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Source: Doering PL, Li RM. Substance-related disorders II: alcohol, nicotine, and caffeine. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed April 12, 2017.


  • Nicotine-related substance abuse involves dependence and withdrawal.

  • Physical dependence: state of adaptation manifested by withdrawal syndrome following:

    • Cessation.

    • Rapid dose reduction.

    • Decreasing blood levels.

    • Administration of antagonist.

  • Withdrawal: development of substance-specific syndrome following cessation or reduced intake of substance that had been used regularly.


  • Nicotine is ganglionic cholinergic-receptor agonist with dose-dependent pharmacologic effects.

  • Effects include:

    • CNS and peripheral nervous system stimulation and depression.

    • Respiratory stimulation.

    • Skeletal muscle relaxation.

    • Catecholamine release by adrenal medulla.

    • Peripheral vasoconstriction.

    • Increased blood pressure, heart rate, cardiac output, and oxygen consumption.

  • Low doses of nicotine increase alertness and improve cognitive functioning.

  • Higher nicotine doses stimulate “reward” center in limbic system.

  • Cigarette smoking is the leading cause of preventable morbidity and mortality in the United States. It increases the risk of:

    • Cardiovascular diseases.

    • Lung cancer.

    • Other cancers (eg, bladder, kidney, pancreatic, esophageal, stomach, and head & neck cancers)

    • Nonmalignant respiratory diseases.


  • In a 2013 study, 25.5% of US population 12 years of age and older (66.9 million people) used tobacco product at least once in month prior to being interviewed.

  • Smoking method data.

    • 55.8 million Americans smoke cigarettes.

    • 12.4 million smoke cigars.

    • 8.8 million use smokeless tobacco.

    • 2.3 million smoke pipes.



  • Abrupt cessation of chronic nicotine use usually results in onset of withdrawal symptoms within 24 hours.

  • Withdrawal symptoms include:

    • Anxiety.

    • Cravings.

    • Difficulty concentrating.

    • Frustration.

    • Irritability.

    • Hostility.

    • Insomnia.

    • Restlessness.


  • Cessation of nicotine use.

  • Resolution of withdrawal symptoms.

  • Avoidance of side effects from pharmacologic therapies.


  • Every smoker should receive at least minimal intervention at every clinician visit.

  • Interventions more effective when they:

    • Last >10 min.

    • Involve contact with multiple types of clinicians.

    • Involve at least four sessions.

    • Provide nicotine-replacement therapy.

  • Group and individual counseling effective, and interventions more successful when they include:

    • Social support and training in problem solving.

    • Stress management.

    • Relapse prevention.

  • First-line pharmacotherapies for smoking cessation.

    • Bupropion sustained release.

    • Nicotine gum, inhaler, lozenges, nasal spray, or patch.

    • Varenicline.

    • Consider combinations if single agent failed.

  • Second-line pharmacotherapies for smoking cessation.

    • Clonidine.

    • Nortriptyline.


  • Figure 1: Model for treatment of tobacco use and dependence.


Model for treatment of tobacco use and dependence. Reprinted with permission from Doering PL, Li RM. Chapter 66. Substance-related disorders: alcohol, nicotine, and caffeine. In: DiPiro JT, Talbert RL, ...

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