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 harms of smoking itself, causing physical and mental 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 poisoning cases. Experts warn of increased adverse effects of nicotine in the form of vapor.

Statistics from the American Association of Poison Control Centers (AAPCC) show that 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 3,900. In 2015-2017, there were more than 2,500 reports of liquid nicotine exposure in children under the age of 6 (84% of children were under the age of three): 93% of nicotine poisoning cases involved ingestion of liquid nicotine for vaping. One fatality due to respiratory arrest was reported in the USA.

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

Nicotine overdose and excessive exposure to nicotine are the causes of acute nicotine poisoning. For adults its one-time lethal dose WHO considers 40-60 mg or 0.5-1.0 mg/kg body weight (orally - 6.5-13 mg/kg), and for children - 0.1 mg/kg. Toxicologists also indicate that about a dozen cigarettes smoked in a row or 10 ml of nicotine-containing solution can be lethal. Smoking overdose is unlikely because the body receives only one-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 (including the use of nicotine gums or lozenges, available as additional tobacco cessation aids), or absorption through the skin (in particular, improper use of patches, which - depending on the brand and size - provide 5-22 mg of nicotine transdermally overnight).

One cigarette or three or four cigarette butts entering the GI tract is potentially toxic to young children.

But lately, electronic cigarettes or vaping - smoking these cigarettes (using Electronic Nicotine Delivery Systems or ENDS) and the concentrated solution to refill them, which contains liquid nicotine and is poisonous, especially to young children - is behind most nicotine poisoning cases. [2],

At the same time, those who try vaping (inhaling vapors of a heated nicotine-containing solution) without any experience with regular smoking are at a higher risk of nicotine poisoning than smokers. Using a nicotine patch or nicotine gum while smoking at the same time can also lead to overdose.

Accidental/suicidal ingestion of pesticides containing nicotine sulphate solution cannot be ruled out. And people who harvest fresh tobacco leaves from plantations have chronic nicotine poisoning, called green tobacco disease, due to the penetration of nicotine through the skin.

Pathogenesis

The mechanism of toxicity, i.e. The pathogenesis of poisoning by nicotine, 3-(N-methylpyrrolidyl-2) pyridine, is well understood. The alkaloid can be absorbed through the oral mucosa, lungs, skin or intestine and pass through all biological membranes. It acts on the cardiovascular, respiratory, digestive and nervous systems of the body by binding to central and peripheral n-cholinoreceptors (transmembrane receptors for the neurotransmitter acetylcholine, which are 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 exposure progresses, there comes a point where the n-cholinoreceptors are blocked and the parasympathetic nervous system is inhibited, resulting in ganglionic and neuromuscular blockade.

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

Symptoms of the nicotine poisoning

Nicotine has not only local effects, but also has a targeted effect on the peripheral and central nervous system. In 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 saliva production, 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-mentioned - there are such symptoms as rapid heavy breathing and coughing; increased heartbeat with its rate of increase (tachycardia); rise in blood pressure; profuse sweating; tremors, muscle fasciations and convulsions.

In the second stage, a few hours later, the depressant effects of nicotine begin, evidenced by a decrease in BP, miosis (pupil constriction), bradycardia (decreased heart rate), atrial fibrillation and dyspnea, pale skin and chills, lethargy, muscle weakness, and drowsiness. In extreme cases, there is difficulty in breathing and its disruption, depression of consciousness (prostration) or loss of consciousness, which can progress to collapse and coma. The possibility of death due to paralysis of respiratory muscles and/or central respiratory failure cannot be excluded.

Chronic nicotine poisoning may be manifested by frequent headache and abdominal pain, decreased physical endurance and sleep disturbance, poor appetite and nausea, dyspnea, BP spikes and changes in HR (from tachycardia to bradycardia) with cardialgia, hyperhidrosis and dehydration, eye irritation and visual impairment, stomatitis and bleeding gums.

Complications and consequences

Quick care for mild acute poisoning ensures a full recovery, but in severe cases and chronic poisoning, there can be long-term effects and complications.

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

Nicotine also causes an increase in plasma free fatty acid levels with an increase in blood viscosity; increases glycogen synthesis (resulting in lower fasting blood glucose levels); decreased coronary blood flow and increased blood flow to 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 experience menstrual disorders, early menopause, and abnormal pregnancy.

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

Is it possible to smoke after nicotine poisoning? In some cases, poisoning, especially severe poisoning, causes aversion to smoking, and doctors advise to take advantage of this and permanently end the addiction.

Diagnostics of the nicotine poisoning

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

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

Differential diagnosis

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

Treatment of the nicotine poisoning

If symptoms of poisoning occur, emergency medical assistance should be summoned. And pre-hospital first aid for nicotine poisoning is provided by ingesting activated charcoal dissolved in water to try to reduce the gastrointestinal absorption of nicotine. If it is absorbed through the skin, the area should be rinsed with running water for at least a quarter of an hour. In addition, a solution of potassium permanganate is used to flush the stomach.

Treatment, which is essentially supportive, is carried out in hospital. If poisoning has occurred through the respiratory tract, oxygen-carbogen inhalation is required; respiratory problems are managed by artificial ventilation. Hemodialysis, hemoperfusion, or other extracorporeal methods do not remove nicotine from the blood, so they are not used.

Medications used include:

• m-choline blocker Atropine (subcutaneous or intramuscular injections of 0.1% solution for bradycardia, hypotension and dyspnea);
• The α-adrenoblocker Phentolamine (Methanesulfonate), which is administered intravenously to relieve vasospasm and dilate the vascular lumen, as well as lower blood pressure;
• anticonvulsant anxiolytics, benzodiazepine derivatives;
• β-adrenoblocker Anapriline (Propranolol, Propamine), relieving tachycardia and cardiac arrhythmia, normalizing elevated BP.

Prevention

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

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

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

In the U.S., the Childhood Nicotine Poisoning Prevention Act has been in effect since July 2016, requiring manufacturers of nicotine-containing e-cigarette liquids to comply with packaging and general certificate of compliance requirements.

Forecast

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

In rare cases, severe nicotine poisoning can be fatal.