Risks of smoking tobacco

Tobacco use is the leading cause of preventable death in Ireland but the rewards of quitting are huge, writes Donna Cosgrove PhD MPSI

Almost 6,000 people die annually from tobacco-related diseases.¹ It is the only legal drug product that kills many of its users when used exactly as intended by manufacturers. People who smoke cigarettes have a higher chance of developing:²

• Breathing problems: Nearly 80 per cent of deaths from COPD are attributable to smoking.

• Cancer: Lung, throat and mouth especially. Ninety percent of lung cancers, and at least 30 per cent of all cancer deaths, are attributable to smoking.³

• Cardiovascular disease: Myocardial infarction, coronary artery disease, hypertension, peripheral vascular disease.

• Eye problems, ie, cataracts.

• Gastrointestinal issues, ie, peptic ulcers and inflammatory bowel disease.²

• Impaired fertility, impotence, spontaneous abortions; also, ectopic pregnancies.

• Mouth ulcers and dental problems.

• Osteoporosis.⁴

• Rheumatoid arthritis.

Most of the harm from smoking is caused by the burning of tobacco, as opposed to nicotine itself. Cigarette smoke contains over 4,000 chemicals (Figure 1) — this includes approximately 69 chemicals that are well-established carcinogens, and over 400 other toxins.

Nicotine Addiction

Nicotine is a highly-addictive compound. Smoking cigarettes, ie, administration through the lung, provides almost instant absorption, permitting nicotine to enter the brain in six seconds. The speed and efficiency of this route reinforces self-administration of nicotine.² The pharmacological basis of nicotine addiction is a due to positive reinforcement: Enhancement of mood, improved functioning, such as better concentration and reaction time; also, avoidance of withdrawal symptoms.

 Smoking is associated with a pleasurable experience and a sense of satisfaction. This is caused by stimulation of the nicotinic cholinergic receptors in the brain, which releases neurotransmitters including dopamine. The release of multiple other neurotransmitters such as noradrenaline, acetylcholine, serotonin, ?-aminobutyric acid, glutamate, and endorphins lead to the arousal, mood modulation, performance enhancement, analgesic, and weight-loss effects associated with smoking.⁵ Tolerance and desensitisation develop with repeated use⁴ due to an increase in the number of binding sites present on nicotinic receptors. This means that higher doses of nicotine are then required to achieve the same level of stimulation. When these desensitised receptors again become responsive in times of prolonged abstinence, craving and withdrawal symptoms such as anxiety and stress then manifest, ie, after waking up from an overnight sleep. Smoking again alleviates cravings and withdrawal symptoms, which provides positive reinforcement, further encouraging the smoking habit. The avoidance of withdrawal symptoms becomes a reason in itself to smoke. With regular smoking, certain cues may be associated with the habit: The mood modulation and arousal caused by nicotine may eventually be associated with the actions of, ie, rolling a cigarette, lighting it, and physical movement of smoking itself, separate to the direct pharmacological effect. The pairing of a significant stimulus or action like smoking or buying cigarettes with a certain signal like relief of anxiety will result in a conditioned response when the stimulus or action is performed.

Medications for Smoking Cessation

Nicotine replacement therapy (NRT) helps reduce withdrawal symptoms by replacing the nicotine from cigarettes with nicotine from alternative, safer forms such as gum, a transdermal patch, nasal spray, inhaler or sublingual tablets/lozenges. Studies indicate that all these types of delivery systems help people increase their chances of successfully stopping. A systematic review of 150 trials comparing NRT to placebo found that NRT increased quitting rates by about 50-to-70 per cent.⁶ No overall difference in effectiveness between the different forms of NRT was identified. However, combining a sustained delivery method, ie, the nicotine patch, with an additional rapid delivery preparation, such as gum, spray or lozenge, is more effective than use of one type of NRT by itself. When discontinuing the patch, abrupt withdrawal did not give rise to any difference in outcome compared to patch tapering. Furthermore, no significant difference in efficacy was observed between the 16-hour patch worn during waking hours only and 24-hour patch. In general, the side-effects from NRT use are mild and include hiccups, jaw pain, orodental problems (from the gum); and local irritation at the site of the patch. There is no association between NRT and an increased risk of adverse cardiovascular events in smokers with a history of cardiovascular disease.

