Tobacco Cessation: Exploring Pharmacological Perspectives and Interventions

Introduction:

Despite the growing body of knowledge on the health dangers of tobacco products over the last 70 years, smoking remains one of the world's leading causes of mortality. In 2020, the global adult smoking prevalence was 6.5% (6.3%–6.7%) for women and 32.6% (32.2%–33.1%) for men. In 2020, 1.18 billion (0.94-1.47) people used tobacco on a regular basis, resulting in 7 million (2-11.2) fatalities.(1) Tobacco usage was prevalent among both male and female adolescents around the world. The information that is now available indicates a definite association between smoking and poor tooth health in youth. Teens who smoke frequently are more likely to develop gingivitis (72.8%), gingival bleeding (51.2%), and oral malodor or halitosis (39.6%). Teenagers who smoke regularly are more likely to develop hyperkeratosis, smoking-related melanosis, hairy tongue, and dental caries.(2)

Nicotine addiction, like any other substance abuse disorder or chronic illness, necessitates medical treatment. The patient should be told about the benefits of quitting, the strategy, and any possible withdrawal symptoms. A treatment strategy that works for the patient should be chosen with their input.(3) The most potent pharmacological agent is nicotine, a potentially lethal alkaloid (1-methyl-2-[3-pyrodyl] pyrrolidine) that impairs pathologic physiological functions. Nicotine in tobacco smoke causes tolerance to its effects over time while also modifying the pathophysiology of smokers' bodies. Smoking cessation is one technique for enhancing life expectancy and decreasing morbidity.(4)

Dentists play an important role in minimising tobacco-related deaths by informing patients about the risks of tobacco use as soon as the oral cavity reveals the first indications of tobacco use. Because it doubles the success rate of quitting smoking across all intervention levels, the most thorough support improves the effectiveness of nicotine replacement therapy (NRT).(5)

A significant portion, accounting for 50%, of individuals who engage in chronic cigarette smoking experience premature mortality due to various diseases such as cancer, cardiovascular disease, pulmonary disorders, and other smoking-related conditions.(6) In light of the elevated mortality rates associated with tobacco use, this comprehensive review synthesizes existing literature on diverse forms of Nicotine Replacement Therapy (NRT) utilized in managing nicotine addiction, alongside alternative medical interventions for addressing tobacco use disorder. 

Therapeutic aspect:

Nicotine Replacement Therapy (NRT):

Nicotine Replacement Therapy (NRT) represents a cornerstone in the pharmacological management of tobacco dependence. Available in various formulations such as transdermal patches, gum, lozenges, nasal sprays, and inhalers, NRT delivers controlled doses of nicotine to alleviate withdrawal symptoms and cravings while gradually weaning individuals off tobacco. The efficacy of NRT in promoting smoking cessation has been well-established through numerous clinical trials and meta-analyses. However, optimal dosing, duration of treatment, and combination therapies warrant further investigation to maximize effectiveness and minimize relapse rates.

Nicotine Gum

Nicotine gum, commercially known as Nicotine Polacrilex, manufactured by McNeil Consumer Healthcare, Fort Washington, PA, USA, represents one of the earliest accessible forms of Nicotine Replacement Therapy (NRT). Available in dosages of two and four milligrams, research indicates that the four-milligram formulation exhibits greater efficacy in aiding smoking cessation compared to the two-milligram variant.(6) Commencement of nicotine gum therapy either on the prescribed cessation date or four weeks prior has demonstrated no significant disparity in outcomes.(7) It is important to note the presence of neuronal nicotinic acetylcholine receptors in the brain, although outcomes may vary due to individual differences in nicotine gum consumption influenced by factors such as daily nicotine intake thresholds, age, body mass index, genetic predisposition, peak concentration, and age.(8)

Rapid-Release Gum

Rapid-release gum features a specialized gum base designed to facilitate biphasic nicotine delivery and rapid initial nicotine release. Additionally, it raises the pH level to accelerate absorption through the oral mucosa.(9) A comparative study assessing the efficacy of Nicorette (McNeil Consumer Healthcare) and rapid-release nicotine gum in alleviating nicotine cravings triggered by smoking cues found that rapid-release nicotine gum provides a distinct advantage by swiftly and fully addressing nicotine cravings, contrasting with conventional nicotine gum.(10)

