Veterinary

Your Pets Care, Customized.

Your Pets Need More Sometimes.

Our compounding pharmacy can prepare:

  • Flavored medication
  • Medicine in ideal size, strength, and dosage form
  • Unavailable medications
  • Combinations to improve compliance
  • Novel devices and delivery systems

Compounding is actually a means to an end. We work together with veterinarians and their clients and patients to solve medication problems by compounding specialized medications that meet the unique needs of each animal - pets, exotics, horses, or zoo animals. Let us know how we can help you and the animals in your care.

Our "specialty service should not be viewed as competition with local veterinarians; rather, compounding allows veterinarians to broaden their prescribing abilities and to offer [dosage] forms that are patient-specific in strength and formulation. Therefore, the goal of compounding for the veterinary patient is to enhance the veterinarian's ability to treat patients in a more effective and efficient manner...

"Compounding can make medicating animals easier if the pharmacist prepares flavored chews that animals accept readily. For example, tranquilizing a feral cat with a liver-flavored chew eliminates the possibility of over- or underdosing. If a chew contains 10mg acepromazine and the dose fails to gain a response, a second flavored chew can be given to the animal. Furthermore, the amount of medication incorporated into the chews, capsules, [topical or transdermal], or liquid preparations can be formulated to the specific request of the veterinarian, thereby eliminating the need to cut-up tablets and divide the contents of commercially prepared capsules... As manufacturers decide that certain products are no longer economically rewarding to market, the list of commercially prepared veterinary medication becomes smaller. At present, the armamentarium of medications available for animals is less than perfect. Cherry-flavored amoxicillin or orange-flavored cephalexin may not be [appealing to a cat or monkey]..."

Avian

Doxycycline Administered in Drinking Water for Treatment of Spiral Bacterial Infection in Birds
 
Spiral bacteria have been found in various portions of the respiratory tracts of cockatiels and lovebirds.  Common signs of infection with this bacterium include red clogged nares, sneezing, reddened and blunted choanal papillae and pharyngeal redness. Infected birds may also show signs of lethargy, anorexia and weight loss. Conjunctivitis, sinusitis and periorbital swelling may also be noted but are less common signs.  A survey of 148 cockatiels seen by a veterinary practice in New York indicated that 37 (25%) were found to be infected with spiral bacteria with most of these having clinical signs of upper respiratory tract infection and red choana. The infection rate was higher in birds <2yrs old and in birds fed poor diets, suggesting that spiral bacteria are opportunistic organisms that cause clinical signs in young and compromised birds.
 

Spiral bacterial infections in cockatiels have been successfully treated with oral administration of doxycycline hyclate at 25mg/kg orally every 12 hours for 3 weeks. However, this regimen requires twice-daily capture and forced administration of doxycycline liquid suspension, which is apparently not palatable to birds. The stress caused by this regimen to both birds and owners caused researchers at the North Carolina State University College of Veterinary Medicine to determine the feasibility of administering doxycycline via drinking water.  A group of 11 cockatiels naturally infected with spiral bacteria were offered solutions of doxycycline at 400mg per liter as the sole source of drinking water and 7 other naturally infected cockatiels acted as the control group receiving untreated tap water as the sole source of drinking water for a treatment period of 30 days.  For the first 14 days, spiral bacteria were isolated from all 18 birds in both the treatment and control group, but after day 21, spiral bacteria were no longer seen in the treatment group.
 
For this study, doxycycline drinking water was prepared by emptying the contents of 4 x 100 mg doxycycline hyclate capsules into a liter of deionized water and stirring with a magnetized stirrer for 4 minutes and made fresh every 24-36 hours.  As most bird owners do not have magnetic stirrers at home, and as the doxycycline hyclate capsules contain excipients other than doxycycline that do not go into solution and settle out at the bottom of the drinking bowl, our compounding pharmacy can provide bird owners with a more efficient method of doxycycline hyclate delivery by preparing 400mg capsules or packets of pure doxycycline hyclate, which the owner can stir into a 1 liter bottle of sterile water for irrigation (eliminating the possibility of contamination as well as preventing any binding of doxycycline by cations in tap water). It is interesting to note that doxycycline monohydrate is more palatable than doxycycline hyclate, but unfortunately, doxycycline monohydrate is not soluble in water and would not be a useful salt for this method of drug administration.   

Antifungal Therapy for Avian Species
In avian species, the most frequent causes of infection have shifted from gram-negative bacteria to gram-positive bacteria and Candida (often non-albican) species. There is a decreased susceptibility of many non-albicans species to available antifungal drugs, perhaps as a consequence of nondiscriminate azole use.

The efficacy of terbinafine has been improved when administered in combination with azoles for treatment of azole resistant oral candidiasis and aspergillosis. Because terbinafine was administered successfully in an African gray parrot at 15 mg/kg every 12 hours for 30 days without adverse effects, it may have potential for use in systemic aspergillosis in these azole-sensitive species. Caution should be used in avian patients with liver or renal disease.

Enrofloxacin in Birds
Enrofloxacin is highly active against most gram-negative bacteria. Doses of 15 mg/kg orally twice daily have maintained effective drug concentrations in most of the psittacine species that have been tested. Senegal parrots have required TID dosing for moderately resistant organisms. Keven Flammer, DVM, Dip ABVP, reports successful treatment of E coliKlebsiella, and Proteus infections. He states that oral administration is well tolerated, but that IM administration should be avoided, and never used for repeated dosing, due to irritation at the site of injection. The IM formulation can be given orally but is unpalatable, even when mixed with flavoring. Dr. Flammer notes that an oral suspension can be compounded and appropriately flavored.

Haloperidol for Feather-Plucking and Self-Mutilation
Neuropeptides, particularly dopamine, are implicated in many self-mutilating disorders. The 1993 Proceedings of the Association of Avian Veterinarians (pg. 119-120) reports the dopamine antagonist  haloperidol is currently being used on cockatiels, lovebirds, ring-neck parakeets, African Greys, and several species of cockatoos and Amazon parrots.  The indications for use in these birds have included severe feather plucking, mutilation of skin and muscle over the back, chest and legs, wing web mutilation, and Amazon foot necrosis syndrome.  Side effects from the use of haloperidol have included depression, depressed appetite, excitability and anorexia. (In most birds, side effects disappeared after discontinuing the drug for several days and then retrying at a lower dose.)  One study reported normal behavior was maintained "by administering haloperidol at approximately 0.4 mg/kg body weight/day for approximately seven months."

Haloperidol for Feather Plucking
by Stacie Fowler, D.V.M., Texas

Signalment:  "Echo", adult male Eclectus Parrot

Chief Complaint:  Feather picking of 4-6 years duration

Diagnosis:  Previous veterinarian had done numerous tests in 1993 to rule out medical causes of feather picking and the final diagnosis was psychological behavioral feather picking.

Feather Picking:  This is a common syndrome in pet "parrot-type" birds that can have medical and/or psychological causes. It is  important to rule out all medical causes of this condition before initiating psychotropic drug therapy. It is also important to institute appropriate dietary and environmental changes as well as behavioral therapy along with psychotropic drug use.

Past History and Medications:  Echo first started picking at his feathers in 1991.  By November of 1994 he had pulled out all his feathers except those which he could not reach on his head. In December of 1994, Echo's previous veterinarian started him on naltrexone (dose unknown) for behavioral feather picking. He failed to respond to this drug and was placed in an Elizabethan collar on 4/20/95 to prevent further plucking.  The author first saw this patient on 1/10/97. He had been wearing the collar almost constantly since 4/95 and all his feathers were in place (but ragged and unkempt looking) except under the collar. Anytime the collar was removed the patient would rip his feathers out.  The owners wished to try Prozac? for Echo's problem but since this author has had little success with Prozac?, we started trials on other drugs. Along with changes in diet and environment and behavioral exercises, we started Echo on Aventyl? elixir at 1/4 teaspoon per 4 ounces of drinking water to be replaced with fresh twice daily. We also initiated every other daily misting of the feathers with a dilute Aloe and Penetran? suspension. By 3/8/97, Echo was still plucking too many feathers when the collar was removed.  To his Aventyl? therapy, we added naltrexone compounded to 5 mg/ml in a strawberry flavored base, 0.16 ml by mouth twice daily. By 3/20/97 he was still plucking badly when the collar was removed. 

The Aventyl and naltrexone were discontinued and we did a brief trial on diazepam 2 mg per 4 ounces of drinking water. The diazepam is not meant to sedate and the owner was instructed to increase the dose to a maximum of 10 mg per 4 ounces of water if feather plucking continued but only if no sedation was noted. The diazepam produced no change in behavior and caused too much sedation for Echo.  On 4/10/97 we began a trial on haloperidol 2 mg/ml at .015 ml by mouth once daily. The owners were instructed that they could increase the dose to maximum of .06cc of 2 mg/ml haloperidol twice daily. By 5/7/97, Echo's owners reported that they were giving .075 cc of 2 mg/ml haloperidol twice daily and he seemed to be responding nicely. On 5/17/97 the haloperidol was refilled and compounded to 1 mg/ml to facilitate easier measuring.  As of 9/2/98, Echo is receiving haloperidol 0.15 mg by mouth twice daily. This is a higher dose than I have seen published in the literature but the owners are pleased with Echo's condition and do not wish to try a lower dose or even possibly wean him off the haloperidol. Echo is not experiencing any noticeable side effects from his haloperidol therapy. Currently, Echo never wears his Elizabethan collar and is totally feathered in except for his neck. I believe that 2 years of constant pressure from the collar has caused atrophy of the feather follicles around the neck.

Equine

Pododermatitis in Exotic Animal Species

Pododermatitis, or “Bumblefoot”, is literally inflammation of the feet. Although most commonly associated with avian species, this disease also occurs in other exotic animal pets including rats, mice, and guinea pigs. Bumblefoot is multifactorial, with many contributing factors that lead to loss of integrity of integument of the feet and excoriation, ulceration, cellulitis, and abscessation, as well as bacterial infection, most often Staphylococcus aureus, but also E. coli and others. Common predisposing factors are puncture wounds, burns, trap injuries, inappropriately shaped perches or cage bottom surfaces, vitamin deficiencies, obesity, lack of exercise due to captive feeding habits. The clinical signs are swelling and inflammation on the plantar surface of the avian foot ranging from excoriation to full thickness ulceration and left untreated results in extensive loss of tissue and bone. Prevention is the best cure for pododermatitis in exotic animal species, because once Bumblefoot occurs, it can be difficult to cure.

The location of Bumblefoot lesions makes them particularly problematic to treat. Once a causative microbial organism is identified, local and systemic therapy with antibiotics is initiated, and a protective bandage is placed around the affected feet. Many exotic animal species will not tolerate such bandages, however, and will chew them off, often inflicting new lesions to the affected foot. Exotic animal veterinarians have tried various substrates (Nu-skin®, dental acrylic, gauze) to create protective bandages for pododermatitis but have met with mixed success. Recently, exotic animal veterinarians and compounding pharmacists have collaborated to develop adhesive and protective antibiotic containing bandages based in a water soluble powder resin of polyethylene glycol known as Polyox®. Polyox WSR-301 is made by Dow Chemical and is a novel way to deliver medication therapy to serosanguineous wounds while at the same time providing an occlusive protective bandage. It has been used in human patients suffering from decubital ulcers and is now being applied to veterinary patients. For example, birds suffering from pododermatitis caused by ticarcillin-susceptible species of Staphylococcus can receive both a systemic injection of ticarcillin as well as a compounded topical bandage of ticarcillin and analgesic in an adhesive dressing such as Polyox® that will provide antimicrobial action, pain relief and at the same time act as a protective “shoe” that does not interfere with the bird’s mobility. Veterinarians interested in applying this therapy to patients with pododermatitis or other ulcerative skin diseases should contact our compounding pharmacist for further information on Polyox® medicated bandages.

Proceedings of the Association of Avian Veterinarians. 1993:135-137.

The use of dental acrylic shoes for the treatment of bumblefoot.
Hess RE.

Would you like a topical medication that is difficult for an animal to lick off or that will adhere to a mucosal surface?

You can prescribe a medicated "polyox bandage" or "mucosal bandage". When moistened, this medicated preparation will adhere to a wound or mucosal surface, thereby providing a protective barrier and increasing the contact between the medication and the affected area.


Wound and Incision Care - Prevent Licking

A common problem encountered by veterinarians and animal owners is preventing an animal from licking an incision or licking medication from the area to which it has been applied. In addition to injury to the wound, pharmacists and veterinarians must consider the consequences of internal consumption of an external preparation. To prevent an animal from licking, a medication can be compounded to contain an extremely bitter substance. Choices include diphenhydramine, quinine, or the non-therapeutic ingredient sucrose octaacetate. Sucrose octaacetate can be added at 1% to 5% to any topical dosage form and the bitterness usually prevents the animal from repeated licking of the area of application. Another way to protect a medicated area from licking is to incorporate the needed medication into CAP (Cellulose Acetate Hydrogen Phthlate) solution. Since CAP solution does not dissolve in an acidic pH, the animal's saliva does not remove it from the skin. CAP solution can also be sprayed directly onto a wound or over stitches to protect them.



