Keywords
Mouth neoplasms - nicotine replacement products - oral health - periodontal diseases
- smoking - tobacco
Introduction
Tobacco-related addiction has huge financial implications, not only for the users
but also for the public.[[1]],[[2]] While rates of smoking are declining in 2015, 11.5% of global deaths were attributable
to smoking worldwide.[[3]]
A key objective of the Government and all health professionals is to eliminate or
to reduce the impact of tobacco usage on the wider population. Current knowledge about
tobacco use and its effects has led to the understanding that there is no safe way
to use tobacco and that total cessation is imperative to avoid any number of debilitating
and eventually fatal conditions.[[4]]
Various methods of achieving cessation have been proposed, including behavioral counseling
and pharmacotherapy. The paradigm for cessation has changed over the years with a
shift toward viewing addiction as a disease and the contemporary approach toward the
management of tobacco addiction centers around a combination of education, counseling,
and pharmacotherapy.[[5]]
A method of assisting users in achieving cessation goals has been through the substitution
of pure nicotine with tobacco-less products.[[6]] Nicotine replacement products (NRPs) are the collective name for a range of over-the-counter
medications containing pure nicotine, designed to aid users of tobacco products in
reducing their intake of such products, or to achieve a total cessation of use.[[1]],[[7]],[[8]] This pathway reduces the withdrawal symptoms associated with a reduction of intake
or total cessation.[[1]],[[7]],[[8]] The use of nicotine substitution through one or more NRPs to aid cessation of tobacco
use is termed as nicotine replacement therapy (NRT), and in the contemporary setting
is considered as first-line therapy for smoking cessation.
NRT products are available in many different forms for consumers, including chewing
gums,[[9]] lozenges or mints,[[10]] inhalers,[[11]] patches,[[12]] and vaporizers (also called E-cigarettes or Electronic cigarettes).[[13]] Nicotine drinks, straws, and lollipops are other developed and marketed products.[[14]] These products are available in varying strengths of nicotine based on the tobacco
user’s habitual intake or “stage of quitting.” Except for nicotine patches (where
nicotine is absorbed transdermally) and nasal sprays (where nicotine is absorbed through
nasal mucosa), all other forms of NRP deliver nicotine by transmucosal absorption
across the lining of the mouth. Oral delivery systems pose potential implications
for the soft- and hard-tissue structures of the oral cavity, and the popularity of
oral delivery methods highlights the need for integration of knowledge of potential
adverse effects and how these may modify treatment outcomes or risk profiles in an
oral and dental context.
NRT products are reported to be an effective adjunct to professional counseling, and
other pharmacological aids in achieving sustained abstinence from tobacco [[1]],[[5]],[[7]],[[8]],[[12]],[[15]],[[16]] with some studies reporting success rates as high as 33% compared to 5% with patients
quitting on their own.[[1]] One meta-analysis found a 50%–70% higher chance of quitting when using NRT.[[17]] Interestingly, NRT has shown to be effective in achieving sustained abstinence,
even in smokers who have no intention of quitting.[[8]]
Combination therapy is a term referring to the use of multiple, different forms of
NRT product simultaneously, for example, a nicotine patch used in conjunction with
a nicotine spray.[[14]],[[18]] It has been shown to be more effective for cessation than the use of anyone product
on its own, independent of the provision of any professional counseling.[[5]],[[7]],[[8]],[[15]],[[16]] Combination therapy is often used when initial attempts at cessation with monotherapy
(the use of one form of NRT product) has failed to show positive benefit.[[12]]
The Effects of Nicotine on the Body
The Effects of Nicotine on the Body
Nicotine is the most pharmacologically active component of tobacco and has a wide
range of effects on the body, affecting blood flow, the immune response, and the body’s
healing mechanisms.[[19]],[[20]],[[21]],[[22]],[[23]] Nicotine has been noted to inhibit revascularization,[[24]] has a direct effect on the function and action of immune cells,[[25]],[[26]],[[27]],[[28]],[[29]] impedes tissue-repair mechanisms [[24]],[[30]],[[31]],[[32]],[[33]],[[34]],[[35]],[[36]],[[37]] in the body, and affects almost every organ in the body, including the brain and
the heart.[[23]],[[38]],[[39]] Some of the more specific pharmacokinetics of nicotine are outlined below.
