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]…”

Veterinary Forum  October 2002, (pp. 62-65)

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.

L-lysine Treatment for Cats Infected with FHV-1

Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus
Maggs et al. of the College of Veterinary Medicine, University of Missouri examined the effects of orally administered L-lysine on clinical signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Fewer cats and eyes were affected by conjunctivitis, and onset of clinical signs of infection was delayed on average by 7 days in cats receiving L-lysine 400 mg once daily for 30 days, compared with cats in the control group. Significantly fewer viral shedding episodes were identified in the treatment group cats, compared with the control group cats. This dose caused a significant but short-term increase in plasma L-lysine concentration without altering plasma arginine concentration or inducing adverse clinical effects.

Am J Vet Res 2003 Jan;64(1):37-42

Dextromethorphan

 Of the seven major human cough suppressants, only dextromethorphan is indicated for treating cough in small animals. If after reviewing the indications and contraindications, cough suppression is desired, the available human products must be screened carefully as a very limited number contain dextromethorphan without other potentially harmful ingredients. Typically, the dose in dogs and cats is 1 to 2 mg/kg three to four times daily. Human products are not flavored to an animal’s taste, and may require administering a significant volume (typical strength is 15 mg/5 ml) to adequately dose an average size dog.

Stool Softeners

Docusate (DSS) can be used to assist in the passage of hard or dry feces that may occur secondary to dehydration or use of opioid analgesics or metoclopramide. While capsules hide the bitter taste, they can not be divided for appropriate dosing in smaller animals. The recommended dose in dogs and cats is 2 mg/kg once daily. For more severe cases, appropriately dosed DSS enemas may offer an alternative to phosphate-solution enemas.

Merck Veterinary Manual, 8th Edition, pp. 1691

Ursodiol for Gallstones

The purpose of this study, reported in Am J Health-Syst Pharm (Vol. 52) was to prepare an oral dosage form of the bile acid ursodiol (also known as ursodeoxycholic acid) from commercially available capsules and to determine the short-term stability of this formulation.  The formula used for this extemporaneous compound was found to be stable for up to 35 days.

Ursodiol in a Dog with Chronic Hepatitis

 A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (ursodiol) orally. After 2 weeks of daily treatment, the dog was more active and had an improved appetite. Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months.

J Vet Intern Med 1997 May-Jun;11(3):195-7

Studies have found an extemporaneously compounded ursodiol suspension to be stable for up to 35 days refrigerated. This drug is well absorbed orally and enters the liver directly from the portal system, and is then secreted into bile. Ursodiol should be administered orally as the first-pass effect is vital for effectiveness.

Aminocaproic Acid for Degenerative Myelopathy (DM) in Dogs

DM appears with relative frequency only in the German Shepherd breed (GSD); confirmation of the diagnosis is important in other breeds before assuming that they have DM of GSD. During the past two decades, R.M. Clemmons, DVM, Ph.D., and other researchers at the University of Florida have provided important new insights into the pathoetiology of DM. Recently, they have found that when combined with the history, neurologic signs, CSF protein concentration and EMG, an elevated CSF acetylcholinesterase level helps confirm the diagnosis. It is increasingly clear that DM is caused by an autoimmune disease attacking the nervous systems of patients, leading to progressive neural tissue damage. In many respects, DM is similar to Multiple Sclerosis in human beings.

The Integrative Medical Approach to Treatment of Degenerative Myelopathy involves four basic approaches:

1. exercise
2. dietary supplementation
3. medication
4. other supportive measures

Conventional medicine has little to offer patients with DM. On the other hand, use of exercise, certain vitamins and selected drugs have delayed or prevented progression of DM in many afflicted dogs.

