PHARMACOTHERAPY OPTIONS FOR SMOKING CESSATION
AMANDA MAYER, PharmD
Amanda Mayer is a graduate of the University of Montana, Skaggs School of Pharmacy. She has clinical experience as a pharmacist in the inpatient mental health setting, which is her passion. She has also done fill-in work at retail pharmacies throughout her career. Amanda appreciates the wide variety of professional opportunities available to pharmacists. Amanda loves spending time with her family and spends most of her free time exploring new restaurants, hiking in the summer, snowboarding, and cross-country skiing in the winter.
Tobacco use is the most common cause of preventable death in the United States. Smoking-related diseases include cardiovascular disease, chronic obstructive pulmonary disease (COPD), cancer, and poor reproductive health outcomes. Smoking cessation is essential for overall public health and quality of life. Withdrawal symptoms from smoking cessation make quitting smoking difficult for many patients. Several over-the-counter (OTC) and prescription products are available to help patients quit smoking, each with potential advantages and disadvantages.
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Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is
Pharmacy Technician 0669-0000-23-059-H01-T
Credits: 2 hours of continuing education credit
Type of Activity: Knowledge
Media: Internet Fee Information: $6.99
Estimated time to complete activity: 2 hours, including Course Test and course evaluation
Release Date: April 13, 2023 Expiration Date: April 13, 2026
Target Audience: This educational activity is for pharmacists.
How to Earn Credit: From April 13, 2023, through April 13, 2026, participants must:
Read the “learning objectives” and “author and planning team disclosures;”
Study the section entitled “educational activity;” and
Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
Credit for this course will be uploaded to CPE Monitor®.
Learning Objectives: Upon completion of this educational activity, participants should be able to:
Identify the harms and effects of smoking and the signs of nicotine withdrawal
Compare the advantages of different over-the-counter nicotine replacement therapy options
Discuss the different mechanisms of action of prescription smoking cessation options
Identify barriers a patient may face with smoking cessation
The following individuals were involved in the development of this activity: Amanda Mayer, PharmD, Jeff Goldberg, PharmD, BCPP, and Pamela M. Sardo, PharmD, BS. Pamela Sardo, PharmD, BS, was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.
ⓒ RxCe.com LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Tobacco use can lead to serious health problems, disability, and death. Quitting smoking can significantly reduce the risk of developing these health problems. However, the long-term use of tobacco products that contain nicotine can cause physical dependence that may induce withdrawal symptoms when a patient tries to quit, and this, as well as other barriers, can impede a person from successfully quitting. Behavioral support may be combined with pharmacotherapy to provide patients with the ability to overcome these barriers. Pharmacists and other healthcare team members should work together to help patients develop an individualized plan to stop smoking.
Statistics Related to Smoking
In the U.S., tobacco use is the number one cause of preventable disease, disability, and death.1 According to the Centers for Disease Control and Prevention (CDC), in 2020, 12.5% of U.S. adults (approximately 30.8 million people) smoked cigarettes.2 It is estimated that each day, approximately 1,600 youth try their first cigarette, with nearly 3.08 million middle and high school students using at least one tobacco product, including e-cigarettes. Each year almost half a million Americans will die prematurely due to smoking or exposure to secondhand smoke.2,3 The use of conventional cigarette smoking among youth and young adults has decreased over the past several decades; however, this population has dramatically increased e-cigarette use.4
According to the 2020 Report of the Surgeon General on Smoking Cessation, more than two-thirds of smokers say they want to quit. Thousands of smokers try to quit each day, but due to the highly addictive nicotine component in cigarettes, it takes multiple attempts for most smokers to quit for good. The 2020 Report identified the cost associated with tobacco use: healthcare spending attributed to smoking exceeds $170 billion each year.1 There is also some positive news since the prevalence of current smoking declined from 52% in 1965 to 15.8% in 2017, with the decline being attributed
to campaigns to keep people from starting the habit, promoting smoke-free environments, and progress made in pharmacological and behavioral smoking cessation treatments.1
