December 23, 2020

A Novel Approach to Smoking Cessation

Panagis Galiatsatos, MD, MHS

This 29-minute audio lecture is part of a high-yield learning activity from AudioDigest’s Family Practice Library.

Educational Objectives ⟶

The goal of this program is to improve management of nicotine addiction. After hearing and assimilating this program, the clinician will be better able to:
1. Explain how components of a cigarette affect nicotine concentration and addiction severity.
2. Determine a patient’s “smoking topography” to guide smoking cessation therapy.
3. Implement a step-up approach to smoking cessation using nicotine replacement therapy and medications.

Speaker Acknowledgements ⟶

Panagis Galiatsatos, MD, MHS
Assistant Professor, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD

Written Summary ⟶

Nicotine and addiction: forms of nicotine — nicotine enters body through lungs and arterial system, reaches brain in purest form; nicotine from use of, eg, transdermal patch, nicotine gum, nasal spray, not as pure (must pass through venous system and undergo first-pass metabolism in liver); genetics — study found that 95% of individuals who quit smoking “cold turkey” had variants of CYP2A6 enzymes, and were slow metabolizers of nicotine; other genetic variation predisposes individuals to more nicotine consumption; questions to ask — asking patient about number of cigarette packs per year smoked not highly useful (“does not tell you anything about the patient”); ask about brand and type of cigarette patient uses to assess severity of addiction based on nicotine concentration and tar content

Anatomy of cigarette: cigarette wrapping paper — higher porosity allows for greater air intake and dilution of nicotine, decreasing delivery of nicotine; tobacco contents — 1) tobacco stem; cigarettes that contain mostly tobacco stem (eg, USA Slims) have longer half-life, but contain less nicotine; patients tend to smoke more cigarettes to have same effect of nicotine; cigarettes have faster burn rate; 2) tobacco leaf; cigarettes that contain mostly tobacco leaf (eg, Newport) have higher nicotine concentration; patients tend to smoke fewer cigarettes per day, but cigarettes more potent and harmful; filter — ineffectual; perforations in filter dilute nicotine; factors that affect nicotine yield — burn rate; tobacco per unit volume; porosity of cigarette paper; ventilation holes in filter wrap paper; temperature and pH of smoke; added chemicals — ammonium (and heat) demethylates nicotine and increases rate of passage through alveoli blood barrier and blood-brain barrier; cigarette companies have reduced amount of nicotine in cigarettes, but have added alkaloids from tobacco leaves (mimic structure of nicotine; as addictive)

Cotinine and anabasine: cotinine — primary metabolite of nicotine breakdown can be detected in urine of patients using nicotine patch; anabasine — found only in tobacco leaf; presence in urine suggests use of cigarettes, chewing tobacco, or e-cigarettes

Menthol: can suppress coughing, and make smoking more enjoyable for first-time smokers; between 1920s and 1960s, smoking was more common in whites than in blacks; studies found that blacks genetically predisposed to having nonfunctional nicotine receptors (ie, nicotine would not have addictive effect; menthol stabilizes nicotine receptors so individuals can become addicted); menthol currently listed as flavoring, and reporting of concentrations not required

Effects of nicotine on brain: extensive remodeling of brain and arborization; cigarette acts on ventral tegmental area (VTA) and nucleus accumbens of brain (areas involved in survival and gratification); when VTA activated, signal sent to nucleus accumbens to motivate smoking; cyclic AMP response element-binding (CREB) protein — involved in tolerance; CREB protein and tolerance diminishes when smokers stop smoking; delta-fosB protein — involved in arborization and permanent brain changes; individuals who quit smoking for 2 to 3 yr can relapse (accumulation of delta-fosB protein and rewiring permanent); ask patients at what age they started smoking (individuals who started smoking before age 25 yr may be at higher risk for relapse)

Evaluation of “smoking topography”: ask about brand and type of cigarette patient smokes (determine nicotine and tar concentration); ask about number of puffs per cigarette (eg, >5 puffs); ask, “How deep is your drag?” (eg, <1 sec); ask, “How deep is your inhalation hold?” (eg, <1 sec); ask, “How many cigarettes do you smoke in 1 day?”; determine whether patient fast or slow metabolizer of nicotine; smoking topography first thing to change after initiation of smoking cessation medication (eg, patients likely to notice taking fewer puffs per cigarette); useful for determining how long medications needed; motivates patients

