Course Authors

E. Neil Schachter, M.D.

Dr. Schachter reports no commercial conflict of interest.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

Learning Objectives

Upon completion of this Cyberounds^®, you should be able to:

• Relate the key historical events in the marketing of cigarettes in the US

• Describe the patterns of "onset" and quitting among smokers by sex, age and race

• Distinguish the four delivery systems for nicotine replacement

• Describe the mechanism for non-nicotine pharmacotherapy for smoking cessation.

 

Introduction

With over 50 million Americans addicted to cigarette smoking, the health consequences of tobacco remain a major public health issue in this country. Thirty-two percent of the male and 27 percent of the female population smoke. Each year 17 million Americans attempt to quit and, of those, less than 10% are successful (1.3 million). The health consequences are staggering. It is estimated that cigarette smoking accounts for 434,000 premature deaths each year, the majority of which are cardiovascular (202,000), neoplastic (142,000) and respiratory (83,000). This amounts to more than one thousand excess deaths daily.

Smoking accounts for more deaths than all other addictions combined (alcohol, heroin, cocaine and crack). If you add to the "addictive deaths," those due to homicide, suicide, car accidents and AIDS, the number of smoking related deaths still exceeds the total for all categories.

Smoking in America

Tobacco was in use in America before Columbus arrived. Large quantities were consumed in the form of chewing tobacco, snuff, pipes and cigars in the eighteenth and nineteenth centuries. Cigarettes, as a form of tobacco use, were uncommon before 1900. Their popularization was the result of the invention of machinery to manufacture large numbers of cigarettes in 1884. This invention, coupled with the discovery of the safety match in 1889, made cigarette smoking practical.

Sales of cigarettes stagnated initially until Camel^® cigarettes launched a tremendously successful promotion campaign in 1913. The World Wars were fertile grounds for cigarette promotion as both the military and the cigarette manufacturers distributed cigarettes to the most vulnerable segment of the population, adolescent and young adult males in the armed services. Promotion and distribution of free cigarettes in World War II led to a smoking prevalence as high as 80%.

Smoking cessation as a legitimate medical intervention was virtually unknown in the first half of the century. Medical authorities were either indifferent or convinced to promote so-called medicinal properties of cigarette smoking (e.g., improved digestion, weight loss). By the 1940s, retrospective and, subsequently, prospective epidemiologic studies of cigarette smokers, initially in Europe and later in the United States, suggested the correlation between smoking and lung cancer.

As additional links between cigarette smoking and morbidity and mortality accumulated, the cigarette companies responded with two strategies. First, they created (1956) the Council of Tobacco Research, purportedly to explore links between tobacco and health but, in fact, the Council functioned to legitimize industry counterclaims. Second, cigarette manufacturers developed and marketed filtered and low tar and nicotine cigarettes.

During the 1960s, both sides maneuvered and the smoking landscape shifted. After the Surgeon General's report on Smoking and Health, 1964 witnessed the banning of tobacco advertisements on radio and TV. Medical research focused on "involuntary" smoking issues, creating new sociopolitical agendas. The non-smoking population became a powerful force and local governments passed clean air acts, which basically portrayed cigarette smoking as an unhealthy, "ugly" habit affecting every one.

Despite a gradual erosion of the prevalence of smoking, tobacco companies stayed financially sound and explored new markets, such as the young smoker (Joe Camel^®), professional women (Virginia Slims^®) and the minorities. The latest round, involving the multi-billion dollar litigation against tobacco companies by the Attorneys' General of state governments,(1) has ended in a seeming defeat for the industry. However, with tobacco companies still financially strong and potential litigation now behind them, the outcome is at best ambiguous.

Uptake and Cessation of the Cigarette Habit

The prevalence of cigarette smoking increased generally for all groups until the 1950s. For all segments of the population, about one half of adult smokers become regular smokers before age 18. For white males, the uptake of the smoking habit has changed little since the beginning of the century. Initiation occurs overwhelmingly in adolescence and early adulthood. For white females, differences in the age of initiation were seen for the first thirty years of the century. Unlike their male counterparts, initiation occurred over a longer period, extending into the fourth and fifth decades of life. The pattern among women in the last three decades has come to reflect those of their male counterparts. Initiation among black males to cigarette smoking is similar to that of white males except that initiation tends to occur in later adolescence. For black females, the initiation pattern is similar to that of white females with the exception of a somewhat older adolescence initiation.

Analysis of long-term (2+ years) successful cessation rates show that these are generally higher at older ages, with generally lower rates for women and for blacks. Before the 1940s, sustained cessation was uncommon. Currently, the cumulative success rate for quitting is approximately 50% of those who have ever smoked. Success may, however, require multiple attempts.

