Contact Terry Maguire by email for Smoking Cessation Help and Advice.

Smoking

The dangers of smoking have been known since the 1960s, however the long-term risk was only fully quantified in the 1990s with the publication of a 40 year cohort study of British doctors.  Comparing overall survival of smokers with non-smokers between 1951 and 1991, this study found that in those aged 39 to 69 years (“middle-age”), 41% of smokers died compared to 20% of non-smokers.  In those who smoked 25 or more cigarettes daily, 50% died in middle-age.  It has been estimated that in 2000 there were 114,000 UK deaths attributable to smoking that equates to 22% of all male and 16% of all female deaths.

Smoking is an important cause of cancers of the lung, larynx, pharynx, oesophagus, bladder, kidney and pancreas.  Overall, around 1/3rd of cancer deaths in men (36%) and 1/5th in women (21%) are attributable to smoking.    Smoking is an important cause of cardiovascular disease.  The British doctors’ cohort study found that mortality from coronary heart disease was 50% higher in smokers (over 75% in heavy smokers) than in non-smokers.  Overall, over 1/8th of cardiovascular deaths (14% in men;12% in women) are attributable to smoking.

Smoking is the main cause of chronic obstructive lung disease (COPD) and a cause of pneumonia and also causes or aggravates a wide variety of non-fatal illnesses including asthma, osteoporosis, peptic ulcer, erectile dysfunction, chronic rhinitis and multiple sclerosis.

Stopping smoking has major health benefits.  Smokers who quit before the age of about 35 years have a life expectancy only slightly less than a non-smoker and quitting at any age provides both immediate and long-term health benefits.

Smoking Cessation Services

Smoking cessation services have been shown to be successful.   Currently 1 in 7 (14.6%) of users of the English Smoking Treatment Service successfully stopped smoking and were still not smoking after 52 weeks.  The study noted that older users, those who smoked for pleasure (rather than to cope) and those who were extremely determined were more likely to quit whereas those from low socio-economic groups, who smoked their first cigarette of the day within 5 minutes of waking or had another smoker in the house were less likely to succeed.  

Similar success rates have been demonstrated in pharmacy based smoking cessation services with 14.3% of smokers who used a combination of pharmacist support plus NRT still not smoking after 52 weeks.  This compared to 2.7% in a control group that did not receive behavioural support but did use NRT.  This shows the impact of behavioural support in smoking cessation initiatives – the more intense the behavioural support the greater the cessation rates at 52 weeks. 

Table 2

Stopping smoking and pharmacy

Most pharmacists agree they have a role in smoking cessation but can identify a number of barriers to doing more in this important area of public health.     Barriers identified included; money and time to provide a service, the lack of know-how or training.   Space may not be readily available within the pharmacy for one-to-one consultation.  Yet  there are considerable benefits from providing smoking cessation services to the pharmacy business and to the profession.

Tackling the barriers

The pharmacy smoking cessation services now provided across the UK are designed to minimise barriers to involvement.  Pharmacies can create profitable income streams from smoking cessation through service payments and sales of NRT products.    Training is available from many organisations.   Yet many pharmacists still view smoking cessation with ambivalence.  Few pharmacists would suggest smoking cessation is not a role for pharmacy but many fail to take a more active role.  In light of what we now know about smoking and its effects on health, it could be viewed as unethical to ignore smoking status during a professional encounter.  

Smokers’ opinions of stopping.

A survey by the Health Education Authority (1996) gave an important insight to smokers needs when stopping.  Smokers believed willpower was key to success and that most products and services do not impact on personal willpower.  Interestingly the survey identified a stigma associated with seeking help to quit smoking.    Smokers didn’t like help from “medical” personnel as they perceived them as “bullying”.   This point has been endorsed recently in a consumers’ survey which showed that 33% of smokers worried about asking their GP for NRT whereas in the same survey 88% said that they would be comfortable approaching their pharmacist  for advice.

In the HEA survey 50% of the smokers were reluctant to use NRT as they thought it caused cancer.  A more recent (2005) survey has shown that public concerns about the safety of  NRT remains a major barrier to the use of  NRT products.

Stopping

Stopping, for many smokers, is difficult.  To succeed, they require education, support and motivation.  Smoking is addictive in three ways;

Willpower alone is not sufficient for the vast majority of smokers.   Behaviour support plus use of NRT or buproprion have been shown to significantly improve the chances of success.  

