Opioid overdose

Opioid overdose can result from the following:

• Complications of substance use disorder in regular users of illicit or prescription opioids

• Unintentional overdose in patients prescribed opioids for pain by taking larger amounts than tolerated

• Intentional overdose and intent of self-harm (suicidality)

• Therapeutic drug error; iatrogenic overdose by a practitioner unfamiliar with opioid prescribing, or an adverse drug reaction.

Opioids are used in the treatment of pain. They reduce the patient's perception of pain by inhibition of synaptic neurotransmission in the central nervous system and peripheral nervous system by binding to opioid receptors.

Opioids are classified as agonists, partial agonists, or agonist-antagonists of the opioid receptors, which contributes to the specific clinical effects in overdose. The three main opioid receptors that mediate the clinical effects of opioids with distinct clinical effects are mu, kappa, and delta. Mu receptors mediate analgesia, sedation, respiratory depression, euphoria, gastrointestinal dysmotility, and physical dependence. Kappa receptors mediate analgesia, miosis, diuresis, and dysphoria. Less is known about delta receptors, which mediate analgesia, inhibition of dopamine release, and cough suppression. Sigma receptors are no longer considered opioid in character because they are not antagonized by naloxone. However, certain opioids are sigma receptor agonists and have distinct clinical effects (including dextromethorphan and pentazocine).

Some opioids have additional pharmacologic properties. For example, propoxyphene can cause sodium channel blockade in myocardial conducting tissue, and dextromethorphan and tramadol are also antagonists at the 5-HT (serotonin) receptor.

Opioids can be administered by injection, orally, insufflated, transdermally, and by smoking. Injection is the most potent route because many opioids have significant first-pass hepatic metabolism; most deaths occur after opioids are injected. The oral bioavailability of some opioids is 50% or less (morphine and methadone), but the oral bioavailability of some synthetic opioids is much higher.

Tolerance occurs rapidly with opioids, but in overdose, patients usually succumb to respiratory failure. Mu receptors cause a medullary decrease response to hypercarbia and a decrease in respiratory response to hypoxia, resulting in no stimulus to breathe and apnea. Tolerance to loss of hypercarbic drive may take longer to develop than other euphoric effects, but opioid-tolerant patients never develop complete tolerance to loss of hypoxic stimulus, which leaves these patients particularly susceptible to death from overdose.

Respiratory depression severity

No formal classification exists, but overdose is often classified into severe and not severe, depending on the degree of respiratory depression. Life-threatening respiratory depression is categorized as severe.

Opioid types

Opioids are classified as agonists, partial agonists, or agonist-antagonists of the opioid receptors.