Benefits of Smoking Cessation

The results of two recently analyzed long-term studies confirm the benefits of smoking cessation. Hrubec and Mclaughlin(2) reported on a follow-up study of 300,000 US Veterans who were originally enlisted in the 1950s by Dorn. The Dorn study's original purpose was, of course, to examine the role of cigarette smoking in the development of lung cancer. The follow-up review of current statistics revealed that, in the first five years following cessation of smoking, mortality for quitters was comparable with that of current smokers but declined dramatically thereafter. By thirty years following cessation, the relative risk of all causes of mortality was indistinguishable from that of never smokers. For lung cancer, relative risk was much reduced after 40 years but was still 50% higher than among never smokers. Mortality for coronary associated disease was indistinguishable between ex-smokers and never smokers at thirty years. Finally, for former smokers with COPD, mortality rates remained elevated, despite smoking cessation, nearly four times that of the non-smoking population.

Data for women and smoking have been relatively rare. In a recent analysis by Kawachi(3) of findings from the Nurses' Health Study, the effects of smoking cessation were reviewed. In 1976, 121,700 women nurses, aged 30 to 55, were surveyed by a mail questionnaire. This questionnaire has been repeated every two years. The risk of total mortality among former female smokers approaches the level of female never smokers 10 to 14 years after cessation. The risk for coronary heart disease declined by one-third within two years and was essentially the same 10 to 14 years after quitting. The incidence of stroke among former smokers, two to four years after cessation, approaches that of the non-smoker.

In summary, the data from these recent studies provide ample proof of the general benefits of smoking cessation on the health consequences of smoking.

Pharmacotherapy for Smoking Cessation

Until the 1980s, there was no established effective pharmacotherapy for smoking cessation. This is not to say that there was no effective smoking cessation therapy prior to that time. The overwhelming majority of smokers who quit do so on their own by a number of strategies including: "cold turkey," "gradual reduction," using modified cigarette holders, or quitting with the help of groups. Simple advice, administered by a physician in the context of an office visit, can be an effective trigger to smoking cessation resulting in one to three per cent long-term benefits.

From the physician's point of view, therapy can be summarized by the following guidelines of the Agency for Health Care Policy and Research (1996):

ASK: Identify tobacco users at each patient encounter

ADVISE: Strongly urge all smokers to quit

IDENTIFY: Determine which smokers are willing to make a quit attempt

ASSIST: Aid the patient in quitting

ARRANGE: Schedule follow-up contact.

As with any drug dependence, cigarette addiction is a complex disorder involving both psychological and pharmacologic elements. Nicotine, the major addictive substance in tobacco, produces a well-defined withdrawal syndrome similar to heroin or cocaine.

Before considering appropriate pharmacologic intervention, a number of demographic factors should be considered:

• Sex
• Race
• Age
• Education
• Socio-economic status
• Presence of other smokers in the household.

Additionally, physiologic and behavioral factors need to be assessed:

• Degree of nicotine dependence (Fagerstrom Nicotine Tolerance Questionnaire, serum cotinine level)
• Fear of weight gain
• Depression
• Underlying tobacco-related illness.

All these factors need to be individually considered in designing a smoking cessation plan for a given patient.

Pharmacologic intervention in cigarette addiction currently involves two separate but potentially synergistic approaches:

• Nicotine replacement
• Modification of the neurohumoral effects of nicotine

Nicotine Replacement

Treatment with pharmacologically administered nicotine has two effects. It diminishes craving for cigarettes, decreasing the number of cigarettes smoked and reducing symptoms of withdrawal. Current protocols suggest pharmacologic supplementation with nicotine for two to six months during which time the withdrawal is consolidated. Four delivery systems are presently available:

• Polacrilex Gum
• Nicotine patch
• Nicotine nasal spray
• Nicotine inhaler.

All systems have the potential for overdosage, with possible toxic effects of nicotine developing. Persons with cardiovascular, peptic ulcer and other illnesses, known to be aggravated by nicotine, should use these modalities with caution. Each modality has its advantages and disadvantages. Both gum and patches are available over the counter. A 1998 study indicated that, since the 1996 FDA decision to approve gum and patch as OTC, the sales of these products increased 152% compared with prior prescription use. The effect of this change on smoking cessation success rates remains to be determined.

Polacrilex Gum

Nicotine containing gum comes in two strengths, 2mg and 4mg. It is currently available as an over the counter product. A protocol to follow in using this product includes:

1. Discontinue smoking.
2. Do not ingest food or liquids for 15 minutes before initiating.
3. Do not exceed 24 pieces a day with a typical initiating schedule of not more than one piece every one to two hours.
4. Continue therapy for at least twelve weeks, tapering the dose beginning with week seven as tolerated. While the manufacturer suggests discontinuing the therapy at twelve weeks, it is more prudent to always carry the gum in case the urge to start smoking recurs.

The actual chewing of nicotine gum differs somewhat from chewing ordinary gum because the gum is much tougher to chew. As a result, it must be chewed slowly and chewing should stop when a tingly sensation or peppery taste is noted, indicating that a sufficient dose has been achieved for the moment. The gum should remain in a different part of the mouth waiting for the sensation to go away. When the taste or tingle disappears, the patient should resume chewing. Usually, chewing continues for about half-hour by which time the nicotine has been totally released.

