CONTRAINDICATIONS/VERY CAREFUL MONITORING AND DOSAGE (or use opiates):

  • Cardiac Drugs:  Diuretics, ACE inhibitors, β-blockers, digoxin (complications from dehydration, blood pressure changes, or competitive protein binding)
  • Glucocorticoids (GI complications)
  • Drugs that are highly protein bound and have low margin of safety (NSAIDS are highly protein bound and can displace other protein bound drugs such as warfarin, digoxin¸anticonvulsants like phenobarbital, and chemotherapeutic agents.)

SYMPTOMS OF PAIN IN CATS may be very subtle.  They include withdrawing from attention, decreased mobility, reduced interactions with humans or other pets, poor appetite, and aggression.

CAUSES OF PAIN IN CATS

  • Degenerative Joint Disease(DJD) is the most common.  It is thought to affect 60 – 90% of cats in the spine or legs.   Treat for obesity, give mild exercise, make environmental modifications to assist mobility.
  • Neoplasiatreatment is sometimes aided by concurrent treatment with NSAIDS.  This is in addition to making the cat feel better.
  • Trauma
  • Lymphoplasmacytic gingivo-stomatitis
  • Idiopathic cystitis
  • Skin disease
  • Uveitis
  • Fever

CYCLO-OXYGENASE/LIPOXYGENASE  INHIBITION (COX/LOX) enzymescause pain by aiding in production of prostaglandins and leukotrienes.  NSAIDS block the actions of COX and LOX enzymes.  Prostaglandins play important roles in normal physiology involving many systems such as vascular homeostasis, gastroprotection, renal developmenet and blood flow, blood clotting, bone metabolism, wound healing, nerve development and growth, and immune responses.  They are also involved in the pathological processes of pain and inflammation and cancer progression.

  • COX-1 is found at pretty constant levels in most tissues unless it is increased due to an exciting factor causing it to help create inflammation.  COX-1 is most usefully active in protecting cells in the gastric mucosa, maintaining normal platelet function, and maintaining renal perfusion.
  • COX-2 shares with the COX-1 enzyme, many of the above-mentioned functions and is found at fairly constant tissue levels.  COX-2, however, rises to dramatically higher levels in the presence of inflammation.  It is more of an induced enzyme.
  • COX-3 is now recognized as  a variant of COX-1 and it seems to have a role in central pain control.
  • 5-LOX enzymes are being researched now but no COX/LOX inhibitory drugs are approved at this time.

SIDE EFFECTS OF NSAIDS occur when the normal physiological roles of prostaglandins and leukotrienes are interrupted.  Inhibition of COX-1 functions seem to be most problematic.  So, drugs were developed that were called either COX-1 sparing or COX-2 preferential NSAIDS.   Debate exists as to whether this is the best approach.  COX-1 and COX-2 enzymes may affect the same tissues in different ways, requiring both to be present for normal function.  This leads some to prefer drugs that inhibit both COX-1 and COX-2  (dual inhibitors). 

 Researchers are looking at inhibition of COX leading to increased LOX activity, another problem in the mix.  Also, since most NSAIDS are weak acids, ion trapping can occur when extracellular pH is lower than intracellular, affecting the liklihood of side effects.  There is little solid research in felines and in vitro studies do not always predict in vivo responses.  Therefor, NSAID product choice and dose for each unique individual results in great variability in the severity or liklihood of adverse drug side effects.  ISFM/AAFP panel recommends that there is little predictably deciding data from cats and that probably the COX-2 preferential drugs may be only slightly superior if at all in blocking pain with the least adverse side effects. 

CLIENT COMPLIANCE is always an issue.  Meloxicam liquid is suggested to be highly palatable for cats.  Other drugs can be compounded.  Liquid products can be measured in increments that may more accurately fit the weight of the patient.  Send home a clearly marked syringe for accurate dosing.

DOSAGE AND TIMINGare very important because some of these drugs are slowly metabolized. 

  • Most NSAIDS are metabolized through the liver and so liver function affects dose.  Piroxicam and meloxicam ar metabolized by oxidation instead.
  • There is no practical way to predict which cats may be fast or slow metabolizers.  Use the lowest dose that works.
  • If the cat will not eat, do NOT administer the NSAID.
  • Dosage may change with time.  Periodically, withdraw or reduce dosage of NSAID to see if its continued use at that specific dose is justified.  Use criteria of mobility, activity, grooming, and temperament to assess level of comfort.  Encourage clients to journal under these four headings.
  • Peaks and troughs in NSAID activity may be timed to either fit the patient’s preferred schedule of activitiy OR may be timed so that the patient is least active when the owner is sleeping.
  • Obese cats should initially have NSAID dosages determined by what their ideal body weight might be.
  • When adjusting NSAID dosages, prefer to change amount of drug rather than interval of dosing.
  • Panel does not recommend pulse therapy unless underlying cause of pain waxes and wanes.

