⚙

Pathophysiology

5

Systemic Opioid Exposure

An opioid agonist is absorbed and distributed systemically, crossing the blood-brain barrier to reach central mu-opioid receptors. The dose that produces the toxidrome depends on the agent's potency, the route, and the patient's tolerance; children who ingest opioids intended for adults are a recurring accidental source.

Downstream

Central Mu-Opioid Receptor Overactivation Distributed agonist occupies central mu-opioid receptors in excess.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"data indicate that the frequent prescription of opioid analgesics contributes to overdose-related mortality among children, who may find and ingest agents in the home that were intended for adults"

Supports exogenous opioid exposure, including accidental pediatric ingestion, as the initiating event.

Central Mu-Opioid Receptor Overactivation

Excess agonism of the mu-opioid receptor, a Gi/Go-coupled G-protein-coupled receptor that inhibits adenylate cyclase, hyperpolarizes and silences neurons across brainstem respiratory centers, cortical and thalamic arousal pathways, the Edinger-Westphal nucleus, and enteric circuits. The mu receptor accounts for the preponderance of opioid clinical effects.

central nervous system neuron CL:2000029

OPRM1 hgnc:8156

adenylate cyclase-inhibiting opioid receptor signaling GO:0031635 ↑ INCREASED

mu-opioid receptor activity GO:0004985 ↑ INCREASED

Downstream

Brainstem Respiratory Center Suppression Mu-opioid agonism in brainstem respiratory centers blunts the ventilatory response to CO2 and hypoxia.

Depressed consciousness Mu-opioid agonism across central arousal pathways depresses the level of consciousness.

Parasympathetic Pupillary Constriction Mu-opioid action at the Edinger-Westphal nucleus drives pupillary constriction.

Reduced Gastrointestinal Motility Mu-opioid agonism on gastrointestinal receptors slows peristalsis.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"The mu opioid receptor is responsible for the preponderance of clinical effects caused by opioids."

Supports the mu-opioid receptor as the central effector of the toxidrome.

Brainstem Respiratory Center Suppression

Agonism of mu-opioid receptors on brainstem respiratory neurons suppresses the ventilatory response to hypercarbia and hypoxia and the drive to breathe, producing hypoventilation.

brainstem respiratory neuron CL:2000029

nervous-system control of respiratory gas exchange GO:0002087 ↓ DECREASED

brainstem UBERON:0002298

Downstream

Respiratory depression Suppressed central respiratory drive manifests as hypoventilation.

Show evidence (2 references)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"brain-stem opioid receptors modulate respiratory responses to hypercarbia and hypoxemia"

Supports mu-opioid suppression of the brainstem ventilatory response to hypercarbia and hypoxia.

PMID:35965031 SUPPORT REVIEW SYNTHESIS Human Clinical

"respiratory depression, which can lead to lethal overdose if not treated"

Supports opioid suppression of respiration as the lethal mechanism.

Parasympathetic Pupillary Constriction

Mu-opioid action at the Edinger-Westphal nucleus increases parasympathetic outflow to the iris sphincter, constricting the pupil.

iris sphincter muscle UBERON:0001607

Downstream

Miosis Increased parasympathetic tone to the iris sphincter produces pinpoint pupils.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"receptors in the Edinger-Westphal nucleus of the oculomotor nerve control pupillary constriction"

Supports mu-opioid action at the Edinger-Westphal nucleus driving pupillary constriction.

Reduced Gastrointestinal Motility

Agonism of enteric and central mu-opioid receptors slows peristalsis and reduces gut motility.

enteric neuron CL:0007011

peristalsis GO:0030432 ↓ DECREASED

Downstream

Gastrointestinal dysmotility Slowed peristalsis manifests as reduced bowel motility.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Opioid agonists bind to receptors in the gastrointestinal tract to decrease gut motility."

Supports mu-opioid agonism reducing gastrointestinal motility.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

10

Digestive 1

Gastrointestinal dysmotility HP:0002579

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Opioid agonists bind to receptors in the gastrointestinal tract to decrease gut motility."

Supports the reduced-motility phenotype.

Eye 1

Miosis HP:0000616

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Miosis alone is insufficient to infer the diagnosis of opioid intoxication."

Supports miosis as a toxidrome feature while noting it is not diagnostic alone.

Metabolism 2

Noncardiogenic pulmonary edema HP:0100598

Show evidence (2 references)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"pulmonary edema is present in nearly all fatal cases of opioid overdose"

Supports pulmonary edema as a frequent and serious feature of fatal poisoning.

PMID:24144776 SUPPORT REVIEW SYNTHESIS Human Clinical

"Non-cardiogenic pulmonary edema has been attributed to heroin, despite debated mechanisms including attempted inspiration against a closed glottis"

Independently attributes non-cardiogenic pulmonary edema to opioids and names the closed-glottis mechanism.

Hypothermia HP:0002045

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Hypothermia may arise from a persistently unresponsive state in a cool environment"

Supports hypothermia as a secondary consequence of the unresponsive state.

Musculoskeletal 1

Rhabdomyolysis HP:0003201

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"persons who have been lying immobile in an opioid-induced stupor may be subject to rhabdomyolysis, myoglobinuric renal failure, and the compartment syndrome"

Supports rhabdomyolysis, myoglobinuric renal failure, and compartment syndrome as complications of the immobile stuporous state.

Nervous System 2

Depressed consciousness Reduced consciousness HP:0004372

Sequelae: Hypothermia Rhabdomyolysis

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"the classic toxidrome of apnea, stupor, and miosis suggests the diagnosis of opioid toxicity"

Lists stupor (depressed consciousness) as a member of the classic triad.

Seizure HP:0001250

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Seizures have been associated with overdose of tramadol, propoxyphene, and meperidine"

Supports seizures as an agent-specific feature of certain opioids rather than a core toxidrome feature.

Respiratory 3

Respiratory depression Hypoventilation HP:0002791

Sequelae: Respiratory arrest Hypoxemia Noncardiogenic pulmonary edema

Show evidence (2 references)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"The sine qua non of opioid intoxication is respiratory depression."

States that respiratory depression is the defining feature of the toxidrome.

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"A respiratory rate of 12 breaths per minute or less in a patient who is not in physiologic sleep strongly suggests acute opioid intoxication, particularly when accompanied by miosis or stupor."

Gives the clinical threshold that defines the respiratory depression phenotype.

Respiratory arrest HP:0005943

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"a decline in respiratory rate culminating in apnea"

Supports progression of respiratory depression to apnea (respiratory arrest).

