Carol McLoughlinTobacco has been smoked for thousands of years and was brought to Europe by Christopher Columbus from the Bahamas in 1492. Today, an estimated 47% of men and 12% of women smoke worldwide (Scholey and Moss, 2005).
Tobacco has been smoked for thousands of years and was brought to Europe by Christopher Columbus from the Bahamas in 1492. Today, an estimated 47% of men and 12% of women smoke worldwide (Scholey and Moss, 2005).
In recent years there have been moves to curb the habit as the evidence for smoking-related illness and disease has grown. About 120,000 deaths a year in the UK are attributed to smoking-related illnesses, with an associated £1,500 million bill for the NHS (NICE, 2002).
UK regulations have led to a reduction in the tar content of cigarettes from 25-35mg in the 1950s to 5-15mg in the 1990s, with an upper limit of 12mg set from 1997. More recently, the government has focused on smoking cessation, investing millions in hard-hitting TV campaigns and smoking-cessation services. Government targets aim to see 1.5 million people stop smoking by 2010 (www.givingupsmoking.co.uk).
Although about 80% of smokers express a desire to stop, only 35% attempt to do so each year, with fewer than 10% being successful (Scholey and Moss, 2005). Government research suggests that smokers are four times more likely to quit with the help of their local NHS Stop Smoking Service using NRT than if they rely on willpower alone (DH, 2004).
NICE approval for the use of NRT and Bupropion (Zyban) (see box) was granted in 2002, with the recommendation that the products are prescribed to smokers who commit to a target stop date. NICE also recommends using pharmacotherapy products in conjunction with advice and behavioural support.
NRT provides a background level of nicotine that reduces craving and withdrawal (NICE, 2002) and does this in a way that is slower and less satisfying than smoking but that is safer and less addictive (Percival, 2003) (Figure 1).
Nicotine is one of a number of alkaloids present in tobacco and makes up about 5% of the dried tobacco leaf. A typical cigarette contains about 9mg of nicotine, of which 1mg is absorbed by the smoker (Scholey and Moss, 2005).
Cigarette smoke is composed of volatile and particulate phases, which account for 95% and 5% respectively of the volume of cigarette smoke. Up to 500 gaseous compounds, including nitrogen, carbon monoxide, carbon dioxide, ammonia, hydrogen cyanide and benzene, have been identified in the volatile phase. More than 3000 compounds constitute the particulate phase of which nicotine is the main one.
The particulate matter without its alkaloid and water content is called tar - this is what poses the greatest health risk (DH, 1998) as it contains many carcinogens, including polynuclear aromatic hydrocarbons, N-nitrosamines and aromatic amines (Royal College of Physicians, 2000).
Nicotine is distilled from burning tobacco, and small droplets of tar containing nicotine are inhaled and deposited in the small airways and alveoli (RCP, 2000). Absorption of nicotine across cell membranes depends on pH - the more alkaline the smoke, the more readily it is absorbed. UK cigarettes are typically acid, requiring deep inhalation for more effective absorption. US brands tend to be more alkaline and are absorbed in the mouth and upper respiratory tract (DH, 1998).
On entering the small airways and alveoli of the lungs, nicotine is buffered to physiological pH and rapidly absorbed into the pulmonary alveolar capillary and venous circulation. It is distributed quickly throughout the body, taking 10-19 seconds to reach the brain (RCP, 2000).
Nicotine is metabolised mainly in the liver and excreted in urine with some metabolism occurring in the lung and brain. (RCP, 2000). About 70-80% of nicotine is metabolised to cotinine via C-oxidation and 4% to nicotine-N'-oxide.
Nicotine has a half-life of two hours and, as smoking occurs throughout the day, its plasma concentration increases to reach 20-40ng/ml (RCP, 2000). Plasma levels are affected by puff volume, the number of puffs per cigarette, the intensity of puffing, the depth of inhalation, and by blocking ventilation holes in the filter.
Nicotine readily crosses the blood brain barrier and stimulates the nicotinic acetylcholine receptors (nAChRs) (Scholey and Moss, 2005). The receptors relay excitation at the neuromuscular junction, autonomic ganglia and at many synapses in the central nervous system (CNS).
They are widespread throughout the brain, but are concentrated especially in the midbrain tegmentum, the striatum and nucleus accumbens, the substantia nigra and the ventral tegmental area (VTA), which connects the limbic system to the cortex (Figure 2). The receptors in the VTA and nucleus accumbens are significant in developing nicotine addiction.
Stimulation of the sympathetic nervous system increases heart rate, blood pressure and cardiac contractility, in turn raising myocardial oxygen consumption and demand for blood flow. Nicotine is also thought to affect lipoprotein synthesis. The release of catecholamines increases lipolysis and releases free fatty acids that are taken up by the liver, promoting increases in very low-density lipoproteins and in high-density lipoproteins (RCP, 2000).
Smoking has endocrine and metabolic effects, increasing adrenal cortical hormone levels and the rate of metabolism (RCP, 2000). Smokers weigh on average 4kg less than non-smokers.
The rapid absorption of nicotine from cigarette smoking, and the high arterial levels that reach the brain allow for rapid behavioural reinforcement. During periods of non-smoking or in sleep, plasma levels of nicotine decrease and the nicotinic receptors gradually recover their active functional state, that is, they become resensitised (Scholey and Moss, 2005).
