Analgesics, Antiinflammatories, Antipyretics-II: Opioids & Adjunct Agents Flashcards
opioids use
- Opioids are a mainstay for acute pain management !! > Efficacious
> Safe - Value in chronic pain….break thru acute-on-chronic pain
<><><><> - Opioids and analgesics improve anesthetic safety !!
- Opioids should be used in most if not all surgeries
Opioids -Select Adverse Effects-
- when are they more likley?
- what are they?
- cats vs dogs?
- ADRs to opioids more likely after rapid IV admin & in pain-free animals
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Sedation appears to be less common in cats compared to dogs - Usually desired as part of the pre-anesthetic
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Excitement in cats may occur with high doses of opioids
Ø “Morphine-like mania”
Ø analgesic doses in cats are typically lower than dogs Ø much less of a concern in the painful patient
Ø explanations……
> distribution of opiate receptors in the CNS
> may be d/t release of excitatory NTs (acetylcholine, histamine ??)
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Hyperthermia in cats
Ø normal rectal temp (38.1-39.2 OC; 100.5-102.5 OF)
Ø cats may develop postoperative hyperthermia
> morphine, butorphanol, fentanyl, hydromorphone
Ø Cats should be monitored for hyperthermia following use of hydromorphone
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Gastrointestinal (vomiting and salivation)
Ø Incidence of vomiting is related to administration route
> SC hydromorphone >IV/IM hyrdromorphone in cats
Buprenorphine
- license?
- mechanism?
- elimination half life
- Licensed in cat for post-operative pain
> IM; repeated once, if necessary, after 2 hrs
<><><><> - High affinity partial μ-receptor agonist and kappa antagonist
Ø Ceiling effect on analgesia; typically, mild to moderate pain
Ø Ceiling effect on respiratory depression; hyperthermia not an issue usually
Ø Mild-moderate pain…….severe pain?
Ø Main effects attributed to μ-opioid receptor activation
<><><><> - Elimination half-life is longer in cats (~6-7 hrs) than dogs (~4 hrs)
Ø Has been used epidural—dose related analgesia
OTM Buprenorphine
- use in cats and dogs
OTM use of buprenorphine in the cat and dog
Ø oral pH in cat ~8-9……..enhances OTM absorption in cat
Ø time to onset (~0.5 hr), peak (~1.5 hr) and duration of action (~6 hr) was similar for OTM and IV—0.02 mg/kg in cat
Ø Bioavailability around 30% in the cat following OTM
Ø Injectable formulation can be used for OTM or buprenorphine compounded for OTM administration with a flavoring agent
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Analgesia (surgical site palpation) for OVX in dogs given injectable buprenorphine IV vs OTM
Methadone
- license
- formulation
- mechanism
- actions
- admin routes
- safety
- Licensed in the cat for post-operative pain
- Formulated as a racemic mixture ie 50:50 of the L- and D- isomers
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L- isomer possesses full μ-opioid receptor activity, and both isomers are able to antagonize the NMDA receptor
Ø May be an attractive opioid alternative because of mild to moderate NMDA antagonist effects and possible benefit in neuropathic pain and wind-up
Ø May also prevent/ameliorate opioid tolerance
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Ø Analgesic potency is approximately equal to that of morphine
Ø Veterinary approved formula is injectable, but also available as oral solution and tablets for human use; OTM route may be possible in cats
Ø Methadone is well tolerated in cats, dogs and horses
Tramadol Hydrochloride (adjunct agent)
- what is this? effects?
- reversal?
- formulations
- mechanism?
- metabolism?
Synthetic centrally acting opiate-like analgesic
Ø no anti-inflammatory effects
Ø naloxone only partially reverses analgesia
Ø also available +/- acetaminophen 325 mg
Ø immediate and extended-release tablets, and compounded formulations (liquid suspension, capsules, injectable)
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Ø Parent tramadol produces NE and 5-HT re-uptake inhibition
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Tramadol is metabolized to many metabolites…. multimodal analgesia
Ø O-desmethyl-tramadol (ODM or M1) is most active metabolite
> much greater μ receptor activity than parent tramadol molecule
> greater M1: parent ratio in cats—-more opiate effects
compared to dogs/humans
Ø N,O-didesmethyl-tramadol (DDM) has limited μ receptor activity
Tramadol
- Elimination t1⁄2 - dogs vs cats
- PO doses?
