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Buprenorphine/Naloxone and Dental Caries: A Case Report
Objectives
The US Food and Drug Administration (FDA) issued a warning about buprenorphine-induced dental caries of unknown mechanism in 2022. To investigate the potential mechanism, the association between local buprenorphine exposure and dental biofilm formation will be explored in this study.
Methods
Female F344 rats were dosed with sublingual buprenorphine film or intravenous injection to explore the oral cavity exposure of the buprenorphine. The buprenorphine distribution in salivary glands after the sublingual and intravenous administration was also evaluated. To investigate the effects of buprenorphine exposure on dental caries formation, buprenorphine's impact on the biofilm formation of S. mutans in vitro was measured.
Results
The absolute sublingual bioavailability of buprenorphine in rats was 17.8% with a high ratio of oral fluid exposure to blood concentration in the pharmacokinetic study. Salivary gland concentrations of buprenorphine and its active metabolite norbuprenorphine were significantly higher than their blood concentrations after both sublingual (s.l.) and intravenous (i.v.) administration. Correlation analysis showed that the oral fluid concentration of buprenorphine and norbuprenorphine was highly correlated to salivary gland concentration rather than blood concentration. These data indicate that the salivary gland serves as an accumulation organ for buprenorphine, allowing prolonged oral fluid exposure to buprenorphine. Lastly, buprenorphine and its metabolites contributed to the biofilm formation of S. mutans in high concentration.
Conclusions
Sublingual administration substantially increased the salivary gland distribution of buprenorphine and norbuprenorphine. Depot effects following sublingual dosing and salivary gland accumulation likely sustained high oral fluid exposure to buprenorphine and stimulated the biofilm formation of S. mutans.
Background:
Prior research has suggested that buprenorphine-containing medications may be associated with an increased risk of dental disorders. However, published data describing adverse dental reactions in buprenorphine users by active ingredient composition and route of administration are limited.
Objective:
The purpose of this study was to evaluate the influence of formulation on spontaneous reporting of dental disorders among patients treated with buprenorphine.
Methods:
Adverse event reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between 2015 and 2022 were analyzed. Reporting odds ratios (ROR) and 95% confidence intervals (CI) were calculated to measure the disproportionality of dental disorder reporting as classified by 39 Medical Dictionary for Regulatory Activities preferred terms.
Results:
Compared to pooled reports for all other drugs across FAERS, both buprenorphine monotherapy (ROR 3.09; 95% CI 2.61-3.66) and combination buprenorphine/naloxone (ROR 14.61; 95% CI 13.34-16.01) were associated with positive disproportionality signals. Signals of disproportionate dental disorder reporting were also detected for buprenorphine medicines administered by sublingual (ROR 20.03; 95% CI 18.04-22.24), buccal (ROR 4.46; 95% CI 3.00-6.61) and oral (ROR 7.17; 95% CI 5.03-10.22) routes, but not for other modalities. In considering active ingredient and route together, sublingual buprenorphine monotherapies (ROR 23.55; 95% CI 17.84-31.11) and sublingual buprenorphine/naloxone (ROR 19.47; 95% CI 17.39-21.80) were each associated with disproportionate reporting of dental disorders.
Conclusion:
Subject to the limitations of spontaneous adverse event data, this study identified significantly disproportionate reporting of dental disorders to FAERS among patients treated with buprenorphine-containing medications, including formulations administered by sublingual, buccal and oral routes. These findings are consistent with prior data and suggest that regular oral care and proper dental hygiene be emphasized for patients undergoing therapy with orally dissolving buprenorphine.
This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.
Opioids have multiple effects on the immune system (IS). Experimentally, the effects of opioid administration range from a severe inhibition to strong activation of immune responses, depending on the compound, schedule administration, experimental model, or clinical condition. On the other hand, endogenous opioids play a central role in the complex circuitry that mediates the IS and nervous system (NS) communication, tuning the intensity of reactions such as inflammation and pain or the mechanisms for sensing tissue damage and triggering a stress response. This chapter reviews studies showing increased susceptibility to infections and altered immune parameters produced by opioids and some mechanisms involved in direct and indirect actions of opioids on innate and adaptive immunity, the influence on genetic factors and aging on opioid effects, and pathologies where opioids exert immunomodulatory actions, including current information about COVID-19.
Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.
