Opioids 2 Flashcards
clinical use of opioids
-premedication
-bolus or infusion intra and perioperatively (dose dependent analgesia, great anesthetic sparing effect)
-analgesia for medical and critically ill patients
-procedural sedation (combined with sedatives; sedation when administered alone in critical ill patients)
Adverse effects of opioids
-behavioural changes
-vomiting and nausea (morphine, hydromorphone)
-increased risk of gastroesophageal reflux (morphine, methadone)
-bradycardia
-respiratory depression
Opioids effect on CNS
-sedation
-euphoria
-dysphoria
Euphoria in dogs vs cats
Dogs: extreme wakefulness, vocalization
Cats: extreme friendliness, kneading, rolling
**may outlast analgesic effects
Dysphoria in dogs vs cats
Dogs: agitation, excitement, restlessness, excessive vocalization, disorientation
Cats: fearful, apparent hallucinatory behaviour, agitation, circling, pacing
**more likely in non-painful animals
Dysphoria
-Rxn to opioids
-animals difficult to distract or calm by interaction
-don’t respond to light palpation or painful area
How to treat dysphoria?
- partial opioid reversal with careful titration
>Butorphanol (mu antagonists, kappa agonist)
>Naloxon (mu antagonist) - sedation (low dose acepromazine, dexmedetomidine)
Respiratory depression from opioids
-hypoventilation and hypercapnia
-dose dependent
-mu- opioid receptor decreases responsiveness of regulatory cells to pCO2 and pH
Eg. panting in dogs
Antitussive actions from opioids
-depression of cough reflex
-independent of respiratory depressant effects
*Butorphanol 100x/4x more effective than codeine/morphine
Cardiovascular effects from opioids
-minimal effects on cardiac output, cardiac rhythm, arterial blood pressure
-vagally mediated bradycardia
-histamine release= vasodilation and hypotension
-reversible with anticholinergic drugs
Nausea and emesis from opioids
**depends on opioid, dose, route of administration
Mu agonist opioids:
1. emetic effect- stimulation of dopamine receptors in chemoreceptor trigger zone (apomorphine)
2.Antiemetic effect- inhibition of emetic center inside BBB. Use of antidopaminergic drugs prior might decrease incidence of vomiting
Kappa opioids:
-Butorphanol: antiemetic for chemotherapy
Opioids effect on GI tract
-Decreased motility
-Gastro-esophageal reflux
Decreased motility from opioids
-inhibit the release of these NTs= impairing coordination of motility and inhibition of GI tract
**initially defecation followed by ileus and constipation
Gastro-esophageal reflux
Gastroesophageal sphincter relaxation
**caused by hydromorphone and methadone
Full mu agonists use
-superior analgesics; treatment of moderate to severe pain
Types of full mu agonists
- morphine
2.hydromorphine
3.methadone
4.fentanyl
5.meperidine - sufentanil, alfentanil, remifentanil
Morphine
-full mu opioid
-gold standard opioid to which others are compared
-administered IV, or neuraxially and intra-articularly
Morphine affects
-histamine release if administered IV= hypotension
-vomiting
Morphine-6-glucuronide
-active metabolite (650x more potent as morphine)
-pharmacological activities indistinguishable from morphine
-contributes significantly to clinical analgesia with chronic morphine administration
Morphine-3-glucuronide
-little affinity for opioid receptors
-may contribute to the excitatory effects of morphine
Hydromorphone
-full mu opioid agonist
-5-10x potent than morphine
-used for moderate to severe pain; adequate for invasive surgery
-dose dependent sedation, respiratory depression, bradycardia
Hydromorphone effects
-vomiting
-panting in dogs
-hydromorphone-3-glucuronide can produce neuro-excitatory behaviours
Methadone
-pure mu agonist; NMDA antagonist
-Ne and serotonin uptake inhibitor
-no active metabolites
-similar to morphine
-Provides analgesia (moderate to severe, works on wind up pain; no vomiting; panting present)
Fentanyl
-more powerful analgesic
-more potent than morphine (75-125x)
-used in intra and peri-operative pain
-anesthetic sparing (isoflurane requirements are reduced by 53% in dogs)
-highly lipophilic (high VD, long half life)
Fentanyl timing
-fast onset
-short half life
>prolong context sensitive half lives (long recovery time, more problems in humans than dogs, cats)
**suitable for repeated boluses or infusions
Fentanyl effects
More potent, so stronger effects
-dose dependent respiratory depressant
-dose dependent bradycardia
**too many repeated doses or to prolonged an infusion. May result in accumulation
Meperidine
-synthetic mu and kappa agonist
-1/10 potency of morphine
Meperidine timing
Short duration
Meperidine effects
-mild analgesia
-histamine release
-decreased incidence of GER compared to morphine
-Cardiovascular effects:
>negative inotropy when administered alone to conscious dogs
>modest atropine-like effects= increase HR rather than typical bradycardia
Remifentanil
-mu opioid agonist
-similar potency to fentanyl
-used for analgesia linked with intra-operative use. Need other analgesics before infusion is stopped
-metabolized by blood and tissue non-specific cholinesterases, so can be used with pregnant animals; independent of hepatic function
Remifentanil timing
-ultra short acting: context sensitive half time (4min)
Tramadol
-atypical mu receptor agonists
-inhibits reuptake of serotonin and NE
-mild analgesia; primarily due to O-desmethyltramadol (M1)
M1
-acts as a full mu opioid agonist
Tramadol in dogs
-do not produce substantial amounts of M1
-analgesic effects are predicted to be weak at best
Tramadol in cats
-produce substantial amounts of M1 therefore likely an effective analgesic
-bitter taste of oral preparation makes dosing a challenge
Buprenorphine
-partial mu agonist, weak kappa antagonist
-1000x higher affinity for mu receptor than morphine
-difficult to antagonize effects
-moderate intrinsic activity, moderate analgesia
Timing of buprenorphine
Slower onset time than other opioids (15-30 mins)
Long duration : 6-8hrs
Butorphanol
-kappa agonist, mu antagonist
-originally labeled as an antitussive agent in dogs
-min effect on cardiopulmonary function
-no histamine released
-short acting (30-90mins)
-mild analgesia
