Urology

Feline Urethral Obstruction

“Blocked” cats are one of the most common life-threatening emergencies presented to veterinary clinics. Urethral obstruction (caused by calculi, urethral plug, or urethral spasm) is a completely curable condition following which most treated cats go on to live happy, normal lives. Cats suffering from urethral obstruction will usually exhibit signs of pollakiuria, dysuria, stranguria, hematuria, vocalizing while straining to urinate, bilateral inguinal alopecia (sometimes with excoriation) and a recent history of peruria (house soiling). Accurate triage of the etiology of feline urethral obstruction is paramount as inability to excrete urine can lead to bladder rupture and life-threatening hyperkalemia resulting in cardiac arrhythmias and death. Complete workup of blocked cats includes a physical exam, EKG, clinical laboratory assessment of hematology and electrolytes, and hydration status assessment. Initial triage involves establishment of an intravenous catheter, analgesia, treatment of electrolyte abnormalities, and resolution of obstruction. Once the obstruction is removed, the bladder is irrigated with saline until the effluent appears to be free of blood, clots or other debris. A urinary catheter is usually left in place for at least 48 hours to ensure continued ability to void urine.

Re-obstruction due to urethral spasm is a common occurrence following removal of calculi or urethral plugs, so treatment with an anti-spasmodic is usually warranted. The proximal (pre-prostatic) portion of the feline urethra is primarily controlled by alpha receptor mediated smooth muscle, while the distal (post-prostatic and penile) portion is primarily controlled by striated muscle. The alpha-1 antagonists, phenoxybenzamine (2.5mg per cat orally every 8-12 hrs) and prazosin (0.25mg per cat orally every 12 hours), are very useful in relieving urethral obstruction. Dosing with phenoxybenzamine and prazosin should be carefully controlled as sedation and profound hypotension can result from overdosage. While extremely effective for relief of urethral spasm in cats, neither phenoxybenzamine nor prazosin are commercially available in dosage forms that are suitable for accurate administration of very small, very specific doses. Fortunately, our compounding pharmacist can formulate both drugs in patient-specific doses. For prevention of recurrence, cats with obstruction from urethral plugs or urethroliths should be changed to canned diets to decrease urine concentration and supersaturation, and plenty of fresh water should be offered to encourage adequate urine dilution. The survival rate for cats discharged after successful treatment of obstructive uropathy is currently 90%, and the availability of patient-specific doses of the alpha-1 antagonists prazosin and phenoxybenzamine will ensure that this survival rate continues to increase.

J Am Vet Med Assoc 199(2): 211-6.
Clinical evaluation of cats with lower urinary tract disease.
Kruger, J. M., C. A. Osborne, et al.
Click here to access the PubMed abstract of this article.

J Vet Emerg Crit Care 13(4): 227-233.
Characterization of the clinical characteristics, electrolytes, acid-base, and renal parameters in male cats with urethral obstruction.
Lee, J. A. and K. J. Drobatz.
Click here to access more information.

J Amer Vet Med Assoc 221(4): 502-505
Evaluation of trends in frequency of urethrostomy for treatment of urethral obstruction in cats.
Lekcharoensuk, C., C. Osborne, et al.
Click here to access the PubMed abstract of this article.

 


 

Treating Feline Urethral Spasm

Feline lower urinary tract disease (FLUTD) is a spectrum of different diseases that present with a common set of clinical signs regardless of the underlying cause. Cats with FLUTD, usually present with signs of dysuria (difficult urination), pollakiuria (increased frequency of urination), hematuria, agitation or vocalization (crying or howling) when unable to urinate due to urethral obstruction. Obstructive FLUTD can be a serious condition and may lead to post-renal azotemia, renal azotemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidemia. These combined metabolic and renal disruptions can rapidly prove fatal. Therefore, cats presenting with lower urinary tract obstruction require immediate treatment. Acute renal failure and death can result in 1-3 day if urinary tract obstruction is left untreated.

