• For adults and children aged 6 years and over, serious toxicity is unlikely to occur from a single ingestion of less than 75mg/kg of paracetamol taken in <1/24
• For children aged under 6 years, serious toxicity is unlikely to occur from a single ingestion of less than 150mg/kg of paracetamol taken in <1/24
• Although the benefit of gastric decontamination is uncertain, activated charcoal should be considered if presentation within 1/24 of ingesting paracetamol >150mg/kg.
• Acetylcysteine treatment should commence:
  • in patients whose paracetamol level is on or above treatment graph line
  • present ≤8/24 with OD of >150 mg/kg of paracetamol if delay of ≥8/24 (post OD) obtaining paracetamol level
  • present 8–24/24 post ingestion of an acute overdose of >150mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available
  • present >24/24 post ingestion of an overdose if
    • clearly jaundiced or have hepatic tenderness
    • raised ALT (patients with chronically elevated ALT should be discussed with the National Poisons Information Service)
    • INR >1.3 (in the absence of another cause)
    • paracetamol concentration is detectable.

• in paracetamol overdose, glucuronidation and sulfation pathways of paracetamol metabolism are saturated, with CYP450 pathway taking greater role, increasing toxic metabolites which deplete glutathione reserves normally responsible for detoxification.
• NAC repletes glutathione reserves by providing cysteine, an essential precursor in glutathione production.
• NAC by itself also binds to the toxic metabolites and scavenges free radicals.
• NAC increases oxygen delivery to tissues, increases mitochondrial ATP production, and alters microvascular tone to increase blood flow and oxygen delivery to the liver etc.

• IV - anaphylactoid reactions in <20%
• oral - vomiting ~30%

• ingestion >150mg/kg of paracetamol in any 24/24 period poses risk of serious toxicity - commence acetylcysteine immediately
• acetylcysteine can then be discontinued if patient considered not at risk:
  • ≥4/24 since the last paracetamol ingestion AND
  • no symptoms suggesting liver damage AND
  • paracetamol concentration <10mg/L AND
  • ALT is within the normal range AND
  • INR is ≤1.3

https://bnf.nice.org.uk/treatment-summary/poisoning-emergency-treatment.html
CUH paracetamol OD guidelines Dec 2020

• extremely variable presentation but potentially life-threatening syndrome that is precipitated by serotonergic agents
• over-activation of both the peripheral and central postsynaptic 5HT-1A and especially 5HT-2A receptors
• Classic Triad:
  1. mental status changes
  2. neuromuscular hyperactivity
  3. autonomic hyperactivity.

• clinical course may be divided into three phases:
  • Prodromal - may last for months/years. Mild nausea and abdo discomfort
  • Hyperemetic - marked by paroxysms of intense and unbearable/incapacitating vomiting.
    • Abdo pain is usually mild/moderate but may be more severe.
    • patients often resort to regular hot baths/showers which offer rapid relief
    • usually lasts ≤48/24
    • Supportive management - Fluids, anti-emetics the latter of which often fail. Haloperidol can be useful
  • Recovery phase.

GI effects result from activation of CB1 receptors:

• inhibition of gastric acid secretion
• lower esophageal sphincter relaxation
• altered intestinal motility
• visceral pain, and inflammation

alcohol_misuse_and_withdrawal_guideline.pdf

Methanol toxicity - StatPearls 2021
Emcrit review of toxic alcohol poisoning 2020