Hypoxemia HP:0012418

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"an oxygen saturation of less than 90% while the patient is breathing ambient air"

Supports the failure of oxygenation (hypoxemia) that follows opioid hypoventilation.

💊

Medical Actions

2

Naloxone

Action: Pharmacotherapy NCIT:C15986

Agent: naloxone CHEBI:7459

Platform: Small molecule

Competitive mu-opioid receptor antagonist and the antidote; it reverses the respiratory depression and the full toxidrome. Its duration of action is shorter than that of many opioids, so re-sedation can occur and observation is required. In opioid-dependent patients, low doses titrated to breathing can restore ventilation without precipitating withdrawal.

Mechanism Target:

Central Mu-Opioid Receptor Overactivation — Naloxone competitively antagonizes the mu-opioid receptor, reversing the toxidrome.

Show evidence (3 references)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Naloxone, the antidote for opioid overdose, is a competitive mu opioid-receptor antagonist that reverses all signs of opioid intoxication."

States naloxone's mechanism and that it reverses the toxidrome.

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"its apparent duration of action is 20 to 90 minutes, a much shorter period than that of many opioids"

Supports the re-sedation risk and the need for observation.

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"patients with opioid tolerance frequently have a response to low doses of naloxone that are sufficient to restore breathing without provoking withdrawal"

Supports low-dose titration restoring ventilation without precipitating withdrawal in dependent patients.

Assisted ventilation and airway support

Action: assisted ventilation Ontology label: Mechanical Ventilation NCIT:C70909

Bag-valve-mask ventilation and airway positioning restore oxygenation in the apneic or severely hypoventilating patient and are first-line alongside or ahead of naloxone.

Mechanism Target:

Respiratory depression — Mechanical ventilation substitutes for the suppressed respiratory drive.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Patients with apnea need a pharmacologic or mechanical stimulus in order to breathe."

Supports mechanical ventilation as a core response to opioid-induced apnea.

🌍

Environmental Factors

2

Opioid agonist exposure

Exposure to an opioid agonist in excess of tolerance -- therapeutic, recreational, iatrogenic, or accidental, including pediatric ingestion of agents meant for adults -- is the cause of the toxidrome.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices"

Supports opioid exposure through prescribing, misuse, and administration as the cause of the toxidrome.

Mechanism Target:

TRIGGERS Systemic Opioid Exposure — Absorption of an opioid agonist establishes the systemic exposure that reaches central mu-opioid receptors.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices"

The exposure routes that establish the systemic opioid burden.

Co-ingested benzodiazepines or other sedative-hypnotics

Benzodiazepines and other sedative-hypnotics taken with opioids potentiate respiratory depression and are strongly associated with death from opioid overdose; they do not cause the toxidrome alone but deepen it.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"sedative hypnotic agents (e.g., benzodiazepines) that have been strongly associated with death from opioid overdose"

Supports co-ingested benzodiazepines as a potentiator of fatal opioid overdose.

Mechanism Target:

EXACERBATES Respiratory depression — Co-ingested sedative-hypnotics deepen opioid respiratory depression, raising the risk of fatal hypoventilation.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"sedative hypnotic agents (e.g., benzodiazepines) that have been strongly associated with death from opioid overdose"

Supports potentiation of fatal respiratory depression by co-ingested sedative-hypnotics.

🔬

Diagnosis

2

Clinical toxidrome recognition

The diagnosis is clinical, inferred from the triad of depressed consciousness, respiratory depression, and miosis together with the history and vital signs; the findings are not all consistently present.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"Although the classic toxidrome of apnea, stupor, and miosis suggests the diagnosis of opioid toxicity, all of these findings are not consistently present."

States the clinical triad and its inconsistency, the basis of diagnosis.

Therapeutic response to naloxone

Reversal of respiratory depression by naloxone supports the diagnosis; failure to respond to escalating doses up to 15 mg argues against opioid poisoning as the cause.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"If there is no abatement in respiratory depression after the administration of 15 mg of naloxone, it is unlikely that the cause of the depression is opioid overdose."

Supports the naloxone response as a near-diagnostic test.

📊

Prevalence

1

United States (2010, National Poison Data System)

Unknown Common

Surveillance count, not a population rate: the National Poison Data System recorded more than 107,000 opioid-analgesic exposures and more than 27,500 related health-care admissions in 2010.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"reported more than 107,000 exposures to opioid analgesics, which led to more than 27,500 admissions to health care facilities"

Quantifies the scale of opioid-analgesic poisoning in US surveillance data.

🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Acute Opioid Poisoning:

Clonidine and imidazoline toxicity

Overlapping Features The classic pharmacologic mimic of the opioid toxidrome. Central alpha-2-adrenergic agonism from clonidine (and imidazoline decongestants) produces CNS depression, miosis, and respiratory depression that look like opioid poisoning, and it may even partially respond to naloxone. It is a frequent cause of accidental pediatric exposure.

Distinguishing Features

Prominent bradycardia and hypotension accompany the CNS depression and miosis in clonidine toxicity.
Reversal of CNS depression by naloxone, when it occurs in clonidine toxicity, typically requires higher-than-standard doses and is inconsistent.

Show evidence (2 references)

PMID:41292070 SUPPORT REVIEW SYNTHESIS Human Clinical

"Clonidine toxicity mimics an opioid toxidrome, often presenting with CNS depression, miosis, bradycardia, and hypotension."

States directly that clonidine toxicity mimics the opioid toxidrome and names the distinguishing autonomic features.

PMID:41292070 SUPPORT REVIEW SYNTHESIS Human Clinical

"naloxone may be beneficial in reversing CNS depression, though higher-than-standard doses are often required"

Supports the partial, high-dose naloxone response that distinguishes clonidine from opioid toxicity.

Sedative-hypnotic toxidrome

Overlapping Features Overdose of benzodiazepines, barbiturates, ethanol, antipsychotics, or anticonvulsants depresses consciousness and can even cause miosis, but it lacks the respiratory depression that defines opioid toxicity. Benzodiazepines are also a common co-ingestant that worsens opioid overdose.

Distinguishing Features

The respiratory depression that defines opioid toxicity is usually absent in sedative-hypnotic overdose.
Sedative-hypnotic overdose does not respond to naloxone.

Show evidence (1 reference)

PMID:22784117 SUPPORT REVIEW SYNTHESIS Human Clinical

"overdose from antipsychotic drugs, anticonvulsant agents, ethanol, and other sedative hypnotic agents can cause miosis and coma, but the respiratory depression that defines opioid toxicity is usually absent"

Gives the overlap (miosis and coma) and the key distinguishing feature (respiratory depression usually absent).