Harm Caused by Smoking
Smoking increases the risk of disease and death from a number of medical conditions. Smoking can increase the risk of disease and death from cardiovascular disease. Smoking can also increase markers of inflammation and hypercoagulability and decrease high-density lipoprotein cholesterol levels. Smokers may see an increase in atherosclerosis as well as an increase in the risk of death from stroke. Types of cancers that can be increased due to smoking are acute myeloid leukemia (AML), bladder, lung, cervix, colon, rectum, esophagus, kidney, liver, mouth, throat, pancreas, stomach, and larynx (voice box). Quitting smoking is beneficial at any age, with better health benefits the earlier a person quits. Quitting smoking can also help protect family members, coworkers, friends, and others from the negative effects of secondhand smoke.1,5
Concerns for babies born to smoking mothers include the risk of small- for-gestational-age babies, delivering a low-birth-weight baby, decreased fetal growth, and risk of preterm delivery.1 Fetal exposure to nicotine can result in sudden infant death syndrome, altered corpus callosum, auditory processing deficits, deficits in attention and cognition, effects on behaviors, and obesity.4,6
Drug Interactions Caused by Smoking
Tobacco smoke produces lung carcinogens, including polycyclic aromatic hydrocarbons (PAHs), which are potent inducers of the CYP-450 isoenzymes 1A1, 1A2, and possibly 2E1. Glucuronide conjugation may also be induced by PAHs. Pharmacokinetic drug interactions are caused by the PAHs in tobacco smoke.7 Nicotine exposure in the absence of PAHs caused by smoking (such as from NRT) has limited pharmacokinetic drug interaction potential.7,8 Pharmacodynamic drug interactions associated with smoking are largely
caused by nicotine activating the sympathetic nervous system, which can counter the actions of certain drugs. Other compounds produced by tobacco smoke produce less significant effects on hepatic enzymes, including acetone, pyridine, heavy metals, benzene, and carbon monoxide. A clinically significant decrease in pharmacologic effect may be seen in drugs that are substrates of CYP1A2 as their metabolism can be induced in smokers. When a person quits smoking, dosages of medications may need to be reduced due to the quick dissipation of CYP1A2 induction. If an individual starts smoking while on medications that are CYP1A2 substrates, doses may need to be increased.7
The induction of CYP1A2 and CYP1A1 by PAHs causes decreased plasma concentrations of caffeine, chlorpromazine, clozapine, estradiol, flecainide, fluvoxamine, haloperidol, melatonin, mexiletine, mirtazapine, olanzapine, propranolol, ropinirole, tacrine, theophylline, and tizanidine.8 Clozapine concentrations have been found to be significantly lower in smokers than non- smokers.7 Clozapine is an atypical antipsychotic, primarily metabolized by CYP1A2, with a narrow therapeutic window that requires monitoring as it may cause life-threatening neutropenia. Patients who are started on clozapine in an inpatient setting may need dosing adjusted in an outpatient setting if they begin or resume smoking.7 Another antipsychotic that is affected by smoking is olanzapine, which is primarily metabolized by direct N-glucuronidation. Olanzapine plasma concentrations have been found to be lower in smokers than non-smokers due to increased drug clearance. Chlorpromazine, flecainide, fluvoxamine, and theophylline may also require an increased dosage in smokers as smoking causes decreased serum concentrations that may affect the therapeutic efficacy. Heparin doses may need to be increased as smokers have an increased clearance of heparin and a decreased half-life, and smoking also has prothrombotic effects.7 Estrogen-containing hormonal contraceptives in combination with smoking increases the risk of adverse cardiovascular effects, including thromboembolism, ischemic stroke, and myocardial infarction. The risk of cardiovascular events combined with oral contraceptives is highest in women over 35 who are heavy smokers; however, the risk is present in all smokers using oral contraceptives. Progestin-only contraceptives are recommended if smoking cessation is not achievable or if other forms of birth control are not an option for the patient. Inhaled
corticosteroids may have a reduced efficacy in patients with asthma who smoke. Patients taking benzodiazepines who smoke may have decreased sedation and dizziness, possibly due to nicotine stimulating the central nervous system. Beta-blockers may be less effective as antihypertensives and at heart rate control, requiring a higher dose, due to nicotine-mediated sympathetic activation.7
Benefits of Quitting Smoking
