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Many pharmacologic approaches have been used to help people stop smoking. In current use are the nicotine replacement therapy (NRT) products and bupropion (Zyban, GlaxoSmithKline; Wellbutrin, GlaxoSmithKline). This chapter discusses methods for assisting the patient to stop smoking. The only drugs that are discussed in detail in this chapter are the NRT products because bupropion is discussed in Chapter 47. Many NRTs are now available OTC, but the patient still benefits from professional guidance on how to use these products.
Therapeutic Overview
Results of a 2012 national survey show that about 1 in 5 U.S. adults smoke cigarettes, a number unchanged since 2004, making it the leading preventable cause of disease and death in the nation. This contrasts with the decline in smoking seen between 1997 and 2004. Smoking is strongly correlated with age, with a new epidemic among school-age children, where almost 1 in 5 high school seniors reporting they regularly smoke, and nearly 90% of adult smokers reporting they started smoking by age 18. Currently an estimated 27.9% of those aged 18 to 24 smoke, followed by 27.3% of those aged 25 to 44, 23.3% of those aged 45 to 64, and only 10.5% of people who are 65 or older. (The relatively low number of older smokers may be due to the fact that many smokers die prematurely as a result of their smoking.) There is an inverse relationship with increased years of education.
Smoking has been associated with more than 420,000 deaths annually, causing risk for cancer of the lung, larynx, esophagus, and others. Cigarette smoking is associated with coronary artery disease/myocardial infarction, COPD, peripheral artery disease, and cerebrovascular disease. The combination of smoking, diabetes, and obesity is associated in many patients with actual shrinking of brain mass and dementia. Cancer and respiratory diseases have also been associated with passive (environmental) smoking. Women smokers have a higher risk of not only heart disease, but of some types of skin cancer. Early morning smokers seem to have the highest cancer risk for some reason. Nicotine and other tobacco-related components (e.g., tar and aromatic hydrocarbons) are probable causative factors for the psychologic and pathologic sequelae of smoking. For mothers who smoke while pregnant, their children were more likely to have problems with eczema and to end up on medications such as antidepressants, stimulants, and drugs for addiction. New research suggests that smoking may affect a baby’s developing brain. Individuals, especially children, who are subjected to passive smoke have a higher risk of developing asthma and childhood leukemia. Current research suggests that children already in danger of developing heart disease because of high cholesterol blood levels face a triple jeopardy if they live in smoke-filled homes, because the passive smoke lowers by about 10% the level of the child’s HDL, or the good cholesterol that protects against heart attacks.
Primary care is an ideal setting in which to institute smoking cessation measures. Most smokers see a primary care provider each year. The provider should screen all patients for smoking behaviors and should recommend that all patients stop smoking. In fact, some third-party payers or insurance companies now require preferred providers to ask about tobacco use and to document recommendations to quit. Some companies are starting to raise health insurance premiums if the purchaser is a smoker, and most life insurance companies already have higher rates for smokers.
Research suggests that many health care providers fail to take advantage of opportunities to recommend that the patient stop smoking. Primary care clinicians especially should be knowledgeable about the components of successful smoking cessation programs.
Although most smoking cessation therapy is aimed at cigarette smokers, cigars and chewing tobacco also contain nicotine and place the patient at risk. These smoking cessation products are helpful in patients who get nicotine from these other products.
Mechanism of Action
Nicotine is rapidly absorbed across the pulmonary capillary membrane and is delivered to the brain in high concentration within seconds of inhalation. The typical smoker (10 to 15 cigarettes/day) delivers 200 to 300 boluses of the addictive drug nicotine to the brain each day.
Nicotine increases heart rate, elevates blood pressure, causes peripheral vasoconstriction, enhances platelet aggregation and fibrinogen levels, decreases nitric oxide, and blunts its vasodilatory effects. It also increases carbon monoxide levels, and this reduces oxygen delivery to the myocardium. Nicotine activates the sympathetic nervous system and can induce coronary vasospasm. A risk of blood clots has been documented for young women on hormonal contraception and who smoke. Research has demonstrated that smokers may lose their cognitive abilities, such as remembering, thinking, or perceiving, more rapidly than elderly nonsmokers.
Cigarette smoking has been found to be particularly hazardous for those who already have some pathologic condition. The risk of vasospasm following subarachnoid hemorrhage is increased in smokers. Cigarette smoking exaggerates risk factors for cardiovascular disease by significantly increasing a protein known as thromboglobulin, which increases the activity and clotting functions of platelets in hypertensive smoking patients. Smoking also increases epinephrine, stimulating the heart and blood pressure in hypertensive patients who smoke.
Even patients who suffer from the results of smoking continue to engage in the behavior. Among smokers who undergo angioplasty or coronary artery bypass surgery, almost three in five continue to smoke after their procedure.
Nicotine, the chief alkaloid in tobacco products, binds stereoselectively to acetylcholine receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of CNS effects are believed to form the basis of nicotine’s positively reinforcing properties: (1) a simulating effect (exerted mainly in the cortex via the locus coeruleus), which increases alertness and cognitive performance, and (2) a reward effect via the “pleasure system” in the brain in the limbic system. At low doses, the stimulant effects predominate, whereas at high doses, the reward effects predominate.
