13 – Opioids II

Question 1

Opioids clinical use

Answer 1

• Premedication
• Bolus or infusion intra- and peri-operatively
  o Dose-dependent analgesia
  o Great anesthetic sparing effect
• Analgesia for medical and critically ill patients
• Procedural sedation
  o Combination with sedatives
  o Sedation

Question 2

Adverse effects of opioids

Answer 2

• Behavioural changes
• Vomiting and nausea
• Increased risk of gastroesophageal reflux (GER)
• Bradycardia
• Respiratory depression

Question 3

CNS

Answer 3

• Sedation
• Euphoria (more common in cats)
• Dysphoria (more common in dogs)

Question 4

Euphoria dogs + cats

Answer 4

• Dogs: extreme wakefulness, vocalization
• *Cats: extreme friendliness, kneading, rolling
• May OUTLAST analgesic effects

Question 5

Dysphoria dogs + cats

Answer 5

• *Dogs: agitation, excitement, excessive vocalization
• Cats: fearful, apparent hallucinatory behaviour, circling, pacing
• More likely in NON-painful in animals
• *reaction to ‘overdose’ of opioids

Question 6

Dysphoria treatment

Answer 6

• Partial opioid reversal (careful titration)
• Sedation (low dose acepromazine, dexmedetomidine)
  o Maybe do not for older animals

Question 7

Partial opioid reversal to ‘treat’ dysphoria

Answer 7

• Butorphanol
• Naloxone

Question 8

Dose-dependent respiratory depression (mu-opioid agonists)

Answer 8

• Hypoventilation and hypercapnia
• Mu-opioid receptor decreases responsiveness of regulatory cells to pCO2 and pH
• Humans are more susceptible than animals
• Panting in dogs (to decrease body T: hypothermia)

Question 9

Antitussive actions

Answer 9

• Depression of cough reflex
• Independent of respiratory depressant effects
• Butorphanol 100x/4x more effective than codeine/morphine

Question 10

CV effects

Answer 10

• Minimal effects on CO, cardiac rhythm, arterial BP
• Vagally mediated bradycardia
• Reversible with anticholinergic drugs
• Histamine release: vasodilation and hypotension (morphine, meperidine)

Question 11

Mu agonist opioids nausea and emesis effects

Answer 11

• Emetic effect: stimulation of dopamine receptors in CTZ (apomorphine)
• Antiemetic effect: inhibition of emetic center inside the BBB
  o Use of antidopaminergic drugs may decrease incidence of vomiting

Question 12

Kappa agonist opioids nausea and emesis effects

Answer 12

• Butorphanol: antiemetic for chemotherapy

Question 13

GI tract effects

Answer 13

• Decreased motility
• Gastro-esophageal reflux (GER)

Question 14

Decreased motility (GI)

Answer 14

• Inhibit release of NT=impair coordination of motility and inhibition of GIT
• Initial effect=defecation
• Followed by ileus and constipation

Question 15

Gastro-esophageal reflux (GER)

Answer 15

• Gastro-esophageal sphincter relaxation
• Hydromorphone, methadone

Question 16

When would you use full mu-agonist opioids?

Answer 16

• Moderate to severe pain
• *superior analgesics

Question 17

Full mu-agonist examples

Answer 17

• Morphine
• Hydromorphone
• Methadone
• Fentanyl
• Meperidine
• Sufentanil, alfentanil, remifentanil

Question 18

Morphine

Answer 18

• Full mu opiod
• ‘gold standard’
• ++ to +++
• Histamine release if administered IV (hypotension)
• Vomiting
• Can be administered neuraxially and intra-articularly

Question 19

Morphine-6-glucruonide

Answer 19

• Active metabolite (650x as potent as morphine)
• Pharmacological activities indistinguishable from morphine
• Contributes to clinical analgesia with chronic morphine administration

Question 20

Morphine-3-glucuronide

Answer 20

• Little affinity for opioid receptors
• May contribute to the EXCITATORY effects of morphine

Question 21

Hydromorphone

Answer 21

• Full mu opioid agonist
• 5-10x more potent than morphine
• Analgesia ++ to +++
• Dose-dependent sedation, respiration, bradycardia
• Vomiting
• Panting
• Adequate analgesia for invasive surgery