Quitting smoking can reduce the risk of coronary heart disease, with risk sharply declining in the first 1 to 2 years after cessation. The risk continues to decrease, but more slowly, after that initial period over the long term.1,5 Women should quit smoking prior to trying to conceive; however, quitting at any time during the pregnancy can benefit the mother and baby’s health.6
Nicotine Withdrawal Symptoms
Long-term nicotine use can cause physical dependence that may induce withdrawal symptoms upon cessation. These withdrawal symptoms make it difficult for individuals to abstain from smoking as they can be unpleasant.1 Symptoms of nicotine withdrawal may be seen within a few hours after the last dose of nicotine and peak on day two or three after going nicotine-free. These symptoms may last for a few days but can last up to several weeks, with the severity decreasing over time after the third day. The most common symptom of nicotine withdrawal is urges or cravings for nicotine. Other common physical symptoms include headaches, nausea, dizziness, constipation, diarrhea, gas, cough, dry mouth, sore throat, nasal drip, chest tightness, and increased appetite/weight gain. Individuals may feel anxious, jumpy, irritable, grouchy, angry, frustrated, sad, or depressed. Some people may also experience trouble concentrating and trouble sleeping.9-12
Individuals may also struggle with the habits formed around tobacco use. For instance, if a person has a cigarette with breakfast each morning, this habit could make quitting more difficult as they have associated having breakfast with also having a cigarette. If a person has a stressful situation at
work and previously smoked each time that happened, they may also be tempted to smoke when put in a similar situation. Environmental cues such as sights, sounds, or other sensations that an individual has associated with nicotine can often induce cravings that tempt a person when trying to quit.1
Smoking Cessation Pharmacotherapy
Smoking cessation pharmacotherapy was not introduced until the 1980s. There are currently seven FDA-approved first-line medications for treating nicotine dependence, five being nicotine-based medications and two being non-nicotine oral medications. Less than one-third of smokers trying to quit use approved cessation medications or behavioral counseling to support the quit attempts. Evidence suggests that cessation medications plus behavioral counseling are very effective in combination, but are also effective in increasing smoking cessation individually. The use of smoking cessation medications helps to reduce physical symptoms that result from nicotine withdrawal, allowing smokers to focus on the behavioral and psychological aspects of quitting. Medication can also provide the benefit of reducing or eliminating the immediate reinforcing effects of nicotine by desensitizing the nicotinic receptors.1
Nicotine Replacement Options
Nicotine replacement products make up the majority of FDA-approved smoking cessation options.1 Prescription nicotine smoking cessation products were first introduced in 1984. In 1996, the FDA allowed over-the-counter (OTC) nicotine products for smoking cessation. Nicotine may be used independently to help patients quit smoking but is ideally combined with behavioral modification and support.13 Nicotine binds to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. It affects the central and peripheral nervous systems. Nicotine produces a stimulating effect mainly in the cortex and a reward effect is exerted in the limbic system. Low doses of nicotine predominantly give a stimulant effect, and high doses produce a predominant reward effect.14
An advantage to nicotine replacement therapy (NRT) is that the patch, gum, and lozenges are available over the counter. If a patient wants these OTC products to be covered by insurance, a prescription by a provider may be required; although, some insurances will deny OTC coverage even with a prescription. Nicotine nasal spray and oral inhaler both require a prescription. All five NRT options are similar in efficacy and deliver plasma nicotine concentrations that are lower than conventional cigarettes. The NRT options deliver the nicotine more slowly and at a lower level than cigarettes, which reduces the behavioral reinforcing effect of smoking.1 During the use of the gum, lozenge, or patches, it is okay if a patient is not fully successful at quitting immediately and smokes a cigarette. In this case, the patient should be encouraged to continue the quit attempt and discard the remaining cigarettes. Patients who use the nasal spray and inhaler should be instructed to stop smoking completely while using the product to avoid the risk of nicotine overdose.15 Using nicotine products can help to preserve lung function in patients who successfully quit smoking.16 Combinations of NRT may include using patches that are slower acting but provide a constant level of nicotine with any of the other forms of NRT, which all act faster and can be used to offset acute cravings. The combination of NRT with bupropion and varenicline can also provide better success rates than either of these options on their own.1