Phenytoin/Lidocaine Poly-Ox Bandage Used to Treat Leg Wound

Problem: Twenty-four hours after an automobile accident, an eight-month old female pit bull presented with a leg injury that appeared as if it would have difficulty healing. The dog had been hit by an automobile, which had scraped a hole in the right front leg. The wound, which extended from the elbow to the carpus, was approximately 3/4" to 1" wide.

Treatment: The tissue of the leg was stabilized using tension-relieving sutures. Because the veterinarian had prior successful experiences with other cases involving wound care, she requested we compound a topical preparation consisting of 2% phenytoin and 2% lidocaine in a methylcellulose/polyoxyethylene (poly-ox) bandage for the dog. The animal underwent hydrotherapy twice daily and the compounded medication was applied just before bandaging was secured.

Outcome: The wound was completely healed after 2 months of therapy and the animal has full use of her leg with no visible ill effects. According to the veterinarian, the animal healed much quicker than usual due to the increased contact time of the medications and she was satisfied with the treatment process.

We have also used this compound with the same positive success on a degloved feline after its paw had been caught in a fence overnight.

In April 1998, I was called to euthanize a 1 1/2 year old female miniature schnauzer that had been burned with hot water from the bath tub and washed in Woolite? 3-4 weeks earlier. The full thickness burns involved about 80% of the skin on the dorsal trunk from neck to tail and elbows to midthigh. The owners were using aloe vera to treat the burns and she had a severe infection, was emaciated (5 lb.) and had not eaten for one week. Since she had survived so long without treatment, I had the owners sign ownership over to me and I contacted the Central Dakota Humane Society. They agreed to take on this project despite the many hours of labor and the potential cost. The dog was immediately given an analgesic and antibiotics.

I literally stopped at the pharmacy with the dog so the compounding pharmacist could see what we were up against. At the pharmacist's suggestion, a Poly-Ox bandage containing phenytoin base 2% and misoprostol 0.002% was compounded and applied in a layered manner. Telfa? pads were used to cover the wound, and a T-shirt was put on to protect the bandages. The dog started eating canned food that night and in several days she was eating four large cans of food daily. In addition to the Poly-Ox bandage, she remained on Cefadrops? and Rimadyl?. She seemed to be uncomfortable and analgesics did not appear to control her pain. The powder was returned to the pharmacy and lidocaine 2% was added. Although this helped somewhat, the dog was becoming non-compliant at the time of her dressing changes. The compound was again modified to contain bupivacaine 0.2% to obtain an extended analgesic effect. This was a significant improvement and therapy continued for several months. As healing occurred, the dog began to experience itching in the regranulated skin and wound areas. Diphenhydramine was given orally along with the Rimadyl? and we began rubbing her stretched skin with Emu oil to keep it moist. Shortly thereafter, the dog "became a schnauzer again." Her activity level has increased greatly and we anticipate a complete recovery.

When I began treating this dog, I thought that skin grafting would be necessary. Due to the success of this therapy, no grafting will be needed. However, I don't expect hair regrowth and the epithelium will remain scarred and easily bruised.

Wound Care

Pododermatitis in Exotic Animal Species

Pododermatitis, or “Bumblefoot”, is literally inflammation of the feet. Although most commonly associated with avian species, this disease also occurs in other exotic animal pets including rats, mice, and guinea pigs. Bumblefoot is multifactorial, with many contributing factors that lead to loss of integrity of integument of the feet and excoriation, ulceration, cellulitis, and abscessation, as well as bacterial infection, most often Staphylococcus aureus, but also E. coli and others. Common predisposing factors are puncture wounds, burns, trap injuries, inappropriately shaped perches or cage bottom surfaces, vitamin deficiencies, obesity, lack of exercise due to captive feeding habits. The clinical signs are swelling and inflammation on the plantar surface of the avian foot ranging from excoriation to full thickness ulceration and left untreated results in extensive loss of tissue and bone. Prevention is the best cure for pododermatitis in exotic animal species, because once Bumblefoot occurs, it can be difficult to cure.

The location of Bumblefoot lesions makes them particularly problematic to treat. Once a causative microbial organism is identified, local and systemic therapy with antibiotics is initiated, and a protective bandage is placed around the affected feet. Many exotic animal species will not tolerate such bandages, however, and will chew them off, often inflicting new lesions to the affected foot. Exotic animal veterinarians have tried various substrates (Nu-skin®, dental acrylic, gauze) to create protective bandages for pododermatitis but have met with mixed success. Recently, exotic animal veterinarians and compounding pharmacists have collaborated to develop adhesive and protective antibiotic containing bandages based in a water soluble powder resin of polyethylene glycol known as Polyox®. Polyox WSR-301 is made by Dow Chemical and is a novel way to deliver medication therapy to serosanguineous wounds while at the same time providing an occlusive protective bandage. It has been used in human patients suffering from decubital ulcers and is now being applied to veterinary patients. For example, birds suffering from pododermatitis caused by ticarcillin-susceptible species of Staphylococcus can receive both a systemic injection of ticarcillin as well as a compounded topical bandage of ticarcillin and analgesic in an adhesive dressing such as Polyox® that will provide antimicrobial action, pain relief and at the same time act as a protective “shoe” that does not interfere with the bird’s mobility. Veterinarians interested in applying this therapy to patients with pododermatitis or other ulcerative skin diseases should contact our compounding pharmacist for further information on Polyox® medicated bandages.

Would you like a topical medication that is difficult for an animal to lick off or that will adhere to a mucosal surface?

You can prescribe a medicated "polyox bandage" or "mucosal bandage". When moistened, this medicated preparation will adhere to a wound or mucosal surface, thereby providing a protective barrier and increasing the contact between the medication and the affected area.


Wound and Incision Care - Prevent Licking

A common problem encountered by veterinarians and animal owners is preventing an animal from licking an incision or licking medication from the area to which it has been applied. In addition to injury to the wound, pharmacists and veterinarians must consider the consequences of internal consumption of an external preparation. To prevent an animal from licking, a medication can be compounded to contain an extremely bitter substance. Choices include diphenhydramine, quinine, or the non-therapeutic ingredient sucrose octaacetate. Sucrose octaacetate can be added at 1% to 5% to any topical dosage form and the bitterness usually prevents the animal from repeated licking of the area of application. Another way to protect a medicated area from licking is to incorporate the needed medication into CAP (Cellulose Acetate Hydrogen Phthlate) solution. Since CAP solution does not dissolve in an acidic pH, the animal's saliva does not remove it from the skin. CAP solution can also be sprayed directly onto a wound or over stitches to protect them.



Phenytoin/Lidocaine Poly-Ox Bandage Used to Treat Leg Wound

Problem: Twenty-four hours after an automobile accident, an eight-month old female pit bull presented with a leg injury that appeared as if it would have difficulty healing. The dog had been hit by an automobile, which had scraped a hole in the right front leg. The wound, which extended from the elbow to the carpus, was approximately 3/4" to 1" wide.

Treatment: The tissue of the leg was stabilized using tension-relieving sutures. Because the veterinarian had prior successful experiences with other cases involving wound care, she requested we compound a topical preparation consisting of 2% phenytoin and 2% lidocaine in a methylcellulose/polyoxyethylene (poly-ox) bandage for the dog. The animal underwent hydrotherapy twice daily and the compounded medication was applied just before bandaging was secured.

Outcome: The wound was completely healed after 2 months of therapy and the animal has full use of her leg with no visible ill effects. According to the veterinarian, the animal healed much quicker than usual due to the increased contact time of the medications and she was satisfied with the treatment process.

We have also used this compound with the same positive success on a degloved feline after its paw had been caught in a fence overnight.

Therapy for Severe Chemical Burns
by Barbara Espe, D.V.M., North Dakota

In April 1998, I was called to euthanize a 1 1/2 year old female miniature schnauzer that had been burned with hot water from the bath tub and washed in Woolite? 3-4 weeks earlier. The full thickness burns involved about 80% of the skin on the dorsal trunk from neck to tail and elbows to midthigh. The owners were using aloe vera to treat the burns and she had a severe infection, was emaciated (5 lb.) and had not eaten for one week. Since she had survived so long without treatment, I had the owners sign ownership over to me and I contacted the Central Dakota Humane Society. They agreed to take on this project despite the many hours of labor and the potential cost. The dog was immediately given an analgesic and antibiotics.

I literally stopped at the pharmacy with the dog so the compounding pharmacist could see what we were up against. At the pharmacist's suggestion, a Poly-Ox bandage containing phenytoin base 2% and misoprostol 0.002% was compounded and applied in a layered manner. Telfa? pads were used to cover the wound, and a T-shirt was put on to protect the bandages. The dog started eating canned food that night and in several days she was eating four large cans of food daily. In addition to the Poly-Ox bandage, she remained on Cefadrops? and Rimadyl?. She seemed to be uncomfortable and analgesics did not appear to control her pain. The powder was returned to the pharmacy and lidocaine 2% was added. Although this helped somewhat, the dog was becoming non-compliant at the time of her dressing changes. The compound was again modified to contain bupivacaine 0.2% to obtain an extended analgesic effect. This was a significant improvement and therapy continued for several months. As healing occurred, the dog began to experience itching in the regranulated skin and wound areas. Diphenhydramine was given orally along with the Rimadyl? and we began rubbing her stretched skin with Emu oil to keep it moist. Shortly thereafter, the dog "became a schnauzer again." Her activity level has increased greatly and we anticipate a complete recovery.

When I began treating this dog, I thought that skin grafting would be necessary. Due to the success of this therapy, no grafting will be needed. However, I don't expect hair regrowth and the epithelium will remain scarred and easily bruised.

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.

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 

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.

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.

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.

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.

Seizure Control

Potassium Bromide for Seizures
by Mollyann Holland, D.V.M., Oklahoma City, OK
Diplomate, American College of Veterinary Internal Medicine

Potassium bromide is frequently helpful in treating refractory seizures in animals. Because potassium bromide is excreted renally, it may also be preferable for use in animals that have developed hepatotoxicity while on other anticonvulsants. My compounding pharmacist prepares this as a liver flavored solution, which can easily be administered to dogs. I feel that it is important to inform my animal owners that potassium bromide solution is compounded from a reagent grade chemical, and is not a commercially available "drug."

KBr is dosed on a weight basis. Maintenance doses range from 20-100 mg/kg body weight/day, and can be given as a single or divided dose. I usually dose at 30-40mg/kg/day as a single dose with food. Due to its long half-life, KBr can take up to four months to reach steady state; therefore, a loading dose may be required if therapeutic blood levels must be reached quickly. The loading dose is 400-600 mg/kg body weight and is administered orally over 30 to 60 minutes to avoid vomiting. A loading dose is not necessary if it is possible to keep the animal on other medications (as in a case of emerging hepatotoxicity) until levels of bromide are therapeutic (0.5-1.5 mg/ml), when the other anticonvulsant can be tapered off. 


Potassium Bromide Chewable "Treats" for Seizure Control 

Contributed by Steve Toney, R.Ph., Erin King, C.Ph.T. and Pam Woodin, D.V.M.

Case Report: 5 y.o. male Golden Retriever with seizure disorder. The owners called our compounding pharmacy to see what we could do as they were having difficulty administering medications to their dog. We suggested medicated canine treats that we have compounded many times with a 100% success rate. The veterinarian was consulted and we prepared potassium bromide (KBr) 150 mg treats coated with liver and beef flavored powder. The owner administers two treats two times daily, and the dog now loves to take his medicine!

Note: Chewable treats can be compounded to contain a variety of medications and flavored for the specific breed or pet. This dosage form has high patient acceptance and a low risk of owner misdosing.

Potassium bromide (KBr) can be also compounded as an oral solution which is easy to flavor and convenient for use as a loading dose. However, the risk of owner misdosing is greater than with a chewie or capsule.

Phenobarbital: Problems and Solutions

While phenobarbital is often used in veterinary medicine to treat seizure disorders, there are several concerns with its use:

  • there are no commercially available veterinary approved products
  • phenobarbital tablets for human use are small, hard, and unscored, making them difficult to divide for individualized dosing
  • phenobarbital elixir has a high alcohol content, which is problematic for cats or any species when chronically administered
  • phenobarbital induces CYP450 hepatic enzymes which can result in substantial drug interactions with oral anticoagulants, steroids, antibiotics, beta-blockers, theophylline, etc.
  • phenobarbital is contraindicated in dogs with hepatic disease

When you wish to prescribe phenobarbital, please be aware that our compounding pharmacy can prepare an alcohol-free, appropriately flavored oral suspension, which is highly bio-available and very easy to use when administering a loading dose or when a flexible dose is needed. Once the maintenance dose is established, the dosage form can be switched to a capsule (with a lower risk of misdosing by the owner) or a flavored chewable medicated "treat", with the added benefit of high patient acceptance.

