Cox1&2
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Transcript of Cox1&2
Pain ManagementPain Management
Why Treat Pain?Why Treat Pain?
Animals feel pain just like usAnimals feel pain just like us Unethical not to address painUnethical not to address pain Animal owner and public concernsAnimal owner and public concerns Many anesthetics have no analgesic effectMany anesthetics have no analgesic effect
– Which do? Which do? Pain results in poor anesthetic recoveryPain results in poor anesthetic recovery
MYTHSMYTHS
“Anesthetics mask symptoms”
“Patient will harm itself if there’s no pain”
“Pain is difficult to assess”
The Truth!The Truth!
Pain is BAD:Pain is BAD:– Decreased cardiovascular functionDecreased cardiovascular function– Decresed appetiteDecresed appetite– Slows wound healingSlows wound healing– Decreased immune functionDecreased immune function
» Greater chance of infectionGreater chance of infection
– Increased fear and anxietyIncreased fear and anxiety
Use of Analgesics in PracticeUse of Analgesics in Practice Overall = poorOverall = poor
– 13-26% dog and cat spay/neuters receive analgesics13-26% dog and cat spay/neuters receive analgesics– 50-70% of non-neutering soft tissue surgery50-70% of non-neutering soft tissue surgery– >80% orthopedic surgery and severe trauma>80% orthopedic surgery and severe trauma
Why not better?Why not better?– DEA / theft concernsDEA / theft concerns– Older vets not trained that wayOlder vets not trained that way– Older drugs dangerousOlder drugs dangerous– Animals are stoicAnimals are stoic
Pain PerceptionPain Perception
Pain sensorPain sensor nerve fiber nerve fiberspinal cordspinal cordbrainbrain
Neurotransmitters>>Neurotransmitters>>– Somatic ( superficial ) painSomatic ( superficial ) pain– Visceral ( internal organ ) painVisceral ( internal organ ) pain– Bone painBone pain
Classification of PainClassification of Pain
Intensity (scale of 1-10)Intensity (scale of 1-10) Acute, sharp, sudden, shortAcute, sharp, sudden, short
– Surgical painSurgical pain– Responds well to drug txResponds well to drug tx
Chronic, dull, prolongedChronic, dull, prolonged– Cancer or arthritisCancer or arthritis– Doesn’t always respond well to txDoesn’t always respond well to tx
Referred (from somewhere else)Referred (from somewhere else) Hyperesthesia (increased sensitivity)Hyperesthesia (increased sensitivity) Neuropathic (Nerve damage)Neuropathic (Nerve damage)
– Poorly responsivePoorly responsive
Degree and Type of Pain Depend OnDegree and Type of Pain Depend On
The procedureThe procedure The animalThe animal
– Pain is an individual experiencePain is an individual experience» Tailor analgesic protocol to the patientTailor analgesic protocol to the patient
Analgesic administrationAnalgesic administration– TimingTiming– DosageDosage
Preemptive AnalgesiaPreemptive Analgesia
If the body doesn’t sense the pain If the body doesn’t sense the pain during the procedure, the pain will be during the procedure, the pain will be easier to deal with post-operativelyeasier to deal with post-operatively
– A patient in surgical anesthesia is not A patient in surgical anesthesia is not aware of pain, but the body is still aware of pain, but the body is still respondingresponding sensitizes the nervous sensitizes the nervous systemsystem
Preemptive Analgesia Results InPreemptive Analgesia Results In
Marked decrease in amount of analgesic Marked decrease in amount of analgesic medication needed post-operativelymedication needed post-operatively
Increased patient comfortIncreased patient comfort
Balanced AnesthesiaBalanced Anesthesia
Several anesthetic drugs are combined Several anesthetic drugs are combined into anesthetic protocolinto anesthetic protocol
Include analgesicInclude analgesic SynergismSynergism
– Smaller dosages neededSmaller dosages needed– Decreased potential for side effectsDecreased potential for side effects
Monitoring Signs of PainMonitoring Signs of PainFacial Expression
Vocalization
Body Posture
Abnormal Gait
Decreased Activity Level
Attitude
Appetite
Grooming
Urination/Defecation Habits
Methods of Pain ControlMethods of Pain Control
Non-pharmacological methods:Non-pharmacological methods: Endorphins = The body’s natural painkillersEndorphins = The body’s natural painkillers Good nursing careGood nursing care
– Comfortable beddingComfortable bedding» Clean and dryClean and dry
– Easy access to bathroom, food, waterEasy access to bathroom, food, water– TLCTLC– Rotate recumbencyRotate recumbency– Allow time to sleepAllow time to sleep
Non-pharmacological MethodsNon-pharmacological Methods
Apply cold to site (acute- 1Apply cold to site (acute- 1stst 24 hours) 24 hours)– Decreases inflammationDecreases inflammation– NumbsNumbs
Apply heat to site (chronic)Apply heat to site (chronic) MassageMassage Acupuncture/acupressureAcupuncture/acupressure Complementary methodsComplementary methods
– Herbs, laser, magnetic, chiropracticHerbs, laser, magnetic, chiropractic
Pharmacologic MethodsPharmacologic Methods
OpioidsOpioids 2 agonists2 agonists SteroidsSteroids NSAIDSNSAIDS Local anestheticsLocal anesthetics Chondroprotective drugsChondroprotective drugs
OpioidsOpioids
Opiate ReceptorsOpiate Receptors
MOA?
