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COMPANION ANIMAL PAIN MANAGEMENT – CATS AND DOGS Cory Theberge, PhD UNE College of Pharmacy MPA Spring Conference CE 2015.

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Presentation on theme: "COMPANION ANIMAL PAIN MANAGEMENT – CATS AND DOGS Cory Theberge, PhD UNE College of Pharmacy MPA Spring Conference CE 2015."— Presentation transcript:

1 COMPANION ANIMAL PAIN MANAGEMENT – CATS AND DOGS Cory Theberge, PhD UNE College of Pharmacy MPA Spring Conference CE 2015

2 Learning Objectives  Identify the physiological characteristics of cats and dogs that affect pain medication absorption, metabolism, and excretion  Recognize the indications, side effects, and counseling points of pain management treatment options in cats and dogs  Recall veterinary-label medications used for cat and dog pain management

3 Outline  Background  Prescribing for Cats and Dogs  Dietary Preferences  Cat Pain Posture  Feline Glucoronidation/APAP  OTC Pain Medications  NSAIDs  Opiods (Brief Section)  Gabapentin  Glucosamine and Chondroitin

4 Veterinary Prescribing Refresher  All of these drug categories require a prescription from a veterinarian:  Veterinary prescription drugs used in any way not on the FDA-approved label  Veterinary OTC products used in any way not on the FDA- approved label  All human prescription and OTC drugs  All compounded drugs  When human-approved OTC drugs are used in animals, pharmacists must dispense these drugs with a prescription label, just like any other prescription drug.

5 Cat and Dog Dietary Preferences  Humans and dogs are omnivorous  Urinary pH varies, depends on the amount of protein consumed  Cats are obligate carnivores  Cats eat meat as their main source of protein.  Grain-free diet  A cat’s urinary pH is relatively acidic. Differences in urinary pH can impact the way a drug is eliminated. ASA and APAP are sensitive to this difference.

6 Cat Pain Posture “Marjaryasana” Majari = cat Head held down or hidden Eyes squinted Hunched back

7 Cats – Glucoronidation/APAP

8 Cats Are Glucuronyl Transferase-Deficient  Cats are deficient in the liver enzyme glucuronyl transferase  Many medications undergo glucuronidation metabolism  Glucuronidation is a major route of elimination of acetaminophen

9 Acetaminophen (APAP) Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 6-7.  Doses:  Dogs: mg/kg PO q12h Beneficial for dogs with renal dysfunction  Contraindicated in cats  Dogs: may be combined with codeine, hydrocodone, or tramadol for moderate pain

10 Cats and Acetaminophen (APAP)  Cats can’t breakdown APAP by glucuronidation  APAP undergoes transformation in the cytochrome P-450 system to a reactive intermediate, NAPQI.  NAPQI is the toxic metabolite of APAP that causes hepatocyte death.  Normally, glutathione binds to NAPQI and forms a non- toxic metabolite.  In cats, most of the drug is transformed into NAPQI,  The glutathione stores are not capable of binding all of the NAPQI, so NAPQI is left unbound.  This causes liver damage and death in cats.

11 APAP Toxicity TOXIC NOT TOXIC

12 What happens if a cat takes APAP?  Methemoglobinemia  Elevated methemoglobin  The hemoglobin has a decreased ability to bind free oxygen  The hemoglobin has an increased affinity for bound oxygen.  This leads to an overall reduced ability of the red blood cell to release oxygen to tissues  Results in tissue hypoxia  Hemolytic anemia  Hepatic necrosis  Facial and paw swelling  Hematuria  Jaundice Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 6-7.

13 APAP Toxicity Treatment  Emesis (if ingested within <2 hours)  Activated charcoal  Acetylcysteine  Precursor to glutathione  Oxygen therapy  Ascorbic acid for methemoglobinemia Ahrens F. Pharmacology: The National Veterinary Medical Series. Blackwell Publishing: Ames, Iowa; Page 175.

14 APAP Counseling Points  Contraindicated in cats at any dosage.  Not overly toxic to dogs at recommended dosages. Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

15 Notable for Cats: Drugs That Undergo Glucuronidation  Morphine  Oxazepam  Bilirubin  Acetaminophen  Carbamazepine  Codeine  Lamotrigine  Lorazepam  Temazepam  Testosterone  Zidovudine  Many NSAIDs  Not meloxicam  Valproic Acid King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. doi: / PMID

16 Human OTC Options for Pain

17 Cats and Aspirin  Aspirin elimination:  Some glucuronidation  Some eliminated unchanged in the urine  Since cats are deficient in glucuronyl transferase, they can only eliminate the aspirin renally  Cats have relatively acidic urine  Aspirin (a weak acid) is more readily reabsorbed in cats. (Like dissolves like)  Unlike APAP, ASA does not form toxic metabolites, so it is not contraindicated in cats.