Nicotine Lozenges

Nicotine lozenges offer an alternative to nicotine gum, particularly suitable for individuals requiring intermittent nicotine doses but unable to chew gum for prolonged periods. Available in 1 mg, 2 mg, and 4 mg formulations, these lozenges present a viable option for managing tobacco dependence.(11) While users experienced a noticeable reduction in tobacco cravings during the initial two weeks of abstinence, individuals utilizing smokeless tobacco did not report significant differences in overall tobacco withdrawal symptoms when using nicotine lozenges. Nonetheless, smokeless tobacco users generally tolerated and endorsed the use of nicotine lozenges.(12)

Transdermal Patch

The transdermal nicotine patch facilitates gradual nicotine absorption through the skin upon application.(13) Tailored to the individual's level of nicotine dependence, users can select from various patch strengths, allowing for a personalized approach to nicotine replacement therapy (NRT). This flexibility enables users to gradually taper their nicotine intake over several weeks, facilitating adaptation to reduced doses and eventual cessation of nicotine use. A key advantage of nicotine patches lies in their simplicity of use and compliance; requiring only a single daily application, they eliminate the need for frequent dosing throughout the day.(14) Commonly reported side effects include localized skin reactions, which can be mitigated by rotating patch application sites as instructed, thus minimizing discomfort.(5)

High-Dose Nicotine Patches

Conventional 22-mg nicotine patches typically restore approximately half of a smoker's baseline blood nicotine and cotinine levels. Consequently, investigations into transdermal nicotine doses exceeding 42 mg were conducted. High-dose transdermal nicotine replacement therapy (NRT) demonstrated a statistically significant increase in cessation rates compared to standard doses [5]. However, despite efficacy findings, the safety and efficacy of high-dose transdermal NRT for smoking cessation have not been conclusively established in medical literature.(15)

Sublingual Nicotine Tablets

Sublingual nicotine tablets offer a novel approach to nicotine replacement therapy (NRT), bypassing the need for chewing and facilitating controlled dosing. Typically prescribed for a duration of 8 to 12 weeks, the regimen is gradually tapered thereafter to wean individuals off nicotine dependence.(13) For patients with high nicotine dependency, a regimen of 16 to 24 sublingual tablets daily is advised, equivalent to a maximum of 302 mg tablets dispersed throughout the day, while those with lower dependency are recommended a dosage of 8 to 12 tablets per day.(16) However, caution is warranted in individuals with a history of nicotine addiction. Commonly reported side effects include oral discomfort and insomnia, necessitating careful monitoring and management.(17)

Nicotine Nasal Spray

Nasal spray substantially doubles the quit rate when compared to a placebo.(18) Nicotine exposure to the foetus is decreased by nicotine patches and nasal sprays as opposed to smoking. Nasal spray, the quickest form of delivery, most closely mimics the increase in nicotine levels seen while smoking. Highly dependent smokers benefit most from the nasal spray since it promptly suppresses appetite.(19)

Non-Nicotine Medications:

Several non-nicotine drugs that target distinct neurobiological pathways linked to nicotine addiction have been approved for use in tobacco cessation in addition to NRT. Dopamine and norepinephrine reuptake inhibitors like bupropion have been shown to be effective in lessening withdrawal symptoms and promoting abstinence. Varenicline functions as a partial agonist of the α4β2 nicotinic acetylcholine receptor and selectively attenuates the rewarding effects of smoking while also reducing cravings. Non-nicotine drugs have been shown to be effective, but they may have side effects. As such, it is important to carefully weigh each patient's risk-benefit profile and to closely monitor them while they are on treatment.

Bupropion

Bupropion, known primarily as an antidepressant, effectively treats nicotine addiction, though its precise mechanism for this remains uncertain.(20) Typically, treatment starts with 150 mg daily, increasing to 150 mg twice daily for 7 to 12 weeks, extendable to 12 months with maintenance dosing. Side effects include insomnia, headaches, dizziness, and dry mouth, with contraindications for individuals with seizure disorders and certain medications.(21) Bupropion inhibits dopamine reuptake primarily, aiding approximately one in five smokers in quitting, with side effects including sleep disturbances and dry mouth. Though rare, caution is advised regarding seizures and potential drug interactions. Despite its efficacy and cost-effectiveness, nicotine replacement therapy remains more commonly used for smoking cessation.(22)