Nicotine replacement therapy: transdermal patch — “controller” therapy; start at highest dose (21 mg); patients allowed to smoke while wearing patch (no risk for nicotine overdose); odds ratio of quitting successfully compared with placebo nearly 2.0; takes ≈6 mo; nicotine gum and lozenges — “rescuer” therapy; used in conjunction with controller therapy; odds ratio of quitting successfully compared with placebo 1.5; educate patients about proper use; gum should be broken and parked on gums like chewing tobacco (should not be chewed or sucked on); lozenge should be parked on gums or placed under tongue to dissolve; onset of action 5 to 10 min; nasal spray — immediately effective; available only by prescription; causes stinging and watery eyes during first 2 times of use; highly effective; odds ratio of quitting successfully compared with placebo 2.3

Medications: bupropion — hepatically cleared (adjust dosing for patients with cirrhosis); start with 75 mg twice daily (can increase to 150 mg twice daily, or 150 mg in morning and 300 mg at night); varenicline (Chantix) — effective; associated with suicidal ideation; odds ratio of quitting successfully compared with placebo ≈2.4; renally cleared (adjust dosing for patients on dialysis; should be taken on same day after dialysis; dose should not exceed 1 mg/day)

Step-up approach: most patients need controller therapy and rescuer therapy; bupropion or varenicline useful for patients who may be fast metabolizers of nicotine (eg, smokers who use many expensive cigarettes); consider nicotine replacement patch for slower metabolizers (eg, smokers who use <10 cigarettes per day); may take 6 mo for patient to quit smoking; relapse rate high (patients must continue therapy for 3-6 mo)

Questions and answers: concentration of nicotine per puff of cigarette — usually <1 mg; consider, eg, demethylation particles of nicotine, alkaloids that increase effectiveness of nicotine; vaping devices (eg, Juul) — e-cigarettes pose same harms as traditional cigarettes

Test Your Knowledge ⟶

1. Compared with cigarettes that contain mostly tobacco stem, cigarettes that contain mostly tobacco leaf have which of the following characteristics? [L1]

(A) Higher concentrations of nicotine *

(B) Less expensive

(C) Burn faster

(D) Contain less ammonium


The correct answer is A.

Cigarettes that contain mostly tobacco leaf have higher nicotine concentrations and burn slower than cigarettes that contain mostly tobacco stem.


2. Adding menthol to cigarettes results in which of the following effects? [L1]

(A) Reduces risk for lung disease by lowering temperature of smoke

(B) Increases risk for addiction by stabilizing nicotine receptors in some populations  *

(C) Decreases potency by diluting nicotine concentration

(D) Increases rate of passage through blood-brain barrier by demethylating nicotine


The correct answer is B.

Menthol in cigarettes stabilizes nicotine receptors and can increase risk for addiction in some blacks who are genetically predisposed to having nonfunctional nicotine receptors.



3. Which of the following questions is LEAST helpful when evaluating a patient who may be addicted to cigarettes? [L1]

(A) “What type and brand of cigarette do you normally smoke?”

(B) “How many packs do you smoke per year?” *

(C) “How many puffs do you take per cigarette?”

(D) “How deep or long is your inhalation hold?”


The correct answer is B.

Asking the patient about the number of packs he or she smokes per year is least helpful because it provides the least amount of information about the nicotine concentration and tar content that the patient typically consumes.


4. Which of the following forms of nicotine replacement therapy has the quickest onset and highest odds ratio of quitting smoking successfully, compared with placebo? [L1]

(A) Transdermal patch

(B) Nicotine gum

(C) Nicotine lozenge

(D) Nasal spray


The correct answer is D.

Nicotine nasal spray is almost immediately effective, and has an odds ratio of 2.3 (vs 1.5-2.0 with transdermal patch and nicotine gum and lozenges).


5. Which of the following smoking cessation therapies should be adjusted for patients with cirrhosis? [L1]

(A) Transdermal patch

(B) Nicotine lozenge

(C) Bupropion

(D) Varenicline


The correct answer is C.

Bupropion is hepatically cleared and should be adjusted for patients with cirrhosis.






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