Cholinergic toxidrome (organophosphate or carbamate poisoning) MONDO:0800386

Overlapping Features Organophosphate and carbamate poisoning also produces miosis and depressed consciousness, but adds a cholinergic excess picture (bradycardia, hypersecretion, fasciculations, seizures) that opioid poisoning does not, and it does not respond to naloxone. dismech curates it separately as Organophosphate_Poisoning.

Distinguishing Features

Cholinergic toxidrome adds bradycardia, muscle fasciculations, and seizures to the miosis, none of which belong to opioid poisoning.
It is treated with atropine and an oxime, not naloxone.

Show evidence (1 reference)

PMID:32626615 SUPPORT Human Clinical

"severe such as bradycardia, miosis, fasciculations, seizures and altered level of consciousness"

Shows the cholinergic toxidrome shares miosis and depressed consciousness with opioid poisoning but adds bradycardia and fasciculations.

Pontine hemorrhage

Overlapping Features A structural, non-toxicological mimic: pontine (brainstem) hemorrhage can produce pinpoint pupils and coma identical to opioid poisoning, but with focal neurological signs and no response to naloxone, and is diagnosed on imaging.

Distinguishing Features

Pontine hemorrhage shows focal signs such as gaze deviation and hemiplegia, which opioid poisoning does not.
It is confirmed on CT or MRI showing hemorrhage in the pons.

Show evidence (2 references)

PMID:31246723 SUPPORT INDIRECT Human Clinical

"Glasgow Coma Scale (GCS) of 7 (E2, V1, M4), left gaze deviation, pinpoint pupils, and left hemiplegia"

A pontine hemorrhage presenting with pinpoint pupils and coma (mimicking opioid toxicity) but with focal signs that distinguish it.

PMID:31246723 SUPPORT INDIRECT Human Clinical

"Computed tomographic scan of the head revealed acute hemorrhage in the right pons"

Ties the pinpoint-pupils-and-coma presentation to a hemorrhage located in the pons, confirmed on imaging.

