Table 1 Differential diagnosis and treatment of different opioid related signs and symptoms

Opioid side effects [4]

Activation of MOP, DOP and KOP receptors

Sedation, dizziness, pruritus, nausea, vomiting, dry mouth, constipation, physical dependence, tolerance, and respiratory depression

-Intended dose increase

-Symptomatic treatment

-Sometimes discontinuation of opioid therapy

Opioid overdose/Intoxication [5]

Occurs when a person has excessive unopposed stimulation of the opiate pathway.

Flushed skin, respiratory depression, bronchoconstriction, peripheral vasodilatation, hypotension, CNS depression, miosis or mydriasis, conjunctival injection, seizures, euphoria, drowsiness, anxiety, agitation, hallucinations, depression, nightmares, gastric aperistalsis, nausea, vomiting,

-Protect Airway-Breathing-Circulation

-Naloxone antidote: 0.1 mg/kg/dose (max 2 mg/dose) IV, repeat every 2–3 min if needed.

(IM, SC and intranasal routes exist but more delayed onset of action)

Continuous IV infusion needed sometimes.

- Isolated opioid toxicity is unlikely if no response is witnessed after administration of Naloxone.

OIN [6]

Accumulation of active metabolites due to reduced clearance such as in liver or kidney dysfunction, elderly, dehydration… leading to CNS toxicity

Acute delirium (with agitation and hyperactivity, or hypoactivity)

Confusion, myoclonus, seizures, hyperalgesia, allodynia, hallucinations

-Opioid rotation

-Hydration

-Symptomatic treatment of severe myoclonus with Benzodiazepines or Baclofen

-Naloxone does not treat OIN and should not be used.

Withdrawal syndrome [7]

It is related to pathways of adenylyl cyclase superactivation-based central excitation. It occurs when a patient who is dependent on opioids suddenly reduces or stops taking opioids, or is given an opioid partial agonist like buprenorphine or antagonists like naloxone.

lacrimation or rhinorrhea, piloerection, myalgia, diarrhea, nausea/vomiting, abdominal cramping, myalgia, arthralgia, pupillary dilation, photophobia, insomnia, autonomic hyperactivity (tachypnea, hyperreflexia, tachycardia, sweating, hypertension, hyperthermia), and yawning.

-Substitution with Methadone, Buprenorphine or Buprenorphine /Naloxone,

-Symptomatic treatment