Opioid analgesics are natural or synthetic morphine-like substance responsible for reducing moderate to severe pain. Opioids are narcotic substance, meaning that they produce numbness or stupor-like symptoms.

Classification of opioids:
Opioids evert their actions by interacting with atleast six different types of receptors: mu (type 1 and 2), kappa, sigma, delta, and epsilon. From the perspective of pain management, the mu and kappa receptors are the most important.
Drugs that stimulate particular receptors are called Opioid agonists.
Drugs that block Opioid receptors are called as Opioid antagonists.

Responses produced by activation of specific receptors

Response Mu receptors Kappa receptor
Analgesia X X
Decreased GI motility X X
Euphoria X
Miosis X
Physical dependence X
Respiratory depression X
Sedation X X



Opioid Agonists

Narcotic Opioid agonists bind to Opioid receptors and produce multiple responses throughout the body. Morphine is the prototype drug used to treat severe pain.
Opioid are the first line of choice for moderate to severe pain. More than 20 different opioids are available as medications, which may be classified by similarities in their chemical structures, by their mechanism of action, or by their effectiveness.
Clinical uses:

  • To suppress cough reflex
    • Opioid are most effective antitussives, act by raising the cough threshold in the CNS. Codeine and Hydrocodone are the most frequently used. The dose needed for the cough suppressant is very low.
  • Slowing the motility of GI tract for cases of severe diarrhea
    • Opioid slows the bowel motility, which helps to relieve diarrhea.
  • Sedative agents in therapeutic level
  • Euphoria and intense relaxation (because of these properties it is abused)
  • General anesthesia

Examples according to the effectiveness:

  1. Opioid agonists with high effectiveness
    1. Hydromorphone hydrochloride
    2. Levorphanol tartrate
    3. Meperidine hydrochloride
    4. Methadone hydrochloride
    5. Morphine sulfate
  2. Opioid agonists with moderate effectiveness
    1. Codeine
    2. Hydrocodonebitartrate
    3. Oxycodone hydrochloride
    4. Propoxyphene hydrochloride
    5. Propoxyphene napsylate

Combination of drugs:
Due to hepatic toxicity related to large doses of acetaminophen, it should be noted that additional doses of combination products might raise the dose of acetaminophen or adjuvant drug to unacceptable levels.

  • Vcodin (Hydrocodone, 5 mg, acetaminophen, 500 mg)
  • Percocet (Oxycodone hydrochloride, 7.5 mg; acetaminophen, 325 mg)
  • Percodan (oxycodone hydrochloride, 4.5 mg; oxycodone terephthalate, 0.38 mg; aspirin, 325 mg)
  • Darvocet-N-50 (propoxyphene napsylate, 50 mg; acetaminophen, 325 mg)
  • Empirin with codeine No.2 (codeine phosphate, 15 mg; aspirin, 325 mg)
  • Tylenol with codeine (single dose may contain from 15 to 60 mg of codeine phosphate and from 300 to 1000 mg of acetaminophen)

Side effects:

  • Physical and psychological dependences
  • Respiratory depression
  • Intense sedation

Opioids antagonists

Opioid overdose can occur because of overly aggressive pain therapy or as a result of substance abuse. Morphine, meperdine and heroin are preferred because of their potency. Although heroin is currently available as a legal analgesic in many countries, it is deemed too dangerous for therapeutic use by FDA and is a major drug of abuse. Once injected or inhaled, heroin rapidly cross BBB to enter the brain, where it is metabolized to morphine. The effects and symptoms of heroin administration are actually caused by the activation of mu and kappa receptors by morphine.
Mechanism of action:
Opioid antagonists are blockers of Opioid activity. They are often used to reverse the symptoms of Opioid addiction, toxicity, and overdose.  Symptoms include sedation or respiratory distress. Acute Opioid intoxication is a medical emergency, with respiratory depression being the most serious problem. Infusion with Opioid antagonist naloxone may be used to reverse respiratory depression and other acute symptoms.

  • Administer naloxone if respiratory rate is fewer than 10 breaths/minute
  • Naloxone should not be used for respiratory depression with nonopioid drugs.
  • Naloxone overdose required oxygen therapy, IV fluids, Vasopressors, and other supportive measures as indicated.

Opioid with mixed agonist-antagonists activity

Although effective at relieving pain, the opioids have a greater risk for dependence han almost any other class of medications. Tolerance develops relatively quickly to the euphoric effects of opioids, causing abusers to escalate their doses and take the drugs more frequently. The higher and more frequent doses rapidly cause physical dependence in Opioid abusers.
When physically dependence patients attempt to discontinue drug use, they experience extremely uncomfortable symptoms the convince many to continue their drug-taking behavior to avoid the suffering. As long as the drug is continued, they feel normal and many can continue work or social activities.
One method of treating Opioid dependence has been to switch the patent from IV and inhalation forms of illegal drugs to methadone (dolophine). Although methadone is an Opioid, it does not cause the euphoria of the injectable Opioids. Methadone also does not cure the dependence, and the patient must continue taking the drug to avoid withdrawal symptoms. The therapy called as Methadone Maintenance.
A newer treatment option is to administer buprenorphine (subutex), a mixed Opioid agonist-antagonists, by the sublingual route. It is used early in Opioid abuse therapy to prevent Opioid withdrawal symptoms.
Another combination agent, suboxone, contains both buprenorphine and methadone.