Urethral spasm may occur in many cases of FLUTD, regardless of the underlying cause. Spasms may be initiated by local pain or inflammation, and may affect the smooth and/or skeletal muscle of the urethra. It may therefore be beneficial to give drugs to counter both smooth and skeletal muscle effects. While these drugs are rarely associated with side effects in young cats, the risk of concurrent renal or cardiac disease should be assessed before these drugs are given to older cats. Smooth muscle anti-spasmodics include prazosin 0.25-1.0 mg/cat PO q8-12h, and phenoxybenzamine 0.5-1.0 mg/kg PO q12h–give for 5 days before evaluating efficiency. The most commonly used skeletal muscle anti-spasmodic is dantrolene given at 0.5-2.0 mg/kg PO q12h.

There have been only a limited number of studies into the use of anti-spasmodic drugs in the relief of urethral spasm in cats; however, prazosin, phenoxybenzamine and dantrolene have been shown to be most beneficial. Unfortunately, all of these drugs are commercially available in capsule forms that cannot be safely and accurately administered to cats. Because prazosin and phenoxybenzamine are smooth muscle alpha adrenergic antagonists, profound hypotension is a potential adverse effect. For this reason, these drugs have a very narrow therapeutic index, and veterinary clinicians prefer to only use these drugs in carefully titrated doses. Our compounding pharmacy is able to provide these valuable anti-spasmodic drugs in palatable, appropriately-sized dosage forms and optimal individualized strengths. While none of these drugs are stable for long periods of time in liquid dosage forms, we can compound capsules containing one or more of the anti-spasmodics individualized for a specific patient, or provide as medicated treats. Due to the delayed onset of transdermal medications, this dosage form is not appropriate for use in treating this potentially life-threatening condition.

AJVR 1995 Jul;56(7):919-23.
Urethral pressure response to smooth and skeletal muscle relaxants in anesthetized, adult male cats with naturally acquired urethral obstruction.
Click here to access the PubMed abstract of this article.

AJVR 1992 Jul;53(7):1161-5.
Urethral pressure response to alpha-adrenergic agonist and antagonist drugs in anesthetized healthy male cats.
Click here to access the PubMed abstract of this article.

AJVR 1996 Oct;57(10):1497-500.
Effects of acepromazine maleate and phenoxybenzamine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats.
Click here to access the PubMed abstract of this article.

 


 

Treatment for Urinary Incontinence

Hormonal Therapy:
Diethylstilbestrol (DES) has been used to treat estrogen responsive incontinence in spayed female dogs. The use of DES is contraindicated in cats as daily use has resulted in pancreatic, hepatic, and cardiac lesions.

Dose for dogs:
Initially 0.1-1.0 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. DES can be given PO to female dogs at 0.1-0.3 mg/kg/day for 7-10 days, followed by a similar dose once weekly. Dogs should be maintained at the lowest possible dose because bone marrow suppression can develop when diethylstilbestrol is given in high doses. 1,4

When therapy is chronic or high dosages are used, packed cell volumes, white blood cell counts, and platelet counts should be done at least monthly. Liver function tests should be done at baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal.

Clients should be informed to contact the veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur. DES is not for human consumption and should be dispensed only in child-resistant containers and stored in a secure location.1

DES is not currently commercially available; however, the medication can be prepared by a compounding pharmacy.

Adrenergic Agonists:
Phenylpropanolamine (PPA) is a weak alphaagonist that increases urethral sphincter tone and produces closure of the bladder neck, and is used to treat urethral sphincter hypotonus and resulting incontinence in dogs and cats.

Dose1:

Dogs: 1.1 mg/kg PO every 8 hours Cats: 12.5mg PO every 8 hours

The effect is short-lived, and the dose needs to be titrated to effect. “Dogs that are older at the onset of clinical signs (median 5 years) and those with a longer period from the time of ovariohysterectomy to the onset of urinary incontinence (median 2.5 years) respond best. PPA is preferred to ephedrine because side effects are less severe; ephedrine has greater cardiovascular side effects and it tends to lose effectiveness over time.”2 In a multicenter, blinded, placebo-controlled trial, 50 dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were treated for 28 days with either PPA (1 mg/kg three times daily) or placebo. At day 28, 85.7 per cent of PPA-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases.3

Potential side effects include restlessness, irritability, hypertension and anorexia. Numerous drug interactions exist.

