SSI Opioids

Morphine

• Type: Full $\mu$-opioid agonist; prototype opioid

• Receptor: Full $\mu$ agonist

• Uses: Moderate–severe pain; premedication; epidural analgesia

• Species: Dogs $\rightarrow$ epidural use; cats/swine $\rightarrow$ excitation at high doses; horses $\rightarrow$ limited use

• Side effects/cautions: Sedation, emesis, constipation, dysphoria, pain on injection, panting, miosis, respiratory depression; horses $\rightarrow$ excitement/increased locomotion

• Differentiator: Preferred opioid for epidural administration because it is more hydrophilic; duration $1\text{--}4\,\text{hr}$; wide safety margin; not preferred in horses

Methadone

• Type: Full $\mu$-opioid agonist; multimodal analgesic

• Receptor: Full $\mu$ agonist + NMDA antagonist + inhibits NT reuptake

• Uses: Moderate–severe pain; chronic or uncontrollable pain

• Species: Dogs, cats, horses; cats $\rightarrow$ transmucosal; horses $\rightarrow$ often combined with $\alpha_2$ agonist/ketamine

• Side effects/cautions: Prominent sedation; euphoria; minimal side effects emphasized

• Differentiator: Particularly effective for uncontrollable pain because of its multimodal mechanism; horses become sedated without becoming recumbent

Fentanyl

• Type: Very potent full $\mu$-opioid agonist

• Receptor: $\mu$ agonist

• Uses: Severe pain; perioperative analgesia; CRI; long-term pain control via transdermal delivery

• Species: Dogs $\rightarrow$ transdermal solution emphasized

• Side effects/cautions: Respiratory depression

• Differentiator: $100\times$ more potent than morphine; extremely lipid soluble; rapid onset + short half-life; IV usually given by CRI; Recuvyra® $\rightarrow$ about $96\,\text{hr}$ analgesia in dogs

Remifentanil

• Type: Derivative of fentanyl; short-acting $\mu$ agonist

• Receptor: $\mu$ agonist

• Uses: Short procedures; induction of anesthesia by CRI

• Species: Rapid clearance emphasized in dogs

• Side effects/cautions: No unique adverse effect emphasized in the lesson

• Differentiator: Metabolized by plasma + tissue esterases; half-life only $3\text{--}6\,\text{min}$; safe for hepatic or kidney disease patients

Carfentanil

• Type: Extremely potent fentanyl derivative

• Receptor: Potent opioid agonist

• Uses: Sedation/immobilization of wildlife

• Species: Zoo and large wild animals such as elephants/moose

• Side effects/cautions: Extreme potency; Schedule II; antagonist must be available; trained personnel only; not preferred for food animals

• Differentiator: $8,000\text{--}10,000\times$ more potent than morphine; most potent opioid emphasized in this lesson

Etorphine

• Type: Extremely potent opioid agonist

• Receptor: Potent opioid agonist

• Uses: Immobilization of large wild animals

• Species: Large wildlife

• Side effects/cautions: Strict regulation; antagonist required; not preferred for food animals

• Differentiator: $3,000\text{--}4,000\times$ more potent than morphine; wildlife immobilization drug

Hydromorphone

• Type: Full $\mu$-opioid agonist

• Receptor: Full $\mu$ agonist

• Uses: Perioperative pain management

• Species: Across species

• Side effects/cautions: General $\mu$-opioid adverse effects; do NOT combine with butorphanol

• Differentiator: Think perioperative pain across species; agonist + antagonist combinations are not recommended

Hydrocodone

• Type: $\mu$-opioid agonist; antitussive opioid

• Receptor: $\mu$ agonist

• Uses: Cough suppression; mild pain

• Species: Especially dogs

• Side effects/cautions: General opioid effects

• Differentiator: Good oral bioavailability $\rightarrow$ particularly useful as a cough suppressant in dogs

Codeine

• Type: Natural opiate

• Receptor: $\mu$-opioid activity

• Uses: Mild pain + cough suppression

• Species: Dogs and cats mentioned for antitussive use

• Side effects/cautions: No unique caution emphasized

• Differentiator: One of the natural opiates; think mild analgesia + antitussive

Buprenorphine

• Type: Semisynthetic high-affinity partial $\mu$ agonist + $\kappa$ antagonist

• Receptor: Partial $\mu$ agonist; $\kappa$ antagonist

• Uses: Analgesia; especially emphasized in cats

• Species: Cats particularly emphasized

• Side effects/cautions: Delayed onset; respiratory depression may be difficult to reverse; may require high-dose naloxone

• Differentiator: About $25\times$ more potent than morphine; binds $\mu$ receptors very tightly and dissociates slowly; duration $6\text{--}12\,\text{hr}$; safer than full $\mu$ agonists

Simbadol® (buprenorphine)

• Type: Formulation of buprenorphine; partial $\mu$ agonist + $\kappa$ antagonist

• Receptor: Same as buprenorphine

• Uses: Analgesia in cats

• Species: Approved for cats

• Side effects/cautions: Same considerations as buprenorphine

• Differentiator: $24\,\text{hr}$ analgesia in cats; lecture dose $0.24\,\text{mg/kg}$ SC once daily

Tramadol

• Type: Centrally acting multimodal analgesic

• Receptor/mechanism: Weak $\mu$ agonist + $\alpha_2$-mediated analgesia + inhibits NE and serotonin reuptake + M1 antagonist

