Analgesic Agents

Morphine and the Opiates -- These agents act as agonists at endogenous opioid receptors in a manner similar to that observed in human medicine.  However, specific differences in pharmacologic effect are notable.
Equine, Bovine, Caprine, Ovine, Porcine, and Feline patients may show CNS stimulation rather than CNS depression.

Canine patients may initially defecate with the opioids.  This is frequently followed decreased GI motility, leading to constipation that is more commonly associated with this class of drugs.  Dogs may also respond to opiates with initial respiratory stimulation, which is then followed by typical respiratory depression.  The opiates are cough suppressants in dogs.  Additionally, dogs will exhibit coronary vasoconstriction, the opposite effect of that observed in humans.

Rabbits, Canines (and primates) exhibit miosis (pupillary constriction) while feline and other species exhibit mydriasis (pupillary dilatation).

Canine and feline patients will exhibit emesis at very high doses, while other species (especially ruminants and swine) do not exhibit emesis.

Dogs and rabbits will typically exhibit hypothermia in response to the opiates while cattle, goats, horses, and cats typically exhibit hyperthermia.

The opiates are used primarily as analgesics in veterinary practice, often administered with an ataractic (such as acepromazine), especially in excitable species.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Similar Drugs
Acetaminophen (Paracetamol, APAP)  APAP is used primarily in small animal practice.
APAP is contraindicated for use in cats at any dose.  The glucuronide metabolic pathway in the cat is very poorly developed.  Since this is the major metabolic pathway of APAP, cats are unable to metabolise APAP efficiently.  The alternate pathway in cats leads to the formation of a toxic metabolite than causes methæmoglobinæmia, hæmaturia, and liver damage often manifested as icterus.  A dose as small as 123-325 mg once can be lethal in cats.  (NOTE that this metabolic deficiency in cats also accounts for their susceptibility to toxicity from the following agents: methylene blue, azo dyes, benzocaine, hexachlorophene, phosphate enemas, trimethobenzamide, organophosphate insecticides, and to a lesser extent, all NSAIDs, morphine, chloramphenicol, tetracycline, aminoglycosides, phenytoin, propylthiouracil, bismuth subsalicylate, sulphasalazine, methimazole, ultramicrosized griseofulvin, and the vehicles propylene glycol and benzoyl alcohol).

The same is true in dogs, but to a much less extent (the dog has a more developed glucuronide pathway that is still less efficient that in humans), allowing cautious use in canine patients.  In dogs, APAP is administered at a dose of 15 mg/Kg no more often than q8h.  The toxic dose of APAP may be as low as 200 mg/Kg in dogs.

Aspirin (ASA)  ASA is somewhat safer than APAP in small animals.  However, glucuronidation is still a major metabolic pathway and toxicity can occur.  If overdose of small animals occurs, the animals may initially present with GI upset that progresses to CNS depression, (hæmat)emesis, anorexia, hyperthermia, and respiratory alkalosis that proceeds to metabolic acidosis.
The analgesic dose for dogs is 10-25 mg/Kg b.i.d. and for cats, 10 mg/Kg q.o.d.  The anti-inflammatory dose (most often used in the treatment of arthritis) is 81 mg MWF of each week.  The toxic dose for ASA (and other salicylates) in cats is 60 mg/Kg.

The large animal dose (producing analgesia and anti-inflammatory actions) is 15-55 Gm orally with copious amounts of water.  ASA is available for large animal use in 240 gr (15.552 Gm) tablets.

Dipyrone (Novin®)
Dipyrone possesses analgesic and antipyretic action with minimal anti-inflammatory effects.  Mechanistically, it is similar to other NSAIDs, inhibiting the enzyme cyclooxygenase.
Dipyrone is used for the treatment of pain and fever in small animals and colic in horses.

Adverse effects of dipyrone include agranulocytosis, leukopænia, and convulsions with overdose.

The small animal dose for dipyrone is 25 mg/Kg either orally or parenterally.  The equine dose is 5-10 Gm parenterally.