4 types of receptors:
mu kappa sigma delta
Should we be wondering why fraternities/sororities name themselves after receptors of pain??
Opioids:Opioids:Backbone of AnalgesiaBackbone of Analgesia
Pure AgonistsPure Agonists – Morphine, oxymorphone, meperidine, hydromorphone, Morphine, oxymorphone, meperidine, hydromorphone,
fentanylfentanyl
Partial agonists, mixed agonist-antagonistsPartial agonists, mixed agonist-antagonists– BuprenorphineBuprenorphine– ButorphanolButorphanol
Pure AntagonistsPure Antagonists (reversal of agonists) (reversal of agonists)– NaloxoneNaloxone
ABUSE POTENTIALABUSE POTENTIAL
Opioid AdministrationOpioid Administration
Systemic: IV, SQ, IM, CRISystemic: IV, SQ, IM, CRI Intra-articular injectionIntra-articular injection Local injectionLocal injection Epidural injectionEpidural injection Transdermal fentanyl patchTransdermal fentanyl patch
Opioid EffectsOpioid Effects
GOOD:GOOD:– Great analgesiaGreat analgesia– Variable muscle relaxationVariable muscle relaxation– SedationSedation
BAD:BAD:– Respiratory depressionRespiratory depression– GI effectsGI effects
» VomitingVomiting» Defecation followed by constipation Defecation followed by constipation
Opioids (other effects)Opioids (other effects)
ExcitementExcitement– PantingPanting– VocalizationVocalization– Noise sensitivityNoise sensitivity
Depression of the cough centerDepression of the cough center– Advantage for?Advantage for?
Fentanyl PatchFentanyl Patch Lag time: Lag time:
– apply 6-12 hours prior to surgery in cats,apply 6-12 hours prior to surgery in cats,– 12-24 hours in dogs12-24 hours in dogs
Lasts about 3 days (up to 6 in cats)Lasts about 3 days (up to 6 in cats) Variation in absorption rateVariation in absorption rate
– Dose of patch (in micrograms/hr)Dose of patch (in micrograms/hr)– Avoid heat sourcesAvoid heat sources
Excessive amounts can cause ataxia, Excessive amounts can cause ataxia, sedation in dogs, excitement, disorientation, sedation in dogs, excitement, disorientation, wide-eyed stare in catswide-eyed stare in cats– Remove patch, can reverse Remove patch, can reverse
Fentanyl PatchFentanyl Patch
Applied to dorsal neck or Applied to dorsal neck or shoulders, lateral thoraxshoulders, lateral thorax
Clip hair, clean skin with Clip hair, clean skin with water onlywater only
Do not cut patchDo not cut patch– Can remove just part of Can remove just part of
backing if small animalbacking if small animal
Apply patch, hold firmly 2 Apply patch, hold firmly 2 minutesminutes
BandageBandage
Opioid Partial AgonistsOpioid Partial Agonists
BuprenorphineBuprenorphine Buprenex®Buprenex® 4-8 hour duration4-8 hour duration
Opioid Mixed Agonist-AntagonistOpioid Mixed Agonist-Antagonist
ButorphanolButorphanol (Torbutrol®, Torbugesic®)(Torbutrol®, Torbugesic®) For mild to moderate painFor mild to moderate pain Duration 1 to 4 hours IM, SQDuration 1 to 4 hours IM, SQ
Less abuse potential than agonistsLess abuse potential than agonists
Opioid AntagonistsOpioid Antagonists
NaloxoneNaloxone Used to reverse opiates/opioidsUsed to reverse opiates/opioids Remember: Reverses analgesia too!Remember: Reverses analgesia too! May not last as long as the agonistMay not last as long as the agonist
– Relapse =“renarcotization”Relapse =“renarcotization”
Partial reversal with butorphanol possiblePartial reversal with butorphanol possible
Alpha-2 AgonistsAlpha-2 Agonists“thiazines”“thiazines”
Alpha-2 AgonistsAlpha-2 Agonists
MOA?MOA?