NRT Formulations

Six formulations of NRT are currently licensed in the UK: chewing gum, transdermal patch, inhalator, lozenges, sublingual tablet and nasal spray.  All are P or GSL medicines. Some were switched to GSL in recent years to improve availability but there is little evidence that this improves cessation rates and it seems that the intervention of a healthcare professional, providing support and encouragement, is important. 

All NRT formulations are available on Health Service prescription which allows their inclusion in PDGs – a tool by which pharmacies can be paid for supply of NRT.   There is little good research to show that any one formulation is superior to another.   However, patient preference is important since if happy with the form of NRT the more likely they are to comply with the regimen and complete the required course of treatment.    It has been shown in a number of studies that many smokers using NRT in a quitting attempt fail too use sufficient NRT to suppress withdrawal symptoms and in this case are likely to blame the NRT product if the quitting attempt fails.

Nicotine blood levels from NRT formulations (maximum daily dose) are generally  30% of the levels seen in smokers who smoke  20 cigarettes per day.  The problem of overdose with NRT products is widely exaggerated. (Figure 2)
 
Chewing Gum

Gum comes in two strengths 2mg and 4 mg per piece.  Nicotine is released from the gum usually over 30 minutes of intermittent chewing and is mainly absorbed through the buccal mucosa.  The recommended dosage is 8 to 12 pieces of the 2mg gum with a maximum daily dose of 15 pieces of the 4 mg gum.   Proper instructions on use of the gum must be given so that smokers can benefit and avoid adverse effects.  

It’s important that clients keep to the chewing cycle.  Users should chew the gum until the taste becomes strong, then the gum is parked between the gum and the teeth, when the taste fades the gum is taken back into the mouth and chewed until the taste becomes strong.   This cycle is repeated over a 20 to 30 minute period for one piece of gum.  Normally if a person smokes more than 20 cigarettes per day and smokes within 20 minutes of rising, they should start with the 4 mg gum.  This is called the twenty-twenty rule and is used to determine the starting patch dose also – if the smokers fits the twenty-twenty rule they use the highest formulation.

Patches

Patches provide a steady state blood level of nicotine and do not mimic the peaks and troughs provided by other formulations.  They are normally used for 10 to 12 weeks and come in three dosage levels which, over the weeks reduce the blood nicotine levels.    Patches are divided into those that are use for 16 hours (taken off before sleep) and those that are 24 hours.   Once removed the nicotine blood level falls off rapidly and therefore the use of the16 hour patch avoids sleep disturbance.

Nasal Spray

Nicotine nasal spray consists of 10mg/ml of nicotine solution with a metered dosage delivery device.  A single spray to the nostril delivers 0.5mg of nicotine.  This is rapidly absorbed mostly through the lining of the nose.  Peak plasma concentrations of nicotine are reached within 10 - 15 minutes.  (Nicotine from a cigarette will reach these levels seconds after inhalation).  The manufactures recommends one spray in each nostril, as required, up to a maximum of twice hourly for 16 hours in every 24 hours.   It is targeted at, and there is some evidence that it has an effect,  those patients who are highly dependent on nicotine – 40 to 60 cigarettes per day.

Inhalator

The inhalator involves  a replaceable nicotine cartridge that is placed in a holder with mouth piece.  Sucking on the inhalator allows nicotine vapour to be drawn into the mouth where it is absorbed into the blood via the buccal mucosa. No  nicotine reaches the lungs.  Each cartridge is used for a 20 minute session.   Manufacturers advise that 6 to 12 cartridges are used daily for the first 8 weeks then reducing to zero in the next 4 weeks.

Sublingual tablets

The sublingual tablet is held under the tongue and allowed to dissolve over a thirty- minute period, during which it releases 2 mg of nicotine, 1 mg of which is absorbed. through the buccal mucosa.   Manufacturers recommend 1-2 tablets hourly, depending on usual cigarette consumption, up to to a maximum of 40 tablets per day.

Lozenge

Three strengths of lozenge are available; 1mg,   2mg and  4 mg.   The lozenge is moved around the mouth   and over   15 to 20 minutes it disintegrate in saliva  releasing nicotine  that is absorbed buccally – they are sugar free.   The 2mg and 4 mg lozenge use a different means, from other formulation, in establishing the starting dose.  Those who smoke within 30 minutes of getting out of bed  use the 4mg strength those who smoke after this use the 2 mg.  This is not dependent on the number of cigarettes smoked.       In addition, rather than change to a lower  strength after 6 weeks users stay with the same strength but reduce numbers of lozenges used daily.