Neurological and cardiovascular effects of nicotine
Nicotine has a very targeted and direct active effect on the nervous systems; nicotinic
cholinergic receptors are found in the brain, autonomic ganglia, and the neuromuscular
junction.[[23]] Intake of nicotine into the body enhances the release of various neurotransmitters,
including adrenaline, noradrenaline, dopamine, acetylcholine, serotonin, vasopressin,
glutamate, nitric oxide, calcitonin growth-related peptide and beta-endorphin [[19]],[[23]] producing a myriad of systemic effects.
The main cardiovascular effect of nicotine is sympathetic neural stimulation.[[20]] Nicotine exposure can increase the heart rate by up to 10–15 beats/min and increase
blood pressure by up to 5–10 mmHg.[[20]] Nicotine’s inhibitory effects on angiogenesis and blood flow locally and systemically
[[40]],[[41]] have ramifications not only in a broader general health context but also its vasoconstrictive
properties lend itself toward the impairment of salivary flow in the oral environment
and has such as implications on a patient’s caries-risk profile. Furthermore, opportunistic
oral bacterial infections such as Candidiasis has been reported as a result of low
salivary flow.[[42]],[[43]],[[44]],[[45]]
Immunological effects and effect on the healing response
Nicotine has profound immunological effects, influencing all aspects of the immune
system, including alterations in humoral and cellular immunity.[[29]] It has been shown to have a range of immunosuppressive actions,[[27]],[[29]],[[46]],[[47]],[[48]] including inhibition of pro-inflammatory cytokines in macrophages, inhibition of
adhesion molecules, and inhibiting proliferation of lymphocytes in the human mixed
lymphocyte reaction.[[48]] Nicotine has been observed to directly impair interleukin-1 β and superoxide and
hydrogen peroxide formation by monocytes as well as the formation of oxygen radical
species by neutrophils, effectively inhibiting the defensive functions of these immune
cells.[[49]],[[50]]
Nicotine exposure has also been shown to inhibit a range of normal neutrophil functions
such as phagocytosis, integrin expression, and protease inhibitor production,[[51]] leading to inhibition of the effectiveness of these immune cells on the body.
It has been documented that nicotine inhibits the actions of B-cells and T-cells [[28]],[[46]] and impairs antigen receptor function and ectonucleotidase activity in lymphocytes,[[25]],[[26]],[[52]] weakening the capacity for these immune cells to respond normally.
Nicotine has been shown to impair cutaneous wound healing,[[30]],[[31]] normal bone healing responses,[[32]],[[33]] revascularization of both hard and soft tissues,[[24]],[[31]],[[32]] as well as healing of the bone following graft and augmentation,[[24]],[[34]] which may be related to the inhibition of various cytokines involved in revascularization
and osteoblast differentiation,[[53]] and therefore affecting the healing of both hard and soft tissues of the body.