Flunixin (Banamine®)
Flunixin is a highly substituted nicotinic acid derivative that irreversibly binds to and inhibits cyclooxygenase.  It possesses anti-inflammatory, antipyretic, and analgesic activity.  Additionally, it increases hæmodynamic flow during septic shock.
Flunixin is primarily used in the treatment of pain associated with musculoskeletal disorders and also in visceral pain associated with colic (primarily in horses).

Adverse effects of flunixin include CNS stimulation (may or may not occur), ataxia, hyperventilation, and muscle weakness.

The parenteral dose of flunixin is 1.1 mg/Kg IM or IV for colic.  It is also available as an oral paste, dosed at 1.1 mg/Kg.  Note that the paste is marketed so that the dose is based upon the weight of the horse (one dosage unit/250 lb).  A 1000 lb horse would receive 1 syringe of paste every 3 days.  Flunixin is also available as oral granules (1 packet/500 lbs).  The drug should be stored between 36^o and 86^oF.

Ketoprofen (Ketofen®)
This standard NSAID is used primarily as an anti-inflammatory and analgesic in horses.  Adverse effects are typically mild, however overdose may cause laminitis.  The dosage is 2.2 mg/Kg (1 ml/100 lb) IV q.d. for 5 days.

Carprofen (Rimadyl®)
This "me-too" proprionic acid derivative is especially effective for the treatment of arthritic diseases in small animals, particularly dogs.  It is being heavily promoted in both professional and lay literature for this purpose.  Dosage is generally twice daily.

Etolodac (EtoGesic®)
Etolodac is also used primarily in the treatment of canine arthritis.  It provides a longer duration of action, with a dose of 10-15 mg/Kg once daily.

Naproxen (Equiproxen® Injectable and Granules)
Naproxen is another standard NSAID that is used for the treatment of pain and inflammation associated with lameness in myositis in horses and osteoarthritis in dogs.  The equine dose is 5 mg/Kg slow IV, then 10 mg/Kg in feed b.i.d. for 14 days.  The canine dose is 5 mg/Kg po initially, then 1.2-2.8 mg/Kg daily.  Adverse effects are uncommon in horses.  Dogs may exhibit an increased sensitivity to the GI effects, nephritis/nephrotic syndrome and hepatotoxicity that is associated with naproxen.

Phenylbutazone (PBZ)
PBZ is an analgesic, anti-inflammatory, and antipyretic that also possesses uricosuric activity.  It is used primarily to provide relief of inflammation associated with musculoskeletal disorders in dogs and horses.  The adverse effects of PBZ include GI erosion, blood dyscrasias, and possible renal damage.  It may be administered topically, orally or intravenously but should NOT be given IM or SC, since it can be very irritating to local tissues.  It is available as an oral paste, tablets, boluses, and injectable (Butazolidin®), gel (Butatron®), and powder (Equipazolazone®).

Meclofenamic Acid (Arquel®)
Another standard NSAID that is used in horses for osteoarthritic disease and soft tissue inflammation and in dogs for hip dysplasia.  Adverse effects include GI irritation.  Additionally, horses infected with bots may develop colic when given meclofenamic acid.  It is available as 5% granules in 10 Gm packets.

Piroxicam (Feldene®)
Piroxicam is used primarily in dogs that suffer from degenerative joint disease and as an adjunct in transitional cell carcinoma of the bladder.  Adverse effects include GI upset and ototoxicity.  The anti-inflammatory dose is 0.3 mg/Kg q.o.d. while the same dose is given daily as a chemotherapeutic adjunct.

Other Anti-Inflammatory Drugs

Colchicine -- Has been used on a limited basis in veterinary medicine for the treatment of amyloidosis (pre-renal failure) and chronic hepatic fibrosis.

Allopurinol -- Is used for its ability to reduce plasma urate levels.

Gold Compounds -- These anti-inflammatory and immunomodulatory drugs are used in the treatment of polyarthritis and immune-mediated pemphigus in small animals.  They may cause renal toxicity and hæmotological changes.