Is Nicotine Dangerous?

Nicotine is only one element of tobacco smoke.  The “tar” produced by smoking contains at least 4,000 different chemicals, including 50 known carcinogens.  Other disease-causing elements include carbon monoxide, oxides of nitrogen and hydrogen cyanide.  In essence nicotine, on it own, is as dangerous as caffeine and therefore presents little danger to public health.

Nicotine Delivery

Inhaling tobacco smoke is a highly efficient method of absorbing nicotine into the blood stream.  The amount absorbed from each cigarette is typically 1-2mg and it produces a rapid “hit” with the arterial peak nicotine levels 40-100ng/ml at about 15-30 seconds and a venous peak at about 5 minutes.  These sharp peaks and troughs tend to rise over the first 6 –8 hours of the day with regular smoking and nicotine blood levels are also detected first thing in the morning (before the first smoke of the day) in regular smokers.  It is the arterial peaks that are linked to the positive reinforcement of nicotine as an addictive drug.   

In contrast nicotine from NRT products does not produce arterial peaks as nicotine is delivered to the blood stream more slowly than from a cigarette, over a period of minutes from oral and nasal products, and hours from a patch, and achieves lower venous blood nicotine levels than does smoking.  Therefore the purpose of NRT is not to provide the “hit” achieved with cigarettes but to produce a nicotine blood level that reduces “withdrawal”.

The Evidence and New CSM guidance

With over 120 robust, well conducted clinical studies on the efficacy and safety of NRT there still remains concern that access to NRT is hampered by a public perception that NRT, like cigarette smoking, presents a risk to health.
 
New CSM recommendations were issued in January 2006 and now support the availability of NRT for;

 In addition,

Adolescents

It is estimated that there are approximately 375,000 young regular smokers in the UK, with the proportion of regular smokers increasing with age; 1% of 11 year olds in England smoke regularly compared to 23% of 15 year olds.  Stopping teenagers smoking would prevent decades of continued tobacco use and subsequent ill-health.
 

 Smoking and cardiovascular disease

Smoking is a major risk factor in cardiovascular disease with cigarette smoking causing acute cardiac events by at least three mechanisms

However, the action of nicotine per se is considered to be the least important of these mechanisms.   When initially introduced there were concerns that NRT could precipitate cardiovascular events in susceptible individuals, because of nicotine’s ability to cause constriction of blood vessels and there have been a few anecdotal reports of smokers on NRT developing angina and atrial fibrillation.  However, there has been a considerable amount of work on the use of NRT in this population of smokers and the data generated indicates that for smokers who have stable cardiovascular disease, those not in hospital, the benefits of using NRT to quit smoking out-weigh any risks there may be with NRT

Smoking in pregnancy

It is well established that smoking during pregnancy can result in miscarriage, premature birth, still-birth and low-weight babies.    There is also a risk of increased neonatal mortality and sudden death syndrome (SIDS) and may even be longer term effects in the children of mothers who smoked during pregnancy such as respiratory disorders and increased cognitive/behavioural problems.

There are some data on the use of NRT in pregnancy but the results, to date, have not clearly shown that NRT helped pregnant patients to stop smoking.  However, the studies were small and not always of a design that would allow the results to determine whether NRT was effective or not.  In addition, nicotine is more rapidly metabolised in pregnancy, so NRT theoretically could be less effective.  NRT (gums and patches) has been shown to cause dose-related increase in maternal blood pressure and heart rate with lesser effects on the fetal heart rate, but these changes are less pronounced than those caused by smoking.

Nicotine is both water and lipid-soluble and has a wide volume of distribution in the body, freely passing in and out of breast milk, with concentrations rising and falling in line with maternal plasma levels.  In smokers, concentrations in breast milk are highly dependent on the number of cigarettes smoked, the frequency of breast-feeding and the time between smoking and breast-feeding.  It has been estimated that breast milk of heavy smokers may contain 0.5mg of nicotine/litre.  It is not clear how much nicotine is transferred into breast milk from NRT.