Nicotine gum is primarily absorbed in the oral mucosa and initially requires use every 1 to 2 hours to suppress withdrawal symptoms. Available flavors of nicotine gum include original, cinnamon, fruit, and mint. Dosing for nicotine gum typically starts with either 2 mg or 4 mg every 1 to 2 hours, then gradually decreases with the goal of 1 piece every 4 to 8 hours from weeks 10-12. Each piece of gum should be chewed slowly, and the gum should be “parked” between the cheek and tongue when a peppery or tingling sensation appears (with approximately 15 to 30 chews). When the tingling fades, the individual should resume chewing and repeat the chew and park method until most of the nicotine is gone (generally about 30 minutes/tingle does not return
when the gum is chewed). The gum should be parked in different areas of the mouth during each interval. Incorrect chewing techniques may cause lightheadedness, nausea/vomiting, and throat and mouth irritation. Individuals using nicotine gum may experience mouth/jaw soreness, hiccups, dyspepsia, and hypersalivation. The gum option may serve as an oral substitute for tobacco, may delay weight gain, and can be titrated by the individual to manage withdrawal symptoms. Nicotine gum can be used as needed and in combination with other products to manage situational urges that an individual may experience. Precautions for use with the gum are myocardial infarction within the last 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, temporomandibular joint disease, pregnancy and breastfeeding, and adolescents.1 A 2019 review by Lindson, et al. (2019) found that using a 4-mg dose as opposed to a 2-mg dose increases the chances of successfully quitting smoking.17
Nicotine lozenges are available OTC and come in 2 mg and 4 mg doses in cherry and mint flavors. Dosing is similar to nicotine gum. Nicotine is absorbed in the oral mucosa, with initial dosages being every 1 to 2 hours, tapering to course completion over 12 weeks. A standard-size lozenge should dissolve in the mouth within 20 to 30 minutes and a mini lozenge takes approximately 10 minutes. The release of nicotine from the lozenge may cause a warm, tingling sensation. Patients should be counseled not to chew or swallow the lozenge, occasionally rotate it to different areas of the mouth, and avoid food or beverages 15 minutes prior to or during the use of the lozenge. Adverse effects of the lozenge include nausea, hiccups, cough, heartburn, headache, flatulence, and insomnia. Like the gum, the lozenge can serve as an oral substitute for tobacco, may delay weight gain, can be titrated for managing withdrawal symptoms, and can be used with other agents for managing situational urges. Precautions for the use of lozenges are a myocardial infarction within 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, pregnancy and breastfeeding, and adolescents.1
Nicotine patches are available in 7 mg, 14 mg, and 21 mg doses. Patches should be applied in the morning and deliver nicotine slowly and continuously over 16-24 hours. If a person complains of insomnia or bothersome dreams, they should be advised to remove the patches at bedtime. Dosing of the transdermal patch varies based on the number of cigarettes smoked daily. Patients who smoke greater than 10 cigarettes per day should start at the 21 mg dose, and those who smoke less than 10 cigarettes per day should start at 14 mg. The dose gets tapered down with the duration of treatment lasting 8 to 10 weeks. The application site should be rotated daily, to avoid the same skin site for at least one week. Advantages of the patch include once-daily dosing to help with adherence, discreteness of use as it can be applied under clothing, the ability to combine with other agents, and consistent nicotine levels over 24 hours.1 Interestingly, the brand marketed as Nicotrol is instructed to be applied upon waking and removed at bedtime; whereas, the other brands, such as Nicoderm, Habitrol, and ProStep are designed to be worn for 24 hours. Adverse effects include local skin reactions (erythema, pruritus, burning), headaches, and sleep disturbances (insomnia, abnormal/vivid dreams). Disadvantages of the transdermal patch include the inability to titrate the dose to manage withdrawal symptoms acutely and it is not recommended for patients with dermatologic conditions. Precautions for the use of transdermal patches are a myocardial infarction within 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, pregnancy and breastfeeding, and adolescents.1 The same 2019 review by Lindson, et al., that suggested a 4-mg dose of gum leads to higher quit rates also found that higher doses of nicotine patches appeared to have an advantage over lower doses of patches in helping abstain from smoking. These findings were less certain than the successfulness of nicotine gum but may be considered when helping patients choose OTC NRT.1,17