18 Cats and Aspirin  Aspirin has a significantly longer half-life in cats  Half-life lengths  Cat: 25 – 45 hours  Dog: 8 – 9 hours  Human: 3 hours  If aspirin is prescribed, the dosing interval is extended to hours to avoid accumulation.  Doses:  Dog: 10 mg/kg PO q12h  Cat: 10 mg/kg PO q48-72h Fink-Gremmels J. (2008) Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences. Eur J Pharmacol 585: Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 83-6.

19 Aspirin Toxicity Ahrens F. Pharmacology: The National Veterinary Medical Series. Blackwell Publishing: Ames, Iowa; Pages Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages  Symptoms: Depression, vomiting, anorexia, hyperthermia, increased respiratory rate  Effects  Hyperpyrexia  Acid-base disturbances  Dehydration (from vomiting and sweating)  Treatment  Gastric lavage, activated charcoal, or dialysis  Sodium bicarbonate Raises the urinary pH and therefore increases aspirin excretion  IV fluids

20 Aspirin Counseling Points  Buffered or enteric-coated is aspirin is recommended to reduce GI side effects.  Cats are relatively sensitive to salicylates (dose carefully).  Dogs are relatively sensitive to GI effects (bleeding).  Always give with food, due to stomach irritation.  Watch for signs of bleeding  Dark, tarry stool  Hematemesis Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

21 Naproxen  Not indicated for cats  Use in dogs is discouraged  Reports of GI ulcers and perforation  May be overly sensitive to the adverse effects Nephritis Nephrotic syndrome Increased liver enzymes  Only give one NSAID at a time  Never give with corticosteroids  Watch for signs of bleeding  Use has declined due to the development of newer, less GI- toxic NSAIDs Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

22 OTC Cat and Dog Summary DrugDogCat Aspirin (only buffered or EC) Yes With food Short-term use only No Only by vet. One 325mg tab is 8x the recommended dose for an 8-lb cat. Acetaminophen Yes Up to 15mg/kg PO TID No One 500mg tab is lethal to a 10-lb cat. IbuprofenNo Naproxen Sodium No Only by vet No

23 Topical OTC Pain Products  Local anesthetics like lidocaine, tetracaine, benzocaine or pramoxine are found in many human topical ointments and suppositories.  Cats can absorb these local anesthetics through their skin or ingest them during grooming.  Cats have a unique hemoglobin structure, which is easily damaged by these anesthetics and are at an increased risk for toxicity.  In large amounts, seizures, tremors and cardiac arrhythmias can occur. Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

24 Never recommend OTC NSAIDs  NSAIDs can cause kidney and liver toxicity  NSAID therapy and organ toxicity must be monitored by veterinarians.  NSAIDs are poorly tolerated by cats  If an NSAID is approved for a cat, a black box warning usually accompanies that drug.  Meloxicam (Metacam) black box warning: repeated doses cannot be given because of risk of renal failure and death in cats.

25 Animal Label Non-steroidal anti- inflammatory drugs (NSAIDs)

26 Background  Used for analgesic and anti-inflammatory properties  MOA  Inhibit COX enzymes  Variable effects on: Gastric mucosal lining Platelet function Renal function and regulation  Many NSAIDs are metabolized in the liver by glucuronidation (Not for cats!)  Meloxicam undergoes oxidation

27 GenericVet-LabeledHuman-LabeledDogCat Carprofen Rimadyl, Vetprofen -Yes Only for post-op pain EtodolacEtogesicLodineYesNo Phenylbutazone Butazolidin, Butatron, Equipalazone -YesNo KetoprofenKetofen Orudis KT, Oruvail Yes MeloxicamMetacamMobicYes Only labeled for a one-time dose. Others uses are off-label. DeracoxibDeramaxx-YesNo FirocoxibPrevicoxYesNo Flunixin Banamine, and many others - Only for horses and cattle. (Remember EPM?) This table does not include NSAID ophthalmic preparations, such as bromfenac and flurbiprofen. Plumb DC. Plumb’s Veterinary Drug Handbook. Seventh Edition.

28 Side Effects  Decrease or increase in appetite or drinking habits  Vomiting  Change in bowel movements  Diarrhea  Black, tarry, or bloody stools  Change in behavior  Decreased or increased activity level  Aggression  Jaundice  Yellowing of gums  Yellowing of skin  Yellowing of whites of the eyes  Change in urination habits  Frequency  Color  Smell  Skin changes  Redness  Scabs  Itching Side effects usually surface hours after starting NSAIDs. Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

29 Counseling Points  Always give with food to minimize GI side effects.  Dogs are particularly susceptible to bleeding and hepatotoxicity.  Cats are particularly susceptible to kidney failure, especially if dehydrated or not eating.  Etodolac  Decreases T4 in some dogs  Less impact on bleeding times than other NSAIDs  A one-day wash-out period is recommended when discontinuing carprofen and switching to another NSAID.