The CSM Working Group advised that pregnancy and lactation should not be a contraindication to the use of NRT and the warnings in the product information should be revised and put into the context of the dangers of continuing to smoke.  Ideally a pregnant woman should stop smoking without NRT, but if this is not possible, NRT could be recommended to assist a quit attempt as the risk of using NRT on the feotus is lower than expected with tobacco smoking and also there is no exposure to the other dangerous elements.  However, as nicotine does pass to the fetus, the decision to use NRT should be made as early on in pregnancy as possible with the aim of discontinuing after 2-3 months use.

Cutting down to stop

Until recently, in the UK, NRT was only authorised for stopping smoking abruptly, although there was evidence that smoking reduction was effective. 

Seven well-designed, double-blind, randomised and placebo-controlled studies demonstrate efficacy and safety in this context – 5 with nicotine gum and 2 with a nicotine containing inhalator.  The primary objective of all studies was a sustained reduction in the number of cigarettes smoked daily by at least 50% with secondary objectives including complete abstinence and the intention and attitudes to stopping smoking.  All studies recruited subjects who smoked at least 15 cigarettes a day and who were interested in reducing their smoking but were unable, unwilling or not planning to quit at the time.

Over 2,500 smokers were recruited and overall the studies showed a significant reduction in smoking compared with placebo with 16% of subjects on NRT becoming “sustained reducers” (i.e. reduced their cigarette consumption by 50%).

Adverse events in the smoking reduction studies did not substantially differ from those seen in other smoking cessation studies.

Combination therapy

There is evidence that the use of a combinations of, for example, gum and patch is more effective than using the products alone.    The clinical rationale for such an application is that the patch would produce a “background” level of nicotine and that the oral form would provide a speedily absorbed supplement when required.  There is some good evidence of safety and efficacy to support this indication and in the near future MHRA will licence a combination product.  However, MHRA has now removed the contraindication of use of two products concomitantly which opens the way for combinations of formulations to be used.

Interactions with NRT

To date the product information for NRT has contained interactions that may occur as a result of quitting smoking rather from NRT per se.  The only interaction that is possibly directly attributable to NRT is with adenosine (adverse haemodynamic effects).  The revised product information for NRT will take this into account.  In other words there are no clinically relevant drug drug interaction listed for NRT.

Varenicline is new drug entity and will be launched by Pfizer late in 2006.
Varenicline binds with high affinity and selectivity at the α4β2 neuronal nicotinic acetylcholine receptors, where it acts as a partial agonist - a compound that has both agonist activity, with lower intrinsic efficacy than nicotine, and antagonist activities in the presence of nicotine.

Varenicline is indicated for smoking cessation in adults.  As with all smoking cessation aids the SMP suggests that smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided with additional advice and support.

The recommended dose of varenilcine is 1 mg twice daily following a 1-week titration as follows:

The patient should set a date to stop smoking. Varenicline dosing should start 1-2 weeks before this date.

Patients should be treated with varenicline for 12 weeks.  For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with varenicline at 1 mg twice daily is allowed and there is some evidence that it increases the likelihood of long-term abstinence.

The main adverse effects associated with use of the drug were nausea sleep disturbances.

The efficacy of varenicline in smoking cessation was demonstrated in 3 clinical trials involving chronic cigarette smokers (³10 cigarettes per day).
Twoidentical double-blind clinical trials prospectively compared the efficacy of varenicline (1 mg twice daily), sustained release bupropion (150 mg twice daily) and placebo in smoking cessation.  In these 52-week duration studies, patients received treatment for 12 weeks, followed by a 40-week non-treatment phase.

The primary endpoint of the two studies was the carbon monoxide (CO) confirmed, 4-week continuous quit rate from week 9 to week 12.  The primary endpoint for varenicline demonstrated statistical superiority to bupropion and placebo with quit rates of  44.4% for varenicline, 29.5% for buproprion and 17.7% for placebo.  These rate fell of to 22.1%, 16.4% and  8.4% respectively at 52 weeks.

Some caution is required in interpreting these results as the high success rate in the placebo group indicates a high level of support for smoking in the study and this is unlikely to be replicated in normal practice.

Conclusion

NRT is safe and effective and should be used by smokers wishing to quit.  The recommendations issued by CSM and adopted by MHRA will go some way to reducing one of the barriers that smokers had with NRT particularly that it presents a risk to health.   Pharmacists and their support staff can contribute to getting this message across not only to those wishing to stop but to all smokers as now there are more ways to use NRT in reducing the impact of smoking on health.  But equally pharmacies should provide smoking cessation services that addresses the behavioural change needed to stop smoking.