Nicotine Nasal Spray
Nicotine nasal spray is an aqueous solution that is only available with a prescription. Each nasal spray dose requires two sprays, one in each nostril,
with each actuation delivering 0.5 mg of nicotine into the nasal mucosa. The nasal spray is typically dosed 1 to 2 doses per hour with best results initially using at least 8 doses per day (the minimum effective dose). A maximum of 5 doses can be used in one hour and a maximum of 40 doses per day. Duration of treatment with the nasal spray typically lasts 3 to 6 months.1 Patients should be counseled to prime the device prior to the first use by pumping the nasal spray into a tissue 6 to 8 times until a fine mist appears. If the nasal spray has been unused for 24 hours, the device should again be primed, but only using 1 to 2 sprays until the mist appears. Patients should be counseled not to sniff, swallow, or inhale through the nose while the spray is being administered, and their heads should be slightly tilted back when administering the dose. An advantage to the nasal spray is that it delivers nicotine most rapidly of all the NRT products; however, inhaling cigarette smoke still delivers nicotine faster than the nasal spray. When starting therapy with the nasal spray, irritation of the nose can cause burning, sneezing, and watery eyes that typically resolve in 1 to 2 days. Adverse effects when using the nasal spray may include nasal and/or throat irritation (hot, peppery, or burning sensation), rhinitis, tearing, sneezing, cough, and headache. The nasal spray can be titrated to rapidly manage withdrawal symptoms and can be used with other agents. The precautions for the nasal spray are the same as the gum, lozenge, and transdermal patch and also include underlying chronic nasal disorders such as rhinitis, nasal polyps, and sinusitis.1
Nicotine Oral Inhaler
The nicotine oral inhaler is available as a prescription medication, with each cartridge delivering 4 mg of nicotine to the patient. Dosing of the oral inhaler ranges from 6 to 16 cartridges per day, with the initial dose of 1 cartridge every 1 to 2 hours. The best effects can be seen with continuous puffing for 20 minutes, with the nicotine in the cartridge being depleted after 20 minutes of active puffing. The cartridge should be inhaled into the back of the throat or puffed in short breaths. Patients should be counseled that, unlike a cigarette, the cartridge vapor should NOT be inhaled into the lungs, and no food or beverages should be consumed 15 minutes before or during medication use. The duration of treatment should last 3 to 6 months. Adverse
effects of the oral inhaler include mouth and/or throat irritation, cough, headache, rhinitis, dyspepsia, and hiccups. Advantages of the oral inhaler include the potential to serve as an oral substitute for tobacco, the dose can be titrated to manage withdrawal symptoms, the device mimics the hand-to- mouth ritual of smoking, and it can be combined with other agents to manage situational urges. A disadvantage to this therapy is that cartridges may be less effective in cold environments. The precautions for the oral inhaler are the same as the gum, lozenge, and patch and include individuals with bronchospastic disease.1
Bupropion sustained-release (SR), marketed as Zyban, for smoking cessation gained FDA approval in 1997 and is only available with a prescription.1 An additional indication was added in 1999 that approved Zyban to be used in combination with nicotine transdermal patches for smoking cessation. Bupropion was originally marketed, and still used, as an antidepressant.1 The exact mechanism of action is unknown, but it is thought that bupropion blocks the reuptake of dopamine, and norepinephrine - to a lesser extent - and it has some nicotine receptor-blocking activity.1 The increase in dopamine at neuronal sites may cause reduced nicotine cravings and a reduced urge to smoke. The increase in norepinephrine may reduce nicotine withdrawal symptoms. The typical dosing for bupropion SR for smoking cessation is 150 mg every morning for 3 days, then increasing to 150 mg twice daily, with a maximum dose of 300 mg/day. The patient should choose a “quit day” and start therapy 1 to 2 weeks prior to the quit day to allow the medication to reach steady state therapeutic levels.1 If a patient uses the nicotine transdermal patch in combination with bupropion, the patch should be initiated on the target “quit day” and the patch can be continued for 8 to 20 weeks. The duration of therapy for bupropion therapy is 7 to 12 weeks, with maintenance dosing up to 6 months in some patients.1 A patient is generally considered non-responsive to bupropion treatment if they have not stopped smoking by the seventh week of treatment. The goal of therapy is complete abstinence from smoking. Patients should avoid taking bupropion right before bedtime as it may cause insomnia. Other adverse effects may