Hyaluronate Sodium
Hyaluronic acid is a naturally occurring, highly viscous mucopolysaccharide that is found in synovial fluid, the vitreous humour, and umbilical cord.  It serves to cushion joints, reduce the influx of proteins and cells into the local area, and to lubricate the joint.  It also scavenges free radicals and reduces levels/activity of prostaglandins, both of which may decrease inflammation.  The sodium salt is used as replacement therapy in synovitis not associated with severe degenerative joint disease in dogs and horses.

Hyaluronate sodium is available in 5 mg/ml, 2 ml dispensing syringes (Equron®); 10 mg/ml, 2 ml syringes (Hyalovet®, Hylartin®); and 10 mg/ml, 5 ml syringes (Synacid®).
 

Glucosamine/Chondroitin Combination (Cosequin®  and Cosequin® DS)
This drug contains glucosamine, condroitin, and manganese ascorbate.  Mechanistically, this combination is stated to provide the basic building components to restore joint cartilage and synovial fluid, thus providing greater support for diseased joints.

Clinical trials have indicated an improvement in mobility and apparent decreases in pain.  Additionally, no side effects have been reported.

Dosage is based upon weight, with small cats and dogs (less than 10 pounds) receiving 1/2 to 1 capsule daily and heavier animals receiving two capsules daily in divided doses.  After an initial six weeks of therapy, improvement is generally seen and the dose may be reduced by half.  Capsules may be opened and the contents sprinkled on or incorporated with food.

Polysulphated Glycosaminoglycan (PSG, PGAG, PSGAG, Adequan®)
Adequan® is another mucopolysaccharide that also inhibits proteolytic enzymes, thus preventing already reduced connective tissue flexibility and increasing compressivity/resiliency of connective tissue.  It also increases synovial concentration of hyaluronic acid and decreases prostaglandin E2.  It is used in the treatment of traumatic joint dysfunction in horses.  It may be given intramuscularly or intra-articularly, however, intra-articular administration may worsen symptoms and cause temporary lameness.  The dose is 500 mg q4d for 28 days, IM and 250 mg weekly for 5 weeks, IA.

Orgotein (Palosein®)
Orgotein is a water soluble metalloprotein weighing approximately 33,000 daltons.  It possesses anti-inflammatory activity by acting in a manner similar to that of the enzyme superoxide dismutase (SOD). This enzyme is responsible for the degradation of superoxide radicals which form at sites of  inflammation.  Superoxide radicals depolymerise hyaluronic acid, thus decreasing the viscosity and lubricant actions of the synovial fluids.  Orgotein and SOD catalyse the conversion of superoxide to peroxide and oxygen and the subsequent conversion of peroxide to water and oxygen.  SOD may also be chemotactic.

Orgotein is used in dogs for the treatment of ankylosing spondylitis, spondylitis, and disc disease.  It is used in horses for the treatment of soft tissue disease.

The canine dose is 5 mg SC once daily for 6 days, followed by doses q.o.d. for 8 days.  The equine dose is 5 mg deep IM q.o.d. for 2 weeks, then twice weekly for 2-3 weeks (it may initially be given daily if the inflammation is severe) or 5 mg IA 1-4 times weekly.  As with PSGAG, an initial worsening of symptoms may occur with intra-articular administration.

Dimethyl Sulphoxide (DMSO)
DMSO is a hygroscopic solvent that has many uses in the chemical industry as a universal solvent.  It exerts anti-inflammatory and analgesic action by scavenging free radicals (especially peroxyl and hydroxyl species) and also produces rubefacient effects.  DMSO is used topically to decrease acute swelling post-trauma and IV to reduce cerebrospinal œdema.  It is also sometimes injected directly into the joint.  Adverse effects include a garlicky, oyster-like, or metallic taste, breath and odour that is reversible over time.  Persons who administer the drug and come in direct contact with it may also experience this effect.  DMSO may also produce myopia that is slowly reversible.  It is available as a gel or solution (Domoso®).  The caregiver should always wear double-rubber gloves to reduce the chances of personal exposure.