Nicotine toxicity

Background

• Nicotine is an alkaloid. Alkaloids are a group of compounds that are typically produced by plants to discourage animals from eating them.
• Nicotine commonly comes from the tobacco plant
• There are 66 other plants from which nicotine can be obtained.
• These plants are apart of the nightshade family (include eggplant, tomato, potato, green pepper)
• Free-base nicotine is used as an insecticide since it is highly poisonous and reactive with oxygen and other chemicals, destroying cells and tissues.

Delivery Mechanisms

• Inhalation
• Cigarettes (~1.0mg)
• Vaporization
• Nasal spray
• Oral Chew
• Gum
• Lozenges
• Tablets
• Transdermal Patch
• Oral bioavailability is 30-40% because of presystemic metabolism and spontaneous vomiting

Receptor Activity

• There are 2 types of neuronal nicotinic receptors, cns and pns (α-bungarotoxin). These are ligand gated ion channels.
• Nicotine binds to these receptors that are located on nerve terminals or on axons on cell bodies, α-bungarotoxin, polypeptide that binds irreversibly to nicotinic receptors with a high binding affinity
• Nicotinic acetylcholine receptors are made up of α and beta subunits that form a pentameric motif
• Different combinations of these subunits have different effects in the body.
• Interferes with the binding of acetylcholine, binds to the receptor which then opens the ion channel releasing sodium into the cell.
• Nicotine’s most important effect is the activation of the reward pathway which is caused by dopamine release.

Clinical Features

Postive	Negative
Anxiolysis	Gastrointestinal Distress
Congnitive Enhancement	Hypothermia
Cerebrovasodilation	Emesis
Neuroprotection	Hypertension
Analgesia	Seizures
Antipscyhotic	Respiratory Distress

Eye pain

• Nicotine is also an irritant and eye pain is a frequent complaint

Fasciculations

• Due to the neuromuscular nicotinic activation

Hypersalivation

At high doses nicotine will activate muscarinic receptors

Differential Diagnosis

• Anticholinergic Toxicity
• Organophosphate Toxicity
• Sympathomimetic Toxicity
• Neuroleptic Malignant Syndrome (NMS)
• Serotonin Syndrome
• Sepsis

SLUDGE Syndrome

• Carbamate toxicity
• Mushroom toxicity, especially:
  • Amanita muscaria
  • Inocybe
  • Clitocybe
• Organophosphate toxicity
• Nerve agent
  • Sarin
  • VX
  • Novichok agent
• Nicotine toxicity (look alike)
• Acetylcholinesterase inhibitor overdose (e.g in myasthenia gravis or post anesthesia reversal)

Evaluation

If there are also muscarinic effects then strongly consider an broader treatment for Cholinergic Syndrome

Management

Decontamination

• Providers should wear appropriate PPE during decontamination.
  • Neoprene or nitrile gloves and gown (latex and vinyl are ineffective)
• Dispose of all clothes in biohazard container
• Wash patient with soap and water

Supportive Care

• IVF, O2, Monitor
• Aggressive airway management is of utmost importance.
  • Intubation often needed due to significant respiratory secretions / bronchospasm.
  • Use nondepolarizing agent (Rocuronium or Vecuronium)
  • Succinylcholine is absolutely contraindicated
• Benzodiazepines for seizures

Antidotes

• Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism
• For exposure to nerve agents, manufactured IM autoinjectors are available for rapid administration:
  • Mark 1
    • Contains 2 separate cartridges: atropine 2 mg + 2-PAM 600 mg
    • Being phased out with newer kits
  • DuoDote
    • Single autoinjector containing both medications
    • Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg

Antidotes

Atropine

• First-line antidote — muscarinic antagonist; treats bronchorrhea, bronchospasm, bradycardia, and secretions
• Does NOT reverse nicotinic symptoms (weakness, fasciculations, paralysis)
• Starting dose: Atropine 1-2 mg IV (double q5min until atropinization) IV — May need 100+ mg in first 24h; endpoint is drying of secretions
• Pediatric: Atropine 0.02-0.05 mg/kg IV (min 0.1 mg), double q5min IV
• Doubling protocol: If inadequate response after 5 minutes, double the dose (1 → 2 → 4 → 8 → 16 mg...) until atropinization is achieved
• Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported
• Endpoints of adequate atropinization (goal of therapy):
  • Drying of bronchial secretions (most important endpoint)
  • Heart rate >80 bpm
  • Systolic BP >80 mmHg
• Do NOT target: Fully dilated pupils, absent bowel sounds, or HR >150 — these indicate atropine toxicity
• After initial atropinization: Consider atropine infusion (10-20% of loading dose per hour) to maintain effect
• Optimize oxygenation before giving atropine to reduce risk of dysrhythmias (though in resource-limited settings, do not withhold atropine waiting for oxygen)

Pralidoxime

• AKA 2-PAM
• Oxime that reactivates phosphorylated AChE → primarily reverses nicotinic symptoms (weakness, fasciculations, respiratory muscle paralysis)
• Must give atropine BEFORE pralidoxime to prevent worsening of muscarinic symptoms
• Must be given before aging occurs (see aging table above)
• Pralidoxime 1-2 g IV over 15-30 min, then 8-10 mg/kg/hr infusion (or repeat bolus in 1 hr) IV
• Pediatric: Pralidoxime 20-50 mg/kg IV, then 5-10 mg/kg/hr infusion IV
• Continue until clinical improvement or patient is off ventilator
• Controversies:
  • Evidence for benefit of pralidoxime is inconsistent; several meta-analyses have not shown clear mortality benefit when added to atropine
  • However, per AHA 2023 guidelines and expert consensus, oximes should still be given for significant OP poisoning, particularly when fasciculations, weakness, or paralysis are present
  • Efficacy depends on timing (before aging), dose, and the specific OP compound involved
• Caution: Administer slowly — rapid IV push can cause hypertensive crisis, cardiac arrest

Disposition

• Depending on severity of symptoms patients can be admitted for continued aggressive supportive care or discharged if symptoms all resolve in the ED

See Also

Electronic cigarettes