include dry mouth, nausea, constipation, seizures, nervousness, difficulty concentrating, dizziness, rash, and on rare occasions, neuropsychiatric symptoms.1 Patients using the nicotine transdermal patch in combination with bupropion should be monitored for treatment-induced hypertension. The advantages of bupropion therapy are the potential delay of weight gain from smoking cessation, it can be beneficial in patients who also have depression, and it may be combined with nicotine replacement agents. Precautions for using bupropion SR are concomitant therapy with medications or conditions known to lower the seizure threshold, hepatic impairment, adolescents, pregnancy and breastfeeding, and treatment-emergent neuropsychiatric symptoms. Bupropion for smoking cessation is contraindicated in patients with a seizure disorder, patients taking concomitant bupropion therapy, current or prior diagnosis of bulimia or anorexia nervosa, simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines, and the use of MAO inhibitors within 14 days of bupropion therapy.1
Varenicline, known by the brand name Chantix, was approved for smoking cessation by the FDA in 2006 and is available by prescription only. Oral varenicline is marketed specifically for smoking cessation and is a partial agonist of the α4β2 nicotinic acetylcholine receptor subtype. This receptor mediates dopamine release and is thought to be a major receptor involved in nicotine addiction. When varenicline activates this receptor, its maximal effect is about 50% that of nicotine. This action is thought to relieve the symptoms of nicotine withdrawal, including cravings, and blocks the effects of nicotine on the receptor if a patient smokes a cigarette which diminishes the rewarding effects of cigarettes and makes the desire and likelihood to continue smoking reduced. Titration is used with varenicline, which is typically 0.5 mg every morning on days 1 to 3, 0.5 mg twice daily on days 4 to 7, then 1 mg twice daily for weeks 2 through 12. Varenicline should be started one week prior to the quit date; however, it may be initiated up to 35 days before the target quit day. After eating, varenicline should be taken with a full glass of water to reduce nausea. The duration of therapy is typically 12 weeks, with some patients requiring an additional 12-week course. Patients may reduce smoking
frequency over the 12-week period prior to quitting and then continue the treatment for an additional 12 weeks. Dose adjustment is necessary for patients with renal impairment. The manufacturer recommends lowering the dosage if patients are not tolerating the medication due to adverse effects. Adverse effects of varenicline include nausea, insomnia, abnormal/vivid dreams, constipation, flatulence, vomiting, and neuropsychiatric symptoms. Precaution should be used in patients with severe renal impairment, pregnancy and breastfeeding, adolescents, and treatment-emergent neuropsychiatric symptoms.1
In 2009, the FDA mandated that bupropion and varenicline-containing products include a black-boxed warning highlighting the risk of serious neuropsychiatric symptoms. These symptoms included changes in behavior, agitation, hostility, suicidal thoughts and behavior, depressed mood, and attempted suicide. In 2016 this black-boxed warning was removed based on the results of a mandated clinical trial; however, pharmacists and providers should still counsel and monitor patients for these symptoms. The clinical trial determined the risk of serious neuropsychiatric side effects was lower than previously suspected.1
Clonidine may be used off-label as an adjunct to psychosocial interventions in managing smoking cessation. Clonidine acts on the central nervous system to help reduce withdrawal symptoms.18 Clonidine should be started up to 3 days before or on the quit date. The initial dose is 0.1 mg by mouth once or twice daily if using oral therapy or 0.1 mg/24-hour patch applied once weekly if using the transdermal patch. The dose may be increased by 0.1 mg/day on a weekly basis if needed, with oral doses being divided throughout the day to increase tolerability. The duration of treatment generally ranges from 3 to 10 weeks. If the patient is on a higher dosage, it is advisable to gradually reduce the dose over 2 to 4 weeks to help decrease the likelihood of rebound phenomena, including increases in blood pressure, agitation, confusion, and/or tremor. Common side effects that may be experienced with clonidine therapy include dry mouth, sedation, dizziness,
