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Tobacco

by Douglas E. Jorenby, PhD

Tobacco use is a major individual and public health problem. Dependence develops rapidly. Major consequences include premature death and morbidity caused by coronary artery disease, lung cancer, COPD, and other disorders. Smokers should be offered smoking cessation interventions.

Tobacco use, although declining in the US, remains quite common. Tobacco is used because of the pleasurable effects of its main active ingredient, nicotine. Nicotine can be toxic, and the combustion products of tobacco contain other substances that can cause significant morbidity and mortality.

Epidemiology

Tobacco is nearly always smoked, primarily as cigarettes. Cigarette smoking is the most harmful form of tobacco use. However, all tobacco products contain toxins and possible carcinogens; even smokeless tobacco products are not safe alternatives to smoking.

Cigarettes

The percentage of people in the US who smoke cigarettes has declined since 1964, when the Surgeon General first publicized the link between smoking and ill health. Nevertheless, about 20% of adults still smoke. Smoking is most prevalent among men, people with less than a high school education, people living at or below the poverty income level, people with psychiatric disorders (including alcohol and substance use), American Indians, and Alaska natives. Smoking is less common among Hispanics and least common among Asian Americans.

Most smokers start during childhood. Children as young as 5 yr may experiment with cigarettes. About 31% become dependent before age 16 and over half before age 18, and age of initiation continues to decrease. The younger the age at which smoking starts, the more likely smoking is to continue. Risk factors for childhood initiation include

  • Parental, peer, and role model (eg, celebrity) smoking

  • Poor school performance

  • A poor relationship with parents or a single-parent home

  • High-risk behavior (eg, excessive dieting, particularly among girls; physical fighting and drunk driving, particularly among boys)

  • Availability of cigarettes

  • Poor problem-solving abilities


Other kinds of tobacco use

Exclusive pipe smoking is relatively rare in the US (< 1% of people 12 yr), although it has increased among middle and high school students since 1999. In 2008, about 5.3% of people > 12 yr smoked cigars; this percentage has declined since 2000. People < 18 yr comprise the largest group of new cigar smokers. Risks of pipe and cigar smoking include cardiovascular disease; COPD; cancers of the oral cavity, lung, larynx, esophagus, colon, and pancreas; and periodontal disease and tooth loss.

About 3.3% of people 18 yr and about 7.9% of high school students use smokeless tobacco (chewing tobacco and snuff). Toxicity of smokeless tobacco varies by brand. Risks include cardiovascular disease, oral disorders (eg, cancers, gum recession, gingivitis, periodontitis and its consequences), and teratogenicity.

Much less commonly, people have inadvertent oral or cutaneous exposure to tobacco, sometimes with serious toxicity. Young children occasionally ingest cigarettes from unguarded packs, cigarette butts from ashtrays, or nicotine gum. For example, from 2006 to 2008, > 13,700 cases of potentially toxic exposure to tobacco products in children < 6 yr were reported to the American Association of Poison Control Centers (AAPCC); the most common source was cigarettes and the most commonly affected age group was < 1 yr. Tobacco harvesters and processors who handle raw tobacco (especially if wet) without protection may absorb nicotine through the skin and develop symptoms of nicotine toxicity, a syndrome termed green tobacco sickness.


Pathophysiology

Nicotine is a highly addictive drug present in tobacco and is a major component of cigarette smoke. Cravings can begin within days of first use. Nicotine stimulates brain nicotinic cholinergic receptors, releasing dopamine and other neurotransmitters, which activate the brain reward system during pleasurable activities in a manner similar to that of many other addictive drugs (see Drug Use and Dependence). Dopamine, glutamate, and γ-aminobutyric acid (GABA) are important mediators of nicotine dependence. Psychologic dependence exists when people smoke to affect their mood or avoid withdrawal symptoms; it can develop within 2 wk after starting smoking and occurs in up to about 25% of adolescents who try smoking. Physical dependence (ie, occurrence of withdrawal symptoms with cessation) also develops within 2 wk. People smoke to feed their nicotine dependence but simultaneously inhale thousands of other components, including carcinogens, noxious gases, and chemical additives that are a part of cigarette smoke. These toxic components, rather than nicotine, are responsible for the multiple health consequences of smoking. Nicotine induces its metabolizing enzyme, CYP2A6, leading to multiple potential drug interactions.