Clemmons et al have found 2 medications which appear to prevent progression or result in clinical remission of DM in up to 80% of patients – aminocaproic acid (EACA) and n-acetylcysteine (NAC). They propose that circulating immune-complexes lead to endothelial cell damage in the vessels of the CNS. Subsequently, fibrin is deposited in the perivascular spaces. When this degrades (point of action of aminocaproic acid), inflammatory cells are stimulated to migrate into the lesions. The inflammatory cells release prostaglandins and cytokines (point of action of vitamin E and C) which lead to the activation of tissue enzymes and the formation of oxygen free-radicals (point of action of acetylcysteine) which, in turn, leads to tissue damage.They recommend giving EACA as a flavored solution, 500 mg orally every 8 hours. A “source for EACA is to have a compounding pharmacy make the solution from chemical grade EACA.”  The only side effects that have been attributed to EACA have been occasional gastrointestinal irritation. This has presented a problem only in a few patients, typically those with pre-existing GI problems. The only known drug interaction is with high dose estrogen compounds.

N-Acetylcysteine is a potent anti-oxidant which has powerful neuroprotective effects. Clemmons et al give 75 mg/kg divided in 3 doses a day for 2 weeks; then, 3 doses every other day. The N-acetylcysteine must be diluted to a 5% solution; otherwise, it will cause stomach upset. “This new treatment is expensive unless purchased through compounding pharmacies.” NAC can produce vomiting (due to the sodium content of the pharmaceutical product, which requires high concentration of base to buffer) and may increase the bleeding time. Giving fresh ginger 30 minutes before NAC or administering NAC with food (or on a full stomach) often reduces this effect.

The chances of successful treatment are improved if the therapy is begun early in the course of DM rather than later. A response to the drugs should be evident within the first 7-10 days.

Chlorpromazine for Anti-Emesis

Chlorpromazine (Thorazine®) is a phenothiazine and works at the emetic center, the chemoreceptor trigger zone, and peripheral receptors; it is this veterinarian’s “all purpose anti-emetic of choice” for cats.1 Chlorpromazine may cause extrapyramidal symptoms in cats when administered at high doses. The drug may discolor urine pink or red-brown, cause mild sedation, and may potentiate hypotension in dehydrated patients. Phenothiazines should not be given within one month of worming with an organophosphate agent. The recommended oral doses in dogs and cats is 3.3 mg/kg PO one to four times daily. Due to extensive first pass metabolism2, it may be necessary to reduce the dose in animals with liver disease. A liquid concentrate can be appropriately flavored for dogs or cats.

Todd R. Tams, DVM, Dip ACVIM in CA VMA C/E Conf Procd, 2000
Veterinary Drug Handbook 3rd edition, Donald C. Plumb, ed.;  pp. 129-30

Managing Anorexia in Uremic Dogs and Cats

H2-receptor antagonists (cimetidine, ranitidine, and famotidine) can be useful to reduce gastric acid secretion. Increased gastrin concentrations in serum during chronic renal failure may stimulate excessive secretion of gastric acid and cause ulcer formation. Some uremic dogs and cats dramatically increase their interest in food and food intake after therapy with an H2 blocker. According to a presentation at the Atlantic Coast Veterinary Conference by Dennis J. Chew, DVM, Dip and C.A. Buffington, DVM, some uremic animals may need this medication for an extended period of time (months to rest of their lives). Much of the experience of these veterinarians has been either with cimetidine at an initial dose of 10 mg/kg, followed by 5 mg/kg PO BID or famotidine at 1 mg/kg daily.

The Capsule Report, Vol. 19, No. 10, Jan. 2001

Doxycycline for Prophylaxis and Treatment of Osteoarthritis in Dogs

Prophylactic administration of doxycycline (a tetracycline) has markedly reduced the severity of canine osteoarthritis (OA) in weight-bearing regions of the medial femoral condyle, and therapeutic administration of oral doxycycline has been shown to reduce the severity of articular cartilage breakdown in various animal models of OA. This disease modifying effect is associated with reductions in the levels of active and total collagenase and gelatinase in articular cartilage of the involved joint.

