Overview

Nicotine is the primary component of tobacco, obtained from the leaves of tobacco (Nicotiana tabacum), which produces craving & withdrawal effects in both humans and animals. It was named after Jean Nicot, who first introduced the Nicotiana tabacum to the French court in 1560.

The mode of administration is mainly through sniffing, chewing, and smoking. Nicotine is from the alkaloid (1-methyl-2-3-pyridylpyrrolidine) category, a major phytoconstituent responsible for addiction.

Acetylcholine receptors and dopaminergic receptors present in the brain are responsible for nicotine action. It stimulates presynaptic acetylcholine receptors to enhance acetylcholine release and metabolism. This stimulation will enhance activation of pharmacological changes, thereby causing nicotine addiction.¹

Nowadays, nicotinehad a huge influence, changes in the younger generation and as a whole as humanity. nicotine an entry substance for other abuse materials like heroin, ganja.

The toxic measure of nicotine is 40-60 mg. For adults, it is 0.8 -1mg /kg, for children, 1 mg/kg.

Nicotine poisoning is the consumption of toxic doses of nicotine, a chemical compound present in tobacco plants. Liquid nicotine is present in the E-cigarettes, a popular form of tobacco products responsible for the increased nicotine poisoning. Due to a smaller size, nicotine poisoning is more common in children. Vomiting, dizziness, confusion, unsteadiness, and increased salivation are the common symptoms.

Increased levels of nicotine in the whole body can lead to nicotine poisoning as a result of the use of pesticides containing nicotine or the accidental ingestion of tobacco or nicotine-containing plants.

In current times, due to the increased availability of liquid forms of tobacco (e-cigarettes) and pure nicotine forms in the markets, many concerns are being raised, as nicotine concentration is higher in such products than in traditional tobacco products. Nicotine in liquid form mainly causes nicotine poisoning.²

Nicotine can affect the nervous system and heart, and exposure to small levels can be fatal.³

The exposure to nicotine during adolescence will alter the structure and function of the developing brain. It will impair cognitive function like memory, attention, impulse control, etc.⁴

Nicotine is the substance that is responsible for tobacco addiction, which leads to a variety of health issues.

Mechanism of nicotine action in the nervous system

Nicotine is found in tobacco, a tertiary amine that consists of pyridine and pyrrolidine rings. It binds to nicotinic cholinergic receptors (nAChRs), acetylcholine receptors found in the brain. 

When a person smokes, the nicotine from the tobacco gets distilled and carried into the lungs through the smoke particles, where it gets absorbed into the pulmonary venous circulation. Then it enters the arterial circulation to the brain. Nicotine is rapidly absorbed by brain tissues. Then it binds to nAChRs, a ligand-gated ion channel.⁵

nAChRs have five subunits, found in both the central & peripheral nervous systems. There are nine 𝜶 and three 𝛽 receptor subunits present in the brain. The 𝛼𝛽₂ receptor subtype present in the brain is responsible for nicotine dependence. The 𝛽₂ subunits are linked to the dependence on nicotine.

Nicotine stimulates the nAChR receptor and releases various other neurotransmitters in the brain, mainly dopamine. Nicotine releases dopamine into the mesolimbic area, corpus striatum, and frontal cortex.

Other neurotransmitters like acetylcholine, norepinephrine, serotonin, GABA (aminobutyric acid) and endorphins are also released to activate the behavioral effects of nicotine.

Dopamine has a pleasurable experience; hence, this will cause the reinforcing effects of nicotine and drug abuse.

Repeated exposure to nicotine will improve the tolerance level and increase the number of nAChR binding sites in the brain.

Dose-dependent effects: from stimulation to inhibition

Low doses of nicotine produce anxiolytic-like behaviour by inhibiting the nAChRs, while higher doses will have an anxiogenic nature.⁶

Inhibition or stimulation of ꞵ₂ nAChRs is responsible for the anxiolytic-anxiogenic-like effects of nicotine.