Varenicline

Varenicline, a selective nicotinic receptor partial agonist developed by Pfizer Inc, targets the α4β2 nicotinic acetylcholine receptors (nAChRs) to counteract nicotine's effects.(23) Acting as a partial agonist, it induces moderate dopamine release, alleviating withdrawal symptoms during smoking cessation attempts, while blocking the effects of subsequent nicotine challenges.(24) Additionally, evidence suggests varenicline may also act as a full agonist at the homomeric α7 receptor. Treatment typically begins with a titration phase, starting at 0.5 mg once daily and increasing to 1 mg twice daily, with lower dosages available for patients experiencing adverse effects. Varenicline can be used for up to six months if tolerated well, with common side effects including nausea, insomnia, nightmares, headaches, and dry mouth. Contraindications include significant skin reactions and hypersensitivity to varenicline, while seizure disorder is not necessarily a deterrent.(25)

Clonidine

Clonidine, a central nervous system medication, was initially used as an antihypertensive to treat withdrawal symptoms from certain addictive behaviours. Existing research suggests that the dose be gradually increased to a maximum of approximately 400 g/day, as tolerated, beginning with 100 g twice daily (orally or with an analogous transdermal patch). If clonidine therapy is planned before the stop date, it should begin 48 to 72 hours in advance.(26) In a trial done by Hilleman et al., no more smokers dropped out when clonidine was given instead of a placebo. At all follow-up visits, women on clonidine abstained at a considerably higher rate than men. Thus, only female smokers may benefit from clonidine.(27)

Nortriptyline

Nortriptyline, a tricyclic antidepressant, has showed promise in smoking cessation.(28)Nortriptyline, a tricyclic antidepressant (TCA), increases serotonin and norepinephrine levels in the synapse by inhibiting their reuptake by presynaptic neuronal membranes. Nortriptyline is typically used orally and is available in capsule dosages of 10, 25, 50, and 75 mg, as well as an oral solution of 10 mg/5 mL. Adult dosages normally begin at 25 mg taken three or four times per day, with changes as necessary. Daily doses greater than 100 mg should be monitored, and doses greater than 150 mg are not advised. Plasma nortriptyline concentrations vary widely between individuals, with higher levels linked with fewer withdrawal symptoms.(29)

Anxiolytics

Anxiolytics have also been proposed as a treatment option. Meprobamate, ondansetron, doxepin, buspirone, diazepam, and the beta-blockers metoprolol, oxprenolol, and propranolol are among the drugs that can aid with anxiety, which is a symptom of nicotine withdrawal.(30)

Recent advances:

Recent breakthroughs in pharmacotherapy for tobacco cessation have prompted the investigation of novel agents and alternate delivery modalities. Innovative techniques, including as nicotine vaccines, cannabinoid receptor modulators, and tailored neurotransmitter agonists, show promise for improving treatment outcomes and addressing specific obstacles in smoking cessation. Furthermore, digital treatments and personalised medicine interventions based on mobile applications, genetic profiling, and behavioural analytics have the potential to improve treatment adherence and tailor interventions to individual preferences and needs.(31)

Challenges and Future Directions:

Despite substantial advancements in tobacco cessation therapy, widespread adoption and sustained abstinence rates remain challenging. Barriers such as limited availability, budgetary restraints, social stigma associated with medicine use, and the impact of environmental factors highlight the need for comprehensive, multifaceted solutions. Future research should focus on understanding the fundamental mechanisms behind nicotine addiction, identifying biomarkers indicative of treatment response, and developing novel techniques to improve treatment adherence and long-term efficacy.(32)

Conclusion:

Pharmacotherapy is vital for tobacco cessation attempts, providing smokers with effective tools to conquer nicotine addiction and achieve long-term sobriety. There are numerous therapeutic options available to help people quit smoking, ranging from nicotine replacement therapy to non-nicotine drugs and new pharmacotherapies. However, tackling the complex nature of tobacco dependence necessitates a multimodal approach that includes behavioural support, policy measures, and public health interventions. By improving our understanding of nicotine addiction and embracing innovation in pharmacological therapies, we may work towards a tobacco-free future while also improving people's health and well-being worldwide.

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