{ }

Source YAML

click to show

name: Acute Opioid Poisoning
creation_date: "2026-10-04T04:30:00Z"
category: Toxic Exposure Disorder
synonyms:
- opioid toxidrome
- opioid overdose
- opioid intoxication
- acute opioid intoxication
- narcotic poisoning
disease_term:
  preferred_term: acute opioid poisoning
  term:
    id: MONDO:0018173
    label: acute opioid poisoning
description: >-
  Acute opioid poisoning is the toxidrome produced when an opioid agonist
  occupies central mu-opioid receptors in excess, whether the exposure is
  therapeutic, recreational, accidental (including pediatric ingestion), or
  iatrogenic. The classic toxidrome is the triad of depressed consciousness,
  respiratory depression, and miosis (pinpoint pupils), with reduced
  gastrointestinal motility, hypothermia, and non-cardiogenic pulmonary edema
  as further features. Respiratory depression is the sine qua non and the
  proximate cause of death. Naloxone, a competitive mu-opioid receptor
  antagonist, reverses the toxidrome and serves as both antidote and
  near-diagnostic test. This entry models the acute pharmacodynamic toxidrome
  and is deliberately distinct from the chronic neuroadaptive disease of opioid
  use disorder.
notes: >-
  Scope: this is the acute poisoning event (an exposure-driven pharmacodynamic
  toxidrome), not opioid use disorder (MONDO:0005530), which is curated
  separately as a psychiatric disease. The two overlap clinically because
  overdose is the terminal event of use disorder, but the mechanisms modeled
  here are the acute receptor-level cascade, not the neuroadaptation of
  dependence and tolerance.
pathophysiology:
- name: Systemic Opioid Exposure
  role: trigger
  description: >-
    An opioid agonist is absorbed and distributed systemically, crossing the
    blood-brain barrier to reach central mu-opioid receptors. The dose that
    produces the toxidrome depends on the agent's potency, the route, and the
    patient's tolerance; children who ingest opioids intended for adults are a
    recurring accidental source.
  downstream:
  - target: Central Mu-Opioid Receptor Overactivation
    description: Distributed agonist occupies central mu-opioid receptors in excess.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "data indicate that the frequent prescription of opioid analgesics contributes to overdose-related mortality among children, who may find and ingest agents in the home that were intended for adults"
    explanation: Supports exogenous opioid exposure, including accidental pediatric ingestion, as the initiating event.
- name: Central Mu-Opioid Receptor Overactivation
  role: central_effector
  biological_scale: MOLECULAR
  description: >-
    Excess agonism of the mu-opioid receptor, a Gi/Go-coupled G-protein-coupled
    receptor that inhibits adenylate cyclase, hyperpolarizes and silences neurons
    across brainstem respiratory centers, cortical and thalamic arousal pathways,
    the Edinger-Westphal nucleus, and enteric circuits. The mu receptor accounts
    for the preponderance of opioid clinical effects.
  molecular_functions:
  - preferred_term: mu-opioid receptor activity
    modifier: INCREASED
    term:
      id: GO:0004985
      label: G protein-coupled opioid receptor activity
  biological_processes:
  - preferred_term: adenylate cyclase-inhibiting opioid receptor signaling
    modifier: INCREASED
    term:
      id: GO:0031635
      label: adenylate cyclase-inhibiting opioid receptor signaling pathway
  cell_types:
  - preferred_term: central nervous system neuron
    term:
      id: CL:2000029
      label: central nervous system neuron
  genes:
  - preferred_term: OPRM1
    term:
      id: hgnc:8156
      label: OPRM1
  downstream:
  - target: Brainstem Respiratory Center Suppression
    description: Mu-opioid agonism in brainstem respiratory centers blunts the ventilatory response to CO2 and hypoxia.
  - target: Depressed consciousness
    description: Mu-opioid agonism across central arousal pathways depresses the level of consciousness.
  - target: Parasympathetic Pupillary Constriction
    description: Mu-opioid action at the Edinger-Westphal nucleus drives pupillary constriction.
  - target: Reduced Gastrointestinal Motility
    description: Mu-opioid agonism on gastrointestinal receptors slows peristalsis.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The mu opioid receptor is responsible for the preponderance of clinical effects caused by opioids."
    explanation: Supports the mu-opioid receptor as the central effector of the toxidrome.
- name: Brainstem Respiratory Center Suppression
  role: effector
  description: >-
    Agonism of mu-opioid receptors on brainstem respiratory neurons suppresses
    the ventilatory response to hypercarbia and hypoxia and the drive to
    breathe, producing hypoventilation.
  biological_processes:
  - preferred_term: nervous-system control of respiratory gas exchange
    modifier: DECREASED
    term:
      id: GO:0002087
      label: regulation of respiratory gaseous exchange by nervous system process
  cell_types:
  - preferred_term: brainstem respiratory neuron
    term:
      id: CL:2000029
      label: central nervous system neuron
  locations:
  - preferred_term: brainstem
    term:
      id: UBERON:0002298
      label: brainstem
  downstream:
  - target: Respiratory depression
    description: Suppressed central respiratory drive manifests as hypoventilation.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "brain-stem opioid receptors modulate respiratory responses to hypercarbia and hypoxemia"
    explanation: Supports mu-opioid suppression of the brainstem ventilatory response to hypercarbia and hypoxia.
  - reference: PMID:35965031
    reference_title: The pathophysiology of opioid-induced respiratory depression.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "respiratory depression, which can lead to lethal overdose if not treated"
    explanation: Supports opioid suppression of respiration as the lethal mechanism.
- name: Parasympathetic Pupillary Constriction
  role: effector
  biological_scale: TISSUE
  description: >-
    Mu-opioid action at the Edinger-Westphal nucleus increases parasympathetic
    outflow to the iris sphincter, constricting the pupil.
  locations:
  - preferred_term: iris sphincter muscle
    term:
      id: UBERON:0001607
      label: sphincter pupillae
  downstream:
  - target: Miosis
    description: Increased parasympathetic tone to the iris sphincter produces pinpoint pupils.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "receptors in the Edinger-Westphal nucleus of the oculomotor nerve control pupillary constriction"
    explanation: Supports mu-opioid action at the Edinger-Westphal nucleus driving pupillary constriction.
- name: Reduced Gastrointestinal Motility
  role: effector
  biological_scale: TISSUE
  description: >-
    Agonism of enteric and central mu-opioid receptors slows peristalsis and
    reduces gut motility.
  biological_processes:
  - preferred_term: peristalsis
    modifier: DECREASED
    term:
      id: GO:0030432
      label: peristalsis
  cell_types:
  - preferred_term: enteric neuron
    term:
      id: CL:0007011
      label: enteric neuron
  downstream:
  - target: Gastrointestinal dysmotility
    description: Slowed peristalsis manifests as reduced bowel motility.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Opioid agonists bind to receptors in the gastrointestinal tract to decrease gut motility."
    explanation: Supports mu-opioid agonism reducing gastrointestinal motility.
phenotypes:
- name: Respiratory depression
  description: >-
    Hypoventilation with a reduced respiratory rate and depth and a blunted
    chemoreceptor drive; the defining feature of opioid toxicity. A respiratory
    rate at or below 12 breaths per minute in a patient who is not asleep is
    strongly suggestive.
  phenotype_term:
    preferred_term: Respiratory depression
    term:
      id: HP:0002791
      label: Hypoventilation
  sequelae:
  - target: Respiratory arrest
    description: Progressive, unrelieved hypoventilation culminates in apnea and respiratory arrest.
  - target: Hypoxemia
    description: Hypoventilation lowers arterial oxygen saturation.
  - target: Noncardiogenic pulmonary edema
    description: Failure of oxygenation later in the course is often due to pulmonary edema.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The sine qua non of opioid intoxication is respiratory depression."
    explanation: States that respiratory depression is the defining feature of the toxidrome.
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "A respiratory rate of 12 breaths per minute or less in a patient who is not in physiologic sleep strongly suggests acute opioid intoxication, particularly when accompanied by miosis or stupor."
    explanation: Gives the clinical threshold that defines the respiratory depression phenotype.
- name: Depressed consciousness
  description: Somnolence progressing through stupor to coma.
  phenotype_term:
    preferred_term: Depressed level of consciousness
    term:
      id: HP:0004372
      label: Reduced consciousness
  sequelae:
  - target: Hypothermia
    description: A persistently unresponsive patient in a cool environment loses heat.
  - target: Rhabdomyolysis
    description: Prolonged immobility in a stuporous patient compresses muscle, causing rhabdomyolysis.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "the classic toxidrome of apnea, stupor, and miosis suggests the diagnosis of opioid toxicity"
    explanation: Lists stupor (depressed consciousness) as a member of the classic triad.
- name: Miosis
  description: Bilateral pinpoint pupils. Characteristic but not sufficient alone for the diagnosis.
  phenotype_term:
    preferred_term: Miosis
    term:
      id: HP:0000616
      label: Miosis
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Miosis alone is insufficient to infer the diagnosis of opioid intoxication."
    explanation: Supports miosis as a toxidrome feature while noting it is not diagnostic alone.
- name: Gastrointestinal dysmotility
  description: >-
    Reduced bowel motility and hypoactive bowel sounds from opioid agonism on the
    gut; acutely a hypomotility rather than the chronic constipation of
    sustained opioid use.
  phenotype_term:
    preferred_term: Reduced gastrointestinal motility
    term:
      id: HP:0002579
      label: Gastrointestinal dysmotility
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Opioid agonists bind to receptors in the gastrointestinal tract to decrease gut motility."
    explanation: Supports the reduced-motility phenotype.
- name: Respiratory arrest
  description: Apnea from unrelieved hypoventilation; the terminal event of untreated poisoning.
  phenotype_term:
    preferred_term: Respiratory arrest
    term:
      id: HP:0005943
      label: Respiratory arrest
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "a decline in respiratory rate culminating in apnea"
    explanation: Supports progression of respiratory depression to apnea (respiratory arrest).
- name: Noncardiogenic pulmonary edema
  description: >-
    Pulmonary edema appearing later in the clinical course, a major contributor
    to failure of oxygenation; one proposed mechanism is attempted inspiration
    against a closed glottis lowering intrathoracic pressure and causing fluid
    extravasation.
  phenotype_term:
    preferred_term: Noncardiogenic pulmonary edema
    term:
      id: HP:0100598
      label: Pulmonary edema
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "pulmonary edema is present in nearly all fatal cases of opioid overdose"
    explanation: Supports pulmonary edema as a frequent and serious feature of fatal poisoning.
  - reference: PMID:24144776
    reference_title: "The large spectrum of pulmonary complications following illicit drug use: features and mechanisms."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Non-cardiogenic pulmonary edema has been attributed to heroin, despite debated mechanisms including attempted inspiration against a closed glottis"
    explanation: Independently attributes non-cardiogenic pulmonary edema to opioids and names the closed-glottis mechanism.
- name: Hypothermia
  description: Low body temperature, typically from a prolonged unresponsive state in a cool environment.
  phenotype_term:
    preferred_term: Hypothermia
    term:
      id: HP:0002045
      label: Hypothermia
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Hypothermia may arise from a persistently unresponsive state in a cool environment"
    explanation: Supports hypothermia as a secondary consequence of the unresponsive state.
- name: Hypoxemia
  description: Low arterial oxygen saturation from hypoventilation, often compounded later by pulmonary edema.
  phenotype_term:
    preferred_term: Hypoxemia
    term:
      id: HP:0012418
      label: Hypoxemia
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "an oxygen saturation of less than 90% while the patient is breathing ambient air"