Nicotine gum offers a flexibility other delivery systems do not. The gum can be used as the urge to smoke arises. Some studies indicate, however, that regular dosing, one piece of gum each hour, may be more effective than the PRN approach. Tapering is much simpler. The down side of this product can easily be appreciated. Many people do not like to chew gum. Denture wearers or individuals with extensive dental work may find this product hazardous to their dental work.

Nicotine Transdermal Patch

As with the gum, nicotine patches offer a nicotine delivery system that allows the addicted smoker to substitute exogenously administered nicotine for the cigarette-administered drug. Compared to a placebo patch, transdermal nicotine patches have twice the efficacy. Nicotine patches come in three strengths, 7, 14 and 21mg, and are meant to serve as a delivery system over a 16 to 24 hour period. The over the counter product is limited to one strength, 15mg, and should be removed before going to bed -- unlike the gum, they are meant to deliver a continuous level throughout the waking hours. The patches are used for a six-week course. However, as with the gum, a rescue system is required in the event that the patient is tempted to smoke again. This can take the form of additional patches or other delivery systems.

Side effects, particular to the patch, include local dermal irritation, if the patch is repeatedly applied to the same area and vivid dreams if the patch is not removed at bedtime and nicotine dosing continues through the night.

Nicotine Nasal Spray

This newly released delivery system is by prescription only and comes as an aqueous spray which contain a total of 100mg of nicotine per bottle (10mg/cc). The actuator delivers 0.5mg per actuation in the form of a large diameter aerosol droplet (>8u) which rains out in the upper airway. A total of 200 actuation are contained in each bottle. The extent of absorption and the time to peak absorption may be altered by such factors as rhinitis or the use of vasoconstrictor nasal sprays.

The recommended usage depends on the individual's tobacco addiction. The range of usage is 8 to 40mg/day by this system. A dose of the nasal spray is defined as one actuation in each nostril for a total delivery of 1mg. The patient should be instructed not to inhale and to tilt their head slightly back. The recommended use is one to two doses per hour, using at least eight doses a day but no more than 40.

Irritation of the upper airway was a very frequent complaint of patients using this delivery system although some improvement occurs with time. Nicotine nasal spray is not recommended in patients with known reactive airways disease.

Efficacy rates appear similar to those with other nicotine delivery systems. As with other delivery systems, a long-term strategy for using this agent is not well defined, although, of those individuals who successfully quit at the end of one year, a little more than one third were still using the spray.

Nicotine Inhaler

This inhalational system consists of a mouthpiece and a plastic cartridge delivering nicotine from a porous plug containing 10mg of nicotine. Frequent puffing, over a period of 20 minutes, absorbs the nicotine. The range of cartridge use per day has been three to 18, with at least six cartridges recommended for effective therapy. As with other delivery systems, dosage needs to be individualized. The obvious advantage (and possibly disadvantage) is that the use of this delivery system mirrors actual cigarette smoking, thereby satisfying pharmacologic as well as psychologic needs of the patient.

Local irritation of the mouth and throat was reported by nearly half of those using this system. Continued use of the inhalers leads to decreased frequency of irritation. This delivery system is not recommended for persons with reactive airways disease.

Non-Nicotine Replacement Therapy

In 1988, Glassman et al(4) published a double blind study indicating the potential efficacy of clonidine in the treatment of nicotine addiction. Subsequent success with other agents, primarily bupropion HCl, suggests that centrally acting psychopharmaceuticals have a role in cigarette addiction. The mechanism by which these agents work is unknown but is felt to involve dopaminergic pathways in the central nervous system associated with the addictive behavior to many substances. Bupropion is an approved anti depressant agent unrelated to tricyclic antidepressants. Bupropion appears to be clinically effective over the short term, enhancing tobacco withdrawal. Its effectiveness appears to be dose-dependent. Preliminary data suggest that an additive effect may be seen when bupropion is combined with nicotine replacement strategies.

The therapeutic strategy recommended for this agent is to prescribe the drug while the patient is still smoking so a therapeutic level can build up before initiating smoking cessation. This is usually done over a two-week period. The patient starts with a dose of 150mg per day for the first three days and then increases the dose to 150mg BID. The patient should initiate the quit date before week two is over. The current course of therapy is recommended to be seven to 12 weeks. As with nicotine replacement, long-term strategies may be required but are as yet not well defined.

This therapy is contraindicated in patients with a seizure disorder. The risk for seizures is dose dependent and reaches an incidence of 4/1000 at doses of 450mg/day. At higher doses, the frequency of seizures rises ten-fold. Patients with psychiatric disorders may experience aggravated psychiatric symptoms. Interestingly, among patients with depression treated with this agent, nearly a third experienced significant weight reduction.

Summary

The reduction of cigarette addiction, despite many gains during the past three decades, remains a major public health challenge in the U.S. Important social and political forces have been moving to control the initiation of tobacco addiction, particularly among the young and other targeted groups. With nearly 50 million addicts in this country, effective strategies, both pharmacologic and interventional, will be required to bring the epidemic under control. Current therapeutic modalities offer significant advantages to smokers that are currently attempting smoking cessation. Both patients and physicians will need to have their awareness and understanding of these agents enhanced before significant progress can be made.