Opioids

[SH4:p87-p90; "Opioid receptors" CEACCP 2005 Vol 5(I) p22-25]

Overview

• Opioids is unique in its ability to produce analgesia without producing loss of touch, proprioception, or consciousness.
• Main difference between opioids are potency, and rate of equilibration

Classifications

By method of synthesis

1. Naturally-occuring opioids

• Phenanthrene
  * Include morphine, codeine, thebain
  * Thebain has insignificant analgesia, but can be changed to etorphine (>1000 times the morphine analgesic potency)
• Benzylisoquinolines
  * Include papaverine, noscapine (both lack opioid activity)

2. Semisynthetic opioids

• Come from relatively simple modification of morphine
• Methylmorphine (codeine)
  * Adding methyl group to C3 in morphine
• Diacetylmorphine (heroin)
  * Adding acetyl groups (R-COCH3) to C3 and C6 in morphine

3. Synthetic opioids

Contains phenanthrene nucleus but are synthesized

• Morphine derivative (4 rings)
  * Levorphanol
  * Butorphanol
• Benzomorphan derivative (3 rings)
  * Pentazocine
  * Cyclazocine
• Phenylpiperidine derivative (2 rings)
  * Pethidine (meperidine)
  * Fentanyl
  * Sufentanil
  * Alfentanil
  * Remifentanil
  * Diphenoxylate (lomotil)
• Diphenylhaptene derivatvies (2 rings)
  * Methadone
  * Propoxyphene

By activity at receptors

1. Opioid agonists

• Morphine
• Pethidine
• Fentanyl
• Alfentanil

2. Opioid agonist-antagonists

• Pentazocine
• Buprenorphine
• Naltrexone
• Meptazinol

3. Opioid antagonists

• Naloxone
• Naltrexone

NB:

• Phenylpiperidine derivatives are similar to amide LA in MW and pharmacokinetics

Structure

• Phenanthrene nucleus consists of 3 benzene rings (14 carbons)
• Most opioid agonists also has a 4th carbon ring (piperidine, a 5 carbon + 1 nitrogen ring)
  --> N in the piperidine ring is a tertiary amine
  * At pH 7.4, tertiary amine is highly ionised --> More water solubility
• Close relationship between stereochemical structure and potency
  --> Levorotatory isomer is most active

Special considerations

• After 60 years of age,
  * Decreased sensitivity to pain
  * Increased analgesic response to opioids