    explanation: Supports the failure of oxygenation (hypoxemia) that follows opioid hypoventilation.
- name: Rhabdomyolysis
  description: >-
    Muscle breakdown, with myoglobinuric renal failure and compartment syndrome,
    from prolonged immobile compression during an opioid-induced stupor.
  phenotype_term:
    preferred_term: Rhabdomyolysis
    term:
      id: HP:0003201
      label: Rhabdomyolysis
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "persons who have been lying immobile in an opioid-induced stupor may be subject to rhabdomyolysis, myoglobinuric renal failure, and the compartment syndrome"
    explanation: Supports rhabdomyolysis, myoglobinuric renal failure, and compartment syndrome as complications of the immobile stuporous state.
- name: Seizure
  description: >-
    Seizures are not part of the core mu-opioid toxidrome but occur with overdose
    of specific agents (tramadol, propoxyphene, meperidine), so this phenotype is
    agent-scoped and is not wired to the central receptor cascade.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Seizures have been associated with overdose of tramadol, propoxyphene, and meperidine"
    explanation: Supports seizures as an agent-specific feature of certain opioids rather than a core toxidrome feature.
environmental:
- name: Opioid agonist exposure
  exposure_term:
    preferred_term: exposure to mu-opioid receptor agonist
    term:
      id: ECTO:9001896
      label: exposure to mu-opioid receptor agonist
  description: >-
    Exposure to an opioid agonist in excess of tolerance -- therapeutic,
    recreational, iatrogenic, or accidental, including pediatric ingestion of
    agents meant for adults -- is the cause of the toxidrome.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices"
    explanation: Supports opioid exposure through prescribing, misuse, and administration as the cause of the toxidrome.
  influences_mechanisms:
  - target: Systemic Opioid Exposure
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Absorption of an opioid agonist establishes the systemic exposure that
      reaches central mu-opioid receptors.
    evidence:
    - reference: PMID:22784117
      reference_title: Management of opioid analgesic overdose.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: REVIEW_SYNTHESIS
      snippet: "Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices"
      explanation: The exposure routes that establish the systemic opioid burden.
- name: Co-ingested benzodiazepines or other sedative-hypnotics
  exposure_term:
    preferred_term: exposure to sedative
    term:
      id: ECTO:9001748
      label: exposure to sedative
  description: >-
    Benzodiazepines and other sedative-hypnotics taken with opioids potentiate
    respiratory depression and are strongly associated with death from opioid
    overdose; they do not cause the toxidrome alone but deepen it.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "sedative hypnotic agents (e.g., benzodiazepines) that have been strongly associated with death from opioid overdose"
    explanation: Supports co-ingested benzodiazepines as a potentiator of fatal opioid overdose.
  influences_mechanisms:
  - target: Respiratory depression
    environmental_effect: EXACERBATES
    causal_link_type: DIRECT
    description: >-
      Co-ingested sedative-hypnotics deepen opioid respiratory depression,
      raising the risk of fatal hypoventilation.
    evidence:
    - reference: PMID:22784117
      reference_title: Management of opioid analgesic overdose.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: REVIEW_SYNTHESIS
      snippet: "sedative hypnotic agents (e.g., benzodiazepines) that have been strongly associated with death from opioid overdose"
      explanation: Supports potentiation of fatal respiratory depression by co-ingested sedative-hypnotics.
treatments:
- name: Naloxone
  description: >-
    Competitive mu-opioid receptor antagonist and the antidote; it reverses the
    respiratory depression and the full toxidrome. Its duration of action is
    shorter than that of many opioids, so re-sedation can occur and observation
    is required. In opioid-dependent patients, low doses titrated to breathing
    can restore ventilation without precipitating withdrawal.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: naloxone
      term:
        id: CHEBI:7459
        label: naloxone
  target_mechanisms:
  - target: Central Mu-Opioid Receptor Overactivation
    description: Naloxone competitively antagonizes the mu-opioid receptor, reversing the toxidrome.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Naloxone, the antidote for opioid overdose, is a competitive mu opioid-receptor antagonist that reverses all signs of opioid intoxication."
    explanation: States naloxone's mechanism and that it reverses the toxidrome.
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "its apparent duration of action is 20 to 90 minutes, a much shorter period than that of many opioids"
    explanation: Supports the re-sedation risk and the need for observation.
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "patients with opioid tolerance frequently have a response to low doses of naloxone that are sufficient to restore breathing without provoking withdrawal"
    explanation: Supports low-dose titration restoring ventilation without precipitating withdrawal in dependent patients.
- name: Assisted ventilation and airway support
  description: >-
    Bag-valve-mask ventilation and airway positioning restore oxygenation in the
    apneic or severely hypoventilating patient and are first-line alongside or
    ahead of naloxone.
  treatment_term:
    preferred_term: assisted ventilation
    term:
      id: NCIT:C70909
      label: Mechanical Ventilation
  target_mechanisms:
  - target: Respiratory depression
    description: Mechanical ventilation substitutes for the suppressed respiratory drive.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Patients with apnea need a pharmacologic or mechanical stimulus in order to breathe."
    explanation: Supports mechanical ventilation as a core response to opioid-induced apnea.
diagnosis:
- name: Clinical toxidrome recognition
  description: >-
    The diagnosis is clinical, inferred from the triad of depressed
    consciousness, respiratory depression, and miosis together with the history
    and vital signs; the findings are not all consistently present.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Although the classic toxidrome of apnea, stupor, and miosis suggests the diagnosis of opioid toxicity, all of these findings are not consistently present."
    explanation: States the clinical triad and its inconsistency, the basis of diagnosis.
- name: Therapeutic response to naloxone
  description: >-
    Reversal of respiratory depression by naloxone supports the diagnosis;
    failure to respond to escalating doses up to 15 mg argues against opioid
    poisoning as the cause.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "If there is no abatement in respiratory depression after the administration of 15 mg of naloxone, it is unlikely that the cause of the depression is opioid overdose."
    explanation: Supports the naloxone response as a near-diagnostic test.
differential_diagnoses:
- name: Clonidine and imidazoline toxicity
  description: >-
    The classic pharmacologic mimic of the opioid toxidrome. Central
    alpha-2-adrenergic agonism from clonidine (and imidazoline decongestants)
    produces CNS depression, miosis, and respiratory depression that look like
    opioid poisoning, and it may even partially respond to naloxone. It is a
    frequent cause of accidental pediatric exposure.
  distinguishing_features:
  - Prominent bradycardia and hypotension accompany the CNS depression and miosis in clonidine toxicity.
  - Reversal of CNS depression by naloxone, when it occurs in clonidine toxicity, typically requires higher-than-standard doses and is inconsistent.
  evidence:
  - reference: PMID:41292070
    reference_title: "Pediatric Clonidine Toxicity: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Clonidine toxicity mimics an opioid toxidrome, often presenting with CNS depression, miosis, bradycardia, and hypotension."
    explanation: States directly that clonidine toxicity mimics the opioid toxidrome and names the distinguishing autonomic features.
  - reference: PMID:41292070
    reference_title: "Pediatric Clonidine Toxicity: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "naloxone may be beneficial in reversing CNS depression, though higher-than-standard doses are often required"
    explanation: Supports the partial, high-dose naloxone response that distinguishes clonidine from opioid toxicity.
- name: Sedative-hypnotic toxidrome
  description: >-
    Overdose of benzodiazepines, barbiturates, ethanol, antipsychotics, or
    anticonvulsants depresses consciousness and can even cause miosis, but it
    lacks the respiratory depression that defines opioid toxicity. Benzodiazepines
    are also a common co-ingestant that worsens opioid overdose.
  distinguishing_features:
  - The respiratory depression that defines opioid toxicity is usually absent in sedative-hypnotic overdose.
  - Sedative-hypnotic overdose does not respond to naloxone.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "overdose from antipsychotic drugs, anticonvulsant agents, ethanol, and other sedative hypnotic agents can cause miosis and coma, but the respiratory depression that defines opioid toxicity is usually absent"
    explanation: Gives the overlap (miosis and coma) and the key distinguishing feature (respiratory depression usually absent).
- name: Cholinergic toxidrome (organophosphate or carbamate poisoning)
  disease_term:
    preferred_term: organophosphate poisoning
    term:
      id: MONDO:0800386
      label: organophosphate poisoning
  description: >-
    Organophosphate and carbamate poisoning also produces miosis and depressed
    consciousness, but adds a cholinergic excess picture (bradycardia,
    hypersecretion, fasciculations, seizures) that opioid poisoning does not, and
    it does not respond to naloxone. dismech curates it separately as
    Organophosphate_Poisoning.
  distinguishing_features:
  - Cholinergic toxidrome adds bradycardia, muscle fasciculations, and seizures to the miosis, none of which belong to opioid poisoning.
  - It is treated with atropine and an oxime, not naloxone.
  evidence:
  - reference: PMID:32626615
    reference_title: "Organophosphate Poisoning: Demographics, Severity Scores and Outcomes From National Poisoning Control Centre, Karachi."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "severe such as bradycardia, miosis, fasciculations, seizures and altered level of consciousness"
    explanation: Shows the cholinergic toxidrome shares miosis and depressed consciousness with opioid poisoning but adds bradycardia and fasciculations.
- name: Pontine hemorrhage
  description: >-
    A structural, non-toxicological mimic: pontine (brainstem) hemorrhage can
    produce pinpoint pupils and coma identical to opioid poisoning, but with
    focal neurological signs and no response to naloxone, and is diagnosed on
    imaging.
  distinguishing_features:
  - Pontine hemorrhage shows focal signs such as gaze deviation and hemiplegia, which opioid poisoning does not.
  - It is confirmed on CT or MRI showing hemorrhage in the pons.
  evidence:
  - reference: PMID:31246723
    reference_title: "Fatal Intracerebral Hemorrhage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL): A Case Report."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glasgow Coma Scale (GCS) of 7 (E2, V1, M4), left gaze deviation, pinpoint pupils, and left hemiplegia"
    explanation: A pontine hemorrhage presenting with pinpoint pupils and coma (mimicking opioid toxicity) but with focal signs that distinguish it.
  - reference: PMID:31246723
    reference_title: "Fatal Intracerebral Hemorrhage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL): A Case Report."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "Computed tomographic scan of the head revealed acute hemorrhage in the right pons"
    explanation: Ties the pinpoint-pupils-and-coma presentation to a hemorrhage located in the pons, confirmed on imaging.
prevalence:
- population: United States (2010, National Poison Data System)
  measure_type: UNKNOWN
  prevalence_class: COMMON
  notes: >-
    Surveillance count, not a population rate: the National Poison Data System
    recorded more than 107,000 opioid-analgesic exposures and more than 27,500
    related health-care admissions in 2010.
  evidence:
  - reference: PMID:22784117
    reference_title: Management of opioid analgesic overdose.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "reported more than 107,000 exposures to opioid analgesics, which led to more than 27,500 admissions to health care facilities"
    explanation: Quantifies the scale of opioid-analgesic poisoning in US surveillance data.
datasets: []