drowsiness, and constipation. Clonidine can be beneficial when a patient withdraws from multiple drugs, as it can also relieve the withdrawal symptoms of drugs other than nicotine.18
Nortriptyline is a tricyclic antidepressant that may also be used off-label as an adjunct to psychosocial interventions in the management of smoking cessation. The dose initially starts at 25 mg once daily and then gradually increases to a target dose of 75 mg to 100 mg once daily. Nortriptyline should be initiated 10 to 28 days before the quit date to attain steady-state concentrations. The duration of therapy in most trials has been approximately 12 weeks and may last for up to 6 months. Nortriptyline may be considered in patients unable to use first-line medications due to contraindications, patients who have failed to quit with first-line therapy, or patients with a current or history of depression.
Naltrexone may be used off-label as an adjunct to psychosocial interventions for smoking cessation. Naltrexone has limited data for use but has been used alone or in combination with nicotine patches to help patients attempting to quit smoking. In a study that evaluated the effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women, naltrexone increased quit rates during treatment as well as reduced weight gain; however, the results were not sustained after discontinuing naltrexone.19
E-cigarettes and Vaping as an Alternative to Smoking
E-cigarettes (EC) are tobacco products that can deliver nicotine and are now the most commonly used tobacco product among youth in the United States. Most, but not all, EC contain nicotine. Nicotine and vaping solutions contained in EC are not regulated in the same way as FDA-approved dosage forms. These devices may also be referred to as “e-cigs,” “e-hookahs,” “mods,” “vape pens,” “vapes,” and “tank systems.” The use of e-cigarettes can further lead to the use of other tobacco products, including conventional cigarettes. According to the 2016 surgeon general report on E-Cigarette Use Among Youth and Young Adults from 2011 to 2015, EC use increased by 900%
among high school students and is now the most used form of tobacco among youth in the US. A draw to e-cigarettes is the wide variety of flavors that may appeal to youth and young adults. E-cigarettes can expose individuals to compounds that may have adverse health effects, including nicotine, carbonyl compounds, and volatile organic compounds.4 The 2020 Surgeon General Report on Smoking Cessation raises the question of the potential impact EC may have on the effort to eliminate disease and death caused by tobacco use due to the growing popularity of EC.1
Vaping and EC were originally seen as a tool for smoking cessation, but over time, they have not only attracted people who are trying to quit smoking but have also drawn the attention of non-smokers because of the efficient nicotine delivery as well as the large variety of available flavors.20-22 An advantage of e-cigarettes and vaping devices is the possibility of being used in smoke-free places. These devices are battery-powered devices made up of an electric atomizer and replaceable cartridges containing water-based liquids called “e-liquids.” E-liquids are primarily composed of propylene glycol, glycerin, water, flavors, and variable amounts of nicotine, and the atomizer heats the e-liquid, which is then vaporized and inhaled by the user.23
Electronic cigarette aerosols come into contact with pulmonary surfactants and impair critical surface tension, which reduces activity in the lungs and can contribute to lung dysfunction. Pulmonary surfactant reduces the surface tension in the lung, which is essential for breathing, and allows the lungs to inflate and deflate with minimal pressure changes. The results of a study by Graham, et al., supported the hypothesis that exposure to EC aerosols resulted in impaired surfactant function and all exposed samples (regardless of device, additive, or vehicle composition) resulted in higher minimum surface tensions than just air-exposed samples. This study used bovine lipid extract surfactant (BLES) to establish the effects of the delivery vehicle on surfactant and the effect of aerosols from a variety of e-liquids that contained flavorings and/or nicotine. When non-aerosolized, the e-liquid mixed with the BLES did not show significant differences in surface tension, showing the significance of aerosolization in inhibiting pulmonary surfactant. Most flavors of aerosol resulted in similar inhibition, except for menthol and