• Uses: Analgesia

• Species: Dogs and cats

• Side effects/cautions: Bitter/unpalatable in cats; repeated administration can be difficult

• Differentiator: Active metabolite O-desmethyl-tramadol (M1) has $\mu$ activity $200\text{--}300\times$ more potent than parent drug; dogs produce the metabolite more slowly than cats

Butorphanol (Agonist–Antagonist Analgesic)

• Type: Mixed opioid agonist–antagonist

• Receptor: $\kappa$ agonist + partial agonist/antagonist at $\mu$

• Uses: Analgesia; pre-anesthetic; mild–moderate sedation

• Species: Dogs, cats, especially horses

• Side effects/cautions: Less analgesic efficacy than full $\mu$ agonists; less respiratory depression

• Differentiator: Effective short-acting analgesic in horses; causes less excitement because of less $\mu$ stimulation; duration $30\text{--}90\,\text{min}$

Nalbuphine (Agonist–Antagonist Analgesic)

• Type: Mixed agonist–antagonist

• Receptor: $\kappa$ agonist + $\mu$ antagonist

• Uses: Moderate–severe pain; anesthesia adjunct

• Species: No specific species emphasized

• Side effects/cautions: Can antagonize $\mu$-mediated effects

• Differentiator: Can reverse respiratory depression caused by a $\mu$-opioid agonist while retaining $\kappa$ activity

Pentazocine

• Type: Mixed opioid agonist

• Receptor: $\kappa$ agonist + partial $\mu$ agonist

• Uses: Colic pain; postoperative pain

• Species: Horses $\rightarrow$ colic; dogs $\rightarrow$ postoperative pain

• Side effects/cautions: No unique caution emphasized

• Differentiator: Remember horse colic + dog postoperative pain

Naloxone

• Type: Pure competitive opioid antagonist

• Receptor: Antagonist at $\mu$, $\kappa$, and $\delta$ receptors

• Uses: Reverse opioid overdose, especially respiratory depression and dysphoria

• Species: General veterinary opioid reversal

• Side effects/cautions: Rapid reversal can cause acute pain; antagonists should be used cautiously

• Differentiator: Blocks ALL opioid receptors; given IV and may be repeated every $2\text{--}3\,\text{min}$ for respiratory depression Emergency Situaions

Naltrexone

• Type: Longer-acting opioid antagonist

• Receptor: Opioid antagonist

• Uses: Reversal of potent opioids

• Species: Particularly important with wildlife opioids

• Side effects/cautions: General risks associated with rapid opioid reversal

• Differentiator: Longer acting; especially used to reverse carfentanil. Large Wildlife.

Butorphanol (Partial Opioid Reversal)

• Type: Mixed agonist–antagonist used for partial opioid reversal

• Receptor: $\mu$ antagonist/partial agonist + $\kappa$ agonist

• Uses: Can antagonize effects of full $\mu$ agonists

• Species: Veterinary use

• Side effects/cautions: May decrease the effects of concurrently administered full $\mu$ agonists

• Differentiator: Can reduce unwanted $\mu$ effects while retaining $\kappa$-mediated analgesia. Similar to Nalbutphine.

Nalbuphine (Partial Opioid Reversal)

• Type: Mixed agonist–antagonist used for partial opioid reversal

• Receptor: $\mu$ antagonist + $\kappa$ agonist

• Uses: Counter $\mu$-mediated respiratory depression

• Species: No specific species emphasized

• Side effects/cautions: Antagonizes $\mu$-mediated effects

• Differentiator: Can reverse some $\mu$ effects without eliminating all opioid analgesia because $\kappa$ activity remains. Same as Butorphanol.

Dextromethorphan

• Type: Central antitussive

• Receptor/action: Central cough suppression

• Uses: Cough suppression

• Species: Listed as an OTC drug; no specific veterinary species emphasized

• Side effects/cautions: No unique caution emphasized in this lesson

• Differentiator: OTC cough-relieving drug; primarily remember it as an antitussive

Apomorphine

• Type: Centrally acting emetic

• Receptor: Dopamine agonist

• Uses: Induce vomiting

• Species: Dogs

• Side effects/cautions: Causes vomiting through stimulation of central dopamine receptors

• Differentiator: Emetic in dogs; dopamine agonist, not primarily an opioid analgesic

Loperamide (Imodium®)

• Type: Peripheral opioid-mediated antidiarrheal

• Receptor/action: Peripheral opioid GI activity; inhibits $\text{Ca}^{2+}$ channels $\rightarrow$ $\downarrow$ ACh release

• Uses: Antidiarrheal

• Species: Veterinary use

• Side effects/cautions: $\downarrow$ GI motility/secretions; $\uparrow$ fluid absorption and sphincter tone

• Differentiator: P-glycoprotein substrate $\rightarrow$ NO CNS effects; think peripheral opioid + diarrhea

Meperidine

• Type: Synthetic opioid receptor agonist

• Receptor: Opioid receptor agonist; further receptor specificity not expanded in the lesson

• Uses: Specific indication not expanded in this lesson

• Species: Not specified

• Side effects/cautions: Combination with MAO inhibitor $\rightarrow$ serotonin syndrome

• Differentiator: Main testable association is MAOI + meperidine = serotonin syndrome