This drug indirectly increases urethral smooth muscle tone and may induce relaxation of the detrusor muscle via beta-adrenergic effects. Nonselectivity may lead to stimulation of vasoconstriction and overall sympathetic activation.
Formulation
Oral
Dosage
Dogs, cats: 1-2 mg/kg PO every 8 to 12 hours1
Extended release: 2-4 mg/kg PO every 24 hours
Extended release not for patients <10 lb (4.5 kg)2
Key Points
Dose escalation or increased frequency over time may be necessary.
Adverse effects include hypertension, restlessness, decreased appetite, and aggression.3
Should be used with caution in patients predisposed to hypertension because of comorbid conditions (eg, kidney disease, hyperadrenocorticism, hyperthyroidism)4
May increase agitation in patients with anxiety disorders
Estrogens
Estriol
Estriol is a naturally occurring estrogen with affinity for both types of estrogen receptors (ie, ER alpha, ER beta). This drug can improve continence by increasing the number and sensitivity of alpha-receptors in the urethral smooth muscle and has a trophic effect on periurethral tissues and vasculature.5 Estrogens should not be used in male dogs because of potential for prostatic metaplasia.
Formulation
Oral
Dosage
Dogs: 2 mg/dog PO every 24 hours for 14 days, reduced in 0.5-mg increments every 7 days to lowest effective dose6
Key Points
Reported efficacy of 82% to 92% improved or complete continence in female dogs7
Although estrogens can lead to bone marrow suppression, this effect has not been reported when this drug is used at 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 (ie, DES) is a potent, synthetic, nonsteroidal estrogen that improves continence by increasing the number and sensitivity of alpha-receptors in the urethral smooth muscle. This drug has a trophic effect on periurethral tissues and vasculature. Estrogens should not be used in male dogs because of potential for prostatic metaplasia.
Formulation
Not commercially available; must be compounded
Dosage
Dogs: 0.5-1 mg/dog PO every 24 hours for 3 to 5 days, then every 7 days8
Administration interval should be titrated to effect.8
Key Points
Reported efficacy of ≈65% complete and 23% improved continence in female dogs9
Although estrogens can lead to bone marrow suppression, this effect has not been reported when this drug is used at recommended doses.10
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 Antidepressants
Imipramine
Imipramine is a norepinephrine reuptake inhibitor and potential anticholinergic that indirectly increases alpha-receptor stimulation in the urethral smooth muscle. This drug may increase bladder relaxation.
Formulation
Oral
Dosage
Dogs: 5-15 mg/dog PO every 12 hours11
Cats: 2.5-5 mg/cat PO every 12 hours11
Key Points
Imipramine has complex mechanisms of action and appears to act via 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 effect in humans and healthy dogs.
Adverse effects include vomiting, diarrhea, hyperexcitability, seizures, and sedation.
May lower seizure threshold in epileptic patients
Should not be coadministered with monoamine oxidase inhibitors
Testosterone Analogs
Testosterone Cypionate
Testosterone is thought to improve urethral smooth muscle tone; however, evidence of the mechanism and efficacy in the treatment of urinary tract disorders in dogs and cats is lacking. Use is only in male dogs.
Formulation
Parenteral for IM injection
Dosage
Dogs: 2.2 mg/kg IM every 30 to 60 days12
Key Points
Anecdotally considered less effective than phenylpropanolamine in male dogs with USMI
Adverse effects include perianal adenoma and prostate enlargement in male dogs and clitoral hypertrophy, masculinization, and aggression in female dogs.
Should not be used in dogs with prostatic carcinoma
Should be used with caution in dogs with renal, cardiac, or hepatic disease
May decrease insulin needs in diabetic patients12
Gonadotropin-Releasing Hormone Analogs
Leuprolide Acetate
Leuprolide acetate is a gonadotropin-releasing hormone analog that suppresses follicle-stimulating hormone and luteinizing hormone increases after ovariohysterectomy in dogs. Some evidence shows alteration of these hormones may play a larger role in USMI development as compared with a change in estrogen levels.13 This drug does not appear to affect urethral pressures but can improve bladder relaxation and compliance.14,15
Formulation
Depot injection
Immediate-release form should be avoided
Dosage (dogs)
20-30 mg IM every 3 months15
Doses are extrapolated from the literature.15 No standard dose regimen has been established.
Key Points
Effects may last >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
Dosage
Dogs: 0.2 mg/kg PO every 8 to 12 hours or 1.25-3.75 mg/dog PO every 8-12 hours16
Cats (extra-label): 0.5-1.25 mg/cat PO every 8 to 12 hours16
Key Points
Primarily used in patients with suspected overactive bladder or detrusor instability
Also acts as an antispasmodic and reduces maximum filling and emptying bladder pressures17
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
Drugs Used to Manage Emptying Disorders in Dogs & Cats
Alpha-Adrenergic Blocking Drugs & Smooth Muscle Relaxants
Different subtypes of alpha1-adrenergic receptors are found throughout the body, especially in smooth muscle and blood vessels. The smooth muscle of the urinary tract contains mostly alpha1a receptors.
Prazosin
Prazosin is a nonselective alpha1 inhibitor used to block alpha receptors in the urethral smooth muscle and treat functional urethral obstruction.18 Use of this drug in male cats with urethral obstruction is no longer advised since the distal region of the urethra most likely to develop obstruction is primarily skeletal muscle.
