Drugs Used to Manage Urinary Incontinence in Dogs & Cats

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 alpha_1a 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