In dogs; tramadol (~1.1 hrs); DDM (~3.6 hrs)
Ø Repeat dosing at 20 mg/kg PO for 8 days….60% decrease in plasma [tramadol]
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In cats; tramadol (~2-2.5 hrs); ODM (~4.5 hrs);
Ø [Tramadol] and [ODM] in plasma were dose proportional from 0.5-4.0 mg/kg PO;
Ø Repeat dosing—not done
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Recommended PO doses…….consider starting low and up titrating
Ø Dog: 4-10 mg/kg q 8 hrs
Ø Cat: 2-4 mg/kg q 12 hrs
Tramadol
Efficacy
- in models and clinical studies? dogs vs cats?
- Models: Pressure threshold model in dogs and thermal threshold model in cats have shown some positive results for oral tramadol, but others have not
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Clinical studies: - Dog: OA study showed no effect for placebo or tramadol
- Cat: OVX study showed Tramadol in addition to an NSAID may be beneficial in cats
Tramadol
Adverse effects
Ø Acute effects include nausea, vomiting, and occasionally sedation
Ø Reduce seizure threshold? caution/avoid in animals prone to seizures
Ø Tramadol is bitter tasting
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Ø Possible increased risk of GI ulcers when given concurrently with NSAIDs
> Serotonin related enhanced HCl acid production via vagus nerve
> Consider mucosal protection
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Ø Serotonin syndrome possible with Tramadol and other agents
> SSRIs, TCAs, MAO inhibitors
Amantadine (adjunct agent)- what is this?
- use? effects?
- half life?
- oral dosage? considerations?
- NMDA antagonist; similar properties to ketamine
Ø Value may be in reducing central windup and allodynia
Ø Not considered effective as a sole agent….added to NSAID, opioid, or
gabapentin; must allow 1-2 weeks treatment to assess potential efficacy - May reverse tolerance to opioids that can develop
<><><><> - On-going research in humans for chronic pain including OA
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t1⁄2 in cats (4 mg/kg PO) of ~6 hrs; dogs (~2.8 mg/kg PO) of ~5 hrs
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Oral dosages of 3-5 mg/kg q24 hrs have been cited for dogs and cats
Ø Activity is improved in clinical trial with OA dogs given amantadine (3-5 mg/kg q24) that were also given an NSAID
Ø Because of short t1⁄2, may need to be dosed q12 hrs
Gabapentin (adjunct agent)
- what is it? effects and use?
- half life? dosing?
> considerations?
- how good?? adverse effects?
An anticonvulsant; analgesic properties may be linked to downregulation of VOCC and release of excitatory NTs
Ø Value in acute pain is questioned; especially as a preventative
Ø Benefits in neuropathic conditions including OA and cancer
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t1⁄2 in dogs (3-4 hrs) and cats (~3hrs)
necessitates dosing q 8 hrs
Ø Doses of 5-10 mg/kg q8 hrs recommended; compliance?
Ø Available as tablets, capsules and oral solution that contains xylitol (caution with insulin release and hypoglycemia)
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Ø Controlled clinical trials lacking in dogs and cats
Ø Generally safe; sedation and ataxia are most noted adverse effects
(tricyclic antidepressant)
Amitryptyline (adjunct agent)
- use? mechanisms?
- adverse effects?
TCA are first line therapeutics for neuropathic pain in humans
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Produce analgesia thru multiple mechanisms
Ø 5-HT and NE reuptake inhibition
Ø NMDA receptor antagonism
Ø Voltage gated sodium channel blockade
Ø Enhance GABAB activity
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Based on human literature, TCA’s could be useful in neuropathic pain
Ø Clinical data in veterinary patients are lacking
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Ø Adverse effects from anticholinergic, antihistamine and α1 blockage
DMSO Dimethyl Sulfoxide (adjunct agent)
- use, properties?
- mechanism?
- when it’s best
Ø Antiinflammatory and weak antimicrobial properties
Ø Oxygen free radical scavenger…..most of antiinflammatory properties
Ø Used topically for tissue swelling
Ø More effective on acute vs chronic conditions; eg. trauma
Corticosteroids as adjunct agents
- mechanism, effects
- when useful?
- adverse effects?
- Antiinflammatory effects thru PLA2 inhibition
- Also immunomodulates PMNs and stabilizes membranes
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Ø Value in short flare-ups and symptomatic relief of OA/inflammation
Ø Adverse effects a concern with long-term use
Ø IA injections: infection, cartilage damage