A prospective, clinical study of eighty-one dogs with OA secondary to spontaneous cranial cruciate ligament (CCL) rupture concluded that doxycycline inhibits nitric oxide production in cartilage in dogs with CCL rupture, and that doxycycline may have a role in the treatment of canine OA. Dogs with OA secondary to CCL rupture were divided into 2 groups before surgery. The Doxy-CCL group (n = 35) received 3 to 4 mg/kg doxycycline orally every 24 hours for 7 to 10 days. The CCL group (n = 46) received no treatment. Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery or immediately after euthanasia from healthy dogs (control group). Total nitric oxide concentrations measured in cartilage were significantly lower in the Doxy-CCL group than in the CCL group, but were not different from those measured in the control group.

In another study, ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament, which resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. The authors concluded that doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.

Vet Surg 2001 Mar-Apr;30(2):132-9
J Rheumatol 1996 Jan;23(1):137-42
J Rheumatol Suppl 1995 Feb;43:149-51
Vet Clin North Am Small Anim Pract 1997 Jul;27(4):863-81
Arthritis Rheum 1992 Oct;35(10):1150-9

Cisapride: A Prokinetic Drug

Cisapride (Propulsid® – Janssen Pharmaceutica), was removed from the U.S. and Canadian markets by its manufacturer because of serious cardiac effects in humans. However, cisapride is now available as a bulk chemical for veterinary use only and can be compounded as per your prescription order.

Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or have antidopaminergic effects or cause extrapyramidal reactions. Cisapride “is more potent and has broader prokinetic activity than metoclopramide, increasing the motility of the colon, esophagus (in cats and guinea pigs), stomach, and small intestine… [Cisapride] has been used in managing gastric stasis, idiopathic constipation, gastroesophageal reflux, and postoperative ileus in dogs and cats. Practitioners found cisapride especially useful in managing chronic constipation in cats with megacolon; in many cases, it alleviated or delayed the need for subtotal colectomy. Cisapride was also used in managing cats with hairball problems.”
“Cisapride appeared to be well tolerated by dogs and cats. Adverse reactions to cisapride have not been reported to the United States Pharmacopeia’s Veterinary Practitioners’ Reporting Program… Disorders of GI motility are common and frustrating clinical problems in dogs and cats. Cisapride, with its extensive prokinetic action, was a welcome addition to veterinary medicine.”

Veterinary Medicine, September 2000, pp. 678-685

Doses for Dogs: as a promotility agent: initially 0.5mg/kg three times daily To reduce regurgitation associated with megaesophagus: 0.55mg/kg; orally one to three times daily, no less than 30 minutes before feeding; As an antiemetic: 0.1-0.5mg/kg orally every 8 hours.

Doses for Cats: for chronic constipation: initially, 2.5mg for cats up to 10#; 5mg for cats 11-15#; up to 7.5mg for cats over 16# three times daily, 30 minutes before food, in combination with stool softener and bulk agent.

Cisapride is contraindicated in patients in whom increased GI motility could be harmful (e.g., perforation, obstruction, GI hemorrhage). Absorption of other orally-administered drugs may be affected. Cisapride may enhance anticoagulants’ effects; additional monitoring and anticoagulant dosage adjustments may be required. Cisapride may enhance the sedative effects of benzodiazepines. Clients should be advised to monitor the animal and report any adverse effects.

Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 139-140

Hairball Remedy

Cat and ferret owners continually search for specialized foods and treats that their pets will readily consume and will also be effective for hairball prevention or elimination. Call us for a customized, flavored hairball remedy for your patients!

