companion animal pain management – cats and dogs cory theberge, phd une college of pharmacy mpa...
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COMPANION ANIMALPAIN MANAGEMENT – CATS AND DOGSCory Theberge, PhD UNE College of Pharmacy
MPA Spring Conference CE 2015
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
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
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.
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.http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-221&fromce=021811
Cat Pain Posture
“Marjaryasana”Majari = cat
Head held down or hidden
Eyes squintedHunched back
http://www.yogajournal.com/poses/2468http://www.scoutshouse.com/wp-content/uploads/2009/12/Pain-Management-in-Cats.pdf
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
http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-221&fromce=021811
Acetaminophen (APAP)
Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 6-7.
Doses: Dogs: 10-15 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
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.
http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-221&fromce=021811
APAP Toxicity
http://archive.ispub.com/journal/the-internet-journal-of-toxicology/volume-6-number-2/acetaminophen-poisoning-case-report.article-g02.fs.jpg
TOXIC
NOT TOXIC
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
http://emedicine.medscape.com/article/204178-overviewPlumb DC Veterinary Drug Handbook. Seventh Edition. Pages 6-7.
APAP Toxicity Treatment
Emesis (if ingested within <2 hours)
Activated charcoal Acetylcysteine
Precursor to glutathione
Oxygen therapy Ascorbic acid for
methemoglobinemiahttp://www.ansci.cornell.edu/plants/toxcat/toxcat.htmlAhrens F. Pharmacology: The National Veterinary Medical Series. Blackwell Publishing: Ames, Iowa; 2007. Page 175.
APAP Counseling Points
Contraindicated in cats at any dosage. Not overly toxic to dogs at
recommended dosages.
Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
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:10.2174/1389200003339171. PMID 11465080.
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.
http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-221&fromce=021811
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 48-72 hours to avoid accumulation.
Doses: Dog: 10 mg/kg PO q12h Cat: 10 mg/kg PO q48-72h
http://pharmacistsletter.therapeuticresearch.com/ce/cecourse.aspx?pc=12-221&fromce=021811.Fink-Gremmels J. (2008) Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences. Eur J Pharmacol 585:502-509.Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 83-6.
Aspirin Toxicity
Ahrens F. Pharmacology: The National Veterinary Medical Series. Blackwell Publishing: Ames, Iowa; 2007. Pages 173-4.Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 83-6.
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
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. 6th Edition.
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. 6th Edition.
OTC Cat and Dog Summary
Drug Dog Cat
Aspirin(only
buffered or EC)
YesWith food
Short-term use only
NoOnly by vet. One 325mg
tab is 8x the recommended dose for
an 8-lb cat.
Acetaminophen
YesUp to 15mg/kg PO
TID
NoOne 500mg tab is lethal
to a 10-lb cat.
Ibuprofen No No
Naproxen Sodium
NoOnly by vet No
http://pets.webmd.com/cats/guide/safe-cat-pain-medicationshttp://pets.webmd.com/dogs/guide/dog-pain-medications
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. 6th Edition.
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.
http://www.scoutshouse.com/wp-content/uploads/2009/12/Pain-Management-in-Cats.pdf
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
http://www.scoutshouse.com/wp-content/uploads/2009/12/Pain-Management-in-Cats.pdf
Generic Vet-Labeled
Human-Labeled Dog Cat
Carprofen Rimadyl, Vetprofen - Yes Only for post-
op pain
Etodolac Etogesic Lodine Yes No
Phenylbutazone
Butazolidin, Butatron,
Equipalazone
- Yes No
Ketoprofen Ketofen Orudis KT, Oruvail Yes Yes
Meloxicam Metacam Mobic Yes
Only labeled for a one-time dose. Others uses are off-
label.
Deracoxib Deramaxx - Yes No
Firocoxib Previcox Yes No
FlunixinBanamine, 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.
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 48-72 hours after starting NSAIDs.
Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
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.
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 89:409-415, 1999.
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, 7th ed. New York: Macmillan, 1985:491-531.Booth NH. Neuroleptanalgesics, narcotic analgesics, and analgesic antagonists. In: Booth NH, McDonald LE, eds. Veterinary Pharmacology and Therapeutics, 5th ed. Ames, IA: Iowa State University Press 1982:267-296.
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. 4th ed. Edited by William J. Tranquilli, John C. Thurmon, and Kurt A. Grimm.Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
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 GABAA or GABAB receptors
Blocks voltage-dependent calcium channels
Modulates excitatory neurotransmitter release that participates in nociception
https://www.caymanchem.com/app/template/Product.vm/catalog/10008346
http://online.lexi.com.une.idm.oclc.org/lco/action/doc/retrieve/docid/patch_f/6961#f_pharmacology-and-pharmacokinetics
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;91:680-687.Plumb, DC. Plumb’s Veterinary Drug Handbook. 6th 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), 235-248.
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. 6th edition.
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. 6th Edition.
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. 6th Edition.
Dosing
Dosing is based on chondroitin component Dogs: 13-15 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. 6th Edition.
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. 6th Edition.
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