This document discusses opioids and analgesia. It provides information on the physiologic effects of opioids like nausea, vomiting, sedation, and constipation. It explains the mechanisms of action of opioids like presynaptic inhibition and hyperpolarization. It describes the different opioid receptors like mu, delta, and kappa receptors. It then discusses various opioid agonists used for pain management like morphine, hydromorphone, codeine, fentanyl, heroin, oxycodone, and tramadol. It also mentions alternatives to opioids for pain like antidepressants, gabapentin, benzodiazepines, muscle relaxants, and NSAIDs.

1. OPIOIDS AND ANALGESIA
Alberto Rivera Sanchez MD FAAPMR, ABPM, ABDA
Pain Management Sub Specialist
American Board of Pain Medicine

2. DISCLOSURES: I HAVE RECEIVED EDUCATIONAL GRANTS FROM
SEVERAL IMPLANT COMPANIES BUT NONE HAVE FUNDED OR
INFLUENCED THE CONTENT OF THIS EDUCATIONAL MATERIAL

3. PHYSIOLOGIC & PHARMACOLOGIC
EFFECTS
Nausea and Vomiting
Sedation, sense of tranquility
Constipation
Anxiolysis, lethargy
Cough suppression
Miosis
Constipation, pruritus, respiratory depression, delayed
gastric emptying, sexual dysfunction, muscle rigidity and
myoclonus

4. MECHANISM OF ACTION
Presynaptic inhibition of of substance P release
Increase K+ conductance (hyperpolarization)
Inactivation of calcium channels

8. OPIOID RECEPTORS
Delta Receptors- its agonists produce
analgesia on inflammatory mediated and
malignant bone pain
Amoxapine, Ketamine, Norbuprenorphine
Kappa receptors- agonists are being
developed to target inflammatory,
visceral and chronic neuropathic pain
 Terpenoids in Cannabis
 Nalbuphine
 Pentazocine

9. MU RECEPTORS
μ1,μ2,μ3 subtypes
Present in the Brain, Spinal Cord, Peripheral sensory neurons and GI tract

10. OPIOID AGONISTS
Morphine
Hydromorphone
Codeine
Fentanyl
Heroin

11. MORPHINE
Agonist for all 3 MOR, KOR and DOR
Can be administered orally (IR & ER)
IV, IM, Epidural, Intrathecal
Approved by FDA for use in IT Pumps
Duration of action in orally administered is longer than IV

12. HYDROMORPHONE
1mg Hydromorphone = 5mg of Morphine
IV, Rectal, SQ, Oral, Epidural, IT
IV ½ life is 2.3 hrs
High abuse potential
Excellent in cancer pain, fractures, burn unit, renal colic
Oral onset is 15 minutes

13. FENTANYL
IV, IT, Oral, Transdermal (most popular for administration)
Patch onset of action is 17 hours
Oral onset of action is 7 minutes
60-134mg Morphine equivalent to 25mcg Fentanyl patch
10 times more potent than hydromorphone
Action is mostly mu1 receptor

14. TRAMADOL
Synthetic mu receptor agonist
Serotonin-NE reuptake inhibitor
1mg Morphine po = 10mg Tramadol
Cardiac effects are rare: low BP, HBP, Inc. HR

15. OXYCODONE
15mg Morphine po = 10mg Oxycodone po
Absorption is increased by fatty meals and
ibuprophen
Gabapentin potentiates its analgesic effects
Has a IR and CR presentation
IR ½ life is 3.2 hrs, onset 10-30 min
CR onset of action 46 min, duration 10-12 hrs (Clin
Pharm 1996)

17. ULTRA RAPID METABOLIZER
1-2% population
Increased enzyme activity.
Increased formation of morphine following codeine
administration, leading to higher risk of toxicity.
Use Morphine or non opioids

18. NON-NARCOTICS FOR PAIN
Anti-depressants
Gabapentin/Pregabalin
BDZs
Muscle relaxants
NSAID’s

19. CHALLENGER IN THE HORIZON
Cannabis derived products with the correct
THC/CBD/terpenoid concentration