Pharmacology of Opioids

Mechanism of Action

Opioids are a class of compounds that elicit analgesic (pain killing) effects by binding to the opioid receptors within the central and peripheral nervous system, and the gastrointestinal tract.  These receptors mediate both the psychoactive and the somatic effects of opioids.

Three major types of opioid receptors are involved in analgesia: mu, delta, and kappa receptors. Activation of mu receptors produces analgesia, sedation, euphoria, respiratory depression, constipation, and physical dependence. Activation of kappa receptors produces mild analgesia and less respiratory depression; delta receptor activation may induce analgesia with fewer adverse effects. Opioids have varying effects on these receptors.

Classification of Opioids

Classification is determined by receptor activity. Classes include full agonists, partial agonists, agonist-antagonists, and antagonists.

• Full agonists: These are morphine, fentanyl, oxycodone, hydrocodone, methadone. They activate mu receptors, producing analgesia.
• Partial agonist: Buprenorphin has a strong affinity for mu receptors, but produces mild analgesia that is accompanied by an analgesic ceiling effect. The mu receptors' strong affinity may displace other mu receptor agonists.
• Agonist-antagonists. These are pentazocine, butorphanol, nalbuphine typically act as antagonists on mu receptors and as agonists on kappa receptors, leading to milder analgesic effects with fewer adverse effects.
• Caution should be exercised in the use of partial agonists or agonist-antagonists in patients currently receiving full agonists because opioid withdrawal syndrome could be precipitated.
• The antagonists. Naloxone and naltrexone block mu and kappa receptor activation, preventing analgesia; they are used mostly as reversal agents.

Comparison of Potency

Opioids are metabolized by the liver, and excreted by the kidneys.Not all opioids are equal in strength, and synthetic opioids can be hundreds time the strength of morphine as shown in the table below.  That’s why street drugs, which may contain semisynthetic or synthetic opioids, are extremely easy to cause overdose that can lead to severe respiratory depression and death of the user.