Question 22

Hydromorphone-3-glucuronide can produce

Answer 22

• Neuro-excitatory behaviours

Question 23

Metadone

Answer 23

• Pure mu-agonist
• NMDA antagonist (more for ‘wind up’ pain)
• NE and serotonin uptake inhibitor
• Analgesia moderate to severe pain
• Clinically similar to morphine
• *NO vomiting
• No active metabolites

Question 24

Fentanyl

Answer 24

• 75-125x more potent than morphine
• Analgesia +++
• Intra and peri-operative pain
• Fast onset, short half-life (suitable for repeated boluses or infusions)
• Dose dependent respiratory depressant and bradycardia
• Anesthetic sparing
• Highly lipophilic (very large Vd and long elimination half-life)
• Too many repeated doses or too prolonged an infusion=may result in accumulation
• Prolong context-sensitive half lives: long recovery time)

Question 25

Merperidine

Answer 25

• Synthetic mu and kappa agonist
• 1/10 potency of morphine
• Short duration, mild analgesia
• Histamine release
• Decrease incidence of GER compared to morphine
• Unique CV effects
• NEGATIVE INOTROPHIC effects when administered along
• Has modest ATROPINE-like effects=increase HR rather than typical bradycardia

Question 26

Remifentanil

Answer 26

• mu opioid agonist
• similar potency fentanyl
• analgesia +++
• ultra-shortening: context-sensitive half time
• only suitable for intra-operative use
• metabolized by blood and tissue non-specific cholinesterases
• independent of hepatic function
• *may use under general anesthetics
• Ex. C-sections (effect on mom but not the puppies)

Question 27

Tramadol

Answer 27

• Atypical mu-receptor agonist
• Inhibits reuptake of serotonin and NE
• Add humans
• Not good for dogs

Question 28

Tramadol dogs

Answer 28

• Do NOT produce substantial amounts of M1
• Analgesic effects are predicted to be weak

Question 29

Tramadol cats

Answer 29

• Produce substantial amounts M1: likely effective analgesic
• Bitter taste of oral preparation=dosing is a challenge

Question 30

Buprenorphine

Answer 30

• Partial mu-agonist (weak K-antagonist)
• 1000x higher affinity for mu-receptor than morphine
• Difficult to antagonize its effects
• Moder intrinsic actiivy
• Analgesia ++
• Slower onset (15-30mins)
• *ceiling effect (bell shape dose response curve, go higher=less effective)
• Long duration: 6-8 hrs

Question 31

Butorphanol

Answer 31

• Kappa agonist, mu antagonist
• Minimal effects on cardiopulmonary function
• No histamine release
• Shorting acting (30-60mins)
• Sedative properties
• Analgesia +

Question 32

Butorphanol was labeled as an

Answer 32

• Antitussive agent in dogs

Question 33

11-month old great pyrenees dog: hit by car, problem=coxofemoral luxation, going to do sedation for radiographs and closed reduction

Answer 33

• Pain level: severe
• Opioid: Hydromorphone (or Fentanyl)
• Side effect example: panting

Question 34

3 year old DSH, ate walnuts, obstructive foreign bodies in stomach, plan: surgery

Answer 34

• pain level: moderate
• opioid: methadone (no vomiting), fentanyl (titre to effect)

Question 35

7 year old DSH, accidental drug overdose->cardiac arrest, successful chest compression

Answer 35

• buprenorphine: every breath=hurt
• butorphanol: no CV or respiratory side effects

Question 36

10 year old Yorkie, goose honking cough, suspect collapsing trachea, scheduled for radiographs under sedation

Answer 36

• pain level: mild
• opioid: butorphanol (no respiratory effect
  o can give IM
  o also mild sedative may decrease/calm breathing

Question 37

5 year old DSH, complicated humerus fracture, amputation (buprenorohine over night)

Answer 37

• pain: severe
• opioid: methadone, fentanyl, hydromorphone
• *stop buprenorophine at midnight so doesn’t interfere with hydromorphine

Question 38

2 year old miniature horse, elective castration

Answer 38

• Pain: mild
• Opioid: don’t give a full mu-agonist, do a partial agonist
• **butorphenol