Examples:Examples:–Xylazine (RompunXylazine (Rompun®®))
–Medetomidine (DomitorMedetomidine (Domitor®®))
Engages receptors in CNS >> decrease norepinephrine
Xylazine: Good ThingsXylazine: Good Things
Moderate analgesiaModerate analgesia
Potent sedative effect Potent sedative effect
Good muscle relaxationGood muscle relaxation
Xylazine: Bad ThingsXylazine: Bad Things
Bradycardia due to stimulation of the Bradycardia due to stimulation of the vagus nervevagus nerveheart blockheart block
Profound cardiac disturbances!Profound cardiac disturbances!– Sensitizes the heart to Sensitizes the heart to
catecholaminescatecholaminesArrhythmiasArrhythmias– Decreased cardiac outputDecreased cardiac output
» Hypotension (BP decreases by 1/4-1/3)Hypotension (BP decreases by 1/4-1/3)
Xylazine: Xylazine: MoreMore Bad Things Bad Things
Vomiting (sometimes used as emetic)Vomiting (sometimes used as emetic)
Xylazine: Reversal?Xylazine: Reversal?
Yohimbine is reversal agentYohimbine is reversal agent
Mixed Alpha- antagonist (blocker)Mixed Alpha- antagonist (blocker) Trade name “Yobine”Trade name “Yobine”
MedetomidineMedetomidine
=DOMITOR®=DOMITOR® More specific to More specific to
CNS alpha-2 CNS alpha-2 receptorsreceptors
Alpha-2 so has Alpha-2 so has reversal agent reversal agent – (Antisedan®)(Antisedan®)
Steroids= corticosteroids,glucocoticoids
• Examples:– Prednisone = Prednisolone– Dexamethasone – Betamethasone– Solu-Delta-Cortef– Solu-Medrol
• Decrease pain
by decreasing inflammation
Steroids: MOAinhibit phospholipase A2>>>inhibits
prostoglandin/leukotrienes
Membrane Phospholipid
Arachidonic Acid
“Bad” ProstaglandinsPain/Inflammation
“Good” ProstaglandinsGI Protection
Renal Blood Flow
Thromboxane“Platelets”
COX-2
COX-1
Phospholipase A2
Steroids inhibit here
NSAIDS inhibit here
Side Effects and Toxicity
• Iatrogenic hyperadrenocorticism– “Cushings Dz”
• Polyphagia• PU/PD• Glaucoma and cataracts• Gastric ulceration• Delayed wound healing• Immunosuppression
More !