Poisoning/Toxicosis

Xylitol Poisoning in DogsCompounding pharmacists are now receiving requests from veterinarians to compound oral medications for dogs and cats in vehicles that are known to be free of xylitol.  Xylitol is an artificial sweetener commonly used to sweeten human medications, gums, mouthwashes and candies, and while not toxic to humans, can be quite toxic to dogs.  Xylitol is not absorbed from the gastrointestinal tract of humans, but is easily absorbed in dogs.  Once in the bloodstream, xylitol acts like glucose, stimulating insulin secretion, which causes life-threatening hypoglycemia.  Profound hypoglycemia can last for 1-2 hours following xylitol ingestion, and has frequently resulted in death.  Many commercially available drugs labeled for humans, such as gabapentin oral suspension, contain xylitol as an inactive ingredient, and all human medications used in dogs should be scrutinized for xylitol content. Compounding pharmacists can play a valuable role for veterinarians and veterinary patients by providing xylitol-free suspensions of medications and by educating clients to avoid all xylitol-containing foods in their pets.  It is not currently known if xylitol is toxic in cats, but for the present, xylitol must also be assumed to be toxic to cats.  For more information, search "xylitol" at http://www.aspca.org/.



Apomorphine to Stimulate Vomiting

Emetic drugs are usually administered in emergency situations after ingestion of a toxin. "Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist)."
Apomorphine dosage for dogs: 4 mg/kg PO; 0.02 mg/kg IV; 0.3 mg/kg SC (from Merck Veterinary Manual, 8th edition, p. 1681); 0.25mg/kg (as a tablet) into the conjunctival sac (from Plumb's Veterinary Drug Handbook, p.51)



Accidental Poisoning 

"is not a rare event; and veterinarians need to have access to antidotes. However, there are relatively few products specifically labeled for use in these instances, so it has not really been legal for veterinarians to have previously prepared antidotes for poisonings on hand in emergency rooms. For example, if a case of lead poisoning is diagnosed and the veterinarian needs some calcium EDTA as an antidote, there is no product available labeled for use in animals... Compounding offers opportunities for facilities to have [items such as calcium EDTA] on hand ... for emergency treatment, in anticipation of a legitimate prescription." 
Intl J of Pharm Comp 1997 July/Aug; 1(4): 240

N-acetylcysteine as an Antidote for Acetaminophen Toxicosis 

   N-acetylcysteine (NAC) is the antidote of choice for the treatment of acetaminophen poisoning, one of the most common types of intoxication in dogs and cats. NAC acts principally by replenishment of intracellular glutathione stores and detoxification of the reactive metabolite (NAPQI). NAC acts as a scavenger of free radicals, blocks the conversion of hemoglobin to methemoglobin, and can reduce the extent of liver injury.
   Although NAC is most effective if administered less than 12 hours after ingestion of acetaminophen, the use of NAC as an antidote is still recommended up to 36 to 80 hours after acetaminophen ingestion. 
   Oral NAC, IV NAC, and IV sodium sulfate were evaluated as treatments for cats who had received toxic sublethal doses of acetaminophen (APAP). At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemo-globinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.
   To determine if rectally administered N-acetylcysteine (NAC) is absorbed into the systemic circulation, NAC was administered into the rectal vault (2.0 g/kg) of swine via a balloon-tipped Foley catheter inserted into the animals' rectums. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC to dogs. 
   In dogs and cats, NAC can be administered intravenously or orally, but has a pungent odor. Oral administration of NAC typically causes nausea and vomiting. The oral solution can be compounded as a chicken-flavored preparation to improve palatability. 
   Rapid intravenous administration of NAC can cause hypotension, bronchospasm, and flushing. Reactions can be minimized by slowing the rate of infusion.
   Activated charcoal may absorb NAC and reduce its effectiveness, so NAC should not be administered within two hours of giving activated charcoal. "Administration of activated charcoal may exacerbate vomiting and lead to aspiration. A strong antiemetic agent (metoclopramide 0.4 mg/kg IV) may be necessary to prevent emesis."
   NAC is currently not approved by the FDA for use in dogs and cats, but is available in human formulations, and upon a prescription order, can be compounded to meet specific veterinary needs.

Dimercaptosuccinic Acid for Lead Poisoning in Cats 
Wright Veterinary Medical Center, Bethlehem, PA

The owners of two nine-year-old cats moved to a new house. One week after moving, both cats were vomiting and losing weight so the owners brought the cats to the veterinary clinic. The veterinarian began intravenous hydration. Blood work showed a very high level of nucleated RBC's. The CBC revealed platelet clumps on feathered edge, few macrocytes, moderate anisocytosis, and occasional acanthocytes (54% and 45.1% NRBC). One cat had two seizures on the first day of hospitalization. Based on the initial signs and nucleated red cells, lead poisoning was suspected, although there was no radiographic evidence of lead ingestion. We tested for lead and began treatment with dimercaptosuccinic acid (DMSA) 40mg/cc.

The cats improved clinically within 24 hours. There were no more seizures and the cats began to eat. The blood lead levels were 164.8 and 210 (normal is 0-25). The cats were treated with 40mg (1cc) of DMSA given orally three times per day for a total of 10 days. DMSA is not commercially available in an injectable or liquid form. Therefore, we worked together with our compounding pharmacist to prepare a sterile formulation that would be suitable for intravenous or oral use.

The second day after therapy had begun, the owners informed us that they had been sanding the painted floors in their new house. The cats probably walked through the dust and in grooming themselves licked the lead paint off their paws. There have been no further problems with the cats to our knowledge. The owner declined to come in for a lead level recheck.



Penicillamine for Long-Term Treatment of Lead Poisoning

Penicillamine chelates a variety of metals, including copper, lead, iron and mercury, forming stable water-soluble complexes that are excreted by the kidneys. Used primarily for its chelating ability in veterinary medicine, it is the drug of choice for copper storage-associated hepatopathies in dogs at a dose of 15mg/kg PO twice daily. Penicillamine may also be used in cystine urolithiasis (penicillamine combines chemically with cystine to form a stable soluble complex that can be readily excreted) and in a different dose for the long-term oral treatment of lead poisoning. "This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested. 1) Give the same total daily dose, but divide into smaller individual doses and give more frequently. 2) Temporarily reduce the daily dose and gradually increase to recommended dosage. 3) Give with meals (will probably reduce amount of drug absorbed)."

Veterinary Drug Handbook, 2nd edition, Donald C. Plumb, Ed. 


4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning
 
Therapy for ethylene glycol poisoning is aimed at preventing absorption, increasing excretion, and preventing metabolism of ethylene glycol to its toxic metabolites. Inhibition of liver alcohol dehydrogenase (ADH), the enzyme responsible for the initial reaction in the metabolic pathway, can be accomplished by giving a compound that combines with the enzyme and renders it inactive. The most effective ADH inhibitor in the dog is 4-methylpyrazole (4-MP), which unlike most competitive inhibitors (ethanol, propylene glycol, and 1,3-butanediol) does not contribute to CNS depression and increased serum osmolality. The recommended dose of 5% (50mg/ml) 4-methylpyrazole is 20 mg/kg body weight IV initially, followed by 15 mg/kg IV at 12 and 24 hr, and 5 mg/kg at 36 hr. While 4-MP is the recommended therapy in dogs, it is not appropriate for use in cats. Although it is non-toxic, it does not effectively inhibit EG metabolism unless administered to a cat at the same time as consumption of EG.

Am J Vet Res 1995;56:825.

Pain Management

Gabapentin for Pain Management

Although the mechanism of action remains largely unknown, gabapentin is a useful adjunct in management of chronic pain in small animals. Recommended doses vary considerably. Anticonvulsant dosages range from 10-30mg/kg q8hrs (dogs) and q8-12hrs (cats). However, analgesic dosages for chronic pain management are substantially lower ranging from 3mg-10mg/kg orally every 8-12hrs, although dosages as high as 30mg/kg orally every 8 hours have been employed. Peak blood levels occur in about 2 hours and the most commonly reported side effect is drowsiness. 

Gabapentin is approved for use in humans and is available in various capsule and tablet strengths as well as a 50mg/ml oral solution. The oral solution, however, contains 300mg/ml xylitol as a sweetener making it inappropriate for use in dogs. The lowest strength solid dosage form available is a 100mg capsule which pet owners cannot reliably split into smaller doses. Small dogs and cats must receive compounded doses of gabapentin to achieve an appropriate dose and to avoid xylitol exposure. Our compounding pharmacists are able to prepare a gabapentin 100mg/ml xylitol-free oral suspension that can be flavored according to patient preference and is stable for 3 months in the refrigerator. Gabapentin capsules, treats and powders to mix with food may also be compounded. A clinical trial is currently underway at NC State College of Veterinary Medicine to determine safety and efficacy of compounded gabapentin transdermal gel for cats.

Transmucosal Buprenorphine: More is Better For Dogs and Horses
 
The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection.  Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats.  It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).
 
Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20 mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection.   A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6 mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.
 
For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use.   Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses. 

Gabapentin in a Xylitol-Free Formulation

Gabapentin is only approved for use in humans, but is widely used in veterinary medicine for both analgesia and neuroleptic indications.Dosed at 10-15mg/kg orally up to three times daily, this drug has become a valuable adjunct in veterinary therapies.Historically, gabapentin was available as a 100 mg scored tablet, enabling dosing of small animals (e.g. those weighing 5 kg or less) by quartering or halving tablets. Recently, gabapentin 100 mg tablets have been discontinued by all manufacturers, resulting in gabapentin 100 mg capsules being the smallest solid dosage form of gabapentin on the market.Because these capsules cannot be easily divided into smaller doses by pet owners, veterinarians have considered using Neurontin® (gabapentin) 50mg/ml oral solution to dose smaller patients.Unfortunately, Neurontin® Solution contains 300mg/ml of xylitol, an artificial sweetener which is known to cause profound hypoglycemia and hepatic necrosis in dogs at single doses of 100mg/kg. Dogs receiving doses of 0.3ml/kg of Neurontin® daily will be exposed to potentially toxic doses of xylitol.For this reason, veterinarians are turning to compounding pharmacists to compound patient-specific doses of gabapentin in capsules or treats, or compounded suspensions of gabapentin that do not contain xylitol.

Gabapentin is also used quite frequently in cats at small doses.  It is not known if cats have the same problems with xylitol that dogs do, but many cats dislike the strawberry taste of Neurontin® liquid, so the compounded preparation is often an appreciated alternative.

Transmucosal Buprenorphine for Cats

The majority of an oral dose of buprenorphine is removed by hepatic first pass metabolism, therefore effective oral doses in dogs and cats may be cost prohibitive. Buprenorphine's uniquely alkaline pKa (8.24) allows it to be administered transmucosally (buccally) to cats by virtue of the high salivary pH of this species (8-9). Administered on the tongue or in the cheek pouch at doses of 0.01-0.03mg/kg up to every 8 hours, buprenorphine has become a widely used and easy to administer analgesic for cats. 

For cats, oral buprenorphine administration is not appropriate, as dosage forms such as oral suspensions encourage complete swallowing of the drug, delivering it to the gastrointestinal system where it will be almost entirely extracted by hepatic first pass metabolism and likely will NOT achieve analgesic blood levels. A preferable dosage form is a 0.3mg/ml solution for transmucosal administration; concentrations should not be lower than 0.3mg/ml as larger administered volumes risk being swallowed before absorption across buccal mucosa.

Some veterinarians also have reported anecdotal success by transdermal administration of buprenorphine at 0.03mg/kg every 8 hours. While there have been no scientific reports evaluating the efficacy of transdermally-administered buprenorphine in cats, a transdermal patch of buprenorphine is available in the United Kingdom and delivers buprenorphine transdermally to humans for up to 7 days.  Transdermal buprenorphine may prove to be a particularly effective analgesic for cats that have received extensive dental procedures and do not wish to have their mouths manipulated for buccal administration of drugs. 




Pain Management in Cats

Pharmacokinetic data developed in other species cannot be safely extrapolated to the cat. Feline deficiency of glucuronidation pathways results in slow metabolism of several NSAIDs, which prolongs the duration of effect and may lead to drug accumulation and toxicity.