The aim of this study was to determine the validity and properties of the Summated Xerostomia Inventory-Dutch Version in samples from Australia, The Netherlands, Japan, and New Zealand.
Six cross-sectional samples of older people from The Netherlands (n = 50), Australia (n = 637; n = 245), Japan (n = 401), and New Zealand (n = 167; n = 86) were enrolled. Data were analyzed by using the Summated Xerostomia Inventory-Dutch Version.
All datasets revealed a single extracted factor which explained about one-half of the variance, with Cronbach alpha values ≥0.70. When mean scale scores were plotted against a "gold-standard" xerostomia question, statistically significant gradients were observed, with the highest score seen in those who always had dry mouth, and the lowest in those who never had it.
The Summated Xerostomia Inventory-Dutch Version is valid for measuring xerostomia symptoms in clinical and epidemiologic research.
Drug abuse is a major problem in the U.S. and most other countries of the world today. Many studies, surveys, and case reports have described the adverse social and medical effects of drug abuse; yet surprisingly little is known about the specific effects of many of these drugs in the oral cavity. This article reviews the current state of knowledge concerning the systemic and oral effects of drugs of abuse and the dental management of addicted patients.
The etiology and pathogenesis of dental caries are known to be multifactorial, but the interplay between intrinsic and extrinsic factors is still not fully understood. As in other host/parasite interactions, there appear to be marked variations in individual susceptibility to the disease. It therefore is likely that intrinsic host factors play a key role in modulating the initiation and progression of caries. The objective of this systematic review was to evaluate critically the evidence supporting the role and effects of saliva in caries pathogenesis. The full-length evidence report, including evidence tables, and the structured abstract presented at the NIH/NIDCR Consensus Development Conference on the Diagnosis and Management of Dental Caries Throughout Life, March 26-28. 2001, can be accessed at the web site http://www.nidcr.nih.gov. The present abridged report is a summary of the main findings from our evidence-based review.
In recent years there has been increased interest in the role of commercial soft drinks in dental diseases namely as dental caries and erosion. The objective of this paper has been to review the past and current literature to determine the present knowledge on this subject. The literature related to dental caries, erosion, drinks, soft drinks and fruit juices was reviewed. The literature shows efforts have been taken to modify soft drinks by either adding or deleting certain components so as to reduce their harmful effects on teeth. A rational protocol to encourage the sensible use of drinks and the modification of drinks to render them less harmful would be advisable.
Dental professionals should be aware that methamphetamine (MA) use is on the rise in North America. MA is a potent central nervous system stimulant with limited therapeutic effects. The allure of this drug is its availability in many different forms that are relatively easy to make and distribute and inexpensive to purchase and that produce prolonged euphoria for the user. This euphoria results from alteration of the normal physiologic processing of several centrally acting neurotransmitters, which also causes neurotoxicity and neurodegeneration with long-term use. Long-term use of MA has been associated with severe oral health effects, the most notable being a distinctive pattern of caries called methamphetamine-induced caries. Dental professionals need to recognize and understand patients who may be using MA and the risk factors associated with its deleterious oral effects. This knowledge will allow appropriate and effective preventive and treatment strategies for users of this drug.
Opioid peptides affect different immune functions. We present evidence that these effects could be mediated by the modulation of TH1/TH2 cytokine production. The acute and chronic treatment with the opioid receptor antagonist naloxone decreased the production of IL-4 by splenocytes of C57BL/6 and BALB/CJ mice, that present a Th1/ Th2 dominance, respectively, immunized with the protein antigen KLH. In contrast, IL-2 and IFN-γ levels were increased after naloxone treatment. These results indicate that naloxone increases Th1 and decreases Th2 cytokine production. Moreover in C57BL/6 mice, naloxone treatment was able to accelerate skin-graft rejection, a Th1-mediated phenomenon, by increasing Th1 cytokine production. The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could activate Th2 and suppress Th1 cytokines.
Little is known about how different types of substances affect oral health. Our objective was to examine the respective effects of alcohol, stimulants, opioids, and marijuana on oral health in substance-dependent persons. Using self-reported data from 563 substance-dependent individuals, we found that most reported unsatisfactory oral health, with their most recent dental visit more than 1 year ago. In multivariable logistic regressions, none of the substance types were significantly associated with oral health status. However, opioid use was significantly related to a worse overall oral health rating compared to 1 year ago. These findings highlight the poor oral health of individuals with substance dependence and the need to address declining oral health among opioid users. General health and specialty addiction care providers should be aware of oral health problems among these patients. In addition, engagement into addiction and medical care may be facilitated by addressing oral health concerns.
