Transcript Companion Animal Pain Management

COMPANION ANIMAL
PAIN MANAGEMENT – CATS
AND DOGS
Cory Theberge, PhD UNE College of Pharmacy
MPA Spring Conference CE 2015
Learning Objectives
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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
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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 FDAapproved label
 All human prescription and OTC drugs
 All compounded drugs
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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
http://www.yogajournal.com/poses/2468
http://www.scoutshouse.com/wp-content/uploads/2009/12/Pain-Management-in-Cats.pdf
Head held down or hidden
Eyes squinted
Hunched back
Cats – Glucoronidation/APAP
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)
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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
Plumb DC Veterinary Drug Handbook. Seventh Edition. Pages 6-7.
Cats and Acetaminophen (APAP)
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Cats can’t breakdown APAP by glucuronidation
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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 nontoxic 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
NOT TOXIC
TOXIC
http://archive.ispub.com/journal/the-internet-journal-of-toxicology/volume-6-number-2/acetaminophen-poisoning-case-report.article-g02.fs.jpg
What happens if a cat takes APAP?
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Methemoglobinemia
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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-overview
Plumb 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 methemoglobinemia

http://www.ansci.cornell.edu/plants/toxcat/toxcat.html
Ahrens F. Pharmacology: The National Veterinary Medical Series. Blackwell Publishing: Ames, Iowa; 2007. Page 175.
APAP Counseling Points
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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
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 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.
Human OTC Options for Pain
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
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Aspirin has a significantly longer half-life in cats
Half-life lengths
Cat: 25 – 45 hours
 Dog: 8 – 9 hours
 Human: 3 hours
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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
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Symptoms: Depression, vomiting, anorexia,
hyperthermia, increased respiratory rate
Effects
Hyperpyrexia
 Acid-base disturbances
 Dehydration (from vomiting and sweating)
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Treatment
Gastric lavage, activated charcoal, or dialysis
 Sodium bicarbonate
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Raises the urinary pH and therefore increases aspirin excretion
IV fluids
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.
Aspirin Counseling Points
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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
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Not indicated for cats
Use in dogs is discouraged
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Reports of GI ulcers and perforation
May be overly sensitive to the adverse effects
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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 GItoxic NSAIDs
Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
OTC Cat and Dog Summary
Drug
Dog
Cat
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.
Ibuprofen
No
No
Naproxen
Sodium
No
Only by vet
No
http://pets.webmd.com/cats/guide/safe-cat-pain-medications
http://pets.webmd.com/dogs/guide/dog-pain-medications
Topical OTC Pain Products
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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
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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
Animal Label Non-steroidal antiinflammatory drugs (NSAIDs)
Background
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Used for analgesic and anti-inflammatory properties
MOA
Inhibit COX enzymes
 Variable effects on:

Gastric mucosal lining
 Platelet function
 Renal function and regulation

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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
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.
Side Effects
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Decrease or increase in
appetite or drinking habits
Vomiting
Change in bowel movements
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Diarrhea
Black, tarry, or bloody stools
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Change in behavior
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Decreased or increased activity
level
Aggression
Jaundice
Change in urination habits
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Yellowing of gums
Yellowing of skin
Yellowing of whites of the eyes
Frequency
Color
Smell
Skin changes
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Redness
Scabs
Itching
Side effects usually surface 48-72 hours after starting NSAIDs.
Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
Counseling Points
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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.
Opioids (Briefly) – Cats and Dogs
Mechanism Of Action
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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
Dogs
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CNS depression
Miosis
Hypothermia
Bradycardia
Respiratory depression
Constipation
Commonly vomit
(especially with
morphine)
Cats
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CNS stimulation
Mydriasis
Sweating
Tachycardia
Panting
Constipation
May vomit
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
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Many opiods utilized in both cats and dogs
Dog dosing is often greater than cat dosing
 Morphine
 Tramadol
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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.
Gabapentin
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
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Blocks voltage-dependent
calcium channels
Modulates excitatory
neurotransmitter release that
participates in nociception
https://www.caymanchem.com/app/template/Product.vm/catalog/1
0008346
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
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Titrate dose to
Dizziness
minimize these
*Sedation*
side effects.
Peripheral edema
Abrupt discontinuation leads to withdrawal
Plumb, DC. Plumb’s Veterinary Drug Handbook. 6th edition.
Glucosamine & chondroitin
Uses
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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
Glucosamine
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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
Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.
Chondroitin Sulfate
•
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.
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
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Overall, well tolerated

Minor GI effects
Flatulence
 Stool softening
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Clinical improvement
may take 2-6 weeks.
Chondroitin sulfate is
extremely hygroscopic
Store in tight containers
at room temperature
 Avoid storing in direct
sunlight

Plumb DC. Plumb’s Veterinary Drug Handbook. 6th Edition.

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

Summary
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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