Meloxicam, a COX2 selective NSAID, has demonstrated clinical efficacy for chronic pain, musculoskeletal pain, and routine soft tissue surgery with few side effects. Based on clinical experience, Lascelles of NCSU College of Veterinary Medicine, now recommends oral meloxicam doses for cats that are less than previously reported in the literature (0.1 mg/kg PO on day 1 followed by 0.05 mg/kg PO daily for 4-6 days, then 0.025 mg/kg daily for 10 days, then lowest effective dose).

Five days of oral treatment with meloxicam or ketoprofen for cats with painful locomotor disorders provided similar analgesia, but meloxicam drops were more palatable than ketoprofen tablets. Appropriately flavored preparations in a convenient dosage form are easier for owners to administer and allow for accurate dosing.

According to Robertson and Taylor, opioids have an unjustified reputation for causing mania in cats, but with refinements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine (0.1 - 0.3 mg/kg) is effective in a clinical setting. Oxymorphone and hydromorphone (0.05 - 0.1 mg/kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Buprenorphine (0.01 - 0.02 mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats.

Amitriptyline (starting dose 2.5 mg/kg PO, once daily) has been used to treat feline interstitial cystitis with few side effects, and there are anecdotal reports of its use for cancer and neuropathic pain management.

Some of the less conventional analgesics including the tricyclic anti-depressants and gabapentin may prove to play a useful role in chronic pain management, but controlled clinical trials are needed to establish the best doses for maximum efficacy. Other less traditional analgesics such as ketamine and local anesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management.

Meloxicam for Analgesia in Dogs

A clinical trial was conducted to evaluate the safety and efficacy of  meloxicam in dogs with chronic osteoarthritis. A scoring system assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior, and demonstrated significant reductions in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.

Ketoprofen

is a potent anti-inflammatory and analgesic which can be used for the management of surgical pain or chronic pain. The drug should not be given to animals with GI ulceration, impaired renal or hepatic function, or coagulation disorders. Ketoprofen should not be used preoperatively when noncompressible bleeding may be a problem. Occasional vomiting has been reported. When an NSAID or other drug that is potentially irritating to the GI tract is needed, topical preparations offer an excellent alternative. Pharmaceutical Research, Vol. 13, No. 1, 1996 reports (in humans) "a topical formulation of ketoprofen has been developed for the temporary relief of minor aches and pains of muscle and joints and to minimize gastrointestinal side effects after oral administration."

Otitis

Therapy for Chronic Canine Otitis 

   Treatment errors, over and under treatment, or inappropriate use of antimicrobial medication can result in a chronically diseased ear. The key to successful management of chronic canine otitis is early intervention, identifying a cause of the condition, and employing specific and appropriate therapy.
   Ears with highly proliferative, chronic disease require deep cleaning and flushing before any topical therapy can be expected to help resolve the condition. Should a myringotomy be performed, the contents of the middle ear can be aspirated as soon as rupture occurs, and the middle ear can be flushed with normal saline or Tris-EDTA using a feline, open-tipped urinary catheter. "Just before the animal wakes, Tris-EDTA and a topical antimicrobial solution should be instilled and a parenteral prednisolone administered." 
   "The pathogens isolated most frequently from chronic external and middle-ear infections include Staphylococcus intermedius, Malassezia pachydermatis, Pseudomonas species, Proteus species, Escherichia coli, and enterococcus. Selection of both systemic and topical antimicrobial medication is based on cytologic evaluation and culture and sensitivity results. Systemic antibiotics are mandatory... Treatment should continue until the infection is resolved (a minimum of 4 weeks). It is not uncommon for treatment of otitis media to continue uninterrupted for 8 to 12 weeks." 

Importance of Medication Vehicle
 

   "Topical antimicrobial therapy is an important part of the treatment regimen, and the vehicle is as important as the active ingredient. Most otic preparations are combination drugs (glucocorticoid plus antibiotic) in an oil or ointment base. Oils and ointments are occlusive, may hold or trap exudate, and may increase the risk of ototoxicity; such preparations are not desirable in cases of chronic otitis in which a moist exudate is present, the canal is stenotic, or the eardrum may be ruptured. The goal of treating a wet ear is to dry it. Solutions and suspensions are primarily composed of water; may contain an astringent (e.g., aluminum acetate); and are designed to evaporate over time, thus helping to dry the ear." Topical antibiotics that are selected initially should be adjusted when the culture and sensitivity results are known. 
   "There is no single topical otic preparation that will satisfactorily treat all conditions. Practitioners tend to dispense a product based on clinical impressions or pick a favorite product rather than selecting one that has specific application for the current condition." Direct application of medication to the ear canal will result in a higher concentration than that obtained with systemic medication. 
Once you have identified the problem, we can compound an otic preparation to most appropriately treat each animal.

Antimicrobial/Anti-inflammatory Otic Suspensions Anhydrous Preparations without Aminoglycosides

   It is desirable to move away from commercially available aminoglycoside-antifungal-steroid otic preparations to avoid animoglycoside induced ototoxicity. Use of a formulation that substitutes a fluoroquinolone for an aminoglycoside constitutes a more effective and less toxic therapy, and is preferred if a tympanum rupture is expected. The efficacy and tolerability of a fluoroquinolone-clotrimazole-dexamethasone (FCD) otic suspension (10 drops per affected ear once daily) was compared with a standard topical treatment containing polymyxin B, miconazole and prednisolone (PMP) in a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Treatments were equally effective, with a cure rate of 58.3% for the FCD prep and 41.2% for the PMP combination. Both medications were equally well tolerated by dogs, but FCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.

While it is a common practice in some veterinary offices to add dexamethasone injection to clotrimazole solution to create an otic preparation with both antifungal and anti-inflammatory properties, it is more desirable to use an anhydrous preparation in the ear to reduce the risk of bacterial growth in the warm, moist environment. Anhydrous preparations also tend to have longer shelf lives. Avoid using products such as miconazole solution which has a high alcohol concentration to avoid irritating a sensitive ear. 

Contact our compounding pharmacy for anhydrous otic preparations.




Helpful Hints Regarding Otitis Therapy

   Ototoxicity manifested as deafness or vestibular toxicity is a potential adverse effect of some medications used to treat otitis, such as aminoglycosides (tobramycin, gentamicin, amikacin and neomycin) and chloramphenicol. Numerous alternatives exist.
   Enrofloxacin, a fluoroquinolone effective against Pseudomonas species, can be compounded as a solution and applied to the ear canal twice daily. "Topical enrofloxacin may achieve a higher antibiotic concentration at the site more economically than systemic medication."
   Silver sulfadiazine is effective in vitro against Pseudomonas species, Staph aureus, Proteus species, and others; a 0.1% to 1% emulsion every 12 hours is adequate to kill Pseudomonas. 
   Topical otic products may contain potent glucocorticoids in ointment or oil bases. However, solutions may be a preferable vehicle, and it may be advisable to use a less potent steroid because the degree of absorption of topical steroids can not be controlled. We can compound a preparation containing your choice of steroid in the most appropriate vehicle to treat the condition.
   "Commercial otic drying agents should be avoided in inflamed, chronically diseased ears because most contain isopropyl alcohol and varying concentrations of benzoic, acetic, salicylic, or boric acid. Each of these products individually can be extremely irritating to an already traumatized epithelium."
   Acetic acid solution can be used to decrease the bacterial population by lowering the pH within the ear canal. Pseudomonas can be killed by 1 minute of contact with a 2% solution. This treatment is especially beneficial when the organism is resistant to other antibacterials. Staph and Strep may be killed by 5 minutes of contact with a 5% solution, according to Kirk's Current Veterinary Therapy XII Small Animal Practice. However, inflammation (which can be severe) is an occasional side effect of treatment with acetic acid concentrations higher than 2.5%.

The common therapy for fungal otitis externa in dogs utilizes an antifungal and topical steroid, sometimes in combination with systemic antibiotics. The three organisms which have been isolated and are thought to be the most common pathogens in recurrent canine otitis externa are Malassezia, Pseudomonas, and Proteus spp. Using a fluoroquinolone along with an antifungal, we are able to have good coverage on all virulent pathogens. For treatment of resistant infections, the synergism of norfloxacin and ketoconazole provides a broader spectrum of coverage than many other therapies, as ketoconazole is a more active antifungal than clotrimazole. We have utilized a compounded otic gel containing norfloxacin 1% and ketoconazole 1% more than 20 times with a very high success rate.
   Infectious otitis externa is a common disease in dogs. Systemic antibiotic therapy is not always required. Thirty-six dogs of mixed sex, breed, and age were treated for... the purpose of evaluating the efficacy of a ketoconazole 1% and norfloxacin 1% otic gel... Treatment consisted of 0.5 to 1.0 ml of the otic gel in each affected ear twice a day for 7 days. Results showed 91.66% satisfactory responses at 7 and 14 days treatment... Failures (8.33%) were related to Staphylococcus associated with Proteus, Malassezia, and Candida... The 7-day treatment was successful in 21 cases. However, since 12 dogs required 14 days of treatment, it would be sensible to recommend a 14-day therapy."

The authors reported the successful use of Tris-EDTA in the treatment of otitis externa. In 24 dogs with clinical otitis, the Tris-EDTA (tris[hydroxymethyl] aminomethane and ethylenediaminetetraacetate) combination was tested against Bacillus spp., Staphylococcus aureus, Candida spp., Pseudomonas aeruginosa, Esherichia coli, Proteus vulgaris, Trichosporon spp., and an a-streptococcus. "Fifteen of the 24 cases were acute; all were evaluated with bacterial culture before and after treatment. The treatment consisted of applying lavage solution to the ears t.i.d. until resolution or for three weeks if there was no clinical response. Dogs were examined for irritation of the ears after treatment... 23 of 24 cases were resolved; no adverse effects were seen, but duration of follow-up was not specified. The case that failed to respond was a chronic, mixed infection of E. Coli and Proteus spp.; inflammation was reduced, but the infection persisted. Most cases responded within one week, but P. aeruginosa infections required one to three weeks of treatment."

Tris-EDTA solution (buffered to pH 8.0) has a direct bactericidal effect on some bacteria by chelating metal ions in the cell wall. "Dogs with chronic disease (e.g. atopy, idiopathic seborrhea) will be predisposed to recurrent otitis; a topical antibiotic solution or Tris-EDTA used two to three times weekly may prevent an infection from occurring with each flare-up of the primary disease."
   The bactericidal effects of Tris-EDTA are synergistic with aminoglycosides. Although an antibiotic can be added to the Tris-EDTA solution, Patricia D. White, DVM, MS states that she prefers to use Tris-EDTA 5 to 10 minutes before the topical antibiotic. The Tris-EDTA/antibiotic combination is ineffective against yeast.

Endocrinology

Low Dose Trilostane for Canine Cushing’s Disease
 

Cushing's Disease (hyperadrenocorticism) is a common condition in older dogs, often mistaken for the aging process itself. Dogs get pot bellies, lose hair, drink and eat excessively, urinate in the house, and make owners begin to prematurely consider euthanasia. Yet, Cushing's disease is treatable and that treatment can result in a longer, more comfortable life for the dog and its owner.
 
  Trilostane is the most promising FDA-approved treatment for canine Cushing’s disease. Current FDA approved labeling for trilostane (Vetoryl™) lists the recommended dose at 3-6mg/kg body weight orally once daily, and Vetoryl™ capsules are available in strengths of 10mg, 30mg and 60mg.  Several studies conducted prior to US-approval of trilostane referenced effective doses ranging from 6-12mg/kg orally per day.  After noting that many dogs treated with trilostane at the labeled dose demonstrated symptoms of hypoadrenocorticism (Addison’s Disease), clinical endocrinologists at the University of California Davis College of Veterinary Medicine evaluated the safety and efficacy of lower doses of trilostane.  Investigators in this trial administered trilostane to dogs diagnosed with Cushing’s disease at doses ranging from 0.5-2.5mg/kg orally every 12 hours and evaluated dogs for therapeutic progress at 3 different treatment intervals over a total treatment period of 8-16 weeks. After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [n =3]). 
 
   Since many dogs that develop Cushing’s disease are smaller breed dogs weighing less than 9kg (e.g. terriers and poodles), the commercially available capsules (10mg, 30mg and 60mg) are too large for appropriate therapy. As a result of the UC-Davis study, many veterinarians are requesting compounding pharmacists to compound smaller doses of trilostane as capsules or oral suspensions. On September 11, 2009, the Center for Veterinary Medicine division of the Food and Drug Administration issued a statement to veterinarians and pharmacists that “trilostane can only be legally compounded by using FDA-approved VETORYL™ as the starting material”, and that “…trilostane should not be imported from other countries or compounded from (the) bulk (chemical)”. As Vetoryl™ is only available for sale to licensed veterinarians in the US, and use of the bulk chemical to compound trilostane will not be tolerated by FDA, veterinarians and pharmacists are advised to collaborate to ensure availability of safe and legal compounded dosage forms of trilostane for dogs requiring lower doses than are commercially available.

