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Smoke out your nicotine habit

By Irish Pharmacist - 02nd Dec 2023

There are numerous health benefits associated with smoking cessation, and even if a patient is already diagnosed with heart disease or COPD, there is a great improvement in their prognosis if they stop smoking, writes Damien O’Brien

Cigarette smoke contains more than 400 toxins, with at least 69 known carcinogens. Nicotine is one of the main components of cigarettes and is very addictive. Smoking harms nearly every organ in the body and can often lead to disease and disability. Cigarette smoking is the leading cause of preventable disease, disability, and death. A 2019 Healthy Ireland survey with a representative of the Irish population has showed that 17 per cent of the population are smokers, with 14 per cent smoking daily and 3 per cent smoking occasionally. Men are more likely to be smokers, with 19 per cent of men being smokers compared to 16 per cent of women. A total of 26 per cent of people in the 25- to 34-year-old group are smokers, which is the highest age category.

Tobacco kills up to eight million people in the world each year, including 1.3 million people exposed to second-hand smoke. Smoking greatly increases the risk of developing cancer, with 90 per cent of lung cancers due to smoking. Smoking can also increase the risk of many other cancers including mouth, throat, larynx, oesophagus, liver, pancreas, stomach, bladder, bowel, cervix, and kidney. Smoking also damages the cardiovascular system and blood circulation, and increases the risk of conditions such as coronary heart disease, hypertension, myocardial infarction, stroke, peripheral vascular disease and cerebrovascular disease. Smoking also damages the respiratory system and can lead to chronic obstructive pulmonary disease (COPD), pneumonia, asthma flare-ups, and respiratory tract infections.

Smoking can lead to erectile dysfunction in men due to reduced blood supply, and can also reduce fertility in both men and women. Finally, smoking can delay the body’s recovery from surgery and infections. Smoking during pregnancy is dangerous for both mother and baby. Smoking increases the risk of complications such as miscarriage, premature birth, low birth weight, and stillbirth. Complications at birth and later in life are possible with smoking during pregnancy, and these include sudden infant death syndrome, infections, and asthma. Smoking cessation should be encouraged in all pregnant women at all stages of pregnancy.

Nicotine, although not completely benign, is not as dangerous as some of the other chemicals found in tobacco. However, it is a highly addictive chemical. When tobacco is inhaled, it enters the bloodstream via the pulmonary circulation system and therefore avoids first pass metabolism and liver metabolism. It rapidly crosses the blood-brain barrier, which only takes about two to eight seconds from the time of inhalation. It binds to nicotinic cholinergic receptors in the brain and has a half-life of approximately two hours. Nicotine acutely causes an increase in activity in the brain and stimulates the release of neurotransmitters, predominantly dopamine, but also noradrenaline, acetylcholine, serotonin, GABA, and endorphins. This activates the reward pathways and leads to the pleasurable feeling that people may get from smoking. After repeated exposure to nicotine, nicotinic receptors are upregulated and may be desensitised, which leads to the development of tolerance. Nicotine is also a sympathomimetic drug that leads to catecholamines release and increases heart rate, increases cardiac contractility, constricts blood vessels, and increases blood pressure.

Due to the addictive nature of tobacco, smoking cessation is very difficult. A total of 46 per cent of those who smoke have attempted to quit in the past 12 months, while a mere 25 per cent of attempts have been successful. The main motivation for 67 per cent of individuals to stop smoking is a health concern, with about 10 per cent stopping due to a concern over cost. A total of 52 per cent of those who have successfully quit smoking in the last 12 months quit using only willpower. Treatment options are available to help an individual stop smoking.

There are numerous health benefits associated with smoking cessation, some of which are felt immediately, and some which are seen in the longer term. The sooner an individual stops, the greater the reduction in risk. Patients of all ages should be encouraged to stop smoking. If an individual stops smoking before the age of 35, their life expectancy is only slightly shorter than that of people who have never smoked. If an individual stops smoking before the age of 50, their risk of mortality from smoking-related disease decreases by 50 per cent. Even if a patient is already diagnosed with heart disease or COPD, there is a great improvement in their prognosis if they stop smoking. Numerous other benefits exist including improved circulation, reduced respiratory symptoms, reduced risk of cardiovascular disease, and reduced risk of cancer.