• Insulin resistance
• Hepatopathy
• CNS: restlessness, seizure activity
• Infection
Non-Steroidal Anti-inflammatory Non-Steroidal Anti-inflammatory Drugs ( NSAIDS )Drugs ( NSAIDS )
AspirinAspirin Carprofen - Rimadyl ®Carprofen - Rimadyl ® Etodolac - Etogesic®Etodolac - Etogesic® Ketoprofen - Ketofen ®Ketoprofen - Ketofen ® Phenylbutazone – “Bute”Phenylbutazone – “Bute” Flunixin - Banamine Flunixin - Banamine ®®
(Acetaminophen - Tylenol (Acetaminophen - Tylenol ®)®)
NSAIDSNSAIDS
Most have effective somatic (superficial) analgesic effect
Some have good visceral analgesic effect also All take 30-60 minutes to take effect, even if
injected All have antiinflammatory properties Reduce fevers
NSAIDSNSAIDS
MOA: cyclooxygenase inhibitors >> MOA: cyclooxygenase inhibitors >> prostaglandin inhibitorsprostaglandin inhibitors
Many side effects are due to “good” Many side effects are due to “good” prostaglandin inhibition (COX 1):prostaglandin inhibition (COX 1):– GI upset/ ulcerationGI upset/ ulceration– Renal toxicityRenal toxicity– Impaired platelet functionImpaired platelet function
NSAIDS: MOANSAIDS: MOAinhibit cyclooxygenase>>>inhibit cyclooxygenase>>>
inhibits prostoglandin/thromboxaneinhibits prostoglandin/thromboxane
Membrane Phospholipid
Arachidonic Acid
“Bad” ProstaglandinsPain/Inflammation
“Good” ProstaglandinsGI Protection
Renal Blood Flow
Thromboxane“Platelets”
Fever
COX-2
COX-1
Phospholipase A2 Steroids inhibit here
NSAIDS inhibit here
NSAIDS - MetabolismNSAIDS - Metabolism Metabolized by the liverMetabolized by the liver Variation in metabolism between speciesVariation in metabolism between species Aspirin half-life 12 hours in dogs, 1 hour in Aspirin half-life 12 hours in dogs, 1 hour in
horses, horses, 38 hours in cats38 hours in cats
Many NSAIDS toxic to cats due to inability Many NSAIDS toxic to cats due to inability to metabolize themto metabolize them
Acetaminophen is toxic in dogs AND cats!Acetaminophen is toxic in dogs AND cats!
NSAIDS Inhibit Production of NSAIDS Inhibit Production of Protective GI ProstaglandinsProtective GI Prostaglandins
Erosion/ulceration of GI tractErosion/ulceration of GI tract Stomach upsetStomach upset InappetanceInappetance VomitingVomiting DiarrheaDiarrhea Melena ?Melena ?
Prostaglandins in the KidneysProstaglandins in the Kidneys
Cause dilation of renal vasculature, allowing Cause dilation of renal vasculature, allowing perfusion despite decreased blood pressure perfusion despite decreased blood pressure due todue to– ShockShock– DehydrationDehydration– Blood lossBlood loss– AnesthesiaAnesthesia
Inhibition of prostaglandin production can cause Inhibition of prostaglandin production can cause kidney cell death due to lack of perfusionkidney cell death due to lack of perfusion
Only an issue if decreased BPOnly an issue if decreased BP
NSAIDSNSAIDS
Cyclooxygenase Cyclooxygenase inhibitioninhibition decreased decreased thromboxanethromboxane decreases platelet decreases platelet adhesion/clumpingadhesion/clumpingdecreases clot decreases clot formation and formation and thromboembolithromboemboli
TYPES of NSAIDsTYPES of NSAIDs
PhenylbutazonePhenylbutazone
COX1 and 2 InhibitorCOX1 and 2 Inhibitor Very PotentVery Potent Commonly used in horsesCommonly used in horses Not recommended in dogsNot recommended in dogs
– GI side effects commonGI side effects common– NEVER IN CATS!NEVER IN CATS!
AspirinAspirin
COX1 and 2 InhibitorCOX1 and 2 Inhibitor Very short half-life in horsesVery short half-life in horses Commonly used in dogsCommonly used in dogs
– Buffered only Buffered only – With foodWith food
Use with caution in catsUse with caution in cats– Can’t metabolize wellCan’t metabolize well– Half-life 38 hoursHalf-life 38 hours– Dosed every 48-72 hoursDosed every 48-72 hours
Neither Ibuprofen Nor Neither Ibuprofen Nor Naproxen Is Recommended Naproxen Is Recommended
for Use in Catsfor Use in Cats
Ibuprofen = “Advil”COX1 + COX2 Inhibitors
Officially not recommended in dogs.