Phenoxybenzamine for Dogs with Pheochromocytoma
 
 Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. Therefore, at the School of Veterinary Medicine, University of California, Davis, it was hypothesized that dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs, and they conducted a retrospective medical record review of 48 dogs that underwent adrenalectomy for pheochromocytoma from January 1986 through December 2005. Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age, lack of intraoperative arrhythmias, and decreased surgical time. Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism

The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism.

PZI and Low-Dose Insulin
The commercial production of traditional beef &/or pork insulins has declined as most human diabetic patients (the majority of the consumers) are being switched to human insulin products because of the reduced risk of allergic reactions. Protamine zinc insulin occurs as a sterile suspension of insulin modified by the addition of protamine sulfate and zinc chloride, and has a long duration of action (up to 30 hours). Therefore, treatment of many dogs and cats has been accomplished with once daily dosing of PZI. 
U-20 and U-40 insulin allow for more accurate measurement of smaller doses required by many pets and birds. Use of U-100 insulin can result in morbidity or mortality caused by dosing errors.


 

Oral Anti-Diabetic Drugs
"may be appropriate for cats that are in good overall health with early or mild clinical signs of diabetes and those with owners who are unwilling or unable to administer insulin injections."1 The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Discontinuation of diabetogenic medications that may be contributing to insulin resistance is important.2

According to Deborah S. Greco, DVM, Ph.D., diplomate ACVIM, glipizide has been used successfully to treat diabetes mellitus in cats at a dosage of 2.5 to 5 mg two times daily, when combined with dietary fiber therapy. Dr. Greco recommends evaluating the patient weekly or every two weeks for a period of 2 to 3 months. If the fasting blood sugar decreases to less than 200 mg/dL, the glipizide should be continued at the same dosage and the cat reevaluated in 3 to 6 months. If the fasting blood glucose remains >200 mg/dL after 2 to 3 months of therapy and the cat is still symptomatic (polyuria, polydipsia, weight loss), glipizide should be discontinued and insulin therapy instituted. If the blood glucose remains >200 mg/dL and the cat becomes asymptomatic, glipizide should be continued indefinitely and the cat rechecked in 3-6 months.

Methimazole for Feline Hyperthyroid Disease 
"Methimazole is the drug of choice for the medical management of feline hyperthyroid disease. It is safer and more potent than propylthiouracil in blocking thyroid hormone synthesis. Use of the drug generally will bring serum T4 into normal ranges within 2 to 3 weeks... Adverse effects have been observed in approximately 15% of cats and generally are transient. Anorexia, vomiting, and transient lethargy have been reported. Serum antinuclear antibodies develop in many cats with long-term use of the drug. A glucocorticoid-responsive pruritus involving the face, ears, and neck may occur. In less than 2% of cases, thrombocytopenia or agranulocytosis have been reported in cats treated with [methimazole]. Withdrawal of the drug and provision of care for thrombocytopenia or agranulocytosis generally results in resolution... Cats on chronic methimazole therapy should be rechecked every 3 to 6 months to assay serum T4 levels and to check for signs of drug toxicity."

Handbook of Veterinary Drugs, 2nd edition, ©1998, pp. 239-240

According to the International Journal of Pharmaceutical Compounding (Vol. 5, No. 2, March/April 2001, p. 96), "it could be theorized that transdermal administration would produce a ... higher blood level of methimazole than that resulting from oral administration of the drug. A higher blood level of [methimazole] might result in a slightly greater risk of adverse effects, so drug therapy might need to be initiated at a slightly lower dose than that of the traditional oral dose." The author of the article (GiGi Davidson, R.Ph., DICVP, North Carolina State University, College of Veterinary Medicine) states that anecdotal evidence indicates that this is true of "most transdermally administered doses of methimazole. The most measurable parameter for efficacy is the response of the serum T4 level."

Note: Methimazole is also used to decrease renal toxicity of cisplatin in dogs.

Transdermal Methimazole Applied to Ear of Hyperthyroid Cats
Francis Arsenault, D.V.M., New Brunswick

The following six cats have received methimazole in a pluronic lecithin organogel (PLO) which the owners apply to the inner side of the ear. Overall, we have found this to be very effective therapy with good compliance. Transdermal administration can be particularly helpful for owners who have arthritis and those who have great difficulty "pilling" the cat. Methimazole doses have ranged from 2.5mg to 12.5 mg daily, divided into two doses.

Cat #1 (S.A.): 17 years old, has been on methimazole 1.25mg/0.1 ml PLO to inside of ear twice daily for nine months. The owner reports that the medicine is easy to administer and absorbs well. I am pleased with the clinical results.

Cat #2 (A.L.): 18 years old, has been using methimazole for six months. This cat was started on 3.5mg/0.1ml PLO BID. Several dosage adjustments were necessary. We increased the concentration of the transdermal gel to 5.0mg/0.1ml PLO, and the owner now applies 7.5mg/0.15ml PLO in the AM and 5mg/0.1ml in the PM. She places plastic wrap over her finger before applying the medication, which she has found to be much easier to use than pills, with no stress to the pet. She states the measurements on the topical dispenser are easy to read, and she needs to wash the cat's ear to remove the coating left by the medication.

Cat #3 (B.M.): was started on methimazole eight months ago at 5mg/0.1ml PLO BID. The dose was decreased to 2.5mg BID. The cat's owner stated the medication was very easy to use. B.M. improved clinically and gained weight, and is no longer on the med.

Cat #4 (S.O.): used medication once only.

Cat #5 (D.O.): same owner as cat #4, received methimazole 2.5mg/0.05ml PLO BID for two months. No longer on medication.

Cat #6 (M.B.): 19 years old, has received methimazole 1.25mg/0.1ml PLO BID for four months. The owner says the medication is easy to apply, and alternates ears. It is necessary to wipe the ear each day as the medication does leave a residue.

Adrenal Disease in Male Ferrets
Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of androgens and/or estrogens, and can cause hair loss, itching, vulvar enlargement in females, prostate enlargement in male ferrets which can block the flow of urine, and in rare cases, bone marrow suppression. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated. 
Flutamide is an androgen blocker that may help relieve prostatic enlargement. It is dosed at 10 mg/kg, PO, every 12-24 hours. Liver enzymes should be checked at one month and every six months thereafter. Mitotane may be effective in younger ferrets but may cause nausea and lethargy. Ketoconazole is usually ineffective.

Mitotane for Canine Hyperadrenocorticism
In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyper-adrenocorticism (PDH) and palliative therapy of adrenal carcinoma, usually in dogs. Systemic drug availability has been found to be very poor from intact tablets in fasted dogs, and best when the powdered drug is mixed in oil and poured on dog food. The interaction between food and mitotane probably contributes to the variation in clinical response of dogs treated with the drug, because it appears that the efficacy is improved considerably when the drug is given with food. Because of the potentially severe toxicity associated with mitotane, clients should be instructed to wear gloves during and wash their hands after administering the medication, and to keep the medication out of reach of children or pets. Dogs with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period, and should be closely monitored until they are clinically stable. Clients should be advised of the symptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated with mitotane, clients should be instructed to wash their hands after administration and to keep the medication out of reach of children or pets.

Dermatologics

Alternative Therapies for Atopy
Dogs with atopic dermatitis (AD) often have concurrent allergies and are prone to relapsing skin and ear infections, which significantly contribute to their discomfort level. Much research has been done in recent years to identify effective and safe alternative treatments. Percutaneous absorption of allergens may be the most relevant route of exposure in dogs. Topical therapy may reduce the amount of allergen absorption through the skin. Several preparations, including glucocorticoids and anesthetics, can be used to reduce pruritus and provide analgesia. 
Cyclosporine , misoprostol, pentoxifylline, and various antihistamines have been effective.

Compendium 2001 May 23(5):454-60

Tetracycline/Niacinamide for Dermatology
The combination of tetracycline and niacinamide is being used for a continually expanding list of dermatologic disorders thought to be of immune-mediated origin. Diseases that may be controlled with this combination include discoid lupus erythematosus, pemphigus erythematosus, vesicular cutaneous lupus erythematosus (idiopathic ulcerative dermatosis) in Collies and Shetland Sheepdogs, pemphigus foliaceus, lupoid onychodystrophy, metatarsal fistulae in German Shepherds, sterile panniculitis, sterile granulomatous/pyogranulomatous dermatitis, vasculitis, cutaneous histiocytosis, idiopathic lymphocytic/plasmacytic ear margin dermatitis, and nodular granulomatous episcleral keratitis.

Antihistamines in Horses
Practitioners may prefer to use antihistamines to reduce urticarial reactions and reduce pruritus in horses because these drugs usually have fewer side effects than steroids. The American Quarter Horse Association recommends a 10 day withdrawal prior to any competition.

Prednisone Administered as a Transdermal Gel to Treat Allergic Dermatitis in a Cat
Submitted by Janna L. Love, Pharm.D.

A 5 y.o. female feline presented with allergic dermatitis accompanied by severe scratching and hair loss.

The cat had previously been treated with oral prednisone tablets. As the owner was unable to "pill the cat", she had tried to crush the tablets and mix with milk or tuna juice, but the cat still would not take the medication.

It has been our experience that transdermal gels work wonderfully in cats. An owner does not have to fight the animal to get a tablet down the cat's throat, and does not have to worry about whether the animal has received the correct dose, as the prescribed amount of gel can be massaged into the vascular surface inside the cat's ear.

The veterinarian prescribed Prednisone 5 mg/0.1 ml in a transdermal gel. We dispensed 3 ml, with instructions to apply 0.1 ml (5 mg) daily to the inside of the cat's ear. The benefits of transdermal administration include the ability to reliably administer the prescribed dose, and ease of administration to a calm, relaxed cat.

The therapy was very successful. The cat's dermatitis resolved and the hair began to regrow within a few weeks. There were no complications and no modification in dosage was necessary. The owner periodically uses the preparation when she first notices signs of a relapse. Relapses have promptly resolved with transdermal prednisone therapy.

Cardiology/Hypertension

Compounding For Feline Hypertension

Therapies for feline hypertension have not often been systematically evaluated. Therapies that have been employed and reported include diuretics (furosemide and spironolactone), angiotensin-converting enzyme inhibitors (ACE-I; captopril, enalapril, lisinopril, and benazepril), beta-blockers (propranolol and atenolol), and calcium channel blockers (diltiazem and amlodipine). Littman retrospectively evaluated 24 cats with chronic renal failure (CRF) and found that the most effective antihypertensive therapy was the combination of a beta-blocker and an ACE-I and that there was a poor response to furosemide. Jensen prospectively studied 12 similarly affected cats and found that the response to an ACE-I or beta-blocker alone was poor. A North Carolina State University study retrospectively found amlodipine to lower blood pressure ? 20% in 30 of 32 hypertensive cats with 28 of 32 becoming normotensive. Diltiazem and beta-blockers alone or with ACE-I also lowered blood pressure in the majority of cats so treated. The literature and clinical experience would, nevertheless, lead one to appropriately conclude that amlodipine is the single best agent for the management of feline systemic hypertension, and that the adjunct therapies mentioned above may be added if indicated.

To reduce stress to the cardiovascular system of the feline patient and to preserve the owner-pet bond, palatable, non-invasive therapy is mandatory for treatment of feline hypertension. Amlodipine is dosed at 0.3mg – 0.625mg orally once to twice daily, and has also been shown to be effective when applied transdermally at approximately twice the effective oral dose. Amlodipine is only FDA approved for human use and is available in tablet sizes far too large to afford safe and effective therapy in cats. Our compounding pharmacists can compound amlodipine into oral suspensions, capsules, treats, and powders to sprinkle on food, as well as into transdermal gels for application to the pinnae. Diltiazem may also be utilized to lower feline blood pressure and is available in several human-approved dosage forms that are, again, far too large for use in cats. Diltiazem controlled-delivery (Cardizem CD®) is the only dosage form of diltiazem that demonstrates pharmacokinetics to support once daily dosing in cats. Available as a capsule containing a 40/60 mixture of immediate release and sustained release beads of diltiazem, compounding pharmacists can reformulate these capsules into 45mg (total) doses for once daily administration to cats. Diltiazem has not been sufficiently evaluated to determine whether or not transdermal administration is effective; however, there are many anecdotal reports of efficacy. Atenolol may be useful in reducing heart rate in hypertensive cats and is dosed empirically at 6.25mg – 12.5mg per cat orally once daily. Again, our compounding pharmacists can provide palatable dosage forms of atenolol that are voluntarily accepted by feline patients. For feline patients requiring multiple therapies, we can also provide combination therapies in a single dosage form. For example, we can compound a single capsule or treat that contains amlodipine, diltiazem and atenolol, further reducing the stress to both patient and owner. We invite veterinarians wishing to explore palatable and non-invasive therapies for cats with hypertension to consult with our compounding pharmacists.