Regular nicotine consumption through smoking is associated with neuroadaptation of nicotinic receptors, which results in increasing numbers of receptors and the development of tolerance and drug dependence. Symptoms from abrupt withdrawal include irritability, restlessness, anxiety, difficulty concentrating, lethargy, depression, increased appetite, weight gain, and minor somatic complaints (e.g., headache, myalgia, constipation, fatigue). These symptoms may be reduced through the use of nicotine-containing smoking deterrents, which produce lower nicotine plasma concentrations (approximately 3 to 17 ng/ml) than those achieved through smoking (approximately 20 to 50 ng/ml).
When the drugs that are helpful in nicotine addiction are examined, the mechanism of action for bupropion cannot be identified. Bupropion is an inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine. Another product, varenicline, partially stimulates nicotine receptors but to a lesser degree than nicotine does. It blocks the ability of nicotine to stimulate the dopamine system, which mediates the pleasurable effects of nicotine. It provides sufficient nicotine effects to decrease the urge to smoke and to ease withdrawal symptoms. If a patient restarts smoking while on varenicline, he or she will not experience the pleasurable effects of nicotine.
Treatment Principles
Evidence-Based Recommendations
Cardinal Points of Treatment
Nicotine replacement therapy does not improve relapse rate. Some patients will relapse regardless of whether they used nicotine replacement products with or without counseling. Table 72-1 lists actions and strategies for the primary care clinician from the Agency for Healthcare Research and Quality (AHRQ) guidelines. Research from the National Ambulatory Medical Care Surveys of 1991 through 1995 has documented that physicians reported counseling patients about smoking or prescribing nicotine replacement far less often than is called for by current practice guidelines, thus missing many opportunities to help their patients quit smoking.
TABLE 72-1
Actions and Strategies for the Primary Care Clinician to Use in Smoking Cessation
∗Repeated assessment is not necessary in the case of the adult who has never smoked or has not smoked for many years, and for whom this information is clearly documented in the medical record.
From The Smoking Cessation Clinical Practice Guideline Panel and Staff: The Agency for Healthcare Research and Quality smoking cessation clinical practice guideline, JAMA 275:1270, 1996.
Prevention and Early Intervention
Research suggests that most smokers want to quit. With each visit to a health care provider, it is critical to ask patients if they smoke and to help them take the next step if they are ready. Smoking cessation programs have a high rate of success. Smoking cessation is a process. Relapsing is often part of the process. Sometimes patients have to try to quit several times but these efforts should be viewed as trials not as failure. If patients do not smoke, praise them for their wisdom and encourage them not to start. This is very important in children and adolescents and former smokers. Emphasize the immediate effects of tobacco, such as bad breath, stains on the fingers and teeth, reduced exercise performance, and dry skin and hair. Early research on addiction suggests that patients are not fully addicted for 3 years after starting to smoke, so this is the time to encourage them to stop.
Pharmacotherapy reduces the physical effects of nicotine withdrawal but does not address the psychologic aspects of smoking cessation. The highest rate of smoking cessation is seen in those individuals who are able to just stop smoking “cold turkey” and avoid replacement therapy. However, many are not able to do this. Pharmacotherapy should be used in conjunction with a behavioral modification program. Brief advice (i.e., 5 minutes) has been shown to be helpful. The five A’s model is recommended as a foundation for counseling (see Table 72-1). Also, a GETQUIT Support Plan is available to assist all patients who are taking varenicline.
Components of Smoking Cessation
For all patients who do smoke, the provider should assess their willingness to attempt to quit (Figure 72-1). If they are unwilling or unready to quit, the provider should focus on motivational issues. The negative consequences of smoking also should be emphasized. Patients are not influenced often by remote events such as COPD or lung cancer but may be motivated by immediate effects such as fewer and milder respiratory infections or asthma. They may particularly respond to suggestions that they are hurting their family, particularly small or unborn children. Discuss the positive consequences of smoking cessation, such as saving money, tasting food better, and feeling better physically.
FIGURE 72-1 Smoking cessation algorithm. (Modified from Mushllin SB, Green HL, editors: Decision-making in medicine, ed 3, St Louis, 2008, Mosby.)
Once the patient is ready to try to quit, the provider should help the patient plan to quit and monitor his or her progress. The patient should be offered specific help on how to quit successfully. Brief interventions are often successful.
Most patients have tried unsuccessfully to quit. They should be encouraged to try again through reminders that most people who succeed in stopping smoking make several attempts before their final successful attempt. Each attempt should not be seen as a failure but as a trial for the next attempt. They should try to find out what went wrong the last time they tried and determine how they can plan to avoid the problem situation.
Nonpharmacologic Treatment
Nonpharmacologic therapies are the mainstay of therapy. How to encourage the patient to explore these strategies is the first critical treatment decision. Patients should have a realistic idea about the difficulty of smoking cessation. They probably will experience withdrawal symptoms such as craving, irritability, restlessness, and increased appetite. With a clear understanding of the difficulties, the patient should set a realistic quit date.