Stanozolol

In a study conducted at the Animal Health Unit and Gastrointestinal Sciences, University of Calgary, Alberta, ten healthy, intact, adult male sled dogs received either stanozolol tablets, 2 mg/dog PO, q12h, for 25 days or an intramuscular injection of stanozolol 25 mg on Days 7, 14, 21, and 28. A 15N amino acid (5.27 mmol) was infused intravenously into each dog on Day 0 (before stanozolol treatment) and on Day 31 (after stanozolol treatment). Both oral and injectable stanozolol resulted in significant increases in amino acid nitrogen retention compared to pretreatment values. Oral stanozolol increased nitrogen retention from 29.2 +/-8.2% to 50.3 +/- 9.2%, while stanozolol injection increased nitrogen retention from 26.6 +/- 9.9% to 67.0 +/- 7.5%. The nitrogen retention action of stanozolol may be beneficial in dogs under stress of surgical trauma and chronic disease.

In a separate blinded crossover trial at the College of Veterinary Medicine, Kansas State University, 22 castrated Beagles with experimentally induced chronic renal failure were treated with stanozolol. Cowan et al. concluded that for dogs with mild-to-moderate, nonuremic, experimentally induced, chronic renal failure, stanozolol had positive effects on nitrogen balance and lean body mass. Stanozolol did not have a significant effect on body fat, bone mineral content, or food consumption per kilogram of body weight.

Anabolic steroids such as stanozolol have been used to treat geriatric dogs. These drugs can increase nitrogen and mineral retention so that the body can better utilize dietary protein. As a result, the dog’s appetite may improve, resulting in more strength, energy, and weight gain. There is one reported case of the use of stanozolol (0.5 mg/kg, SQ, BID, PRN) to stimulate appetite in a rabbit. However, this class of drugs is not without potentially serious side-effects which must be considered before using them. Anabolic steroids should be used with caution in animals with heart, liver, or kidney problems, or in animals with breast or prostate cancer. Stanozolol should not be used in pregnant animals, during lactation, in young animals, or in male breeding animals. Anabolic steroids may increase the effects of warfarin and other anticoagulants.

In dogs, reported side effects are mainly androgenic, including increased aggression, increased activity, weight gain and mood alterations. However, in cats with and without chronic renal failure, there are reported cases of hepatotoxicity that appear to be related to the use of stanozolol.

J Am Vet Med Assoc. 1997 Sep 15;211(6):719-22
Can J Vet Res. 2000 Oct;64(4):246-8
Veterinary Forum. April 1999

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.

Veterinary Clin North Am Exot Anim Pract. 2003 May;6(2):337-50, vi

Treatment of a Systemic Fungal Infection in a Parrot with Itraconazole Flavored Suspension and Nebulized Clotrimazol

A Solomon Island Eclectus parrot, female aged 1.5 years, presented in a weakened state. Examination and culture revealed a systemic Aspergillus infection. Due to its significant cost as well as concern for the pet, the owner was highly motivated to treat the parrot.
Treatment posed a challenge because the parrot only eats brightly-colored foods, and there was no commercially available clotrimazole solution for nebulization for veterinary use. The veterinarian contacted the local compounding pharmacy to discuss how compounded medications might help solve this therapeutic dilemma. It was decided that an oral suspension flavored with equal parts orange, banana, and strawberry could mask the bitter flavor of itraconazole, and that a customized dosage (20mg/ml) could be compounded for the parrot. The veterinarian also prescribed clotrimazole 1% for nebulization.
The owner administered 0.2ml (4mg) of itraconazole suspension to the bird each day by mouth using an oral syringe. Therapy continued for three months. Clotrimazole 1% solution was nebulized (1ml BID to TID) by placing a pediatric nebulizer mask over the cooperative bird’s head. After 30 days, the bird still had a productive cough. Therefore, nebulizer therapy with clotrimazole continued after total resolution of signs and symptoms of infection, for a total of four months (one month after the oral itraconazole was finished).
The parrot fully recovered. This case represented the pharmacy’s first attempt at avian therapy, and was 100% successful. The same therapy was used later for another bird that also fully recovered from a systemic Aspergillus infection.

Michael Briggs, Pharm.D.

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 coli, Klebsiella, 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.

10th U Wisc Exotic Pet Conf Procd 04:01
The Capsule Report, Small Animal/Exotic Edition Jan 2002;20, 10: page 3

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.”