Low Dose Anti-platelet Therapies for Feline Arterial Thromboembolism (FATE)
 
   Feline hypertrophic cardiomyopathy (HCM) is the most common form of heart disease in cats and is characterized by concentric thickening of the left ventricle. The clinical consequences of ventricular hypertrophy include arrhythmias, congestive heart failure, and feline aortic thromboembolism (FATE).  FATE carries an extremely poor prognosis with a 66% mortality rate.  The formation of aortic clots in FATE leads to paralysis, severe leg pain and, often, death.  There is no cure for HCM; hypertrophy of the heart wall is irreversible.  Therapies demonstrating benefit to HCM patients include beta-blockers, diuretics, ACE inhibitors, and antiplatelet drugs.  Because systemic warfarin therapy is associated with a high occurrence of hemorrhagic events, aspirin has historically been utilized as the primary oral antiplatelet therapy to prevent FATE in cats with HCM. It was initially dosed at 81mg every 72 hours as this was the smallest commercially available dosage form of aspirin. A study in 2003 revolutionized low dose aspirin therapy in cats through utilization of a compounded 5mg aspirin capsule administered orally every 72 hours. Results of this study indicated that the same degree of antiplatelet activity was achieved but the inhibition of endothelial production of prostacyclin (PGI), an antagonist to platelet aggregation and vasoconstriction, is not affected with the 5mg dose as is seen with the 81mg dose. This study also demonstrated a lower incidence of gastrointestinal adverse effects with the 5mg dose when compared to the 81mg dose of aspirin. 
   Clopidogrel (Plavix™) has been shown to be more effective than aspirin in preventing myocardial infarction, stroke and peripheral vascular events in humans. Clopidogrel has recently been evaluated in cats and has been shown to significantly inhibit multiple platelet functions. Investigators concluded that a low dose of 18.75mg of clopidogrel (1/4 of a commercially available 75mg tablet) given orally once daily was safe and effective anti-platelet therapy for cats.  Investigators also commented that a considerably lower compounded dose of clopidogrel may prove to be as effective, safer, and considerably less expensive than quartering the commercially available tablets and recommended that studies be performed with lower doses of clopidogrel as were done with aspirin in 2003. Some veterinary teaching hospitals are utilizing doses of 6mg and 7mg clopidogrel orally once daily in combination with low dose aspirin therapy although the efficacy of these therapeutic regimens have not been evaluated.  The multi-centric Feline Arterial Thromboembolism – Clopidogrel vs. Aspirin Trial (FAT-CAT) initiated at Purdue University College of Veterinary Medicine has been accepting FATE cats for enrollment for the last two years to determine if there is clinical superiority of either agent when prophylaxing against recurrence of FATE.  Initial results show a significant (41.6%) reduction of FATE recurrence in one of the two treatment groups; however, study coordinators will not unblind the treatment arms to investigators until the full enrollment of 30 cats per treatment group is achieved. Clinicians interested in learning more about the FAT-CAT study should visit http://www.vin.com/FATCAT/    Veterinarians interested in exploring use of low dose aspirin and low dose clopidogrel therapy can collaborate with our compounding pharmacists regarding formulation of patient-specific doses. 

Transdermal Diltiazem for Treatment of Hypertrophic Cardiomyopathy in Cats
 
Diltiazem has direct coronary vasodilating properties, a beneficial therapeutic effect not provided by the beta-adrenergic blocking agents for the management of feline hypertrophic cardiomyopathy (HCM). “Orally administered diltiazem appears to have sustained beneficial effects on left ventricular filling and cardiac performance based on its ability to reduce resting heart rate, decrease blood lactate concentration, increase venous oxygen tension, improve echocardiographic parameters, and resolve radiographic abnormalities. Long-term diltiazem administration may also reverse myocardial hypertrophy in some patients. There appear to be few if any side effects of this drug. Diltiazem, therefore, provides a safe and effective approach for the management of feline HCM.”
 
At North Carolina State University, College of Veterinary Medicine, analysis of diltiazem in Lipoderm® transdermal gel showed that diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days, no matter the storage conditions explored in the study. 
 
 A formula is available for Diltiazem 5% for veterinary use.

Transdermal Atenolol and Feasibility of Transdermal Administration

Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

“In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.”

Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose.

Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.

Enalapril for Cardiomyopathy and CHF
 "Enalapril maleate is an angiotensin-converting enzyme (ACE) inhibitor labeled to treat mild to severe heart failure in dogs." Research has shown that enalapril in combination with diuretics - with or without digitalis glycosides - "produces statistically significant clinical improvement in dogs with advanced heart failure due to mitral regurgitation or dilated cardiomyopathy" and has demonstrated "beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with CHF... Dogs treated with enalapril and conventional CHF therapy survived two times as long as did those receiving standard therapy alone."

Enalapril has also "been effective in treating cardiomyopathy and CHF in cats and ferrets, and its effects on blood pressure in horses and camels have been studied." Because enalapril is a prodrug and can not be converted to its active form enalaprilat in patients with severe liver dysfunction, captopril or lisinopril might be a better choice in those patients. Renal function should be checked before starting enalapril therapy and at least every two months thereafter. The most common side effects are gastrointestinal, but there have been reports of enalapril-induced cough in dogs and a bird. Hypotension is a major concern if overdose occurs. NSAIDs, including aspirin, may reduce enalapril's effect. The injectable form (enalaprilat) should not be given orally because it is very poorly absorbed.

"The recommended dose for enalapril in dogs is 0.5 mg/kg orally every 12 to 24 hours. The dose for cats is 0.25 to 0.5 mg/kg orally every 12 to 24 hours."

Amlodipine to Treat Feline Systemic Hypertension 
Amlodipine, a calcium channel blocker, has an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high blood pressure (BP). In a retrospective study, medical records from 69 cats with systemic hypertension and hypertensive retinopathy were reviewed. 68.1% of the cats were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Amlodipine decreased BP in 31 of 32 cats and improved ocular signs in 18 of 26 cats. Primary hypertension in cats may be more common than currently recognized.

In a study at the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, amlodipine was shown to be a safe and effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg daily as monotherapy. Researchers at the Department of Medical Sciences, University of Wisconsin-Madison, administered amlodipine at an oral daily dosage of 0.625 mg per cat (range = 0.08 to 0.23 mg/kg body weight). Average indirect systolic blood pressure measurements in those 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected.

Relationship between ocular lesions and hypertension
Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years).

Behavioral Medicine

An 11 year-old male cat showed aggressive behavior towards other cats and also started urinary spraying.  Buspirone 2.5mg/ml flavored suspension was tried.  It was extremely difficult for the owner to give the oral suspension and after a few days the cat was vomiting the medication.

Treatment
The owner was instructed to apply 0.1ml of transdermal buspirone 2.5mg/0.1ml pluronic lecithin organogel (PLO) topically inside the tip of the ear twice a day.

Outcome
After the first dose, the owner noticed the medication made the cat too sleepy and the dose was decreased to 0.05ml (1.25mg of buspirone).  The cat's aggressive behavior has been controlled on the lower dose with a few exceptions and the owner then increased the dose to 2.5mg of buspirone for a couple of doses.  The owner is amazed how easy it is to apply the medication. 



Amitriptyline for Behavioral and Urinary Disorders
Amitriptyline hydrochloride is one of the most widely used  tricyclic antidepressants (TCAs) in companion animal behavioral medicine, exerting antihistaminic, anti-inflammatory, analgesic, and antidepressant effects. Amitriptyline increases synaptic activity of serotonin and norepinephrine, has significant central and peripheral anticholinergic activity, and stimulates beta-adrenergic receptors in smooth muscle (e.g. the bladder), causing a decrease in smooth muscle excitability and a subsequent increase in bladder capacity and storage.

Although amitriptyline has been used successfully to treat behavior-related and urinary tract disorders in cats and dogs, the drug is not approved by the FDA for veterinary use and therefore is not available as a veterinary preparation.

Imipramine
In animals, tricyclic antidepressants have actions similar to those of phenothiazines in altering avoidance behaviors. Imipramine has been used for the following indications:

Cats:  urethral incompetence

Dogs: treatment of separation anxiety and other behaviors, cataplexy, urethral incompetence

Horses:  narcolepsy and ejaculatory dysfunction




Naltrexone for Self-Mutilating Behavior
"Naltrexone may be useful in the treatment of self-mutilating or tail-chasing behaviors in dogs or cats... [A synthetic opiate antagonist,] naltrexone is generally considered to be contraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acute hepatitis."

Doses for Dogs:

As adjunctive therapy in behavior disorders:

For tail chasing or excessive licking: First give 0.01mg/kg SubQ of naloxone to determine if narcotic antagonists may be effective. If so, give naltrexone PO at 1 - 2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992)

For the adjunctive treatment of acral pruritic dermatitis:

2.2mg/kg PO once daily for one month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited...    (Rosychuck 1991)




Canine Acral Lick Dermatitis
involves excessive licking of the paws or flank, even to the point of self-mutilation, and can produce ulcerations and infections that require medical treatment. Based on patterns of behavior and response to medication, veterinary scientists propose that canine acral lick dermatitis, also known as canine compulsive disorder (CCD), is an animal model of human obsessive-compulsive disorder. A randomized, placebo-controlled, double-blind crossover clinical study evaluated the efficacy of the medication clomipramine for treatment of CCD. Fifty one dogs with CCD were given clomipramine 3 mg/kg [1.3 mg/lb] of body weight orally every 12 hours for 4 weeks and then placebo for 4 weeks. While drug therapy can be helpful, therapy may need to include behavior modification to optimally manage CCD.

Fluoxetine for Refractory Owner-Directed Dominance Aggression
Evidence suggests that social dominance aggression may be modulated by serotonergic mechanisms. Fluoxetine (Prozac?), a specific inhibitor of serotonin reuptake, is a popular human antidepressant which has been used successfully to decrease social aggression in dogs and monkeys.

Fluoxetine for Urine Spraying in Cats
Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. Pryor et al. recommend that most cats should be treated more than eight weeks before treatment is withdrawn. Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine (1mg/kg PO daily- dosage individualized for each cat by a compounding pharmacy) or fish-flavored liquid placebo. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats.

Inappropriate Elimination in Cats: Fluorescein to Find the Culprit
In a multi-cat household, it is important to determine which cat is inappropriately eliminating so that the proper intervention can be made. Even if one cat is observed marking or urinating outside the box, it does not rule out the possibility that other cats are also behaving inappropriately. When it is necessary to identify which cat in a multi-cat household is spraying or inappropriately eliminating, fluorescein can be orally administered once daily in the evening with food for three days. That cat's urine will fluoresce under ultraviolet light for approximately 24 hours. To detect urine containing the fluorescein indicator, the client needs to scan the household with a commercial black light or black light purchased from a novelty store. Although urine will commonly glow, fluorescein treated urine fluoresces a characteristic bright yellow. Caution clients that they may reveal previously undiscovered sites of elimination; advise them not to become alarmed or angry. By administering the dye to different cats at two day intervals, the culprit can be identified.

Pharmacological support for urine spraying or marking is usually needed only for cases with underlying anxiety or problems with social interactions between cats (clomipramine), or for cats with interstitial cystitis (amitriptyline, doxepin). Administration of fluoxetine hydrochloride for treatment of urine spraying in cats may also considerably reduce the rate of urine marking. 



Cyproheptadine to Control Urine Spraying and as an Antipruritic in Cats
A 10-year-old castrated male domestic cat was admitted to the hospital at the School of Veterinary Medicine, Tufts University. A diagnosis of territorial urine marking was made. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. It was recommended to continue cyproheptadine administration for at least 1 year before any attempt to withdraw its use. Another study recommended a dose of 2 mg, p.o., every 12 hours. This antihistamine, also prescribed for its appetite stimulant effects in cats, has antiandrogenic effects in other species.

Cyproheptadine hydrochloride was administered to 20 presumed or proven allergic cats to determine its efficacy in controlling pruritus. Each cat received 2 mg, orally, every 12 hours. The pruritus was satisfactorily controlled in 9 cats. Side effects were seen in 8 cats, and included polyphagia, sedation, vocalization, affectionate behavior, and vomiting. 

Clomipramine for Feline Anxiety
A study of 11 cats assessed the clinical response to a treatment regimen that included clomipramine and behavior modification in cats diagnosed with anxiety-related or obsessive-compulsive disorders. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalization in one. Clomipramine was administered orally once daily, with a mean starting dose of 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. The average maintenance dosage was 0.3 mg/kg once daily. The researchers concluded that clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behavior modification, and the drug was well tolerated.