In November2000, human PPA preparations were removed from the market due to reports of serious side effects in humans. PPA continues to be available as a bulk chemical for veterinary use only.

1 Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, ed. pp.193-5, and 508-9

2 Handbook of Veterinary Drugs, 2nd edition, pp. 277-8

3 J Small Anim Pract. 2002 Nov;43(11):493-6
Evaluation of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.
Click here to access the PubMed abstract of this article.

4 http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/191024.htm&word=ppa

Per your prescription, we can compound customized dosage forms to meet the specific needs and flavor/texture preferences of each animal.

 


 

Piroxicam for Canine Bladder Cancer

Traditional chemotherapy (using cisplatin, carboplatin, adriamycin, and others) has been used in canine Transitional Cell Carcinoma (TCC). The response has been rather disappointing with <20% of dogs having remission.

Interest in non-steroidal anti-inflammatory (NSAID) therapy began when dogs with various forms of spontaneous cancer had remission while receiving the NSAID piroxicam for pain control, and no other therapy. Two of the first dogs treated (one with metastatic carcinoma, one with undifferentiated sarcoma) had advanced cancer and had remission of their cancer when only receiving piroxicam. This has led to numerous studies of piroxicam in animals with cancer at Purdue University Veterinary Teaching Hospital (PUVTH). In an attempt to improve the response of TCC to therapy, PUVTH conducted a study comparing chemotherapy (cisplatin) alone to chemotherapy plus piroxicam. The combination of cisplatin and piroxicam was more effective against the cancer, but the combination treatment caused a rise in BUN. In several instances, the cisplatin therapy was withdrawn (so as to not cause renal damage) while the tumors were still shrinking.

In a phase I study of piroxicam in 62 dogs with various histopathologically confirmed, measurable tumors, gastrointestinal toxicity was dose-related and dose limiting, but anti-tumor activity occurred at lower, less toxic doses of piroxicam. Partial remission occurred in 8 dogs, including 3 of 10 dogs with TCC. A phase II clinical trial of piroxicam in dogs with histologically confirmed, measurable, nonresectable TCC was performed. The dogs lived at home with their owners and were evaluated at the PUVTH at monthly intervals. Piroxicam was given orally at a dosage of 0.3 mg/kg every 24 hours (the accepted canine dosage prior to this trial). Tumor response in 34 dogs included 2 complete remissions (CR), 4 partial remissions (PR), 18 stable disease (SD), and 10 progressive disease (PD). Piroxicam therapy was generally well tolerated, with gastrointestinal toxicity noted in six dogs and renal papillary necrosis in two dogs. The median survival was 180 days. Fifty-five additional dogs were treated with piroxicam, and tumor response included 2 CR, 7 PR, 32 SD, and 14 PD.

It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has metasticized. The median survival in dogs treated with cisplatin or carboplatin at PUVTH was 130 days. Median survival with piroxicam treatment in 55 dogs with TCC was 190 days. The survival times in all of these studies, however, vary tremendously from only a few days to more than one year. Longer survival times have been reached when chemotherapy is combined with piroxicam, but the optimal combination treatment is still being determined.

Cancer Chemother Pharmacol 1992;29:214-218
Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors.
Click here to access the PubMed abstract of this article.

J Vet Intern Med 1994;8:273-278
Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder.
Click here to access the PubMed abstract of this article.

Cancer Chemother Pharmacol 2000;46:221-226
Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer.
Click here to access the PubMed abstract of this article.

Urologic Oncology 2000;5:47-59
Naturally-occurring canine transitional cell carcinoma of the urinary bladder: A relevant model of human invasive bladder cancer.