• Methanol (CH3OH) - a toxic alcohol (includes: methanol, ethylene glycol, and isopropyl alcohol) found in various household and industrial agents.
• Products that contain methanol include windshield washer fluid, gas line antifreeze, carburetor cleaner, copy machine fluid, perfumes, food warming fuel, and other types of fuels
• primary treatments are either ethanol or fomepizole, and unlike ethylene glycol toxicity, dialysis is often recommended
• oxidises to formic acid which is not easily excreted - accounts for the associated anion gap metabolic acidosis and end-organ damage.
• potentially lethal dose = 30 to 240 mL or 1g/kg
• Permanent visual damage may occur with minimum ingestion of 30mL - said to be due to formic acid oxidative stress
• parkinsonian-like symptomatology associated with observed basal ganglia lesions, particularly in the putamen and globus pallidus.
• usually present with abdo pain, N&V, hyperventilation, CNS depression
• visual symptoms - blurry vision, decreased visual acuity, photophobia, and “halo vision.”
• salicylate and ethanol levels important - in Ix of metabolic acidosis but also because ethanol inhibits methanol metabolism
• anion gap develops later therefore observation for at least 12/24
• There is an inverse relationship between osmolar gap and anion gap. The osmolar gap should be elevated early after ingestion of alcohol and progressively decrease as anion gap metabolic acidosis develops. This increased osmolality is due to the abundance of the osmotically active parent compound, and the acidosis is due to the production of its metabolites. When calculating the osmolar gap, it is important to include ethanol in the calculation since ethanol is also osmotically active. The equation to measure the osmolar gap is as follows:
  • Serum osmolality = [2(Na) + BUN/1.6 + Glucose/18 + Ethanol/4.6]
• Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and theoretically, folate. Fomepizole is the antidote for toxic alcohols, and its mechanism of action is the inhibition of alcohol dehydrogenase. Ethanol may also be utilized therapeutically to inhibit alcohol dehydrogenase when fomepizole is unavailable.

https://www.ncbi.nlm.nih.gov/books/NBK537009/

• Conclusions: Systemic poisoning with ethylene glycol or methanol results in hospitalisation at least 2–3 times per week on average in the UK.
• No difference in outcome was detected between ethanol and fomepizole-treated patients, but ethanol was associated with more frequent adverse reactions.

Mx of ethylene glycol and Methanol review by Poison Centre 2016

• N2O is a short-acting anaesthetic agent
• also used as an aerosol spray propellant in food preparation (eg cream ‘chargers’ or cannisters for manufacturing whipped cream)
• Chronic N2O exposure results in dose-dependent inactivation of vitamin B12 - a co-factor required for methionine synthesis.
  • Nitrous oxide oxidises the cobalt moiety on B12 and renders it inactive, irreversibly blocking methionine synthase leading to depletion of methionine and tetrahydrofolate
  • these are required for DNA synthesis and maintenance of nervous system myelin sheaths
  • creates a clinical picture of pernicious anaemia with demyelination and bone marrow suppression and MRI will demonstrate Subacute Combined Degeneration

• short-lived confusion, hallucinations or falls as a result of temporary ataxia.
• Pneumothorax may rarely occur as the result of forceful inhalation
• Chronic use results in insidious onset of:
  • Altered sensation
  • Muscle weakness
  • Gait disturbance
  • Rarely: depression, irritability, personality change

• Sensory deficits - dermatomal but can be patchy (similar to multiple sclerosis)
• Impaired proprioception and coordination (affects dorsal columns first)
• Sensory ataxia
• Reduced power in limbs
• Hyporeflexia

• B12
• methionine

RCH nitrous misuse
https://www.emra.org/emresident/article/nitrous-oxide-toxicity/

(Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome)
Drug rash with eosinophilia and systemic symptoms syndrome is a severe idiosyncratic drug reaction with a long latency period with a diverse array of clinical symptoms, anywhere from 2 to 8 weeks after initiating the offending drug

• often to anti-epileptic drugs
• seen with co-amoxyclav
• fever, rash, lymphadenopathy, haematological findings (eosinophilia, leukocytosis, etc.), and abnormal liver function tests, which can mimic viral hepatitis.
• cutaneous manifestation - morbilliform eruption, facial oedema, and mucous membrane involvement in nearly half of patients
• Visceral involvement (hepatitis, pneumonitis, myocarditis, pericarditis, nephritis, and colitis) is the major cause of morbidity and mortality. The life-threatening potential of DRESS syndrome is high and the mortality is estimated to be around 10 percent in multiple studies.
• Treatment is largely supportive and symptomatic; corticosteroids are often used, but the evidence regarding their effectiveness is scant.
• various criteria:

Serotonin review 2013
Cannabinoid Hyperemesis Syndrome
Cannabinoid Hyperemesis syndrome - Case report and review