Similarly, nicotine affects fibroblast attachment,[[35]],[[36]],[[37]] integrin expression [[54]] and inhibits collagen production while enhancing collagenase production,[[55]] leading to impairment of the normal healing response. In a recent publication,
it was observed that when nicotine gum was placed directly adjacent to a tooth extraction
site, it was reported to produce osteonecrosis of the jaw.[[56]]
Oral and periodontal effects of nicotine
In some studies, it has been reported that nicotine impairs gingival blood flow [[57]] and leads to local vasoconstrictive effects.[[58]] It has been reported that chronic use of nicotine products could lead to dose-dependent
suppression of gingival bleeding.[[59]] However, smoking cessation improves gingival blood flow and gingival crevicular
fluid (GCF) flow in humans.[[60]] This impairment of normal blood and GCF flow poses potential issues in the modification
of the desired response in periodontal healing and can affect the risk profiles for
oral and dental pathology such as dental caries and Candidiasis.[[43]],[[44]],[[45]] Furthermore, nicotine binds directly to the root surfaces and results in impaired
gingival fibroblast attachment to those periodontally involved root surfaces. Katti
et al. reported that nicotine levels can be significantly reduced by root planning in the
course of periodontal debridement procedures, suggesting the importance of professional
oral health maintenance in patients on nicotine products.[[61]]
Similarly, nicotine has been implicated as a standalone modifying factor in periodontal
destruction by the way of inducing COX-2 expression in human gingival fibroblasts,[[62]] inducing higher levels of interleukin-1 and interleukin-6 in gingival keratinocytes
and fibroblasts,[[63]],[[64]] upregulating lipopolysaccharide-mediated human monocyte secretion of prostaglandin-E2,[[65]] and matrix-metalloproteinases [[66]] which degrade connective tissue, as well as having a stimulatory effect on polymorphonuclear
cell apoptosis.[[50]] These processes lead to an upregulation of the inflammatory response and promote
the destruction of the tissue.
The negative effects on the immune response, blood flow, and salivary status have
the capacity to modify periodontal disease, periodontal treatment outcomes, postsurgical
healing and implant placement, and maintenance outcomes. The compromised healing response
in both hard and soft oral tissues, as identified above leads to the progression of
periodontal disease and impairs surgical healing of extraction sites and other regenerative,
mucogingival, and implant surgical procedures.[[51]]
Adverse Effects of Nicotine Replacement Therapy on Oral Health
Adverse Effects of Nicotine Replacement Therapy on Oral Health
The smoking status of the patient is always considered in dental management; however,
the effect of NRT usage and its implications are not routinely considered in the oral
and dental management of patients.
One of the most commonly reported side effects of nicotine and NRT use is dry mouth,
resulting in an impairment of the buffering capacity of the saliva.[[16]] Modification of the quality and quantity of saliva by NRT may result in an increase
in the patient’s caries-risk profile and increased the risk of such conditions as
candidiasis, oral mucositis, mouth soreness, taste impairment, dryness, and cracking
of the vestibular tissue, and multiple issues for denture wearers as a result of a
dry oral cavity including difficulty in speech.[[42]],[[43]],[[44]],[[45]] Nicotine delivered orally may also produce other forms of oral changes leading
to discomfort, including numbness and tingling, hyperkeratosis, oral lichenoid reactions,
burning mouth syndrome, and localized mucosal irritation.[[17]],[[67]],[[68]] Nicotine is a carcinogen and has been shown to modify the progression of oral cancer.
Its consumption through an NRT product orally may place a patient at risk of oral
neoplastic changes.[[69]],[[70]],[[71]],[[72]],[[73]] There is limited research of NRT links to oral malignancy and impacts in conjunction
with head-and-neck radiotherapy.
Adverse Impact of Nicotine or Nicotine Replacement Therapy in Periodontal and Oral
Surgical Management
Adverse Impact of Nicotine or Nicotine Replacement Therapy in Periodontal and Oral
Surgical Management
Smoking cessation in the management of periodontal conditions is well established,
due to its major impact factor in the posttreatment and modifying factor in the progression
of periodontitis.[[74]],[[75]],[[76]],[[77]] Similar complications in postsurgical outcomes following dental implant placement,
hard- and soft-tissue grafting procedures, surgical exposure for orthodontics, and
excisional procedures are reported.
The above issues are due to nicotine’s effects on the immune system and complications
of the normal postsurgical healing response in the oral cavity, with delayed healing.
An extraction site with impaired blood flow will take longer to heal, and therefore
produce an increased risk of secondary infection, impaired soft tissue and bone healing,
as well as an extended period of the patient discomfort with a poorly healing socket.