SWITCHING DRUGS has little evidence-based data. 

  • Switching from aspirin to NSAIDS requires washout period of 7 to 10 days.
  • Switching between NSAIDS thought to need washout of 3 to 5 days or potentially even longer if previous NSAID has a prolonged half-life.

CONCOMITTANT DISEASES AND CONDITIONS affect dosage and usefulness of NSAIDS.  DO NOT give NSAIDS if patient does not eat.

  • Renal Diseasemay force a lowered NSAID dose because normal adequate kidney function may depend upon the normal positive effect of prostaglandins.
    • Be especially careful to have adequate organ perfusion during surgery.  Prostaglandin levels become crucial when there is low renal blood flow and so NSAIDS can cause Acute Kidney Failure (AKF).
    • Annectdotally, Chronic Kidney Disease (CKD) patients generally showed no worsening of blood chemistries when they were maintained on oral meloxicam at .02 mg/kg/day or on oral piroxicam at doses of .2 to .3 mg/kg/day on long term bases.
    • Get baseline serum and urinalysis data before embarking upon long term NSAID useage.  Monitor blood chemistries regularly and respond accordingly if kidney function begins to deteriorate.  Opioid therapy may replace NSAIDS if necessary. 
    • Use wet diet to increase water consumption.
    • Extreme caution should be used when cardiac disease is also present.  Lowest possible doses and careful monitoring still allow NSAID use where needed.
    • Monitor K+.
  • Gastrointestinal Disease is the most common side effect of NSAID usage in mammals.
    • Vomiting occurred in 16% of cats in one large study of piroxicam but these cats were in a cancer study and getting other drugs as well.
    • Vomiting occurred in about 4% of cats receiving .1 mg meloxicam daily over a long term.
    • Upper GI bleeding is the most common serious adverse side effect.
    • Factors increasing the risk include, age, dosage, previous NSAID GI disease, pre-existing GI ulcers, and concurrent anti-coagulant or glucorticoid use.
    • Can use a mucosal protectant such as a prostaglandin analogue (ie. misoprostol at 5 µg/kg PO q8h) or a proton pump inhibitor (ie. omeprazole at .7 to 1 mg/kg PO q24h).
    • If GI bleeding or ulceration occurs, stop NSAID until healed.  Resume carefully, using mucosal protectants listed above.
  • Cardiovascular Disease patients’ risk of using NSAIDS is virtually unknown.  
    • Hypertensive cats receiving NSAIDS should have BP monitored closely.
    • Titer NSAIDS to lowest possible dose.
    • High prevalence of thromboembolic disease in cats makes it questionable whether long term therapy might increase chance of embolism as it does in some humans.
  • Liver Disease due to long term NSAIDS is occasional in other species and we may see it eventually in cats as NSAID therapy becomes more commonplace.
    • Monitor liver enzymes routinely.
    • Dose reduction should be considered in cats with pre-existing liver disease.  In the presence of severe liver dysfunction (eg, as evidenced by moderately to severely elevated bile acids.) and/or hypoalbuminemia (of any cause), NSAIDS should be used with extreme caution, if at all.

MONITORING CAT ON NSAIDS

  • Before beginning treatment get good history, including all other drugs recently or currently in use.  Blood pressure reading, chemistries focused on renal and hepatic systems along with plasma proteins and hematocrit.  These considerations direct frequency of future monitoring and may impact dose or even cause the clinician to seek other remedies.
  • Client information about monitoring and signed acknowledgment of risk prevent misunderstandings and help create a successful outcome.   The client should cease treatment and discuss changes with the veterinarian whenever a new problem arises.
  • Routine monitoring during treatment is crucial.
    • Initial reassessment at 5 to 7 days (or sooner if complications arise) could be done in the clinic or over the phone.
    • Next reevaluation should be at 2 to 4 weeks depending upon owner’s observations and perceived risk by veterinarian.
    • Continuing reevaluations should be done every 2 to 6 months determined by informed evaluation of risks.