As a result, after a night's sleep, a smoker has a greater number of active receptor sites compared with a non-smoker, and it is thought that this may contribute to withdrawal symptoms and craving. Nicotine intake then acts as a powerful reinforcer of smoking behaviour in the dopamine pathway, producing a heightened response and alleviating withdrawal symptoms in the cholinergic system.
Types of NRT product
The choice of pharmacotherapy aid will depend on patient preference and on the number of cigarettes smoked previously. Different strength products allow heavier smokers to start with higher doses of nicotine and to facilitate weaning and gradual withdrawal. All forms are recommended for three months, with a reduction in dose over the treatment period.
The BNF lists six types of NRT product:
- Chewing gum: Nicorette (Pharmacia); Boots; Nicotinell (Novartis)
- Patches: Nicorette; Boots NRT; NiQuitin CQ (GSK); Nicotinell TTS
- Nasal spray: Nicorette
- Sublingual tablet: Nicorette Microtab
- Inhalator: Nicorette ; Boots
- Lozenges: Nicotinell; NiQuitin CQ.
Cautions and contraindications
While the British National Formulary cites several contraindications for the use of NRT, McNeill et al (2001) recommend considering a risk-versus-benefit analysis, while stressing that continued dependence on tobacco is likely to be more harmful. Caution is recommended in pregnancy and in breastfeeding mothers, and in teenagers aged under 18 years. Disease-specific contraindications include cardiovascular disease, peptic ulcers, hyperthyroidism, diabetes mellitus, and renal and hepatic impairment.
Side-effects of NRT products
The toxic or adverse effects of nicotine on the body range from local and acute systemic effects to chronic systemic effects. Acute systemic toxic effects of nicotine include:
- CNS effects: headache, dizziness, insomnia, abnormal dreams, nervousness
- Gastrointestinal distress: dry mouth, nausea, vomiting, dyspepsia, diarrhoea
- Musculoskeletal symptoms: arthralgias, myalgia.
In terms of NRT, these effects tend to be mild (RCP, 2000). However, distinguishing the CNS effects of nicotine in smokers who have recently quit can be difficult as withdrawal symptoms can be similar to some of the toxic effects of nicotine. Its local toxic effects include:
- Sore mouth and mouth ulcers from nicotine gum
- Cutaneous sweating, itching, burning, erythema from patch application
- Nasal irritation with burning, itching and sneezing
- Watery eyes with nicotine nasal spray.
The chronic systemic toxicity effects of nicotine include:
- Cardiovascular disease, particularly coronary heart disease and stroke
- The aggravation of hypertension
- Delayed wound healing
- Peptic ulcer disease
- Foetal effects including low birthweight.
The acute fatal dose of nicotine is estimated to be 60mg in adults. However, fatality is rare as much of the nicotine is destroyed as it burns and what reaches the stomach is broken down/ionised by stomachs acid. Smokers can also 'self-titrate' the amount of nicotine intake by regulating consumption and depth of inhalation (Scholey and Moss, 2005).
Clinical trials have shown that NRT doubles the chance of success of smokers wishing to stop (West et al, 2000). NICE believes the use of smoking cessation pharmacotherapy aids will result in huge long-term savings for the NHS. With an increasing number of people considering quitting, health care-professionals must be able to provide accurate information and advice on using NRT (Percival, 2003).
With 42% of children living in a household where at least one person smokes, much progress remains to be made (www.giving up smoking.co.uk).
Bupropion (Zyban) is a non-nicotine smoking-cessation aid that inhibits the nicotinic acetylcholine receptors (Percival, 2003). Treatment is initiated up to two weeks before smoking stops at which point the dose is increased from 150mg to 300mg. Treatment lasts eight weeks.
- History of seizures
- Bulimia or anorexia nervosa
- Monoamine oxidase inhibitor antidepressants
- Concurrent medication may lower seizure threshold (antidepressants, antimalarials, antipsychotics, theophylline, systemic steroids, oral hypoglycaemics and insulin).
- Dry mouth, insomnia, drowsiness, skin disorders, headaches, and dizziness.
British National Formulary 48, http://bnf.org/bnf
Department of Health. (1998) Annex L: Review of emissions in cigarette smoke. In: Department of Health. Report of the Scientific Committee on Tobacco and Health. London: The Stationery Office. Available at: www.archive.official-documents.co.uk/document/doh/tobacco/annex-l.htm (accessed February 11, 2005).
Department of Health. (2004)Choosing Health: Making healthy choices easier. London: The Stationery Office.
McNeill, A., Foulds, J., Bates, C. (2001)Regulation of nicotine replacement therapies (NRT): a critique of current practice. Addiction 96: 12, 1757-1768.
National Institute of Clinical Excellence. (2002)Guidance on the Use of Nicotine Replacement Therapy (NRT) and Bupropion for Smoking Cessation. Technology Appraisal Guidance No. 39. Available at: www.nice.org.uk (accessed February 11, 2005).
Percival, J. (2003)The place of pharmacotherapy products in smoking cessation. Professional Nurse 19: 2, 113-117.
Royal College of Physicians Tobacco Advisory Group. (2000)Nicotine Addiction in Britain, A report of the of the Royal College of Physicians. London: RCP.
Scholey, A., Moss, M. (2005)Human Psychopharmacology: Nicotine and Caffeine. Available at: http://psychology.unn.ac.uk/mark/PY116/HPnicotine/HPNICOTINE.htm (accessed February 11. 2005).
West, R., McNeil, A., Raw, M. (2000)Smoking cessation guidelines for health professionals: an update. Thorax 55: 12, 987-999.