What medications can cause pinpoint pupils (miosis)?

Medications That Cause Pinpoint Pupils (Miosis)

Opioids are the primary class of medications that cause pinpoint pupils, with morphine and other opioid agonists producing characteristic miosis through activation of μ-opioid receptors in the central nervous system. 1, 2

Primary Causative Agents: Opioids

Natural and Synthetic Opioids

• Morphine produces dose-dependent miosis and is considered the prototype opioid causing this effect 1, 2
• Heroin (diamorphine) causes significant pupillary constriction, with tolerance developing in chronic users 3
• Codeine produces miotic effects similar to other opioid agonists 4
• Hydrocodone, oxycodone, and oxymorphone all cause dose-related decreases in pupillary size 4
• Fentanyl and other synthetic opioids produce miosis through the same μ-opioid receptor mechanism 5
• Methadone causes sustained miosis, with peak effects best detected under moderately dim lighting conditions 5, 6

Clinical Characteristics of Opioid-Induced Miosis

• Pinpoint pupils are a pathognomonic sign of opioid overdosage, though pontine lesions can produce similar findings 1
• Miosis occurs even in total darkness, distinguishing it from physiologic pupillary responses 1
• The effect is dose-dependent and can be quantified objectively 2, 6
• Tolerance develops with chronic opioid use, requiring larger doses to produce the same degree of pupillary constriction 2, 3
• Lighting intensity affects detection: peak opioid miosis is best observed under moderately dim interior lighting (4-16 foot-lamberts) 6

Important Clinical Caveat

• In severe opioid overdose with hypoxia, marked mydriasis (pupil dilation) rather than miosis may occur, representing a critical warning sign 1

Secondary Causative Agents: Cholinergic Medications

Anticholinesterase Agents

While the provided evidence focuses primarily on anticholinergic agents that cause pupillary dilation 7, cholinergic agonists and anticholinesterase inhibitors (such as pilocarpine, physostigmine, and organophosphate poisoning) cause miosis through parasympathetic stimulation—this is established general medical knowledge complementing the evidence provided.

Diagnostic Utility

Opioid Detection and Monitoring

• Pupillary constriction serves as one of the most sensitive objective indices of opioid effects 6
• The naloxone reversal test can confirm opioid-induced miosis: naloxone eye drops cause ipsilateral mydriasis when endogenous or exogenous opioids are present 8
• Dynamic pupillary responses (velocity of constriction and redilation) are systematically altered by opioids and may quantify drug-induced impairment 4

Neonatal Withdrawal Assessment

• Opioid withdrawal in neonates produces CNS irritability and autonomic overreactivity, though the evidence notes miosis as an acute opioid effect rather than a withdrawal sign 5

Clinical Pitfalls to Avoid

• Do not assume all pinpoint pupils indicate opioid use: pontine hemorrhage or ischemia can produce identical findings 1
• Do not overlook paradoxical mydriasis in severe overdose: this indicates life-threatening hypoxia requiring immediate intervention 1
• Do not assess pupillary response under bright lighting: opioid miosis is best detected in dim conditions 6
• Do not forget that tolerance affects pupillary response: chronic opioid users require higher doses to produce equivalent miosis 2, 3