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Pain Management Pain Management

Cox1&2

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Page 1: Cox1&2

Pain ManagementPain Management

Page 2: Cox1&2

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

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MYTHSMYTHS

“Anesthetics mask symptoms”

“Patient will harm itself if there’s no pain”

“Pain is difficult to assess”

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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

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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

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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

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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

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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

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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

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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

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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

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Monitoring Signs of PainMonitoring Signs of PainFacial Expression

Vocalization

Body Posture

Abnormal Gait

Decreased Activity Level

Attitude

Appetite

Grooming

Urination/Defecation Habits

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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

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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

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Pharmacologic MethodsPharmacologic Methods

OpioidsOpioids 2 agonists2 agonists SteroidsSteroids NSAIDSNSAIDS Local anestheticsLocal anesthetics Chondroprotective drugsChondroprotective drugs

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OpioidsOpioids

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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??

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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

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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

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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

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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?

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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

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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

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Opioid Partial AgonistsOpioid Partial Agonists

BuprenorphineBuprenorphine Buprenex®Buprenex® 4-8 hour duration4-8 hour duration

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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

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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

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Alpha-2 AgonistsAlpha-2 Agonists“thiazines”“thiazines”

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Alpha-2 AgonistsAlpha-2 Agonists

MOA?MOA?

Examples:Examples:–Xylazine (RompunXylazine (Rompun®®))

–Medetomidine (DomitorMedetomidine (Domitor®®))

Engages receptors in CNS >> decrease norepinephrine

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Xylazine: Good ThingsXylazine: Good Things

Moderate analgesiaModerate analgesia

Potent sedative effect Potent sedative effect

Good muscle relaxationGood muscle relaxation

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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)

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Xylazine: Xylazine: MoreMore Bad Things Bad Things

Vomiting (sometimes used as emetic)Vomiting (sometimes used as emetic)

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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”

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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®)

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Steroids= corticosteroids,glucocoticoids

• Examples:– Prednisone = Prednisolone– Dexamethasone – Betamethasone– Solu-Delta-Cortef– Solu-Medrol

• Decrease pain

by decreasing inflammation

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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

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Side Effects and Toxicity

• Iatrogenic hyperadrenocorticism– “Cushings Dz”

• Polyphagia• PU/PD• Glaucoma and cataracts• Gastric ulceration• Delayed wound healing• Immunosuppression

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More !

• Insulin resistance

• Hepatopathy

• CNS: restlessness, seizure activity

• Infection

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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 ®)®)

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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

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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

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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

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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!

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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 ?

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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

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NSAIDSNSAIDS

Cyclooxygenase Cyclooxygenase inhibitioninhibition decreased decreased thromboxanethromboxane decreases platelet decreases platelet adhesion/clumpingadhesion/clumpingdecreases clot decreases clot formation and formation and thromboembolithromboemboli

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TYPES of NSAIDsTYPES of NSAIDs

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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!

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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

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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

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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

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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

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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

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EtodolacEtodolac

Etogesic Etogesic ®® COX 1 and 2 Inhibition Once dailyOnce daily administration administration DOGS ONLYDOGS ONLY

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DerramaxDerramax

Use in dogsUse in dogs COX 2 SpecificCOX 2 Specific SID dosingSID dosing $$$$

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““Metacam” =MeloxicamMetacam” =Meloxicam

COX-2 Specific Use in dogs and cats Liquid Well tolerated $$

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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

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NSAID ContraindicationsNSAID Contraindications

Renal of hepatic dysfunctionRenal of hepatic dysfunction Decreased circulating blood volumeDecreased circulating blood volume CoagulopathiesCoagulopathies GI diseaseGI disease PregnancyPregnancy

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Local AnestheticsLocal Anesthetics

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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

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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

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Commonly Used With Commonly Used With NeuroleptanalgesicNeuroleptanalgesic

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CapsaicinCapsaicin

Hot peppersHot peppers Excites then fatigues nerve Excites then fatigues nerve

transmissiontransmissionlocal local analgesiaanalgesia

Also get endorphin releaseAlso get endorphin release

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St. JohnswortSt. Johnswort

Arthritic pain Hypericin

– Stimulates neural inhibitory pathways analgesia

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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.

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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

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QuestionsQuestions????