6.2 The physiological effects of nicotine
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More than 4000 compounds are found in tobacco smoke, many of which are pharmacologically active, toxic, mutagenic or carcinogenic.13 Of these, nicotine appears to be the most important acute-acting pharmacological agent. The chemical name for nicotine is (S)-3-(1-methylpyrrolidin-2-yl)pyridine, and its formula is C10H14N2.1
In large quantities, nicotine is an extremely toxic and potentially lethal nerve poison. A dosage of 40-60mg is sufficient to kill an adult human, but acute poisoning is rare. Poisoning usually occurs through accidental swallowing or skin contact with pesticides containing nicotine as an active ingredient. Workers who harvest tobacco leaves commonly experience a low level of intoxication through handling the leaf, known as 'green tobacco sickness,'14 but this diminishes with increased duration of exposure.1 Nicotine poisoning in children generally occurs through ingestion of tobacco products such as cigarettes, cigarette butts, or products developed as nicotine replacement therapy (See also Chapter 3, Section 3.19).
Tobacco smoke delivers nicotine in much lower quantities to the smoker, much being destroyed through the heat from burning the leaf. However even taken in low quantities, nicotine is a potent chemical. It causes a range of physiological changes and creates dependency, which in turn is reinforced by unpleasant sensations upon withdrawal.
The uptake of nicotine into the body is dependent on the pH levels of its transport system (generally via smoke, but also possible through sucking, chewing and inhaled tobaccos). Cigarette smoke provides the most rapid and effective means of nicotine delivery. Nicotine is swiftly absorbed through the acidic tobacco smoke being drawn into the lungs, which due to their large surface area and facility for cross-membrane transfer, quickly deliver large and intensive doses of the chemical via the bloodstream to the brain.2 Smoke from pipes and cigars is more alkaline, allowing for slower uptake of nicotine through the lining of the mouth.2 Smokeless tobacco products such as snus, and nicotine chewing gum (an aid in cessation) are specially treated during manufacture to facilitate oral absorption. However nicotine chewing gum is designed to deliver nicotine at lower and slower sub-addictive rates.2 Nicotine may also be absorbed through the skin.
New smokers may experience nausea and dizziness from nicotine, but soon develop a tolerance following chronic tobacco use.1 Once the body has become accustomed to functioning with a level of nicotine in the blood, it seeks to maintain this level and smokers feel the need to continue self-administering the drug. Repeated use results in diminished effects, possibly leading to increased intake of nicotine.1 Smokers soon learn to manipulate their smoking behaviour by varying puff frequency and depth in order to obtain the amount of nicotine required.2
In regular smokers nicotine levels rise and fall during the day, with declining levels leading to the urge to smoke another cigarette. Nicotine has a half life of 68 hours, meaning that it gradually accumulates over the course of the day, and decreases during the night.2 One of the commonly used measures of an individual's addictiveness is how soon he or she reaches for their first cigarette on waking.15
Once it enters the bloodstream, nicotine reaches the brain in 10–19 seconds,2 and acts through specialised cell receptors located in the brain and other organs and muscles. When the receptors signal the presence of nicotine, a wide range of physical reactions take place. Heart rate and blood pressure increase. Blood flow is altered, some sites (for example the skin) receive less flow and experience a drop in temperature, while others (such as skeletal muscle) experience increased blood flow. Vasoconstriction occurs in the coronary arteries.2 Additionally, brain waves are altered, a number of endocrine changes occur, and skeletal muscle relaxation takes place.1 Nicotine also increases metabolic rate, and suppresses appetite, with the result that smokers weigh an average of 4 kilograms lighter than non-smokers.2
The primary sites for metabolism of nicotine are the liver, and to a much lesser extent, the lung and brain.2 The main metabolites of nicotine are cotinine and nicotine-N-oxide. Cotinine has a much longer half life than nicotine (up to 20 hours). Cotinine is further metabolised into trans-3'-hydroxycotinine, the main nicotine metabolite found in urine. Up to a third of nicotine by-products are eventually excreted in the urine.2
Nicotine is known to interact with a range of drugs, with important implications for drug therapy. Drugs may be processed by the body in a different way when nicotine is present, and nicotine may also mediate the effectiveness of certain drugs. Drug types known to be affected by co-use of nicotine include oral contraceptives, sedatives, analgesics, and drugs to treat a number of different conditions, including aspects of heart disease, mental health problems, and breathing difficulties. These interactions are capable of causing clinically significant outcomes, making it vital that health professionals are aware of a patient's smoking status.16, 17
Nicotine, as administered via tobacco smoke by addicted smokers, is not in itself strongly associated with the chronic diseases caused by smoking. These arise instead through prolonged exposure to the thousands of noxious and carcinogenic substances contained in tobacco tar.2 The Royal College of Physicians has concluded that based on current evidence, 'pure nicotine may be harmful to the fetus in pregnancy but is likely to be far less hazardous than the effects of smoking,'2 which has implications for use of nicotine replacement therapy to aid in cessation during pregnancy (see Chapter 7).
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