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

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

Sources

• PubMed: pathophysiology of opioid-induced respiratory depression (PMID:35965031)
• PMC8997313
• PMC8424565
• Frontiers in Neuroscience 2023
• CDC 2024 overdose data, news summary
• CDC 2025 overdose data, news summary
• Intranasal vs IM/IV naloxone summary
• Intranasal naloxone vs nalmefene (UIC)
• 2 Minute Medicine

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

All extracted references resolved successfully.

Term Validation

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

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