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.

J Vet Pharmacol Ther. 2005; 28(5):453-460.
PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
Click here to access the abstract of this article.

Vet Ther. 2008 Summer;9(2):83-93.
Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
Click here to access the PubMed abstract of this article.

 


 

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.

Aust Vet J. 2005 Oct;83(10):602-8.
Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent.
Click here to read the PubMed abstract of this article.

JAVMA 229: 1113-1117, 2006.
Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs.
Click here to read the PubMed abstract of this article.

Vet Clin North Am Small Anim Pract. 2005 Jan;35(1):129-46
Managing Pain in Feline Patients.
Click here to read the PubMed abstract of this article.

 


 

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.

http://www.vetmash.com/pdf_files/dr_duncan_lascelle04.pdf (accessed January 2012)

J Small Anim Pract 2001 Dec;42(12):587-93
Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.
Click here to access the PubMed abstract of this article.

Journal of Feline Medicine and Surgery; 6(5), Oct 2004: 321-333
Pain management in cats—past, present and future. Part 2. Treatment of pain—clinical pharmacology
Click here to access the PubMed abstract of this article.

 


 

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
Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis.
Click here to access the PubMed abstract of this article.

 


 

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.”

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