most do OK if used like aspirin
KetoprofenKetoprofen
KetofenKetofen® (COX1 and COX2)® (COX1 and COX2) Licensed in horsesLicensed in horses Approved for use in dogs and cats in Approved for use in dogs and cats in
Canada, EuropeCanada, Europe Good analgesia, potent antipyreticGood analgesia, potent antipyretic Injectable Injectable
– Limit useLimit use– Blood clottingBlood clotting
Flunixin meglumineFlunixin meglumine
BanamineBanamine® ® (COX1 and COX2)(COX1 and COX2)
InjectableInjectable HorsesHorses
– ColicColic– Good analgesiaGood analgesia
DogsDogs– GI side effects common, severeGI side effects common, severe
CarprofenCarprofen
Rimadyl Rimadyl ®® COX-2 inhibitor: “spares” COX-2 inhibitor: “spares”
“good” prostaglandins “good” prostaglandins Fewer side effectsFewer side effects DOGS ONLYDOGS ONLY Black labs…Black labs…
– 0.06% of 0.06% of allall dogs develop dogs develop hepatic problems (rare)hepatic problems (rare)
BID DosingBID Dosing
EtodolacEtodolac
Etogesic Etogesic ®® COX 1 and 2 Inhibition Once dailyOnce daily administration administration DOGS ONLYDOGS ONLY
DerramaxDerramax
Use in dogsUse in dogs COX 2 SpecificCOX 2 Specific SID dosingSID dosing $$$$
““Metacam” =MeloxicamMetacam” =Meloxicam
COX-2 Specific Use in dogs and cats Liquid Well tolerated $$
NSAID PrecautionsNSAID Precautions
Use only 1 NSAID at a timeUse only 1 NSAID at a time
Never combine NSAIDS with glucocorticoidsNever combine NSAIDS with glucocorticoids– Gastric UlcerationGastric Ulceration
Taper to lowest effective dose Taper to lowest effective dose
Change to alternative NSAID if poor Change to alternative NSAID if poor responseresponse
NSAID ContraindicationsNSAID Contraindications
Renal of hepatic dysfunctionRenal of hepatic dysfunction Decreased circulating blood volumeDecreased circulating blood volume CoagulopathiesCoagulopathies GI diseaseGI disease PregnancyPregnancy
Local AnestheticsLocal Anesthetics
Local AnestheticsLocal Anesthetics
The “-caine” family: Lidocaine, The “-caine” family: Lidocaine, bupivicaine, mepivicaine, bupivicaine, mepivicaine, proparicaine, tetracaine, etc.proparicaine, tetracaine, etc.
MOA= Block nerve impulses by MOA= Block nerve impulses by blocking Na+ channels in nerve blocking Na+ channels in nerve membranesmembranes
Local AnestheticsLocal Anesthetics
Local infiltration of surgical siteLocal infiltration of surgical site Intravenous regional anesthesiaIntravenous regional anesthesia Intra-articular injectionIntra-articular injection Nerve blocksNerve blocks EpiduralEpidural Topical on skin/ eye/ larynxTopical on skin/ eye/ larynx
http://www.cvm.okstate.edu/courses/vmed5412/Lect23.asp
Commonly Used With Commonly Used With NeuroleptanalgesicNeuroleptanalgesic
CapsaicinCapsaicin
Hot peppersHot peppers Excites then fatigues nerve Excites then fatigues nerve
transmissiontransmissionlocal local analgesiaanalgesia
Also get endorphin releaseAlso get endorphin release
St. JohnswortSt. Johnswort
Arthritic pain Hypericin
– Stimulates neural inhibitory pathways analgesia
Chondroprotective AgentsChondroprotective Agents
NutraceuticalsNutraceuticals– Chondroitin sulfateChondroitin sulfate– GlucosamineGlucosamine– Hyaluronic acidHyaluronic acid– Building blocks for Building blocks for
cartilage and cartilage and synovial fluidsynovial fluid
Examples: (oral) Synovi, Glycoflex (injectable) Adequan
Can be mixed with many other ingredients
(MSM, Creatine) to enhance effects.
Antibiotic AnalogyAntibiotic Analogyto understand pain controlto understand pain control
Antibiotics prescribed based on clinical signs, not Antibiotics prescribed based on clinical signs, not always based on culture and sensitivityalways based on culture and sensitivity
Rely on return to normal function to confirm diagnosisRely on return to normal function to confirm diagnosis If doesn’t help, add to or change drug protocolIf doesn’t help, add to or change drug protocol May need a loading doseMay need a loading dose May need a combination of drugsMay need a combination of drugs
QuestionsQuestions????