Chronic effects

Smoking harms nearly every organ in the body. Smoking is the leading cause of preventable mortality in the US, accounting for an estimated 435,000 deaths/yr, or about 20% of all deaths. About half of all current smokers die prematurely of a disease directly caused by smoking, losing 10 to 14 yr of life (7 min/cigarette) on average. The major chronic effects are an increased likelihood of the following:

  • Coronary artery disease

  • Lung cancer

  • COPD

Coronary artery disease accounts for about 30 to 40% of all tobacco-related deaths. Risk of MI is increased by probably > 200% if smoking < 1 pack/day and risk of cardiovascular mortality is increased by > 50% over a 35-yr period. Mechanisms may include endothelial cell damage, transient increases in BP and heart rate, induction of a prothrombotic state, and adverse effects on serum lipids.

Lung cancer accounts for about 15 to 20% of tobacco-related deaths. Tobacco is the most common cause of lung cancer in North America and Europe. Inhaled carcinogens are directly exposed to lung tissue.

COPD accounts for roughly 20% of tobacco-related deaths. Smoking impairs local respiratory tract defense mechanisms and, particularly in genetically susceptible people, tends to accelerate decline in pulmonary functions. Coughing and dyspnea on exertion are common.

Less common smoking-related disorders include noncardiac vascular diseases (eg, stroke, aortic aneurysm), other cancers (eg, bladder, cervical, esophageal, kidney, laryngeal, oropharyngeal, pancreatic, stomach, throat), and pneumonia.

Smoking is a particular risk during pregnancy, potentially causing spontaneous abortion, ectopic pregnancy, and preterm birth. In addition, smoking is a risk factor for other conditions that convey significant morbidity and disability, such as acute myelocytic leukemia, frequent URIs, cataracts, infertility, premature menopause, peptic ulcer disease, osteoporosis, and periodontitis.

Passive exposure to cigarette smoke (secondhand smoke, environmental tobacco smoke) has grave health effects. For adults, passive exposure is linked to the same neoplastic, respiratory, and cardiovascular diseases that threaten active smokers. The risk of illness is less than that of active smokers and is related to dose. For example, between spouses, average risk is increased by about 20% for lung cancer and by about 20 to 30% for coronary artery disease. Infants born of mothers who smoke tend to have a lower birth weight and are at increased risk of SIDS, asthma and related respiratory illnesses, and otitis media. Children exposed to cigarette smoke lose more school days because of illness than nonexposed children. Treating children for smoking-related illnesses is estimated to cost $4.6 billion/yr. Overall, secondhand smoke is estimated to cause 50,000 to 60,000 deaths each year in the US (between 2% and 3% of all deaths). These findings have led states and municipalities across the US to ban smoking within workplaces in an effort to protect the health of workers and others from the substantive risks of environmental tobacco smoke. Currently, > 50% of the US population lives in a state that has implemented a comprehensive indoor smoke-free ordinance.

Indirect effects of smoking can be serious. Smoking-related fires kill probably > 350 people each year and injure > 900; such fires are the leading cause of deaths resulting from unintentional fires in the US. In addition, each year, 43,000 children lose one or more caregivers who die from smoking-related diseases.

Drug interactions with nicotine are common. Levels and sometimes clinical effects of the following drugs are decreased by chronic smoking, in most cases by induction of CYP2A6 enzymes:

  • Antiarrhythmics (some): Flecainide, lidocaine, mexiletine

  • Antidepressants (some): Clomipramine, fluvoxamine, imipramine, trazodone

  • Antipsychotics (some): Chlorpromazine, clozapine, fluphenazine, haloperidol, olanzapine, thiothixene

  • Benzodiazepines

  • β-Blockers

  • Caffeine

  • Estrogens (oral)

  • Insulin (delayed absorption caused by skin vasoconstriction)

  • Pentazocine

  • Theophylline


Symptoms and Signs

Acute effects

Nicotine slightly increases heart rate, BP, and respiratory rate. Smokers may feel increased energy, increased ability to concentrate, ability to overcome fatigue, and a sense of well being. Nausea is common on a person's first exposure to nicotine. Nicotine reduces appetite and can be a behavioral substitute for eating. Exercise tolerance tends to decrease because of respiratory tract irritation. Low-grade carbon monoxide toxicity can also limit exercise tolerance, but this is probably only a factor in elite athletes.


Toxicity or overdose

Acute nicotine poisoning is usually caused by oral or dermal exposure, rather than smoking.