Treatment

Due to the numerous health benefits associated with smoking cessation, treatment is often necessary. However, due to the highly addictive nature of nicotine, cessation can be extremely difficult. A total of 52 per cent of those who have quit in the last 12 months have used willpower alone, but treatment is still an important option and can help many people. There are several pharmacological and non-pharmacological treatment options available.

Pharmacological

Nicotine replacement therapy (NRT)

Due to the fact that almost all the toxicity in tobacco is due to other components, NRT is a safe and effective treatment option in smoking cessation. NRT has the objective of delivering nicotine to the patient to reduce the motivation to consume tobacco, and reduce physiological and psychomotor withdrawal symptoms. Evidence has demonstrated that NRT is very effective in helping patients to quit smoking, increasing cessation rates by 50-70 per cent compared to placebo, and it is therefore recommended as a first-line treatment for smoking cessation. NRT products come in several different formulations and include a transdermal patch, gum, oromucosal spray, lozenge, and oral inhaler. Different formulations can be used to provide general relief of cravings and breakthrough craving relief. All the different delivery methods can have differing levels of efficacy, but they are most effective when the patient also receives smoking cessation counselling. However, they can also be effective as monotherapy.

Transdermal nicotine patches are applied to the skin and deliver nicotine through it. Patches are available in a range of dosages, which allows users to gradually decrease their nicotine over a period of time to allow an incremental adjustment. Patches can help with compliance, and allow nicotine plasma concentrations to remain relatively steady. The most common adverse effects are local skin reactions and sleep disturbance.

Nicotine gum delivers nicotine across the mucosal membrane – it is intermittently chewed and held in the mouth for about 30 minutes to allow nicotine absorption. It is available in both 2mg and 4mg dosage forms – with 2mg dosage indicated for smokers of less than 20 cigarettes per day and 4mg dosage indicated for smokers of more than 20 cigarettes per day. Gum is a rapidly absorbed form of NRT and can be used in conjunction with a transdermal patch. The number of doses per day can be gradually reduced over a number of weeks or months. Common side effects include mouth irritation, gastric irritation, jaw pain, nausea, vomiting, excess salivation, and headaches. Lozenges are very similar to gum as they are also absorbed across the buccal mucosa membrane, and it comes in the same dosages. It provides a useful alternative to gum for individuals who need intermittent nicotine dosing but don’t enjoy the gum. It has a very similar adverse effect profile to nicotine gum.

The nicotine oral inhaler consists of a plastic cartridge containing nicotine and a mouthpiece to allow delivery of nicotine. It mimics the ‘hand-to-mouth’ habit of cigarette smoking, while also delivering nicotine that reduces physiological withdrawal symptoms. The majority of nicotine is delivered to the oral cavity, oesophagus and stomach. Similar to other formulations, the dosage should be reduced gradually over six to 12 weeks. The most common side effects include mouth and throat irritation, and cough.

Other formulation options, including oromucosal spray and nasal spray, are also available. The nasal spray is absorbed more quickly than those which are absorbed via the oral mucosa, which provides a more rapid increase in plasma nicotine concentration. Dosage is reduced over six to 12 weeks, similarly to other formulations. Adverse effects tend to be localised to the site of administration.

Bupropion

Bupropion is an antidepressant that works by inhibiting noradrenaline and dopamine reuptake, and therefore increases their levels in the brain. It is not fully clear how bupropion exerts its mechanism of action in smoking cessation, but it is thought that it may act as an antagonist at the nicotinic receptor. Additionally, it may be due to the involvement of dopaminergic pathways in the reward circuit of drug dependence. Prolonged-release bupropion has been shown to be effective in helping smokers quit smoking, with a similar efficacy to NRT. It can also be used in combination with NRT, which is more effective than both as monotherapy. Use is not recommended for those aged under 18 years, and should be used with caution in the elderly with a maximum dose of 150mg daily.

Bupropion is started one to two weeks before the patient plans to quit smoking at a 150mg daily dose. On day seven, the dose should be increased to 150mg twice daily for seven to nine weeks, with or without food. If there is no improvement after seven weeks, treatment should be discontinued. Bupropion can be continued for up to one year if abstinence is attained. The maximum single dose is 150mg and the maximum daily dose is 300mg. The main side effects include insomnia, headache, dizziness, weight loss, nausea, and vomiting. Insomnia is very common but can be avoided by avoiding bedtime doses, provided there are at least eight hours between doses. Some contraindications of bupropion include a history of seizures, anorexia, abrupt withdrawal from alcohol, bipolar disorder, and concomitant use with monamine-oxidase inhibitors.