This is particularly relevant when the oral NRT product is applied directly adjacent
to the healing site (s) and periodontally treated, operative sites after a crown lengthening
or mucogingival procedures.
Incidences of postoperative discomfort and superinfection, resulting in opportunistic
infections such as candidiasis in the oral environment have been reported.[[43]],[[44]] For patients on bisphosphonate medications, NRT may produce an increased risk of
medication-related osteonecrosis of the jaws in the absence of other risk factors
or other medical complications such as poorly controlled diabetes.[[56]]
Smoking Cessation and the Dental Professional
Smoking Cessation and the Dental Professional
The practitioner, on considering future treatment directions and clinical management
of a periodontal patient may encounter differences in healing and treatment outcomes
as a result of the direct/indirect impacts of NRT in the absence of any significant
medical implications in a susceptible individual. The clinician should have knowledge
of NRT’s oral and dental effects on the patient, for accurate diagnosis, appropriate
management and minimization, or elimination of risk factors. Dolan et al. found that 65% of dentists advise smoking cessation, few provided specific counseling
on cessation methods, strategies, or routine prescription of products, as this is
not a part of the general dental practice.[[78]] At present, there are no guidelines readily available for counseling the patient
in the use of NRT and smoking cessation advice, support/counseling as a routine part
of the general dental practice.[[78]]
The primary message that the health professionals’ recommends in relation to these
products is obtained from the manufacturers’ advice notes on the effectiveness of
such products in smoking cessation. Although various research has highlighted the
efficacy of NRT contribution in smoking cessation,[[7]],[[8]],[[79]] the adverse effects of NRT is usually left to the patient themselves.
A deeper understanding of the impact that NRT products have on the oral cavity and
the role they play in dental management will have far-reaching positive outcomes for
patients, as well as instilling confidence in clinician’s advice on smoking cessation.[[80]] There is no formal training provided in the Australian dental school curriculum,
regarding the provision of smoking cessation services in a dental setting for oral
health professionals. Most patients are simply told that they “must quit smoking,[[78]] sometimes followed by a recommendation for NRT in general, rather than advice on
specific products or their use. Follow-up usually centers on patients’ success with
cessation rather than considering adverse events that may be associated with NRT.
Of interest to dentists are the questions raised regarding oral and dental pathology
risks, as well as postsurgical, periodontal, and implant outcomes for patients utilizing
NRT and how to proceed. This is due to increased caries risk, xerostomia, oral mucosal
changes, oral cancer, and development of the oral lesions. Currently, there is inadequate
knowledge with regard to how NRT may modify treatment outcomes, risk profiles, or
the modification of the natural history of particular diseases or conditions.
Research has highlighted patients’ safety concerns and fears with respect to NRT products,
so the provision of accurate safety information will ensure the highest levels of
compliance with therapy and successful smoking cessation.[[80]],[[81]],[[82]] These studies present a strong case for furthering the available knowledge regarding
the specific potential adverse effects of NRPs for health professionals prescribing
the use of NRT and managing patients using NRT.
Given the imperative need for evidence-based practice in all health-care settings,[[83]] it is desirable that further information can be obtained regarding specific effects
of NRT, to aid diagnosis and prevention of adverse effects on the oral and dental
tissues for all health professionals, as well as to ensure appropriate recommendations
are made regarding the use of particular products and to ensure the best chances of
cessation for patients.[[80]],[[81]],[[82]] Pharmaceutical companies and manufacturers of NRT products might also benefit from
this knowledge in furthering the development of NRT products or the provision of information
regarding their appropriate usage.
Conclusions
While the clinical implications of patients’ smoking status are well known in the
management and treatment of the dental patient, the effects of NRT usage are not routinely
considered in general patient management. The current body of evidence indicates a
lack of knowledge of the effects on the oral cavity of the use of NRT. Further investigation
and subsequent promotion of the information to oral health professionals will ensure
better dental and oral health outcomes.
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