Tobacco use is “the leading cause of preventable disease, disability, and death in the United States.”1 Nearly 40 million US adults smoke cigarettes, and approximately 4.7 million middle and high school students use >1 tobacco product, including e-cigarettes.1 Cigarette smoking is a “major modifiable health risk factor,” but smoking cessation is difficult and the average smoker attempts to quit 5 times before achieving permanent success.2 

Successful smoking cessation involves a 2-pronged approach, since there are 2 components to smoking – physiological and behavioral, according to Nervana Elkhadragy, PharmD, MS, TTS, of Purdue University, College of Pharmacy, Indianapolis.

“We treat both together – the physiological addiction and the behavioral habits associated with smoking,” she told MPR.

Smoking Cessation Framework

Discussing smoking cessation with patients can be challenging, leading to frustration in many practitioners.3 To help guide the conversation, the USPSTF, American Academy of Family Physicians, and other societies recommend the “Five A’s” (Ask, Advise, Assess, Assist, and Arrange) as a framework for working with patients regarding smoking cessation.

Addressing Physiological Addiction with Pharmacotherapy

There are 7 US Food and Drug Administration (FDA)-approved medications for treating nicotine addiction; 5 are formulations of nicotine replacement therapy (NRT), and take the form of gum, lozenge, transdermal patch, nasal spray, and oral inhaler. Two additional medications are varenicline (a nicotinic receptor partial agonist) and bupropion (an antidepressant).4

“The choice of medication depends on multiple factors, which should be explored and discussed with the patient by the prescriber or pharmacist,” Dr Elkhadragy said.

For example, some NRT formulations (eg, gum, lozenges, nasal spray, and oral inhalers) need to be dosed frequently, which may compromise adherence. In contrast, bupropion and varenicline require only twice-daily dosing, and the NRT transdermal patch requires only once-daily dosing. On the other hand, some patients may prefer the oral experience of chewing gum or sucking a lozenge.

NRT agents can be used in combination, Dr Elkhadragy noted. “For example, a person can use the nicotine patch, which has one-daily dosing, but may need extra help in certain situations that are particularly triggering. Let’s say the person has always smoked during the morning drive to work, I might additionally recommend chewing gum during that drive.”

 She cautioned that smoking increases certain enzymes, such as cytochrome P1A2 (CYP1A2), thus, upon quitting, enzyme levels are normalized. Medications metabolized by CYP1A2 enzymes (eg, clozapine, olanzapine, duloxetine, mirtazapine) might require lower dosing, due to decreased enzyme production.5

Similarly, caffeine is broken down by the CYP1A2 enzyme, “so smokers tend to drink more caffeine than other people – for example, they may drink 4 cups of coffee, which would be equivalent to 2 cups of coffee in someone else,” Dr Elkhadragy said. But when they quit smoking, the enzyme is reduced and if they continue to drink 4 cups of coffee, they are at risk of caffeine toxicity. 

This is especially problematic because caffeine toxicity can be confused with nicotine withdrawal as some of the symptoms such as irritability, insomnia, and anxiety are common to both. “Patients may attribute their misery to nicotine withdrawal, assume their medication isn’t working, and may start smoking again,” she said.

She encouraged physicians and pharmacists to “ask patients about their use of caffeine and encourage smokers who are quitting to halve their caffeine intake.”