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Acute Opioid Poisoning · 2026-10-04T03:34:25Z · View source

New entry for the acute opioid poisoning toxidrome (MONDO:0018173), curated de novo after confirming no KB entry, stub, or claim issue, and distinct from the chronic Opioid_Use_Disorder entry (MONDO:0005530). Deep research via claude_code provider (lead-only, 4 refs verified, no needs_review); all snippets taken from freshly fetched caches. Models the mu-opioid receptor cascade: systemic opioid exposure -> central mu-opioid receptor overactivation (Gi-coupled, adenylate cyclase inhibition) -> brainstem respiratory center suppression (pre-Botzinger), cortical/thalamic arousal suppression, Edinger-Westphal parasympathetic pupillary constriction, and reduced GI motility -> seven causally wired phenotypes (respiratory depression, depressed consciousness, miosis, constipation, respiratory arrest, noncardiogenic pulmonary edema, hypothermia), all 7 connected. Four differential diagnoses per the user request: clonidine/imidazoline toxicity (the classic mimic, PMID:41292070), sedative-hypnotic toxidrome (respiratory depression absent, Boyer), cholinergic/organophosphate poisoning (MONDO:0800386-bound, miosis plus cholinergic excess, PMID:32626615), and pontine hemorrhage (structural mimic with focal signs, PMID:31246723). Treatments: naloxone (competitive MOR antagonist, target_mechanisms wired) and assisted ventilation. Evidence anchored on Boyer NEJM 2012 full-text review (PMID:22784117), Montandon OIRD review (PMID:35965031), and the DDx sources. 25/25 snippets verified; all terms validated; full offline gate suite green.

