Nicotine poisoning: acute, chronic

A derivative of the nitrogenous compound of pyridine, the tobacco alkaloid nicotine, is a potent neuro- and cardiotoxin. In addition to the actual harm of smoking, which causes physical and mental dependence, there can be direct nicotine poisoning of both adults and children.

Epidemiology

Until recently, nicotine poisoning was relatively rare and was usually associated with exposure to insecticides containing water-soluble nicotine salts. However, the popularity of e-cigarettes has significantly increased the number of reported cases of poisoning. Experts warn of an increase in the negative effects of nicotine in the form of vapor.

According to statistics from the American Association of Poison Control Centers (AAPCC), from 2011 to 2014, rates of poisoning from e-cigarettes and liquid nicotine increased 14.6 times - from 271 cases per year to more than 3.9 thousand in 2015-2017. There have been more than 2,500 reports of exposure to liquid nicotine in children under 6 years of age (84% of children were under three years of age): in 93% of cases, nicotine poisoning occurred when liquid nicotine was ingested for vaping. In the United States, one death was recorded as a result of respiratory arrest.

According to some reports, the prevalence of green tobacco disease worldwide ranges from 8.2 to 47%. And in India, an average of 73% of tobacco leaf pickers have symptoms of chronic nicotine poisoning.

Causes of the nicotine poisoning

An overdose of nicotine and its excessive effect on the body are the causes of acute nicotine poisoning. For adults, WHO considers it a single lethal dose of 40-60 mg or from 0.5-1.0 mg / kg of body weight (orally - 6.5-13 mg / kg), and for children - 0.1 mg / kg. Toxicologists also point out that about a dozen cigarettes smoked in a row, or 10 ml of a nicotine-containing solution can be deadly. An overdose when smoking seems unlikely, since the body receives only a tenth of the nicotine (about 1 mg) contained in a regular cigarette (10-15 mg). [1]

So the risk factors for nicotine intoxication are inhalation, ingestion by ingestion (including when using nicotine chewing gums or lozenges available as additional means for smoking cessation), or absorption through the skin (in particular, if patches are used incorrectly)., which - depending on the brand and size - during the day provide a transdermal intake of 5-22 mg of nicotine into the body).

Potentially toxic for young children is the ingestion of one cigarette or three or four cigarette butts.

But in recent times, e-cigarettes or vaping have been behind most cases of nicotine poisoning   - smoking these cigarettes (using Electronic Nicotine Delivery Systems or ENDS), as well as a concentrated solution for refilling them, which contains liquid nicotine and is poisonous, especially for young children. [2], [3]

At the same time, those who try vaping (inhaling the vapors of a heated nicotine-containing solution), without the experience of regular smoking, are at a greater risk of nicotine poisoning compared to smokers. Using a nicotine patch or chewing gum with nicotine while smoking is also fraught with an overdose.

Accidental/suicidal ingestion of pesticides containing nicotine sulfate solution cannot be ruled out. And people who collect fresh tobacco leaves on plantations experience chronic nicotine poisoning, called green tobacco disease, associated with the penetration of nicotine through the skin.

Pathogenesis

The mechanism of toxicity, that is, the pathogenesis of nicotine poisoning - 3-(N-methylpyrrolidyl-2) pyridine - is well understood. The alkaloid can be absorbed through the oral mucosa, lungs, skin or intestines and pass through all biological membranes. It acts on the cardiovascular, respiratory, digestive and nervous systems of the body, binding to the central and peripheral n-cholinergic receptors that provide the transmission of nerve impulses (transmembrane receptors for the neurotransmitter acetylcholine, sensitive to nicotine).

As a result, the ganglia of the autonomic nervous system are exposed, which stimulates the  sympathetic nervous system . As this impact, there comes a moment when n-cholinergic receptors are blocked, and the work  of the parasympathetic nervous system  is inhibited, which leads to ganglionic and neuromuscular blockade.

Nicotine also unpredictably acts as an m-cholinergic receptor agonist (muscarinic acetylcholine receptors), causing parasympathetic-type reactions.

Symptoms of the nicotine poisoning

Nicotine has not only local effects, but also purposefully affects the peripheral and central nervous system. In case of poisoning, the first signs depend on the amount of nicotine ingested and body weight and are manifested by irritation and burning in the mouth and throat, increased salivation, dizziness and headaches, nausea and vomiting, abdominal pain and diarrhea (due to increased gastrointestinal peristalsis).

Typically, acute nicotine poisoning occurs in two stages or phases. During the first 15-60 minutes - in addition to the above - there are symptoms such as rapid, heavy breathing and coughing; increased heart rate with its increase (tachycardia); rise in blood pressure; profuse sweating; tremor, muscle fasciculations and convulsions.