 


 

Citrate Salts as Alkalinizing Agents
Citrate salts are a source of bicarbonate, but are much more palatable than bicarbonate preparations. “They are used as urinary alkalinizers when an alkaline urine is desirable and in the management of chronic metabolic acidosis accompanied with conditions such as renal tubular acidosis or chronic renal insufficiency. Potassium citrate alone has been used for the prevention of calcium oxalate uroliths. The citrate can complex with calcium thereby decreasing urinary concentrations of calcium oxalate… When urine is alkalinized by citrate solutions, excretion of certain drugs (e.g. quinidine, amphetamines, ephedrine, …tetracycline) is decreased, and excretion of weakly acidic drugs (e.g. salicylates) is increased. The solubility of ciprofloxacin and enrofloxacin is decreased in an alkaline environment [and patients] should be monitored for signs of crystalluria.” (Plumb’s Veterinary Drug Handbook, 2nd ed.) In combination with potassium citrate preparations, these agents may lead to severe increases in serum potassium levels: NSAIDs, ACE-inhibitors, cyclosporine, digitalis, heparin and others.

Fludrocortisone Acetate
Fludrocortisone is a long-acting corticosteroid with potent mineralocorticoid and moderate glucocorticoid activity. It is used in small animal medicine for the treatment of adrenocortical insufficiency, where it promotes sodium retention and urinary potassium secretion. It is commercially available only as the human product, a tablet containing 0.1 mg fludrocortisone acetate. The maintenance therapy for animals (particularly dogs) can require administration of multiple tablets for each daily dose. Therefore, it may be more convenient for owner and animal to administer fludrocortisone acetate as a flavored suspension, or single flavored solid dosage form.

Aluminum Hydroxide for Hyperphosphatemia
For dogs and cats, aluminum hydroxide is initially dosed at 30 – 90 mg/kg orally one to three times daily. A preparation that can be mixed with food may be preferred as it is more easily dispersed throughout ingesta. Dosage must be individualized, and serum phosphate levels should be evaluated at 10-14 days to determine optimum dosage.

Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 48-49

 


 

Calcitriol for Chronic Renal Failure
Submitted by Shirley Russman, D.V.M.

Our protocol for treating chronic renal failure includes a special diet, adequate hydration, potassium supplementation, stomach acid control and calcitriol therapy to control phosphorus levels. Calcitriol (a vitamin D3 metabolite) may also be used to prevent or reverse secondary hyperparathyroidism in dogs and cats with chronic renal failure.

Calcitriol is dosed in nanograms. Commercially available products are for humans, and the dose is much too high for dogs or cats (for example, the capsule contains 250 nanograms or 0.25 micrograms). Our compounding pharmacist has been able to prepare any capsule (8 nanograms and up) or liquid (i.e. 4 nanograms/0.25ml) necessary to meet our needs. We have used this compounded remedy over one hundred times and have found it to be very successful in lowering phosphorus levels in our patients with chronic renal failure. Serum calcium levels should be monitored as hypercalcemia is a possible consequence of calcitriol administration.

Editor’s Note:

Calcitriol “has a rapid onset of action (1-4 days) and a short half-life (4-6 hours). Oral calcitriol is administered to patients after initial stabilization with fluid therapy, dietary protein and phosphorus restriction, the use of intestinal phosphate binders and H-2 blockers as needed. Serum phosphorus should be less than 6 mg/dL (1.9 mmol/liter) before initiating calcitriol.

“Hypercalcemia usually only occurs if calcitriol is used in conjunction with intestinal phosphate binders, especially calcium carbonate… Long-term use of phenytoin and the barbiturates may interfere with the action of the drug, necessitating higher doses of calcitriol… Thiazide diuretics may enhance the effects of calcitriol predisposing to hypercalcemia. Calcitriol-induced hypercalcemia may antagonize the antiarrhythmic effects of calcium channel-blocking agents.”

Handbook of Veterinary Drugs, 2nd edition, pp. 105-106

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