30 Opioids (Briefly) – Cats and Dogs

31 Mechanism Of Action  Three opioid receptors: μ, δ, κ  Raise the pain threshold  Decrease the perception of pain  Act at the dorsal horn of the spinal cord and several other brain areas  Opioids inhibit postsynaptic nociceptive projection neurons  May inhibit release of substance P presynaptically  Opioids generally have less bioavailability in dogs than in humans Keates HL, Cramond T, Smith MT. Intra-articular and periarticular opioid binding in inflamed tissue in experimental canine arthritis. Anesth Analg 89: , 1999.

32 Side Effects  CNS depression  Miosis  Hypothermia  Bradycardia  Respiratory depression  Constipation  Commonly vomit (especially with morphine)  CNS stimulation  Mydriasis  Sweating  Tachycardia  Panting  Constipation  May vomit Dogs Cats Jaffe JH, Martin WR. Opioid analgesics and antagonists. In: Gilman AG, Goodman LS, Rall TW, eds. The Pharmacologic Basis of Therapeutics, 7 th ed. New York: Macmillan, 1985: Booth NH. Neuroleptanalgesics, narcotic analgesics, and analgesic antagonists. In: Booth NH, McDonald LE, eds. Veterinary Pharmacology and Therapeutics, 5 th ed. Ames, IA: Iowa State University Press 1982:

33 Counseling Information  Many opiods utilized in both cats and dogs  Dog dosing is often greater than cat dosing  Morphine  Tramadol  DDI: Meperidine plus MAOIs = Serotonin Syndrome  Tylenol 3 OK for Dogs, NOT for Cats  Pharmacists should be alert to owners seeking opiates for diversion Lumb and Jones’ Veterinary Anesthesia and Analgesia. 4 th ed. Edited by William J. Tranquilli, John C. Thurmon, and Kurt A. Grimm. Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

34 Gabapentin

35 Mechanism of Action  What is gabapentin?  A GABA molecule covalently bound to a lipophilic cyclohexane ring  Designed to be a GABA agonist, but does not bind to GABA A or GABA B receptors  Blocks voltage-dependent calcium channels  Modulates excitatory neurotransmitter release that participates in nociception https://www.caymanchem.com/app/template/Product.vm/catalog/

36 Gabapentin  Uses in animals  Incisional pain  Arthritis  Reduces “wind-up” pain  Good for chronic pain management in dogs and cats  Typically not used for adaptive pain  Don’t use the xylitol-containing human-labeled liquid in dogs Mao J, Chen LL. Gabapentin in pain management. Anesth Analg 2000;91: Plumb, DC. Plumb’s Veterinary Drug Handbook. 6 th edition. Hellyer, P., Rodan, I., Brunt, J., Downing, R., Hagedorn, J. E., & Robertson, S. A. (2007). AAHA/AAFP pain management guidelines for dogs & cats. J Am Anim Hosp Assoc, 43(5),

37 Side effects  Dizziness  *Sedation*  Peripheral edema  Abrupt discontinuation leads to withdrawal Titrate dose to minimize these side effects. Plumb, DC. Plumb’s Veterinary Drug Handbook. 6 th edition.

38 Glucosamine & chondroitin

39 Uses  Classified as nutraceuticals  *Adjunctive treatment for osteoarthritis in cats, dogs, and horses*  Used for feline lower urinary tract disease (FLUTD) Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

40 Mechanism of Action  Cartilage cells use glucosamine to produce glycosaminoglycans and hyaluronan  Regulates the synthesis of collagen and proteoglycans in cartilage  Mild anti-inflammatory effects due to its ability to scavenge free radicals  Chondrocytes normally make glucosamine from glucose and amino acids, but this ability diminishes with age, disease, or trauma.  FLUTD: Works due to the presence of glycosaminoglycans in the protective layer of the urinary tract Inhibits destructive enzymes in joint fluid and cartilage Stimulates the production of glycosaminoglycans and proteoglycans in joint cartilage Thrombi formation in microvasculature may be reduced Shellfish derived – may cause allergic reactions in clients/owners. Glucosamine Chondroitin Sulfate Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

41 Dosing  Dosing is based on chondroitin component  Dogs: mg/kg PO qd or qod  Cats: 15-20mg/kg PO qd or qod  Many veterinary-labeled products – always check dosing!  Bioequivalence between products cannot be assumed. Independent analysis has shown a wide variation in products. Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

42 Counseling Points  Overall, well tolerated  Minor GI effects Flatulence Stool softening  Clinical improvement may take 2-6 weeks.  Chondroitin sulfate is extremely hygroscopic  Store in tight containers at room temperature  Avoid storing in direct sunlight  Administration  Pets can be pilled  Tablets Given with a treat Crumbled and mixed with food  Capsules Pulled apart and sprinkled over food Wet or moist food works best Wrapped in food Plumb DC. Plumb’s Veterinary Drug Handbook. 6 th Edition.

43 Summary  Human-label OTC NSAIDs should not be used without a veterinary Rx  Dosing cats with aspirin or human OTC NSAIDs is not common and not recommended  A variety of animal-label NSAIDs are available  Opiate side effects and dosing are distinctly different between cats and dogs  Nutraceuticals glucosamine and chondroitin are used in cats and dogs as adjunctive pain therapy for OA


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