Varenicline

Varenicline is a partial agonist on two nicotinic receptors, which mediates the release of dopamine. This partial agonism helps to decrease the intensity of withdrawal symptoms. It also reduces nicotine binding to the receptor which generates the reward effect, and thereby reduces the pleasure from nicotine consumption. Varenicline has been demonstrated to be effective in achieving abstinence, and has been shown to be superior as monotherapy in comparison to placebo, bupropion, and NRT. It may be used in combination with NRT for greater efficacy. This may be due to the fact that both individual drugs have a partial agonist effect which can lead to a synergistic effect. It may also be due to both drugs having an effect on different receptors. Additionally, NRT products can be useful as they allow ‘as required’ dosing for breakthrough withdrawal symptoms.

The patient should set a date to quit smoking and varenicline should start one to two weeks before this date and continue for 12 weeks in total. The recommended dosing schedule is 0.5mg once daily for three days, followed by 0.5mg twice daily for four days and followed by 1mg twice daily until the end of treatment. Varenicline can be taken with or without food. For patients who have stopped smoking after 12 weeks of treatment, another 12-week course may be considered up to a total of 24 weeks of treatment. In patients with adverse effects, lower doses may be used. No dosage adjustment is necessary for the elderly, but dosage reduction is necessary for patients with decreased renal function. Common side effects of varenicline include abnormal dreams, insomnia, headache, weight gain, nasopharyngitis, and nausea.

The only main contraindication is a history of hypersensitivity reactions to varenicline, but some caution may be required. It should be used with caution in patients with a history of seizures. Patients should be advised to notify their doctor of cardiovascular symptoms after commencing therapy. Post-marketing reports of neuropsychiatric effects, including depression and suicidal ideation, have been reported with use of varenicline. This led to observational studies, randomised clinical trial, and meta-analyses which concluded that the use of varenicline is not associated with an increase in suicide ideation or other neuropsychiatric events. Depressed mood is sometimes a symptom of nicotine withdrawal, so consideration should be given to possible neuropsychiatric symptoms in smoking cessation and treatment re-evaluated.

Non-Pharmacological

Complementary and alternative medicine

Some complementary and alternative medicine practices are often used as either monotherapy or in combination with another method for smoking cessation. Hypnotherapy is often used but studies have shown it does not have a greater effect on six-month quitting rates than no interventions. A systematic review demonstrated that yoga and meditation therapies may have some effectiveness in smoking cessation, but larger, high-quality studies are needed. They are considered relatively safe when practised with a well-trained instructor. Some studies have suggested possible short-term benefits with acupuncture but there is no consistent evidence to suggest long-term positive effects on smoking cessation. When acupuncture is not delivered appropriately, it can lead to adverse effects including infections and punctured organs. These complementary and alternative methods have the benefit of being used as combination therapy with pharmacological treatments, and they can be safe when delivered correctly by an appropriate practitioner.

Counselling

Many psychological interventions to assist smoking cessation exist, and include self-help materials, multisession group therapy, intensive counselling delivered on an individual basis, or advice from a healthcare professional. Self-help materials may have a small effect on cessation rates, but the evidence is unclear. Group-based therapy has been shown to help a person to stop smoking, while there is clear evidence that individual counselling increases the likelihood of cessation compared to no support or less intensive support. All of the pharmacological treatment options, including NRT, varenicline, and bupropion, are more effective when combined with counselling.

Pharmacist’s role

Pharmacists can make a significant contribution in the promotion of smoking cessation. Pharmacists have the knowledge and communication skills to effectively counsel patients on the pharmacological treatment of smoking. This can include information on how to take the medication, potential adverse effects, the importance of compliance, and duration of treatment. Pharmacists can also contribute with the motivation and behavioural approach due to their closeness with the population, accessibility, and ability to reinforce smoking cessation interventions. Evidence has shown that greater contact with a healthcare professional through follow-ups increases the chance of success with smoking cessation programmes. Studies have shown that smokers who had thorough follow-ups with pharmacists had a greater chance of giving up smoking compared to smokers who had fewer sessions with a pharmacist. l

References on request

Disclaimer: Brands mentioned in this article are meant as example only and not meant as preference to other brands.

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