Nicotine - The Nerve Poison

[Thomas3.20.2010]

Which of the following poisons is the most deadly?   

1.    Arsenic                    

2.    Strychnine

3.    Nicotine                            

If you guessed # 3, you are correct. The lethal dosage for a 150 pound adult is 60 mg. The lethal dosage for # 2 is 75 mg and the lethal dosage for # 1 is 200 mg. In other words, nicotine is three times as toxic as arsenic and one and one half times as toxic as strychnine.

 (source: Poisoning/Toxicology, Third Edition, Jay M. Arena, B.S., M.D.)

Nicotine - a poisonous volatile alkaloid, derived from tobacco and responsible for many of the effects of tobacco. It first stimulates (small doses) and depresses (large doses) at autonomic ganglia and myoneural junctions. It is also used as an insecticide and fumigant.

 (source: Black's Medical Dictionary, thirty-fourth edition)

Recent research has shown in fine detail how nicotine acts on the brain to produce a number of behavioral effects. Of primary importance to its addictive nature are findings that nicotine activates the brain circuitry that regulates feelings of pleasure, the so-called reward pathways. A key brain chemical involved in mediating the desire to consume drugs is the neurotransmitter dopamine, and research has shown that nicotine increases the levels of dopamine in the reward circuits. Nicotine's pharmacokinetic properties have been found also to enhance its abuse potential.

Nicotine - one of the most toxic and addicting of all drugs and it is toxic by all routes of exposure including the intact skin. ....also used as a contact insecticidal.

 Lewis' Dictionary of Toxicology

 Overdose can occur if a person uses too many nicotine patches or chews too much nicotine gum or chewing tobacco, as well as smoking. It can also occur through direct contact with e-cigarette liquids sold in large quantities for refills.

Poison centers are reporting a recent uptick in calls about exposures to e-cigarette devices and liquid nicotine.

Slightly more than half of these reported exposures have occurred in young children under the age of six. However, this is consistent with National Poison Data System exposures to all substances combined.  Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring ER visits with nausea and vomiting being the most significant symptoms. 

219% INCREASE

2013 vs. 2012 E-cigarette Devices and Liquid Nicotine Reported Exposures

As nicotine can be absorbed into the bloodstream easily through the skin, if an extremely high concentration of nicotine is spilt on the skin, this can lead to toxicity and death.

Nicotine has not yet been clearly identified as a cancer causing agent and is not yet officially listed as a carcinogen. However, Nicotine activates MAP kinases, increases adrenergic signalling in bowel cancer and disrupts apoptosis or programmed cell death. This cell death actually clears the body of cells that have been damaged or have undergone mutations.

Although there is no solid evidence supporting that nicotine is a carcinogen, the carcinogenic potential of the substance has been demonstrated in various animal and cell culture studies over the last ten years.

Impairment of apoptosis means damaged and altered cells remain, creating a pathway for cancers to develop. Nicotine has also been shown to promote angiogensis or the formation of new blood vessels which can help a tumour to survive and grow.

Nicotine has strong mood altering effects and can act on the brain as both a stimulant and a relaxant.

Effects

Once within the bloodstream, nicotine may circulate around the body until it reaches the brain. This can occur in as little as 7 seconds.

Once in the brain, it binds to and activates receptors called the cholinergic receptors. These cholinergic receptors are also abundant in other areas of the body such as the muscles, heart, adrenal glands and other vital organs. Normally, these receptors are activated when they bind to a neurotransmitter called acetylcholine which is produced at nerve endings in the brain and in the nerves of the peripheral nervous system. Stimulation of the receptors by acetylcholine is important in maintaining healthy respiration, heart function and muscle movement, as well as cognitive function.

Since nicotine has a similar structure to acetylcholine, it can activate the cholinergic receptors. However, unlike acetylcholine, nicotine enters the brain and disrupts its normal functioning. Regular use of cigarettes leads to an increase in the number of cholinergic receptors and changes in the sensitivity of these receptors which may lead to nicotine tolerance. A smoker then needs to maintain a regular supply of nicotine to maintain normal brain function and the habit becomes addictive.

Nicotine also stimulates the release of several neurotransmitters such as norepinephrine,epinephrine, vasopressin, dopamine, arginine and beta-endorphin. Pain, anxiety and other negative symptoms are relieved and positive pleasant sensations are increased.

Nicotine intake also increases blood glucose levels, which is generally thought to be the result of the increased adrenalin levels that occur with nicotine intake stimulating the liver to release glucose. The increased availability of glucose along with adrenalin is thought to be responsible for the increased learning ability, memory and alertness that has been associated with smoking.

An increase in the rise of blood glucose also reduces appetite, which raises metabolic rate and eventually causes weight loss in the long term.

Nicotine stimulates the reward centres in the brain, providing pleasure and euphoria when taken. On binding to receptors present in the brain, nicotine causes release of the neurotransmitter dopamine, amongst others, a chemical involved in reward sensations

With continued use, nicotine leads to a decrease in the release of dopamine at a dose the body is used to. There is also a down regulation or decreased production of other stimulatory neurotransmitters in the brain.

Furthermore, the number and sensitivity of the nicotinic acetylcholine receptors in the brain significantly reduces. To compensate, the brain increases production of a number of receptors for important neurotransmitters. Therefore, the reward pathways of the brain become more sensitive, with an increased number of receptors. This increases a smoker's craving to smoke and leads to addiction.

Stopping smoking or intake of nicotine may lead to unpleasant symptoms called withdrawal symptoms. Some of the withdrawal symptoms of nicotine include:

·         Nicotine cravings

·         Irritability, frustration, anger and mood swings

·         Depression and anxiety

·         Weight gain

The International Programme on Chemical Safety (IPCS) notes that: “Nicotine is one of the most toxic of all poisons and has a rapid onset of action. Apart from local caustic actions, the target organs are the peripheral and central nervous systems.”