Find out why the patient uses nicotine. Is it for stimulation, handling, pleasure, stress reduction, or weight reduction, or does it result from feelings of social pressure, craving, or habit? The patient then should develop specific strategies to cope with reasons for smoking. Patients for whom smoking is a habit should plan to alter their patterns of behavior to avoid common cues to light a cigarette. Those who like to handle cigarettes need to find something to keep their hands busy to replace handling cigarettes. Patients who use cigarettes for stimulation should replace cigarettes with another stimulating exercise, such as walking, and should avoid fatigue. Other methods of stress reduction such as deep breathing or other relaxation exercises should be encouraged. Weight lifting and vigorous exercise almost doubles the chance of smoking cessation in some studies.
All patients should make plans for how to handle difficult situations. Exercise such as walking can promote a feeling of well-being. Patients should set up a reward system for staying nicotine free, such as using the money saved to buy something they have been wanting.
Many patients are concerned about weight gain if they stop smoking. They should be warned that they may gain weight, but that watching their diet and increasing their exercise can minimize this. They should prepare themselves by having healthful, low-calorie meals and snacks available.
Specific nonpharmacologic approaches include aversive conditioning, hypnosis, acupuncture, behavior modification, and multicomponent programs. Intensive treatment programs are often necessary for patients who have great difficulty stopping and have failed several times.
Pharmacologic Treatment
When patients commit to stopping smoking, they often feel a loss of control of their lives. It may be helpful to describe different forms of smoking cessation therapy and to have them help select the mechanism. Nicotine replacement therapy (NRT) is often especially good for patients who are heavily dependent on nicotine and who smoke more than two packs a day. However, NRT may be offered to most patients as an option.
Make sure the patient receives an adequate dose; one of the main reasons for failure of nicotine treatment is underdosing. Another cause of failure is incorrect use of the product.
First, help the patient choose the dosage form that will work best for him. The patch is usually best for patients who smoke at regular intervals. Gum may work better for patients who smoke at irregular intervals. The patch offers a more convenient, once-a-day application. Gum offers more direct control of the amount of nicotine the patient receives. The gum can be used when the patient has a craving. The nasal spray is useful for responding quickly to a craving. The nasal spray is especially beneficial for highly dependent smokers. The inhaler mimics the act of smoking and will be useful for patients who enjoy handling cigarettes. Conversely, this technique may interfere with the need to change behavior, and patients eventually will have to learn to break the habit of handling something if they are to be successful. The inhaler is also useful when gum will not work because of concomitant consumption of acidic foods or beverages, alcohol, or coffee. Social occasions involving alcohol are often especially difficult, and the inhaler might be most acceptable in this situation. Gum might be more acceptable at work. Patients who have a stomach ulcer or diabetes should not use gum or lozenges but may use patches. However, patients who have an allergy to adhesive tape or preexisting skin problems should not choose NicoDerm CQ or Nicotrol. All replacement products are meant for those who smoke more than 10 cigarettes a day. Nicorette 2 mg is used for those who smoke fewer than 25 cigarettes daily; Nicorette 4 mg is best for those who smoke 25 or more cigarettes daily. Commit Lozenges use a different index for the initial choice. Those who smoke their first cigarette more than 30 minutes after waking should begin with the 2-mg lozenge, and those who smoke their first cigarette within 30 minutes of waking should begin by using the 4-mg lozenge.
Although many NRT products are now available OTC, certain patient populations should seek the advice of a health professional before starting therapy, particularly with the patch. These include people younger than 18 years, those with heart disease or an irregular heartbeat or who have had a recent heart attack, people with high blood pressure that is not controlled with medication, those taking prescription medicine for depression or asthma, and people with skin problems or who are allergic to adhesive tape. Pregnant or nursing women first should try to stop smoking without the nicotine patch and should seek the advice of a health professional before using a nicotine patch. Previously, no health insurance plan covered these medications. However, recently, Medicare has been paying for smoking cessation counseling for patients who have health problems caused by their smoking.
Many people are concerned about the safety of using NRT. The risk of using NRT must be weighed against the risk of continued smoking, as well as the risk of using the patch while smoking. Cigarette smoking is known to promote myocardial ischemia. This can be seen on an ECG in patients with CAD who smoke a cigarette. Patients with CAD may be especially vulnerable to the ischemic effects of nicotine. Studies have shown that patients with CAD who use NRT to stop smoking do not have an increased incidence of adverse cardiac effects. NRT has been shown to have no platelet activation effects and no clinically meaningful effects on heart rate and blood pressure. It is especially important that patients with CAD stop smoking for their health, and NRT has proved safe and effective in this population.
Whatever method is chosen, the patient should use only one particular product. Patches cannot be combined with gum or lozenges. While using any product, the patient must not use nicotine in any form (e.g., cigars, cigarettes, dip, snuff, pipes). Additional use of any of these products may cause serious nicotine toxicity.
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