Selegiline
is a monoamine oxidase (MAO) inhibitor indicated for use in dogs to control signs associated with canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism (PDH). Studies suggest that selegiline may enhance survival rates. The recommended dose for cognitive dysfunction is 0.5 to 1 mg/kg, and for PDH is 1 mg/kg, orally each morning. If no improvement is seen after 2 months, the dose can be increased to the maximum of 2mg/kg/day. If there is no clinical improvement after 1 month at 2mg/kg/day, alternative therapy or further evaluation should be considered. "Overall, selegiline is well tolerated... Gastrointestinal disturbances, particularly vomiting and diarrhea, are the most common side effects reported. Diarrhea may resolve when the drug is discontinued or the dose decreased. Other adverse effects include hyperactivity, agitation, restlessness, and insomnia. A dose reduction or discontinuation of therapy also resolves these problems."

Anti-infective Therapy

Penicillin Gelatin Guttural Pouch Lavage
 
   Streptococcus equi is the bacterial pathogen responsible for a highly contagious equine disease known as strangles.  Strangles most commonly occurs in younger horses, but can be seen in horses of any age, particularly performance horses encountering sites where high density and high turnover of horses occurs (competition grounds, fairs, auctions, and boarding facilities). Infection by S. equi causes a severe inflammatory response manifesting as fever (102°-106°F), inappetance, lymphadenopathy with abscessation and resulting stridor, and a copious, mucopurulent nasal discharge. The guttural pouch has been identified as the site most likely to harbor S. equi organisms after infection due to draining abscesses from the mandibular lymph nodes.  While systemic beta-lactam therapy has proven very valuable in treatment of active disease, antibiotics do not achieve high enough concentrations in the guttural pouch to eliminate organisms.  Recently, the use of penicillin G sodium impregnated gelatin has been utilized to fill the guttural pouches following guttural pouch lavage in order to allow prolonged, bacteriocidal concentrations of penicillin in the guttural pouch after a single application.  The penicillin sodium gel should be prepared in an aseptic environment and refrigerated for at least 24 hours prior to administration. Our compounding pharmacists are able to provide this preparation for equine veterinary patients.
 
For further reading on equine strangles consult the American Association of Equine Practitioners at http://www.aaep.org/strangles.htm.


 
Clotrimazole 1% in Pluronic Gel for Nasal Aspergillosis
 
   Nasal aspergillosis is a common fungal condition in dogs that results in massive turbinate destruction, pain and death or euthanasia due to lysis of surrounding skeletal structures such as the cribiform plate. Systemic treatment with oral antifungals is very expensive and often accompanied with serious adverse effects, and often is not successful (40-70% success).  Traditionally, the treatment of choice for nasal aspergillosis in dogs was a one-hour intranasal irrigation of 1% clotrimazole solution while the patient was anesthetized. The prolonged anesthesia was necessary to allow maximal contact time of the 1% clotrimazole solutions that immediately ran out of the sinuses once introduced. This therapy resulted in a success rate of almost 70% after a single treatment, but many dogs require multiple treatments for complete resolution.  Because of the expense and risk of multiple surgical and prolonged anesthetic procedures, a method to provide prolonged contact of 1% clotrimazole solutions in the nasal sinuses has been considered. A recent study assessed the retention, toxicity and stability of several viscous preparations of clotrimazole 1% in canine frontal sinus. Six compounds were evaluated including commercially available 1% clotrimazole cream, and 1% clotrimazole in varying concentrations of hydroxypropyl methylcellulose, carboxymethylcellulose, and poloxamer gel.  Results of this study indicate that clotrimazole 1% delivered in 25% poloxamer gel resulted in the least amount of sinus inflammation and was accompanied by a reasonable retention time.  Researchers concluded that use of poloxamer gels holds much promise for prolonged delivery of clotrimazole in nasal sinuses, potentially reducing anesthetic time as well as accomplishing fungal organism eradication after a single course of treatment. Veterinarians interested in pursuing use of this therapy for nasal aspergillosis can contact our compounding pharmacist to prescribe clotrimazole 1% in 25% poloxamer gel.

Antibiotic/Antifungal/Antiviral Therapy
Please scroll down for more information on the following topics:
Metronidazole
Esophageal Strictures Secondary to Administration of Doxycycline Tablets
Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
Chloramphenicol Suspension for Birds & Small Animals
Fluoroquinolone Antibiotics
Antibiotic Treats for Feline Abscess 
Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
Azithromycin 
Azithromycin for R. equi Infections in Foals
Idoxuridine Ophthalmic Drops for Cats
Feline Ocular Toxoplasmosis
Itraconazole/DMSO for Fungal Keratitis in Horses

Metronidazole
Metronidazole is effective against a variety of obligate anaerobic bacteria as well as anaerobic protozoa such as Giardia and Trichomonas. "Various salts of metronidazole with improved palatability are now available for veterinary patients... Cats and birds accept the benzoate salt much more willingly than they accept metronidazole HCl and do not seem to be stressed by its administration."
Metronidazole should be used with caution in patients with hepatic dysfunction. Therapy should be promptly discontinued if abnormal neurological signs appear, including nystagmus, ataxia, seizures, and rigidity. All benzene moieties must be conjugated with glucuronide to facilitate elimination and this pathway is inefficient in cats. Therefore, doses of metronidazole benzoate above 200 mg/kg/day may produce signs of cumulative toxicity in cats within 48 to 72 hours.

Compendium Dec. 2000: 22(12); pp. 1104, 1105, 1107, 1130


Esophageal Strictures Secondary to Administration of Doxycycline Tablets 

"The most common causes of esophageal strictures in dogs and cats are gastroesophageal reflux during anesthesia, persistent vomiting, or ingestion of foreign bodies or caustic agents. In humans, esophageal retention of oral medication is a common cause of severe esophagitis. Of the medications proven to lead to esophageal ulceration, doxycycline is most often implicated. It has been suggested that pill-induced esophagitis also could occur in small animals..." Drug-induced esophageal ulceration usually occurs when tablets are taken with little or no water and adhere to the esophageal mucosa. Once this occurs, flushing with large quantities of liquid fails to wash the medication into the stomach. Melendez et al. of Colorado State University College of Veterinary Medicine report on three cases of presumptive doxycycline-induced esophagitis in cats, with resultant stricture formation. All cats had been administered fractions of doxycycline tablets one to three weeks before presenting with a chief complaint of regurgitation. "Two of the cases developed regurgitation within 7 days after initiation of therapy with doxycycline. One cat, which was treated while at an animal shelter, was noted to be regurgitating the day that it was adopted, approximately 2 weeks after being treated with doxycycline. No other cause of esophageal stricture formation could be identified." If a pet that has received a doxycycline tablet shows sign of esophagitis (dysphagia, excessive salivation, inappetence, and regurgitation), the doxycycline tablets should be discontinued. Suggested therapy for esophagitis includes sucralfate slurries, a prokinetic agent (i.e. cisapride) to increase lower esophageal sphincter tone, and anti-inflammatory doses of glucocorticoids to prevent stricture formation. 

Doxycycline can be compounded as a stable flavored liquid preparation or other palatable dosage form to meet the specific needs of each animal and owner. 

Feline Practice 28:2; 10-12 (Mar/Apr 2000)

Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis 
Itraconazole could be an effective alternative to griseofulvin that has toxic effects (particularly in puppies based on this author's experience) and frequent therapeutic relapses. Itraconazole has also been used to successfully treat M. canis infection of cats and guinea pigs.

J Am Vet Med Assoc 1998;213:993-995



Chloramphenicol Suspension for Birds & Small Animals

by J. Terry McGrath, VMD, Pennsylvania

Since chloramphenicol palmitate is no longer commercially available, we contacted our compounding pharmacist for an alternative for use in our avian and other small patients, such as rabbits and rodents. The pharmacist prepared a cola flavored suspension containing 30 mg/ml of chloramphenicol palmitate, which could be administered using a small oral syringe. However, birds did not like the taste and it was reformulated into a tutti fruitti and pina colada syrup. The "animal appropriate" flavor has really helped with compliance, because now the birds and small animals like to take their medicine!

Note: To avoid potential antagonism, chloramphenicol should not be administered simultaneously with penicillin or streptomycin. Chloramphenicol-containing preparations should not be administered in conjunction with, or two hours prior to, the induction of general anesthesia with pentobarbital.

When administered orally in dogs, chloramphenicol is well-tolerated, has high clinical efficacy, and a low incidence of side effects. The recommended canine dosage is 25 mg/lb of body weight every six hours.

Precautions: Chloramphenicol should be administered cautiously to animals with hematopoietic dysfunction, or impaired kidney or liver function.



Antibiotic Treats for Feline Abscess 

Submitted by: Michael Briggs, Pharm.D. Veterinarian: Rich Marchetti, D.V.M.
Patient: One year old non-castrated short-haired male cat with abscess from wound received in fight. The owner reported that the cat, who is usually affectionate and friendly toward the owner and house dog, had been withdrawn, on guard, and growling for approximately three days. A thorn-like projection near the tail was found by the owner, who immediately took the cat to the veterinarian. The cat was anesthetized and the veterinarian cleaned, debrided, and shaved the area of the wound, and prescribed amoxicillin 100 mg daily for ten days. The owner was instructed to keep the cat inside for the duration of therapy, to minimize the risk of superinfection and avoid additional injury. 
Medication Problem: The cat refused to take liquids, and was also resistant to taking tablets ("pilling"). The required dose of antibiotic was too high for transdermal treatment (due to the amount of gel that would need to be applied for each dose).

Solution: The veterinarian called our compounding pharmacy and asked if we could come up with a palatable dosage form. We formulated a fish-flavored chewable treat containing amoxicillin 100 mg to be given once daily for ten days. This dosage form offers the advantage of ease of administration, decreases the potential for dosing errors, and greatly increases patient compliance. The cat readily consumed the amoxicillin "treat". The wound did not heal in a ten day period, so five additional days of therapy were required. 
Comment: Our pharmacy has compounded this preparation more than ten times with a 100% success rate.



Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs 

"Treatment of nasal aspergillosis with systemic antifungal medications, such as thiabendazole, ketoconazole, and fluconazole, has been disappointing because the response rate is only 43 to 60%. Response to oral administration of itraconazole has been approximately 60 to 70%... Topical administration of the imidazoles, enilconazole, and clotrimazole is more effective than orally administered antifungal medications."

Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications. Nasal discharge ceased in most dogs 2 weeks after topical treatment, and the authors now recommend re-treatment with clotrimazole if nasal discharge has not improved 2 weeks after treatment.

"[Damage] of the cribriform plate may contraindicate use of topical treatment; complications arising from leakage of antifungal medications into the CNS in dogs with fungal rhinitis have not been evaluated."

Azithromycin 
is a form of erythromycin with improved action against gram-negative organisms, resistance to acid degradation, improved tissue penetration, and a prolonged elimination half-life. Azithromycin shows potential for use in veterinary medicine, particularly in cats and certain avian and exotic species. 
"Lacking the prokinetic action of erythromycin, azithromycin appears to cause fewer GI side effects and is generally well tolerated after oral administration. Cats appear to tolerate the drug particularly well... Animals with a history of arrhythmias should be monitored while receiving the drug. Some reduction in dose may be warranted in patients with hepatic or biliary dysfunction, although no reduction appears necessary in patients with renal dysfunction." Please consult our compounding pharmacist regarding dosing.

Compendium of Continuing Education 23:3 (March 2001), pp. 242-7


Azithromycin for R. equi Infections in Foals
On the basis of pharmacokinetic values, minimum inhibitory concentrations of R. equi isolates, and drug concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.

Itraconazole/DMSO for Fungal Keratitis in Horses
Fungal keratitis is a serious complication of trauma to the eye. Approximately one-half of the cases of fungal infections have involved the use of eye ointments containing corticosteroids after trauma to the globe of the eye. 

"Itraconazole is a third generation triazole that has superior penetration properties and a wide spectrum of activity. A 1% solution of itraconazole in a 30% DMSO and petroleum base has been shown to reach high concentrations within the stroma of the cornea when administered every 4 to 6 hours. In general, every 6 hours is suitable for all but Fusarium sp which requires every 4 hour administration."

Disease which is rapidly ulcerating "should also receive treatment that helps block the enzymes (collagenase) responsible for ulceration. A 5% acetylcysteine solution and autologous serum in which 4 mg/ml of EDTA has been added has been recommended. These need to be instilled hourly for best effect. The antimicrobial can be added to the serum."

Idoxuridine Ophthalmic Drops for Cats 
The ocular signs of feline herpesvirus I (FHV-1) infection include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. If corneal involvement is present, topical antivirals are prescribed. Research indicates that idoxuridine is effective against FHV-1. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. Previously marketed as Stoxil?, the ophthalmic solution is not commercially available at this time. 