At the second stage - after a few hours - the depressant effect of nicotine begins, evidenced by: a decrease in blood pressure, miosis (narrowing of the pupils), bradycardia (decrease in heart rate), atrial fibrillation and shortness of breath, pallor of the skin and chills, lethargy, muscle weakness, drowsiness. In extreme cases, there is difficulty in breathing and its violation, depression of consciousness (prostration) or its loss, which can progress to collapse and coma. The possibility of death is not excluded - due to paralysis of the respiratory muscles and / or central respiratory failure.

Chronic nicotine poisoning can be manifested by frequent headache and abdominal pain, decreased physical endurance and sleep disturbance, poor appetite and nausea, shortness of breath, jumps in blood pressure and changes in heart rate (from tachycardia to bradycardia) with cardialgia, hyperhidrosis and dehydration, eye irritation and visual impairment, stomatitis and bleeding gums.

Complications and consequences

Prompt treatment for mild acute poisoning guarantees a full recovery, but in severe cases and chronic poisoning, there can be long-term consequences and complications.

After suffering poisoning, increased drowsiness and chills, stiffness of individual muscles, lethargy, and breathing problems may remain.

Nicotine also causes an increase in the level of free fatty acids in blood plasma with an increase in its viscosity; increases glycogen synthesis (which leads to a decrease in fasting blood glucose levels); a decrease in coronary blood flow and an increase in blood flow in skeletal muscles.

Chronic nicotine poisoning complicates the course of peptic ulcer disease and allergies; affects insulin resistance and predisposes to metabolic syndrome; leads to arterial hypertension, heart failure and angina pectoris. Women may have menstrual irregularities, early menopause, abnormal pregnancy.

Voluntary nicotine poisoning, which doctors consider smoking, causes increased lipid peroxidation, increased oxidative stress and neuronal apoptosis, and DNA damage. Prolonged exposure to n-cholinergic receptors causes a wide range of negative long-term effects on organ systems, immunity, and reproductive health.

Can I smoke after nicotine poisoning? In some cases, poisoning, especially severe poisoning, causes an aversion to smoking, and doctors advise taking advantage of this and putting an end to the addiction forever.

Diagnostics of the nicotine poisoning

In nicotine poisoning, diagnosis is based on symptoms and history.

To confirm acute nicotine poisoning, urine and blood tests can be done - for the content of nicotine or its metabolite cotinine, which remains in the serum for 18-20 hours.

Differential diagnosis

Differential diagnosis is carried out with poisoning by organophosphorus substances, methyl alcohol, opiates, drugs of the group of n-cholinomimetics and cholinesterase inhibitors.

Treatment of the nicotine poisoning

In case of symptoms of poisoning, emergency medical attention should be called. And first aid for nicotine poisoning is by ingestion of activated charcoal dissolved in water to try to reduce the gastrointestinal absorption of nicotine. If it is absorbed through the skin, this area must be washed with running water for at least a quarter of an hour. In addition, the stomach is washed with a solution of potassium permanganate.

Treatment, which is essentially supportive, is carried out in a hospital. If poisoning occurred through the respiratory tract, oxygen-carbogen inhalations are necessary; breathing problems are solved by artificial ventilation of the lungs. Hemodialysis, hemoperfusion, or other extracorporeal methods do not remove nicotine from the blood, so they are not used.

Medicines are used such as:

• m-anticholinergic Atropine (subcutaneous or intramuscular injections of a 0.1% solution for bradycardia, hypotension and shortness of breath);
• α-blocker Fentolamine (Methansulfonate), which is administered intravenously to relieve spasms of blood vessels and expand their lumen, as well as lower blood pressure;
• anticonvulsant anxiolytics, benzodiazepine derivatives;
• β-blocker Anaprilin (Propranolol, Propamine), which relieves tachycardia and cardiac arrhythmia, normalizes high blood pressure.

Prevention

The most effective way to prevent nicotine poisoning is to stop smoking and use other nicotine-containing substances.

Other preventive measures include protecting the skin when using e-liquids containing nicotine; safe storage of nicotine products away from children; proper disposal of nicotine products, including cigarette butts and empty e-cigarette nicotine cartridges.

In May 2016, the European Parliament adopted the EU Tobacco Products Directive, which regulates the use of electronic cigarettes in the 28 EU member states. According to this official document, nicotine-containing liquid can only be sold if the nicotine concentration does not exceed 20 mg/ml.

In the United States, the Childhood Nicotine Poisoning Prevention Act came into force in July 2016, requiring manufacturers of nicotine-containing e-liquids to comply with packaging requirements and a general certificate of conformity.

Forecast

The outlook for people with nicotine poisoning depends on how much nicotine is ingested and how quickly they seek treatment. With prompt medical treatment, the prognosis is good and most people make a full recovery without any long-term effects.

In rare cases, severe nicotine poisoning can be fatal.