Mild toxicity, as is common with green tobacco sickness and minor ingestions by children (eg, < 1 cigarette or 3 butts), typically manifests with nausea, vomiting, headache, and weakness. Symptoms spontaneously resolve, usually in 1 to 2 h after ingestion if poisoning is mild; however, symptoms can persist for 24 h if poisoning is severe.

Severe nicotine poisoning causes a cholinergic toxidrome with nausea, vomiting, salivation, lacrimation, diarrhea, urination, fasciculations, and muscle weakness. Patients usually have crampy abdominal pain and, if poisoning is very severe, arrhythmias, hypotension, seizures, and coma. The fatal dose of nicotine is about 60 mg in adult nonsmokers, 120 mg in adult smokers, and as little as 10 mg in young children. Each cigarette contains about 8 mg of nicotine (only about 1 mg is absorbed by smoking). However, the amount ingested by children is usually difficult to ascertain by history because ingestion is rarely observed; any ingestion should be considered potentially dangerous.


Chronic effects

Findings due to smoking itself include yellow stains of teeth and fingers and, in comparison to age-matched controls, weight is slightly lower (≤ 5 kg difference), skin is drier and more wrinkled, and hair is thinner.

Other symptoms are those of smoking-related lung and cardiovascular disease. Chronic cough and dyspnea on exertion are common. Circulatory and respiratory impairments decrease exercise tolerance, often resulting in a more sedentary lifestyle and thus further lowering of exercise tolerance.


Withdrawal

Smoking cessation often causes intense nicotine withdrawal symptoms, primarily a craving for cigarettes but also other symptoms (eg, anxiety, difficulty concentrating, sleep disruption, depression―see Smoking Cessation : Withdrawal) and eventual weight gain.


Diagnosis

  • Direct questioning

Acute toxicity is not always apparent on history. Children may not have been observed ingesting tobacco or nicotine gum, and patients with green tobacco sickness may not think to mention that they handle tobacco. Thus, children and agricultural workers presenting with typical symptoms, particularly cholinergic manifestations, should be queried about possible tobacco exposure. Testing is not necessary.

Of the > 70% of smokers who present in a primary care setting every year, only a minority receive counseling and drugs to help them quit. To maximize identification of smokers and thus the public health benefit of smoking cessation, all patients should be asked about smoking during medical visits regardless of presenting symptoms and all patients should be asked about smoking particularly during visits for symptoms possibly related to smoking (eg, circulatory or respiratory symptoms).

Treatment

  • Symptomatic treatment for acute poisoning

  • Smoking cessation measures

Skin exposed to nicotine should be irrigated. Otherwise, treatment for acute nicotine poisoning is supportive. Gastric emptying is not recommended. In patients with mild symptoms or who have vomited, charcoal is not given; some clinicians would recommend charcoal for patients who have severe symptoms or have ingested large quantities and have not vomited. Airway protection and assisted ventilation may be needed for patients who are obtunded, have excessive respiratory secretions, or have respiratory muscle weakness. Seizures are treated with benzodiazepines. Shock is treated with IV fluids and, if fluids are ineffective, pressors. Atropine can be considered for patients who have excessive respiratory secretions or bradycardia; otherwise, anticholinergics are not recommended.

Smoking-related disorders are treated. All smokers should be helped to quit by smoking cessation counseling and typically drug treatment (see Drugs).

Key Points

  • Cigarette smoking, the leading cause of preventable mortality in the US, tends to begin early in life, with about 31% of smokers becoming dependent before age 16 and over half before age 18.

  • Cravings can begin within days of first use.

  • Components of cigarette smoke other than nicotine (eg, carcinogens, noxious gases, chemical additives) are responsible for most of the adverse health effects that cigarettes cause.

  • Harmful effects include increased risk of fatal disorders (eg, lung cancer, COPD, coronary artery disease), indirect effects (eg, fires), and drug interactions.

  • Nicotine acts as a mild stimulant acutely in the usual doses but can cause a cholinergic toxidrome in acute overdose (usually due to oral or dermal exposure).

  • Ask all patients about smoking, regardless of presenting symptom.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • COMMIT, NICORETTE, NICOTROL
  • No US brand name
  • NAVANE
  • ANAFRANIL
  • OLEPTRO
  • HALDOL
  • TOFRANIL
  • ZYPREXA
  • XYLOCAINE
  • TALWIN
  • CLOZARIL
  • No US brand names
  • LUVOX
  • ELIXOPHYLLIN
  • ATROPEN

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