Formulation
Oral
Dosage
Dogs: 1 mg/dog PO every 8 to 12 hours for dogs weighing <33 lb (15 kg); 2 mg/dog PO every 8 to 12 hours for dogs weighing >33 lb (15 kg)9
Cats (controversial): 0.25-1 mg/cat PO every 8 to 12 hours19
Key Points
Because prazosin blocks all alpha1-receptor subtypes, adverse effects include 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 beta-blocking agents and calcium channel blockers, as prazosin may induce significant hypotension.
Has been found to be more effective than phenoxybenzamine at decreasing urethral pressures20
Prazosin may also be effective in treating ureterospasm in patients with ureteral obstruction or ureteritis.21
Tamsulosin
Tamsulosin is a selective alpha-1a–adrenergic blocker that is more selective to the urinary tract (ie, prostatic urethra, bladder neck) and thus has limited cardiovascular adverse effects.
Formulation
Oral
Dosage
Dogs: 0.4-0.8 mg/dog or 0.01-0.2 mg/kg PO every 8 to 24 hours22
Cats: 0.004-0.006 mg/kg PO every 12 to 24 hours; compounded formulation required22
Key Points
Effectively inhibits hypogastric nerve-induced urethral pressure rise in dogs without clinically significant vasodilation and hypotension23
May be useful in treating ureterospasm associated with ureteritis or ureteroliths21
Oral bioavailability in dogs is approximately one-third of that in humans.24
Bioavailability may be increased when the drug is 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 alpha-adrenergic blocker used to reduce urethral pressures and treat hypertension.
Formulation
Oral
Dosage
Dogs: 0.25 mg/kg PO every 12 hours or 5-20 mg/dog PO every 12 hours25
Cats: 2-4 mg/cat PO every 12 to 24 hours; compounded formulation required25
Key Points
Cost is significantly higher compared with other alpha-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
Diazepam
Diazepam is a benzodiazepine used for relaxation of primarily skeletal muscle in the urethra in dogs with functional urethral obstruction.
Formulation
Oral
Dosage
Dogs: 2-10 mg/dog PO 30 minutes before voiding (≤3 times a day)26
Key Points
Serum half-life in dogs and cats is significantly shorter than in humans.26
Adverse effects include CNS depression, appetite stimulation, and sedation.
May cause disinhibition in aggressive patients
Should be used carefully in debilitated patients or those with liver dysfunction
Oral formulation should not be used in cats, as there is significant potential for hepatotoxicity.
Alprazolam
Alprazolam is a benzodiazepine that produces sedation, anxiolysis, and skeletal muscle relaxation. This drug may be used to relax the skeletal muscle of the urethra in patients with urethrospasm; however, data on this use in dogs or cats are not available.
Formulation
Oral
Dosage
Dogs: 0.02-0.05 mg/kg PO every 6 to 12 hours27
Cats: 0.125-0.25 mg/cat PO every 8 to 24 hours27
Doses are extrapolated from anxiolytic use.
Acepromazine
Acepromazine is a phenothiazine that has antispasmodic and alpha-adrenergic blocking effects. This drug is used in dogs and cats with functional urethral obstruction.
Formulation
Oral, injectable
Dosage
Dogs, cats: 0.55-2.2 mg/kg PO every 6-12 hours or to effect28
Dogs: 0.02-0.05 mg/kg IM, SC, or IV to effect; total dose should not exceed 2-3 mg/dog
Cats: 0.02-0.08 mg/kg IM, SC, or IV to effect; total dose should not exceed 1 mg/cat
Key Points
Can significantly decrease preprostatic and prostatic urethral pressures in intact male cats29
Dose should be reduced in patients with possible breed-related multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene) mutation (also known as ABCB1-1delta) (eg, collies, Shetland sheepdogs, Australian shepherds).28,30
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
Cholinergic Agents
Bethanechol
Bethanechol is a cholinergic agent that directly stimulates muscarinic receptors in the detrusor smooth muscle of the bladder, leading to detrusor contraction.
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.
Dosage
Dogs: 2.5-15 mg/dog PO every 8 hours31
Cats: 1.25-5 mg/cat PO every 8 hours31
Key Points
May not be effective in patients with chronic bladder overdistension resulting from loss of smooth muscle tight junctions
Adverse effects, including 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 Agents
Cisapride
Cisapride is a 5-HT4-receptor agonist that enhances 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.
Dosage
Dogs: 0.1-0.5 mg/kg PO every 8 to 12 hours32
Cats: 2.5-7.5 mg/cat PO every 8 to 12 hours32
Key Points
May help increase bladder contraction and reduce residual urine volume33
Commonly used to treat cats with megacolon
Removed from commercial manufacture in 2002 because of arrhythmias seen in humans34
These effects are not well demonstrated in dogs and cats.
Adverse effects include diarrhea, vomiting, and ataxia.
Administration should start at low end of the dose range and be titrated up to avoid adverse effects.
Cisapride is metabolized by cytochrome P-450 (CYP) 3A and should be used with caution in patients receiving CYP3A-inhibitors (eg, azole antifungals, cimetidine, diltiazem, chloramphenicol).
Dose reduction may be necessary in patients with hepatic dysfunction.
Should be avoided in patients with GI obstruction