red wedding flavors, which resulted in significantly higher minimum surface tensions than other flavors. The study also mentions that chemicals in e- liquids are not highly regulated so that effects can be variable due to variations in e-liquid formulations as well as differences in vehicle delivery. Aerosolization of different liquid formulations can also lead to the generation of harmful chemicals, including formaldehyde, acetaldehyde, and acrolein. An interesting result from this study is that there were no significant differences in power levels (wattage) on the highest power device tested, which suggests two possible things: the lowest wattage was able to affect surface tension maximally or reactive oxygen species production was not a major contributor to inhibit surfactant. Although the study was done in vitro, these effects should be extrapolated to the in vivo setting as a potential downfall of e-cigarettes and vaping. In the human setting, it should be noted that even if vaping does not induce surfactant alterations that are sufficient to cause lung dysfunction, settings in which surfactant is further challenged may cause more impairment, ultimately leading to decreased lung function.24
Barriers to Smoking Cessation
Quitting smoking can be difficult and interventions used for smoking cessation should be individualized based on patient history and readiness for change. Behavioral counseling and cessation medications, especially when used in combination, increase the likelihood of successfully quitting. Ensuring that medication is covered under the patient’s insurance is helpful for compliance and aiding in smoking cessation. Some insurance plans do not cover over-the-counter products, such as nicotine gum and patches, which may cause a patient to have an unsuccessful quit attempt if they must pay a cash price. Counseling and quitlines play an important role as patients cannot control their surroundings. Quitlines are available to individuals in every state and offer support through counseling, referrals to local programs, and free medications to people who want to quit tobacco. Pharmacies should have the 1-800-QUIT-NOW number readily available for patients. This phone number is a national portal that can help patients contact local state resources.26 Friends, family, and coworkers may still smoke around the patient, causing
temptation. Patients going through a particularly stressful event may also relapse as a coping mechanism.25
Smoking cessation is vital in helping improve a patient’s overall health. Several medication options are available to help aid patients in smoking cessation. The availability of OTC products can be especially useful for these patients. Pharmacists and pharmacy technicians should be able to help patients find these products in the pharmacy and be sure to keep them fully stocked for ease of access. Smoking cessation medications combined with behavioral modification and support can help patients succeed in their smoking cessation goals.
Smokers may see
an increase in high-density lipoprotein cholesterol levels.
a decrease in hypercoagulability.
a decrease in markers of inflammation
cancers such as bladder, lung, esophagus, liver, mouth, and throat.
When a person quits smoking, medication dosages of CYP1A2 substrates
may need to be discontinued.
may need to be reduced.
may need to be increased.
do not need to be adjusted.
Smoking increases the risk of in patients who are taking estrogen-containing hormonal contraceptives.
All of the above
Peak symptoms of nicotine withdrawal typically occur after the last dose of nicotine.
True or False: All nicotine replacement therapies are available without a prescription.
When counseling patients on the use of nicotine gum, they should be instructed that the gum should be “parked” between the cheek and tongue
when the gum has a peppery taste or tingling sensation (at approximately 15 to 30 chews).
when the tingling peppery taste or tingling sensation fades (at approximately 5 chews).
after every 10 chews.
with or without chewing.
Bupropion therapy may
increase weight gain from smoking cessation.
benefit patients with depression.
not be combined with nicotine replacement agents.
help patients with a seizure disorder.
True or False: Varenicline should be started at least one week prior to the patient's target quit date; however, it may be initiated up to 35 days before the target quit day.
is a tricyclic antidepressant that may be used off- label for smoking cessation.
Which of the following about electronic cigarettes is true?
All electronic cigarettes contain nicotine.
Electronic cigarettes containing nicotine are an FDA-approved smoking cessation tool.
Electronic cigarette aerosols can contribute to lung dysfunction.
Electronic cigarettes are a proven safe and effective alternative to traditional cigarette smoking.
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