Nicotine poisoning: acute, chronic

A derivative of the nitrogenous compound pyridine, the tobacco alkaloid nicotine, is a potent neuro- and cardiotoxin. In addition to the harm of smoking itself, which causes physical and psychological dependence, there can be direct nicotine poisoning in 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 increased negative effects of nicotine in vapor form.

According to statistics from the American Association of Poison Control Centers (AAPCC), from 2011 to 2014, the 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, more than 2.5 thousand reports of exposure to liquid nicotine in children under 6 years old were registered (84% of children were under 3 years old): in 93% of cases, nicotine poisoning occurred when vaping liquid nicotine was ingested. In the United States, one fatal case was recorded due to respiratory arrest.

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

Causes nicotine poisoning

Overdose of nicotine and its excessive effect on the body are the causes of acute nicotine poisoning. For adults, the WHO considers a single lethal dose to be 40-60 mg or 0.5-1.0 mg/kg of body weight (orally - 6.5-13 mg/kg), and for children - 0.1 mg/kg. Toxicologists also indicate that about ten cigarettes smoked in a row or 10 ml of a nicotine-containing solution can be fatal. Overdose from 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 its inhalation, ingestion (including through the use of nicotine chewing gum or lozenges available as additional means for smoking cessation) or absorption through the skin (in particular, through the incorrect use of patches, which - depending on the brand and size - provide transdermal delivery of 5-22 mg of nicotine into the body over the course of 24 hours).

One cigarette or three or four cigarette butts can be potentially toxic to small children if they enter the gastrointestinal tract.

But in recent years, most cases of nicotine poisoning have been attributed to e-cigarettes or vaping – smoking these cigarettes (using Electronic Nicotine Delivery Systems or ENDS) and the concentrated solution used to fill them, which contains liquid nicotine and is poisonous, especially to young children. [ 2 ]

Those who try vaping (inhaling vapors of a heated nicotine-containing solution) without having experience with regular smoking are at greater risk of nicotine poisoning than smokers. Using a nicotine patch or nicotine gum while smoking is also fraught with overdose.

Accidental/suicidal ingestion of pesticides containing nicotine sulfate solution is not excluded. And people who collect fresh tobacco leaves on plantations suffer from chronic nicotine poisoning, known as green tobacco disease, associated with nicotine penetration through the skin.

Pathogenesis

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

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

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

Symptoms nicotine poisoning

Nicotine has not only local effects, but also specifically affects the peripheral and central nervous system. In case of poisoning, the first signs depend on the amount of nicotine that has entered the body 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).

Acute nicotine poisoning usually occurs in two stages or phases. During the first 15-60 minutes – in addition to the above – symptoms such as rapid, heavy breathing and coughing; increased heart rate with its acceleration (tachycardia); increased blood pressure; profuse sweating; tremors, muscle fasciculations and convulsions are noted.

In the second stage – after several hours – the depressant effect of nicotine begins, evidenced by: decreased blood pressure, miosis (narrowing of the pupils), bradycardia (decreased heart rate), atrial fibrillation and shortness of breath, pale skin and chills, lethargy, muscle weakness, drowsiness. In extreme cases, difficulty breathing and its impairment, depression of consciousness (prostration) or its loss are observed, which can progress to collapse and coma. The possibility of a fatal outcome is not excluded – due to paralysis of the respiratory muscles and / or central respiratory failure.

Chronic nicotine poisoning can manifest itself as frequent headaches and abdominal pain, decreased physical endurance and sleep disturbances, poor appetite and nausea, shortness of breath, blood pressure surges and changes in heart rate (from tachycardia to bradycardia) with cardialgia, hyperhidrosis and dehydration, eye irritation and deterioration of vision, stomatitis and bleeding gums.

Complications and consequences

Quick help for mild acute poisoning guarantees a full recovery, but in severe cases and chronic poisoning there may be long-term consequences and complications.

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

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. Women may have menstrual irregularities, early menopause, and abnormal pregnancy.

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

Can you smoke after nicotine poisoning? In some cases, poisoning, especially severe, causes an aversion to smoking, and doctors advise taking advantage of this and ending the bad habit forever.

Diagnostics nicotine poisoning

In case of nicotine poisoning, diagnosis is made based on symptoms and anamnesis data.

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

Differential diagnosis

Differential diagnostics are carried out with poisoning by organophosphorus substances, methyl alcohol, opiates, drugs of the n-cholinomimetic group and cholinesterase inhibitors.

Treatment nicotine poisoning

If symptoms of poisoning occur, you should call for emergency medical care. And pre-hospital first aid for nicotine poisoning is provided by taking activated charcoal dissolved in water - to try to reduce the gastrointestinal absorption of nicotine. If it has been absorbed through the skin, this area should 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.

The following medications are used:

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

Prevention

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

Other preventive measures include protecting your skin when using liquids containing nicotine; storing nicotine products safely out of the reach of children; and properly disposing of nicotine products, including cigarette butts and empty nicotine e-cigarette cartridges.

In May 2016, the European Parliament adopted the EU Tobacco Products Directive, which concerns the regulation of 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.

Since July 2016, the Childhood Nicotine Poisoning Prevention Act has been in effect in the United States, requiring manufacturers of nicotine-containing e-cigarette liquids to comply with packaging requirements and the presence of a general certificate of conformity.

Forecast

The outlook for people with nicotine poisoning depends on how much nicotine they ingested and how quickly they seek treatment. With prompt medical treatment, the outlook is good, and most people make a full recovery with no long-term effects.

In rare cases, severe nicotine poisoning can be fatal.