opioid withdrawal

Pathophysiology: Chronic opioid use causes downregulation of endogenous opioid signaling and upregulation of the cAMP pathway in the locus coeruleus, leading to increased noradrenergic activity when opioids are withdrawn, producing a sympathetic surge. Onset and duration depend on the opioid's half-life: short-acting agents like heroin cause symptoms within 6-12 hours peaking at 1-3 days; long-acting agents like methadone have delayed onset (24-48 hours) with a more protracted course. Clinical features: mydriasis, lacrimation, rhinorrhea, yawning, piloerection ('cold turkey'), diaphoresis, nausea, vomiting, diarrhea, abdominal cramping, myalgias/arthralgias, tachycardia, hypertension, insomnia, anxiety, and drug craving. Unlike alcohol or benzodiazepine withdrawal, opioid withdrawal does not cause seizures or significant risk of death in healthy adults, though it is extremely uncomfortable and can be dangerous in neonates, pregnant patients (can precipitate fetal distress/labor), or medically fragile patients. Clinical Opiate Withdrawal Scale (COWS) is used to quantify severity. Management: Buprenorphine or methadone for opioid replacement/tapering; clonidine (alpha-2 agonist) to blunt autonomic symptoms; symptomatic treatment with antiemetics, antidiarrheals (loperamide), NSAIDs for myalgias, and hydroxyzine for anxiety. Precipitated withdrawal can occur if naloxone/naltrexone is given to an opioid-dependent patient, or if buprenorphine is given too soon after full agonist use (due to its high receptor affinity displacing other opioids while having only partial agonist activity). Neonatal abstinence syndrome describes withdrawal in infants born to opioid-dependent mothers. High-yield board associations: differentiate from opioid intoxication (miosis, respiratory depression, CNS depression) and from sympathomimetic toxidrome. Withdrawal timeline and non-lethal nature are frequently tested distinguishing points from CNS depressant withdrawal syndromes.