Drug abuse III: nicotine and smoking

Cigarette smoking remains the greatest single cause of preventable illness and premature death. In the United States, smoking kills more than 443,000 adults each year—about 1 of every 5 deaths. Around the world, tobacco kills over 5 million people each year. On average, male smokers die 13.2 years prematurely, and females die 14.5 years prematurely. As shown in Table 39–1, most deaths result from lung cancer (125,522), heart disease (101,009), and chronic airway obstruction (79,898). Not only do cigarettes kill people who smoke, every year, through secondhand smoke, cigarettes kill about 50,000 nonsmoking Americans, and about 600,000 nonsmokers worldwide. The direct medical costs of smoking exceed $95 billion a year. Indirect costs, including lost time from work and disability, add up to an additional $97 billion. In the United States, the prevalence of smoking among adults fell steadily from 1965 (42%) through the 1980s and 1990s, but has now leveled off, remaining constant between 2004 (20.9%) and 2008 (20.6%).

TABLE 39–1

Average Annual Smoking-Attributable Mortality (United States, 2000–2004)*

	Smoking-Related Deaths
Disease Category	Male	Female
Malignant Neoplasms
Lip, oral cavity, pharynx	3,749	1,144
Esophagus	6,961	1,631
Stomach	1,900	584
Pancreas	3,147	3,536
Larynx	2,446	563
Trachea, lung, bronchus	78,680	46,842
Cervix, uteri	0	447
Kidney and renal pelvis	2,827	216
Urinary bladder	3,907	1,076
Acute myeloid leukemia	855	337
Subtotal	104,472	56,376
Cardiovascular Diseases
Ischemic heart disease	50,884	29,121
Other heart disease	12,944	8,060
Cerebrovascular disease	7,896	8,026
Atherosclerosis	1,282	611
Aortic aneurysm	5,628	2,791
Other circulatory diseases	505	749
Subtotal	79,139	49,358
Respiratory Diseases
Pneumonia, influenza	6,042	4,381
Bronchitis, emphysema	7,536	6,391
Chronic airway obstruction	40,217	38,771
Subtotal	53,795	49,543
AVERAGE ANNUAL TOTAL	237,406	155,277

^*Data are for adults ages 35 and older, and do not include deaths caused by burns or secondhand smoke.

Data were obtained online at apps.nccd.cdc.gov/sammec/—the web site of the Centers for Disease Control and Prevention: Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC).

Although tobacco smoke contains many dangerous compounds, nicotine is of greatest concern. Other hazardous components in tobacco smoke include carbon monoxide, hydrogen cyanide, ammonia, nitrosamines, and tar. Tar is composed of various polycyclic hydrocarbons, some of which are proven carcinogens.

What is the regulatory status of cigarettes? Good question, given that cigarettes are the single most dangerous product available to U.S. consumers. Until recently, cigarettes had avoided virtually all federal regulation. However, strong regulations are now in place. Under the Family Smoking Prevention and Tobacco Control Act, passed in June 2009, the Food and Drug Administration (FDA) now has the authority to

• Strengthen advertising restrictions, including the prohibition on marketing to youth.

• Require revised and more prominent warning labels.

• Require disclosure of all ingredients in tobacco products and restrict harmful additives.

• Monitor nicotine yields, and mandate gradual nicotine reduction to nonaddictive levels.

Basic pharmacology of nicotine

Effects during pregnancy and lactation.

Nicotine exposure during gestation can harm the fetus, and nicotine in breast milk can harm the nursing infant. Nonetheless, as discussed in Box 39–1, since pharmaceutical nicotine is safer than tobacco smoke, it is reasonable to consider using nicotine therapy during pregnancy to help a woman quit smoking.

BOX 39–1 SPECIAL INTEREST TOPIC

SMOKING CESSATION DURING PREGNANCY

Smoking is the largest modifiable risk factor for pregnancy-related morbidity and mortality. Smoking increases the risk of ectopic pregnancy, placenta previa, placental abruption, chorioamnionitis, stillbirth, preterm birth, and spontaneous abortion. In addition, fetal exposure increases the risk of low birth weight, perinatal mortality, sudden infant death syndrome (SIDS), and cognitive, behavioral, and emotional deficits in childhood.

Of the many harmful chemicals in tobacco smoke, reproductive toxicity is due is large part to just three: nicotine, carbon monoxide, and oxidizing agents. Nicotine reduces placental blood flow (by promoting vasoconstriction), delays or impairs fetal brain development (by direct neurotoxic effects), inhibits maturation of fetal pulmonary cells, and increases the risk of SIDS. Carbon monoxide reduces the oxygen-carrying capacity of blood and, in high levels, is neuroteratogenic. Oxidizing agents increase the risk of thrombotic events and, by decreasing the availability of nitrous oxide (a smooth muscle relaxant), they contribute to placental vasoconstriction and preterm labor.

Clearly, smoking during pregnancy is dangerous and should be stopped. Ideally, women should quit prior to conception or early in pregnancy. However, quitting later is still beneficial. To aid smoking cessation, the authors of Treating Tobacco Use and Dependence: 2008 Update recommend that clinicians offer effective interventions at the first prenatal visit, and throughout the course of pregnancy as needed. Intensive, person-to-person psychosocial intervention should be offered to all pregnant smokers. Pharmacologic intervention—mainly nicotine replacement therapy (NRT)—may also be offered, but only if psychosocial intervention alone has failed. Of note, quit rates with a combination of psychosocial intervention plus NRT are higher than with psychosocial intervention alone.

What do we know about NRT during pregnancy? Not as much as we would like. Studies on the efficacy of NRT in pregnant smokers have been inconclusive—probably because the nicotine dosage was too low. (During the later stages of pregnancy, nicotine is metabolized at a high rate. Hence, if conventional NRT doses are used, nicotine blood levels may be too low to be effective.) Nonetheless, even if we are uncertain about NRT efficacy, it seems likely that NRT is much safer than smoking. After all, cigarette smoke contains thousands of harmful chemicals (in addition to nicotine), whereas NRT contains nicotine only. In fact, among women who switched from smoking to NRT, there was no evidence of serious adverse effects, and there was an important benefit: birth weight was increased.

Who should use NRT? According to a 2009 review,* use of NRT should be based on the number of cigarettes smoked. Pregnant woman who smoke no more than 5 cigarettes a day should be offered psychosocial support, but not NRT. Conversely, pregnant woman who smoke a lot should be offered NRT, along with psychosocial support.

What about bupropion and varenicline? Compared with NRT, bupropion has two advantages: (1) it lacks the potential adverse effects of nicotine and (2) it can counteract weight gain and cravings brought on by smoking cessation. One prominent voice—the American College of Obstetricians and Gynecologists (ACOG)—says that bupropion may be considered when behavioral interventions have failed. However, another prominent voice—the Motherisk Program—says that bupropion should be avoided until we know more about its safety and efficacy. As for varenicline, we have no human data on safety in pregnancy, but we do have animal data showing fetal harm. Accordingly, varenicline should not be used.

^*Osadchy A, Kazmn A, Koren G: Nicotine replacement therapy during pregnancy: recommended or not recommended? J Obstet Gynaecol Can 31:744–747, 2009.