Journal of Small Animal Practice 1993; 34:564-566

Haloperidol for Feather Plucking

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.

Stacie Fowler, D.V.M.

Electrolyte Paste to Restore Fluid and Acid Base Balance in Horses

“Prolonged exercise in horses, particularly when performed in hot and humid conditions, brings about large fluid and electrolyte loses which, if not restored, may impair thermoregulatory responses and result in hyperthermia.” In horses, administration of oral rehydration solutions (ORS) is problematic, because many horses refuse to drink fluids containing electrolytes. Therefore, administration of ORS typically requires placement of a nasogastric tube with its inherent risks. An alternative is to give a concentrated electrolyte mixture as a paste. Leon et al. of Department of Veterinary Clinical Sciences, University of Sydney, NSW, Australia studied six Thoroughbred geldings to determine “whether oral administration of a concentrated electrolyte paste would promote the restoration of fluid, electrolyte, and acid base balance as well as fluid and electrolyte deficits induced by furosemide administration” (a standard model which induces significant contraction of plasma volume and consistent electrolyte deficit against which the effects of treatment could be measured). “As a general conclusion, horses that received concentrated electrolytes [and had free access] to water consumed more water, regained more weight, lost considerably less electrolytes in urine, and maintained plasma electrolyte concentrations and acid base balance closer to baseline values than did those that had ad libitum access to water only.” Administration of electrolyte paste provided a more practical source than supplementation using feed or salt blocks.

Am J Vet Res 1998 Jul;59(7):898-903

Progesterone for Estrus Induction in Mares

According to Robert R. Foss, DVM, progesterone in sesame oil, 150 mg per day, IM is equally as efficacious as altrenogest. The optimal formulation is the combination of progesterone and estradiol 17-beta; the addition of estradiol provides a greater feedback than progesterone alone, so cessation produces a more dramatic response. The estradiol is somewhat protective against exacerbation of endometritis. Dr. Foss commonly uses this combination at 150 mg progesterone and 10 mg estradiol 17-beta, IM, daily for 10 days. Estrus will usually begin in 6-8 days with ovulation around day 10-12. This combination has been effective in situations where altrenogest has failed.

114th IL VMA Proceedings, February, 1996

Prednisone (Oral) Ineffective in Horses

Jackson et al. compared the effects of prednisone with environmental management to environmental management alone for the treatment of heaves (recurrent airway obstruction), and reported that oral prednisone has no additional benefit.

To be effective, oral prednisone must be absorbed and metabolized to its active form prednisolone. Robinson et al. designed a study with two objectives:  

1. to compare oral prednisone with intravenous dexamethasone for the treatment of horses with heaves; and
2. to measure serum prednisolone levels in horses after oral administration of prednisone and prednisolone.

Each of five horses received five drug formulations (prednisone and prednisolone in tablet and liquid form, as well as intravenous prednisolone sodium succinate as a positive control, all at a dose of 2.2 mg/kg) in a Latin square design study. Severity of airway obstruction was measured, and there were no significant differences between prednisone administration and no medication at any time. Prednisolone was detectable in serum immediately after intravenous administration, peaking at around 1000 ng/ml at 12 min. Oral administration of prednisolone tablets or liquid yielded peak serum prednisolone concentrations of 377-1032 ng/ml at 30-45 min. When horses received oral prednisone tablets or liquid, prednisolone never reached detectable levels in the serum. The authors concluded: “in order for the drug prednisone to be effective after oral administration it must be absorbed from the gastrointestinal tract and converted to the active drug prednisolone by the liver. Although trace serum levels of prednisone were detected, prednisolone never appeared in the serum. Our data do not allow us to determine if prednisone is poorly absorbed, rapidly excreted, or not converted to prednisolone by the liver. However, it is clear that prednisone is unlikely to have any anti-inflammatory effect when administered by mouth. Oral administration of prednisolone is likely to be beneficial because it is rapidly absorbed and achieves serum levels close to those that result from intravenous administration.”