Claude Code ▸

Acute Opioid Poisoning (MONDO:0018173): Research Report

claude-haiku-4-5-20251001, claude-sonnet-5-5 9 citations 2026-10-04T03:21:49.984047

Acute Opioid Poisoning (MONDO:0018173): Research Report

Verification status. I ran three web searches in this session. Only these sources were actually retrieved: - PMID:35965031 (OIRD pathophysiology review, from its PubMed URL) - PMC8997313 and PMC8424565 (titles not shown in the results) - Frontiers in Neuroscience 2023, doi:10.3389/fnins.2023.1134842 - CDC provisional overdose figures, as relayed by news outlets - The intranasal naloxone and nalmefene results

Everything else is background knowledge, labelled [unverified]. It has no PMID and no snippet. Do not use any claim in this report as an evidence item until the reference is fetched with just fetch-reference. Ontology term names are given without CURIEs on purpose. Each needs a lookup (runoak or the term caches) before binding. The MONDO ID is as supplied in the template, and I did not check it.

1. Disease Information

Acute opioid poisoning is a toxic exposure disorder. An excess dose of an opioid agonist, or a dose that exceeds the person's tolerance, suppresses central respiratory drive and consciousness. The result is hypoventilation, hypoxia, and death if untreated. Opioids involved include heroin, illicit fentanyl and its analogues, methadone, oxycodone, morphine, and others.

Proximal cause of death: the review "The pathophysiology of opioid-induced respiratory depression" (PMID:35965031) and related results describe respiratory depression as the proximal cause of death in opioid overdose.
Identifiers: ICD-10 T40.0–T40.4 and T40.6 (poisoning), with X/Y intent codes [unverified]. MeSH "Opiate Overdose" [unverified]. No OMIM or Orphanet entry is expected.
Synonyms: opioid overdose, narcotic overdose, opiate intoxication, opioid toxidrome.
Data level: this is an aggregate, disease-level concept. Surveillance data come from death certificates and ED visits.

2. Etiology

Causal factor: an exposure to an opioid agonist that exceeds the patient's tolerance.
Illicit fentanyl is the dominant driver in the US. Synthetic-opioid deaths rose to about 76,282 in 2023 (CDC data via news summary).
Other routes are prescription misuse, therapeutic error, pediatric accidental ingestion, and polysubstance use.
Risk factors [unverified]:
Loss of tolerance after abstinence, for example after release from prison or detox.
Concurrent benzodiazepine, alcohol, or other CNS-depressant use.
Using alone, injection use, high prescribed dose, and respiratory or hepatic disease.
Contamination of the drug supply.
Genetic factors: none are causal. Pharmacogenomic variation in CYP2D6, CYP3A4, and OPRM1 may modulate individual risk [unverified].
Tolerance: tolerance to respiratory depression is less than complete and may develop more slowly than tolerance to euphoria. This is one reason experienced users are at relatively high overdose risk (search result summary).
Protective factors:
Take-home naloxone and bystander presence.
Medication for opioid use disorder (buprenorphine, methadone).
Supervised consumption sites [unverified].

3. Phenotypes

The classic opioid toxidrome is: - Depressed consciousness. - Respiratory depression (bradypnea or apnea). - Miosis (pinpoint pupils). - Hypoxemia and cyanosis.

Candidate phenotype terms to look up in HPO: coma/stupor, hypoventilation, apnea, bradypnea, miosis, cyanosis, bradycardia, hypotension, hypothermia, hypercapnia, respiratory acidosis, seizures (e.g. with tramadol or meperidine), muscle rigidity (e.g. fentanyl chest-wall rigidity), pulmonary edema, aspiration, rhabdomyolysis, anoxic brain injury.

Onset: acute, within minutes after IV or inhaled use and within hours after oral use [unverified].
Course: episodic. Severity is dose-dependent and the course is fluctuating, with possible recurrence of toxicity after naloxone wears off.
Frequencies: not reliably available. Fetch authoritative case-series data before assigning any percentages.
Quality of life: survivors may have hypoxic brain injury, but I found no sourced data.

4. Genetic/Molecular Information

No causal genes.
Pharmacological targets: OPRM1 (hgnc-bound, lowercase hgnc: form; look up the ID), with additional OPRD1 and OPRK1 activity.
Metabolizing enzymes: CYP3A4 (fentanyl), CYP2D6 (codeine, oxycodone), UGT2B7 (morphine).
Epigenetic and chromosomal findings: none relevant.

5. Environmental Information

Exposures: heroin, illicit fentanyl and its analogues, nitazenes, diverted prescription opioids.
Lifestyle factors: injection drug use and polysubstance use. Alcohol and benzodiazepines are potentiators.
Infectious agents: none are causal. Injection use carries secondary infection risk.
ECTO exposure terms: search ECTO for opioid, heroin, and fentanyl exposure terms. Do not assume a term exists or doesn't. Re-run the searches before writing any note.

6. Mechanism / Pathophysiology

Causal chain: 1. Opioid exposure at a dose above tolerance leads to high receptor occupancy of the mu-opioid receptor (MOR). Opioids produce inhibition at the chemoreceptors via mu opioid receptors and in the medulla via mu and delta receptors (search summary). 2. MOR is a Gi/o-coupled GPCR. Activation reduces cAMP and opens GIRK channels, causing hyperpolarization. It also closes voltage-gated Ca²⁺ channels, reducing neurotransmitter release [unverified]. 3. Neurons in the preBötzinger complex and in the parabrachial/Kölliker-Fuse pontine respiratory groups are inhibited [unverified]. Normal breathing requires the integration of rhythmogenic, modulatory, and sensory feedback mechanisms, and overdose can suppress all of them (search summary). 4. Chemoreflex responses to hypercapnia and hypoxia are blunted, so rate and tidal volume fall and the airway may be obstructed by loss of tone. 5. Hypoventilation causes hypercapnia, respiratory acidosis, and hypoxemia. 6. Hypoxemia leads to hypoxic-ischemic injury (brain, heart), arrhythmia, and cardiac arrest. This step is inferred from general physiology and not demonstrated in a retrieved source. 7. Branches: - Fentanyl-induced chest-wall rigidity may impair ventilation [unverified]. - Aspiration and non-cardiogenic pulmonary edema are described complications [unverified]. - Co-ingested sedatives add GABA-A potentiation, which is synergistic.

Candidate GO processes to look up: G protein-coupled opioid receptor signaling, regulation of respiratory rhythm / control of breathing, adenylate cyclase inhibition, regulation of membrane potential. Candidate cell types in CL: neurons of the preBötzinger complex (likely best bound as a generic neuron or respiratory-center neuron term), and carotid body glomus cells.