The inhibition of 𝛽nAChRs will relieve anxiety in chronic smokers.

Neurological symptoms of nicotine poisoning 

Symptoms of nicotine poisoning will occur in two phases; it happens based on how much nicotine is used and the way of taking nicotine, like ingestion, drinking, patches, etc.

1. Initial phase: symptoms will appear within 15 minutes to 1 hour of nicotine ingestion. Vomiting is the most common symptom
2. Late phase: it occurs within 30 minutes to 4 hours²

Dizziness

Dizziness is an early sign of nicotine poisoning. It will stimulate the body to produce adrenaline, which raises the blood pressure, in turn reducing the supply of blood to the brain by constricting the blood vessels, resulting in a dizzy state.⁷

The contents present in e-cigarettes, like vaping, are dehydrating; hence, dehydration causes dizziness.

Confusion

This can be a symptom in people who are tobacco smokers & those who are in a stage of nicotine withdrawal. It is caused by an imbalance in neurotransmitter signaling in the brain as a result of metabolic derangements, acute stress response, and psychoactive medication.

It will alter the attention and cognitive function.

Seizures

Seizure is reported in people after high-dose exposure to nicotine vapes, nicotine patches, and fluid-containing nicotine vapes. This is due to the proconvulsive effect of nicotine that will activate nicotinic acetylcholine receptors (nAChRs) in the brain, hence neuronal hyperexcitability.

Teens and children are commonly affected even with low doses of nicotine because of their low body mass.⁸

Diagnosis and clinical evaluation

• Nicotine and its metabolic product, cotinine, can be easily detected in blood, urine, and saliva⁹
• Acute nicotine poisoning is diagnosed by an elevated blood nicotine level
• Ask patients about the use of e-cigarettes, especially the brand, the duration of vaping, and the frequency¹⁰
• Ask about the intentional or accidental swallowing of E-liquids, pesticides, or tobacco products
• Do a typical urine toxicology test
• Check for any early neurological signs within less than one hour of exposure, like agitation, fasciculations, and seizures
• Later, clinical signs of exposure are more than 4 hr. Check for lethargy, muscle paralysis, and coma¹¹

Treatment and management

1. Activated charcoal, a dose of 1 g/kg, is given to reduce the absorption of nicotine in the intestine in a hospital setting
2. Anticonvulsants like benzodiazepines are given for seizure treatment⁹
3. Injection of intravenous fluids (IV) for low blood pressure treatment
4. Atropine is given for reduced heart rate (bradycardia)
5. Oxygen supply through a ventilator in the case of respiratory failure
6. Instil supportive care for airway, breathing, and circulation, including cardiorespiratory monitoring
7. For significant skin exposure, wash the area with soap and water
8. Consult the pediatric team in the case of children when the exposure is large¹²

Prevention and public health considerations

• Public education is especially needed on the risk of high-concentration nicotine in e-liquids
• Keeping all tobacco products, e-cigarette devices, and e-liquid containers out of reach of children
• Make the nicotine-containing products less appealing and less accessible to youth & children
• Nicotine products should be stored in a safe, original container
• Make sure the proper packaging and sealing of nicotine products are used to avoid spilling
• Stop the use of nicotine products; seek a physician's help¹³

Summary

Nicotine poisoning can lead to a wide variety of neurological symptoms. Exposure will develop headache, dizziness, and confusion to severe outcomes such as seizure, respiratory failure, and coma.

Long-term exposure contributes to long-term neurocognitive impairment.

Early recognition of these neurological signs is critical, as timely intervention can reduce long-term impairments and hence improve patient outcomes.

Nicotine poisoning is mainly from e-liquids due to the high concentration of nicotine. To address this growing public health concern, there is a critical need for increased awareness among health care providers, caregivers and the public about the prevention strategies, which must be prioritised among adolescents and children.

Timely medical intervention will mitigate the neurological consequences of acute nicotine toxicity.