Robert N. Oglesby, DVM (The Horseman’s Advisor, www.horseadvice.com) reports his reaction to hearing the above presentation at the November, 2000 meeting of the American Association of Equine Practitioners: “I was shocked and looking around me hundreds of other vets were also: oral prednisone doses are in every equine medicine text with many descriptions of its indications. Why has no one noticed the lack of effect before now? The reason is simple: no one believed it was possible that [prednisone] was not effective [in horses]. Its usefulness in other species was too well established… we did not even question its use. Looking back on it, it was the management changes that were responsible for the clinical improvement…”

We can compound prednisolone into the most appropriate dosage form, including oral pastes or “chewies” that horses will love!

Equine Vet J 2000 Sep;32(5):432-8
AAEP Proceedings, Vol. 46, 2000, pp. 266-267
Equine Vet J. 2002 May;34(3):283-7

Pentoxifylline

In horses, a dose of 8.5 mg/kg orally two times daily is recommended for reducing the cytokine effects in endotoxemia. For the treatment of navicular disease, 6 g/day orally for 6 weeks should be used.

Compendium 23(7), July 2001, 603-4

Anti-Diarrheals for Foals & Horses

Treatment of diarrhea should always be based on establishing a diagnosis and correcting the basic cause. Anti-diarrheal products are not a substitute for adequate fluid and electrolyte therapy when dehydration or shock threatens. When the veterinarian deems anti-diarrheal therapy is appropriate, the following options may be considered.

According to James L. Becht, D.V.M., M.S., Diplomat ACVIM, preparations containing bismuth subsalicylate seem superior to those containing kaolin, pectin, or activated charcoal for treating the foal with diarrhea. Bismuth subsalicylate neutralizes bacterial toxins, has some antibacterial activity, and may exert an antisecretory effect. It can be administered at a dosage of 4 oz q 6h; darkened feces will result. If no effect is seen within 48 hours, continued administration is probably not indicated. (105th Ohio VMA).

Wendy E. Vaala, V.M.D., Diplomate ACVIM reports (ACVIM 16th Veterinary Medical Forum) that delayed gastric emptying and gastroduodenal dysmotility can be improved  in some foals with  metoclopramide (0.25-0.6 mg/kg, PO q4-6h), erythromycin (1.0-2.0 mg/kg PO q6h), or cisapride (10 mg/kg PO q6h). If colic, ileus, and gastric reflux are present, Dr. Vaala recommends an abdominal sonogram to rule out the presence of an intussusception prior to initiating prokinetic therapy. Diarrhea may be treated symptomatically with bismuth subsalicylate (1-2 ml/kg, PO, q4-6h) and may also respond to psyllium administration. Intestinal probiotics containing Lactobacillus bacteria … may be given to foals receiving antibiotics to help reestablish intestinal flora.

Adult horses may be treated with bismuth subsalicylate 1 oz per 8 kg of body weight PO TID-QID (Clark and Becht 1987).

Headshaking in Horses

Headshaking may include additional signs such as nose rubbing, striking at the nose with the forelegs, or active avoidance of light, warmth, or wind on the face. Newton et al studied 20 mature horses with typical headshaking of 2 week to 7 year duration, and concluded that the etiopathology may be a trigeminal neuritis or neuralgia. In 12 of 20 horses, drug therapy was initiated. Cyproheptadine (CP) alone was ineffective but the addition of carbamazepine (CM) resulted in 80-100% improvement in 80% of cases within 3 to 4 days of beginning drug therapy. Seven cases were treated with a combination of CM (4 mg/kg, three to four times daily) and CP (0.2-0.5 mg/kg every 12 to 24 hours).