Feline Ocular Toxoplasmosis 
"The anterior uveitis seen in cats with a positive serum titer to Toxoplasma gondii may result from immune-mediated mechanisms and not the presence or replication of the organism itself. As a result, it is unclear whether systemic antitoxoplasmic therapy is beneficial in these cases." Michael G. Davidson, DVM, of North Carolina State University, College of Veterinary Medicine reports in Vet Clin N Amer, Sep 2000, that he "usually treats cats with ocular lesions and concurrent systemic findings of toxoplasmosis with systemic clindamycin (12.5 mg/kg PO twice daily for 14-21 days) and anti-inflammatory therapy. Other sources recommend clindamycin 10-12.5 mg/kg every 12 hours for 4 weeks. Oral trimethoprim-sulfonamide combination therapy (15 mg/kg every 12 hours for 2 to 4 weeks) can also be used to treat toxoplasmosis but is less suitable because of potential side effects caused by folic acid deficiency in cats.2 In T gondii seropositive cats exhibiting anterior uveitis alone and with no systemic signs, Dr. Davidson recommends topical steroids and atropine alone. If the cat fails to respond to topical therapy alone within 1-3 weeks, systemic clindamycin should be added to the treatment regimen. The rationale for the use of corticosteroids is to suppress the damaging inflammation in the retina, which may affect vision. Corticosteroids are typically administered 1-2 days after antibiotic therapy has been initiated to allow adequate tissue levels of the antimicrobial agent to be achieved. [Dr. Davidson] does not recommend systemic steroids in cats with suspected ocular toxoplasmosis because of the risk of exacerbating systemic replication of T gondii."
Swift and aggressive treatment of uveitis is necessary to avoid such secondary complications as glaucoma, cataract formation, and retinal degeneration or detachment.

Transdermal Medications

Have you ever thought about applying a transdermal preparation to the inside of an animal's ear or another hairless area as an alternate route of systemic administration? It's quick and easy, and many medications are compatible with transdermal bases. Transdermal delivery is particularly useful for animals who should not be stressed due to cardiovascular or hypertensive illness. Also, it is appreciated by owners who no longer have to deal with an animal who resists being medicated, and the resulting scratches! We can also prepare topical medications for application at the site of inflammation or infection.

Advantages of Transdermal Dosage Forms
Various alternative dosage forms permit medication to be absorbed via non-oral routes to meet an animal's specific needs. Although the parenteral and rectal routes are traditional alternatives to oral administration, transdermal absorption offers many advantages.

For example:

  • When medication is absorbed directly into the bloodstream without first entering the gastrointestinal system, a smaller amount of active ingredient may be required for therapeutic effect.
  • Direct application and absorption at the target site can mean higher tissue levels and lower blood levels of various medications. Side effects such as GI irritation can be eliminated.
  • Various types of drug interactions may be avoided when one or more interacting medications are administered transdermally.

A substantial number of references exist in human medical literature with regard to the efficacy of transdermal administration of non-steroidal anti-inflammatory drugs and other types of analgesics, antiemetics, and other medications. We can compound transdermal and topical medications using a suitable base, and add penetrant enhancers if desired. 



Transdermal Atenolol and Feasibility of Transdermal Administration

Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

“In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.”

Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose.

Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.

Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism

The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism.

Endocrinology

Low Dose Trilostane for Canine Cushing’s Disease
 
   Cushing's Disease (hyperadrenocorticism) is a common condition in older dogs, often mistaken for the aging process itself. Dogs get pot bellies, lose hair, drink and eat excessively, urinate in the house, and make owners begin to prematurely consider euthanasia. Yet, Cushing's disease is treatable and that treatment can result in a longer, more comfortable life for the dog and its owner.
 
  Trilostane is the most promising FDA-approved treatment for canine Cushing’s disease. Current FDA approved labeling for trilostane (Vetoryl™) lists the recommended dose at 3-6mg/kg body weight orally once daily, and Vetoryl™ capsules are available in strengths of 10mg, 30mg and 60mg.  Several studies conducted prior to US-approval of trilostane referenced effective doses ranging from 6-12mg/kg orally per day.  After noting that many dogs treated with trilostane at the labeled dose demonstrated symptoms of hypoadrenocorticism (Addison’s Disease), clinical endocrinologists at the University of California Davis College of Veterinary Medicine evaluated the safety and efficacy of lower doses of trilostane.  Investigators in this trial administered trilostane to dogs diagnosed with Cushing’s disease at doses ranging from 0.5-2.5mg/kg orally every 12 hours and evaluated dogs for therapeutic progress at 3 different treatment intervals over a total treatment period of 8-16 weeks. After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [n =3]). 
 
   Since many dogs that develop Cushing’s disease are smaller breed dogs weighing less than 9kg (e.g. terriers and poodles), the commercially available capsules (10mg, 30mg and 60mg) are too large for appropriate therapy. As a result of the UC-Davis study, many veterinarians are requesting compounding pharmacists to compound smaller doses of trilostane as capsules or oral suspensions. On September 11, 2009, the Center for Veterinary Medicine division of the Food and Drug Administration issued a statement to veterinarians and pharmacists that “trilostane can only be legally compounded by using FDA-approved VETORYL™ as the starting material”, and that “…trilostane should not be imported from other countries or compounded from (the) bulk (chemical)”. As Vetoryl™ is only available for sale to licensed veterinarians in the US, and use of the bulk chemical to compound trilostane will not be tolerated by FDA, veterinarians and pharmacists are advised to collaborate to ensure availability of safe and legal compounded dosage forms of trilostane for dogs requiring lower doses than are commercially available.

Phenoxybenzamine for Dogs with Pheochromocytoma
 
 Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. Therefore, at the School of Veterinary Medicine, University of California, Davis, it was hypothesized that dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs, and they conducted a retrospective medical record review of 48 dogs that underwent adrenalectomy for pheochromocytoma from January 1986 through December 2005. Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age, lack of intraoperative arrhythmias, and decreased surgical time. Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism

The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism.

PZI and Low-Dose Insulin
The commercial production of traditional beef &/or pork insulins has declined as most human diabetic patients (the majority of the consumers) are being switched to human insulin products because of the reduced risk of allergic reactions. Protamine zinc insulin occurs as a sterile suspension of insulin modified by the addition of protamine sulfate and zinc chloride, and has a long duration of action (up to 30 hours). Therefore, treatment of many dogs and cats has been accomplished with once daily dosing of PZI. 
U-20 and U-40 insulin allow for more accurate measurement of smaller doses required by many pets and birds. Use of U-100 insulin can result in morbidity or mortality caused by dosing errors.


 

Oral Anti-Diabetic Drugs
"may be appropriate for cats that are in good overall health with early or mild clinical signs of diabetes and those with owners who are unwilling or unable to administer insulin injections."1 The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Discontinuation of diabetogenic medications that may be contributing to insulin resistance is important.2

According to Deborah S. Greco, DVM, Ph.D., diplomate ACVIM, glipizide has been used successfully to treat diabetes mellitus in cats at a dosage of 2.5 to 5 mg two times daily, when combined with dietary fiber therapy. Dr. Greco recommends evaluating the patient weekly or every two weeks for a period of 2 to 3 months. If the fasting blood sugar decreases to less than 200 mg/dL, the glipizide should be continued at the same dosage and the cat reevaluated in 3 to 6 months. If the fasting blood glucose remains >200 mg/dL after 2 to 3 months of therapy and the cat is still symptomatic (polyuria, polydipsia, weight loss), glipizide should be discontinued and insulin therapy instituted. If the blood glucose remains >200 mg/dL and the cat becomes asymptomatic, glipizide should be continued indefinitely and the cat rechecked in 3-6 months.

Methimazole for Feline Hyperthyroid Disease 
"Methimazole is the drug of choice for the medical management of feline hyperthyroid disease. It is safer and more potent than propylthiouracil in blocking thyroid hormone synthesis. Use of the drug generally will bring serum T4 into normal ranges within 2 to 3 weeks... Adverse effects have been observed in approximately 15% of cats and generally are transient. Anorexia, vomiting, and transient lethargy have been reported. Serum antinuclear antibodies develop in many cats with long-term use of the drug. A glucocorticoid-responsive pruritus involving the face, ears, and neck may occur. In less than 2% of cases, thrombocytopenia or agranulocytosis have been reported in cats treated with [methimazole]. Withdrawal of the drug and provision of care for thrombocytopenia or agranulocytosis generally results in resolution... Cats on chronic methimazole therapy should be rechecked every 3 to 6 months to assay serum T4 levels and to check for signs of drug toxicity."

Handbook of Veterinary Drugs, 2nd edition, ©1998, pp. 239-240

According to the International Journal of Pharmaceutical Compounding (Vol. 5, No. 2, March/April 2001, p. 96), "it could be theorized that transdermal administration would produce a ... higher blood level of methimazole than that resulting from oral administration of the drug. A higher blood level of [methimazole] might result in a slightly greater risk of adverse effects, so drug therapy might need to be initiated at a slightly lower dose than that of the traditional oral dose." The author of the article (GiGi Davidson, R.Ph., DICVP, North Carolina State University, College of Veterinary Medicine) states that anecdotal evidence indicates that this is true of "most transdermally administered doses of methimazole. The most measurable parameter for efficacy is the response of the serum T4 level."

Note: Methimazole is also used to decrease renal toxicity of cisplatin in dogs.

Transdermal Methimazole Applied to Ear of Hyperthyroid Cats
Francis Arsenault, D.V.M., New Brunswick

The following six cats have received methimazole in a pluronic lecithin organogel (PLO) which the owners apply to the inner side of the ear. Overall, we have found this to be very effective therapy with good compliance. Transdermal administration can be particularly helpful for owners who have arthritis and those who have great difficulty "pilling" the cat. Methimazole doses have ranged from 2.5mg to 12.5 mg daily, divided into two doses.

Cat #1 (S.A.): 17 years old, has been on methimazole 1.25mg/0.1 ml PLO to inside of ear twice daily for nine months. The owner reports that the medicine is easy to administer and absorbs well. I am pleased with the clinical results.

Cat #2 (A.L.): 18 years old, has been using methimazole for six months. This cat was started on 3.5mg/0.1ml PLO BID. Several dosage adjustments were necessary. We increased the concentration of the transdermal gel to 5.0mg/0.1ml PLO, and the owner now applies 7.5mg/0.15ml PLO in the AM and 5mg/0.1ml in the PM. She places plastic wrap over her finger before applying the medication, which she has found to be much easier to use than pills, with no stress to the pet. She states the measurements on the topical dispenser are easy to read, and she needs to wash the cat's ear to remove the coating left by the medication.

Cat #3 (B.M.): was started on methimazole eight months ago at 5mg/0.1ml PLO BID. The dose was decreased to 2.5mg BID. The cat's owner stated the medication was very easy to use. B.M. improved clinically and gained weight, and is no longer on the med.

Cat #4 (S.O.): used medication once only.

Cat #5 (D.O.): same owner as cat #4, received methimazole 2.5mg/0.05ml PLO BID for two months. No longer on medication.

Cat #6 (M.B.): 19 years old, has received methimazole 1.25mg/0.1ml PLO BID for four months. The owner says the medication is easy to apply, and alternates ears. It is necessary to wipe the ear each day as the medication does leave a residue.



Adrenal Disease in Male Ferrets

Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of androgens and/or estrogens, and can cause hair loss, itching, vulvar enlargement in females, prostate enlargement in male ferrets which can block the flow of urine, and in rare cases, bone marrow suppression. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated. 
Flutamide is an androgen blocker that may help relieve prostatic enlargement. It is dosed at 10 mg/kg, PO, every 12-24 hours. Liver enzymes should be checked at one month and every six months thereafter. Mitotane may be effective in younger ferrets but may cause nausea and lethargy. Ketoconazole is usually ineffective.

Mitotane for Canine Hyperadrenocorticism
In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyper-adrenocorticism (PDH) and palliative therapy of adrenal carcinoma, usually in dogs. Systemic drug availability has been found to be very poor from intact tablets in fasted dogs, and best when the powdered drug is mixed in oil and poured on dog food. The interaction between food and mitotane probably contributes to the variation in clinical response of dogs treated with the drug, because it appears that the efficacy is improved considerably when the drug is given with food. Because of the potentially severe toxicity associated with mitotane, clients should be instructed to wear gloves during and wash their hands after administering the medication, and to keep the medication out of reach of children or pets. Dogs with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period, and should be closely monitored until they are clinically stable. Clients should be advised of the symptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated with mitotane, clients should be instructed to wash their hands after administration and to keep the medication out of reach of children or pets.

References

Research

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