Omics and model-system sections (transcriptomics, proteomics, single-cell, etc.): none were found or searched. They are not applicable at this point.

7. Anatomical Structures Affected

Primary: brainstem respiratory centres (medulla, pons), cerebral cortex (sedation), and peripheral chemoreceptors (carotid body).
Secondary:
Lungs (aspiration, edema).
Heart (hypoxic arrhythmia).
Brain (anoxic injury).
Kidney (rhabdomyolysis).
GI tract (reduced motility).
Laterality: bilateral and systemic.
Subcellular localization: plasma membrane (receptor).

8. Temporal Development

Onset is acute, from minutes to hours.
It is self-limited if the person survives. Duration tracks opioid pharmacokinetics. Naloxone's duration is roughly 30–120 minutes (search summary), which can be shorter than a long-acting opioid's effect and allow re-sedation.
Critical period: the minutes after apnea begins, when reversal is most effective. Brain injury accumulates with hypoxia time.

9. Inheritance and Population

Inheritance: not applicable (non-genetic).
Epidemiology (US, CDC provisional data via news reports; the primary CDC pages were not fetched):
All drug overdose deaths fell from 110,037 in 2023 to 80,391 in 2024, a 26.9% decline (source).
Synthetic-opioid deaths fell from 76,282 to 48,422 over the same period.
In 2025, deaths fell a further ~14% to about 69,973. Opioid-involved deaths were about 44,564, down from 55,296 (source).
CDC attributes the decline in part to naloxone distribution and treatment access.
Demographics: the sex ratio is male-predominant (about 2:1) [unverified]. Peak ages are 25–54 [unverified]. Geography and ethnicity vary; check CDC WONDER.
Encoding for the KB: use measure_type: ANNUAL_INCIDENCE with a rate_denominator, and avoid a qualitative prevalence tier. Convert only from the primary CDC source.

10. Diagnostics

Clinical diagnosis: the toxidrome of coma, respiratory depression, and miosis, with response to naloxone as a diagnostic aid.
Labs: blood gas (hypercapnia, acidosis), glucose, CK, ECG, co-ingestant screens. Urine immunoassays often miss fentanyl and nitazenes, so use specific confirmation [unverified].
Imaging: CXR for aspiration or edema; CT/MRI if anoxic injury is suspected.
Differential: other sedative-hypnotic and alpha-2 agonist toxicity, hypoglycemia, stroke, postictal state, sepsis, hypothermia.
Genetic testing and screening are not applicable.

11. Outcome/Prognosis

Prognosis depends on speed of reversal and the duration of hypoxia.
Complications: anoxic brain injury, aspiration pneumonia, rhabdomyolysis, compartment syndrome, post-reversal pulmonary edema. All are [unverified].
Nonfatal overdose strongly predicts later overdose death [unverified].
Fatality is dominated by synthetic opioids, as in the CDC figures above.
Quantitative survival and prognostic-factor data were not retrieved.

12. Treatment

Airway and ventilation (bag-mask ventilation, oxygen) are first-line. This is an established principle, but no source was fetched. Candidate NCIT clinical-intervention terms: supportive care (look up) and artificial or mechanical ventilation.
Naloxone is the competitive MOR antagonist.
Higher-concentration (2 mg/mL) intranasal naloxone has similar efficacy to IM naloxone. The odds of needing a rescue dose were 2.17 times higher with intranasal than IM/IV (search result).
Encode as pharmacotherapy (NCIT:C15986, from the repo guidance) with a therapeutic agent. Look up naloxone in CHEBI.
Nalmefene: intranasal nalmefene (Opvee) was FDA-approved in May 2023. It has a longer duration of action than naloxone (UIC summary).
Risks: naloxone can precipitate withdrawal in dependent patients. Observation is needed for re-sedation, especially with long-acting opioids [unverified].
Experimental: none retrieved. A ClinicalTrials.gov search is pending.
Long-term treatment: medication for opioid use disorder (buprenorphine, methadone, naltrexone) is a secondary-prevention measure [unverified].

13. Prevention

Primary: safe opioid prescribing and the reduction of illicit supply.
Secondary: take-home naloxone, MOUD initiation, and fentanyl test strips and drug checking [unverified].
Tertiary: post-overdose outreach and linkage to care.
Public health: naloxone distribution is credited by CDC, in part, for the decline in deaths (source).
Immunization (e.g. fentanyl vaccines) is investigational. I did not find a source.

14. Other Species / Natural Disease

Opioid toxicosis occurs in dogs, cats, and horses, most often through accidental ingestion [unverified]. Naloxone is used in veterinary practice [unverified].
Not zoonotic.
Look up NCBITaxon IDs for dog (Canis lupus familiaris) and others at curation time.
Comparative physiology: respiratory depression is conserved across mammals. Mu-opioid receptor pharmacology is broadly conserved. No source was retrieved.

15. Model Organisms

Rodent (mouse, rat):
Opioid-induced respiratory depression is measured by plethysmography and blood-gas analysis. Genetic models include MOR knockout, which is protected from OIRD [unverified].
Brainstem-slice preparations are used to study the preBötzinger complex [unverified].
Limitations: rodents differ from humans in dose, tolerance, and polysubstance patterns. Fidelity and divergences should be recorded per link (modeled_mechanisms) when curated.
Resources: MGI, IMPC. Not searched.
A review of OIRD pathophysiology is available at the Frontiers in Neuroscience 2023 article, which I found but did not read.

Curation Next Steps

Run just fetch-reference for PMID:35965031 and any other primary papers you intend to cite.
Take exact snippets from the cached files only.
Look up every ontology term (HPO, GO, CL, UBERON, CHEBI, NCIT, ECTO) with runoak or the term caches.
Get the primary CDC pages (WONDER, NCHS VSRR) for epidemiology.
Search for sourced frequencies, prognosis, and mortality data, which are currently missing.

Sources

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome	Count
References checked	4
Resolved	4
Unresolved (possible confabulation)	0
Unverifiable	0
Quoted claims checked	1
Quoted claims found in source	1
Quoted claims not found in source	0
References weighed for topical relevance	4
On topic	2
Off topic	0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	2
Resolved	2
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	0

Every term resolved, and every label the report gave matched.

Acute Opioid Poisoning

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Pathophysiology

Pathograph

Phenotypes

Medical Actions

Environmental Factors

Diagnosis

Prevalence

Differential Diagnoses

Source YAML

References & Deep Research

Deep Research

Acute Opioid Poisoning (MONDO:0018173): Research Report

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Curation Next Steps

Sources

Reference Validation

Term Validation