Carbamazepine alone has been effective in 88% of cases. Some headshaking horses have responded well to CM doses of 1.6 – 2.4 grams every six hours without apparent side effects. Horses are treated for 10 to 20 days and if they respond, the treatment is discontinued. If clinical signs of headshaking recur, treatment is restarted. In practice, there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other studies have reported that cyproheptadine alone was beneficial in more than two thirds of treated horses.

Equine Vet J  2000 May;32(3):208-16
Equine Vet J Suppl 1998 Nov;(27):28-9
J Am Vet Med Assoc  2001 Aug 1;219(3):334-7
ISU Vet Med Sept 2000
The Pennsylvania State University Veterinary News, Dec 2000, pp 9-10

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.

Randy S. Carr, R.Ph., FIACP
Pamela Doskey, D.V.M.

Therapy for Severe Chemical Burns

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.

Barbara Espe, D.V.M.

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.

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.

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

Adrenergic Agonists:

Phenylpropanolamine (PPA) is a weak alpha agonist 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.

Dose for Dogs: 1.1 mg/kg PO every 8 hours; Dose for 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.” 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.

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

In November 2000, 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.

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

Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, ed. pp.193-5, and 508-9
Handbook of Veterinary Drugs, 2nd edition, pp. 277-8
J Small Anim Pract. 2002 Nov;43(11):493-6
Source

Piroxicam for Canine Bladder Cancer

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

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

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

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

Cancer Chemother Pharmacol 1992;29:214-218
Cancer Chemother Pharmacol 2000;46:221-226
J Vet Intern Med 1994;8:273-278
Urologic Oncology 2000;5:47-59

Citrate Salts as Alkalinizing Agents

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

Fludrocortisone Acetate

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

Aluminum Hydroxide for Hyperphosphatemia

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

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

Calcitriol for Chronic Renal Failure

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

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

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

Shirley Russman, D.V.M.

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

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

Potassium Bromide for Seizures

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.

Mollyann Holland, D.V.M., Oklahoma City, OK

Potassium Bromide Chewable “Treats” for Seizure Control

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.

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

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.

Please scroll down for more information on the following topics:

• Apomorphine to Stimulate Vomiting
• Accidental Poisoning
• N-acetylcysteine as an Antidote for Acetaminophen Toxicosis
• Dimercaptosuccinic Acid for Lead Poisoning in Cats
• Penicillamine for Long-Term Treatment of Lead Poisoning
• 4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning

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

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 methemoglobinemia, 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.

Compendium 2003 Apr;25(4):276-280
Am J Vet Res 1985 Jul;46(7):1485-9
Vet Hum Toxicol 1997 Dec;39(6):329-31
Vet Med 1997;92(2):158-165

Dimercaptosuccinic Acid for Lead Poisoning in Cats

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.

Wright Veterinary Medical Center, Bethlehem, PA

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 for 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.

Source
J Small Anim Pract 2001 Dec;42(12):587-93
Journal of Feline Medicine and Surgery; 6(5), Oct 2004: 321-333

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.

Can Vet J 2000 Apr;41(4):296-300

Ketoprofen

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 reported (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.”

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.”

Patricia D. White, DVM, MS
Compendium on Continuing Education 21:8 August 1999, pg 716-28

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.

Compendium on Continuing Education 21:8 August 1999, pgs. 716-728

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%.

Compendium on Continuing Education 21:8 August 1999, pgs. 716-728
Kirk’s Current Veterinary Therapy XII Small Animal Practice, 1995, Bonagura & Kirk, ed.

Treatment of Canine Otitis with Norfloxacin 1% & Ketoconazole 1% 

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.”

Canine Practice, Vol. 21, No. 2, pp. 26-28
T. D. Flack, D.V.M.

Tris-EDTA Solution for Canine Otitis

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.”

Veterinary Forum, June 1999, p. 52

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.

Compendium on Continuing Education 21:8 Aug. 1999, pgs. 716-728
Richard E. Wooley, D.V.M., Ph.D.
William R. Engen, D.V.M.
Harry W. Dickerson, B.V.Sc., Ph.D.