3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
 3.1.3.5. Opioids 

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
Keywords Opioids