Other smoking cessation medication available on prescription, such as bupropion (Zyban), provides a selective inhibitor of the neuronal re-uptake of catecholamines (noradrenaline and dopamine). When NRT use was compared with bupropion use, they were found to be equally effective. In contrast, a study found varenicline (Champix) to be superior to bupropion and NRT as a smoking cessation aid for both short and long term.⁷ Varenicline acts as a partial agonist at the ?4?2 neuronal nicotinic acetylcholine receptors. There is also evidence for the efficacy of nortriptyline and clonidine as second-line therapies for smoking cessation. 

Electronic Cigarettes

The use of electronic cigarettes (e-cigarettes) as a smoking aid has become increasingly controversial. Although non-combustible tobacco products have offered a way for adult smokers to move away from more harmful forms of nicotine delivery, it is important that these opportunities do not come at the expense of leading a generation of young people towards nicotine addiction. Young people who have tried e-cigarettes are more likely to try combustible tobacco products later.

There have been several recent newspaper reports based on a study by researchers in Germany published at the end of 2019 in the European Heart Journal.⁸ One report⁹ describes the damage of e-cigarettes to brain, heart, lungs and blood vessels; another is about the Irish Heart Foundation calling for a ban on all e-cigarette advertising.¹⁰ The results of the study in question strongly indicate that the perceived ‘safety’ of e-cigarette products (compared to tobacco) is not warranted. Contributing to the drive for this research is the increase in e-cigarette use among high school students in the US from 1.5 per cent to 20.8 per cent between 2011 and 2018. In addition, there are ongoing investigations on severe pulmonary disease and deaths among people using e-cigarettes in the US. The authors state that there is lack of clarity as to the overall population health consequences of e-cigarette use: A majority of available studies provide evidence that e-cigarette vaping is the ‘lesser of two evils’ when compared to tobacco cigarette smoking, but considering that e-cigarette vaping is associated with a decrease in the average age of first-time (e)-cigarette users, the ‘healthier’ e-cigarette profile might easily be negated by the higher portion of adolescent users.

In the study,⁸ experiments were performed in mice, administering unflavoured e-cigarette liquids with and without nicotine to determine the impact on vascular (endothelial) function. The researchers characterised the mechanisms behind oxidative stress and inflammation, and validated findings in human endothelial cells and in healthy smokers. 

Results show that in otherwise healthy smokers (n = 20), e-cigarette vapour exposure reduced arterial dilation, increased blood pressure, and increased arterial stiffness. This indicates induction of endothelial dysfunction by e-cigarette vaping. This dysfunction was also identified in mice and in human endothelial cells. 

Results show that the act of e-cigarette vaporisation adds additional toxicity to its components. This mechanism has been identified by the authors to be due to NADPH oxidase 2 (NOX-2) mediation, which induces oxidative stress. Toxic compounds including formaldehyde, acetaldehyde, butyraldehyde, and acrolein were identified in e-cigarette liquid, but to much larger extent in vapour condensate. 

To examine the toxicity of these vapour-enhanced products, cultured human endothelial cells were incubated with mixtures of these aldehydes. This resulted in concentration-dependent cell death and increased expression of the inflammatory marker COX-2. 

Overall, e-cigarette vapour exerts a broad negative influence on the vasculature due, in part, to vaporisation-enhanced aldehyde generation that activates NOX-2, leading to oxidative stress, inflammation, and endothelial dysfunction.

Much data in this publication seems to indicate that e-cigarette vapour shares many of the same adverse vascular consequences of traditional tobacco smoke. Both the smoking of combustible cigarettes and e-cigarettes increase oxidative stress and appear to degrade blood-brain barrier integrity and to induce vascular inflammation in endothelium. Likewise, both tobacco smoke and e-cigarette vapour induce cerebrovascular inflammation and post-stroke ischaemia/reperfusion damage in mice. 

After 10 years, lung cancer risk decreases to about half that of a smoker.

It has been estimated that 75-to-85 per cent of people who smoke would like to quit smoking. Pharmacists in the community, often the first point of contact with the health services, can help by providing these individuals with advice on smoking cessation.¹¹ As part of the conversation, the pharmacist can assess the readiness of the individual to quit and enquire about previous attempts. Pharmacists should discuss the potential withdrawal symptoms following smoking cessation (sleep disturbance, nausea, headache, dizziness, cough, mouth ulcers). These symptoms, along with the urge to smoke, can lead to relapse. Most withdrawal symptoms, however, stop after two-to-four weeks, so it is especially important for the individual to have support during this time.

The Irish website www.quit.ie offers further help and information for people who want to stop.