Saliva plays an important protective role in the oral environment, and reductions in saliva quantity are known to increase the risk of oral diseases. Importantly, xerostomia or the perception of a dry mouth is now being recognized as an important risk factor for dental diseases. Furthermore, the subjective sensation of a dry mouth is a debilitating condition in itself that impacts on the quality of life of sufferers. With approximately 1 in 5 people reporting some form of dry mouth, and an increasing prevalence in the elderly, it is important for clinicians to have a thorough understanding of this problem. The aim of this paper is to review some of the literature relating to xerostomia in order to provide an evidence based update for clinicians.
Concepts and beliefs about the cause of dental caries have evolved over many centuries, with the involvement of microorganisms being recognized since the late 1800s. A main thrust of enquiry since then has been to tackle the question of the relative importance of different bacteria in the disease and this article will consider how technical advances in our ability to identify, cultivate and count different species has influenced our understanding. Over the last decade, molecular biological approaches have had a major impact on views of the relative contribution of particular species of plaque bacteria to the caries process. At a more detailed level, molecular genetic studies of species such as Streptococcus mutans have given new insights into the way in which particular genes and the functions that they encode may affect virulence.
Today, many patients regularly take prescription and over-the-counter medications that may be a risk factor for periodontal disease and caries. The sugar in many medications presents a serious caries challenge, which, in some cases, is compounded by an acidic pH. Attitude-altering medications may inhibit compliance with oral hygiene. Many medications cause xerostomia, which can lead to root surface caries and candidiasis. In many cases, these drugs cannot be substituted and dosages cannot be reduced, so it is essential to detect adverse conditions early and begin oral hygiene treatment planning to prevent more severe dental conditions from developing. This article discusses the impact of medications on treatment planning for patients who have clinical manifestations of dental problems that are attributed to medications.
Unlabelled:
For some time dentists have successfully promoted the benefits of sugar-free medications. There are now over 180 sugar-free medicines manufactured and prescribed. Methadone, used in the rehabilitation of drug-users, is available as a sugar-free preparation; however, the sugar-based version is most often used. This article examines the content of methadone, explains some of the reasons for prescribing patterns and explores how a multi-disciplinary approach can be used to help methadone users with their rehabilitation and minimize risks to oral health. The wider public health and health policy implications of methadone use are discussed and the available literature reviewed.
Clinical relevance:
Dentists are most likely to encounter patients on methadone as a dental emergency and they need to be aware that methadone users are at greater risk of decay and erosion from methadone sugar syrup, as well as perhaps their lifestyle. For dental practitioners, addressing the oral health needs of methadone users can contribute to their general well-being.
Methamphetamine is a highly addictive powerful stimulant that increases wakefulness and physical activity and produces other effects including cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. The prevalence of methamphetamine use is estimated at 35 million people worldwide and 10.4 million people in the United States. In the United States, the prevalence of methamphetamine use is beginning to decline but methamphetamine trafficking and use are still significant problems. Dental patients who abuse methamphetamine can present with poor oral hygiene, xerostomia, rampant caries ('Meth mouth'), and excessive tooth wear. Dental management of methamphetamine users requires obtaining a thorough medical history and performing a careful oral examination. The most important factor in treating the oral effects of methamphetamine is for the patient to stop using the drug. Continued abuse will make it difficult to increase salivary flow and hinder the patient's ability to improve nutrition and oral hygiene. Local anesthetics with vasoconstrictors should be used with care in patients taking methamphetamine because they may result in cardiac dysrhythmias, myocardial infarction, and cerebrovascular accidents. Thus, dental management of patients who use methamphetamine can be challenging. Dentists need to be aware of the clinical presentation and medical risks presented by these patients.
The present report describes the result of a clinical trial in which a group of adults have been maintained on a proper oral hygiene standard over a 6‐year period. In 1971–72, 375 individuals were recruited to a test group and 180 to a control group. During the 6 years of trial, 65 persons from the test group and 34 controls were lost. The patients were divided into three age groups; I <35 years, II 36–50 years, III >50 years. The members of the test and control groups were first subjected to a Baseline examination which included assessments of oral hygiene, gingivitis, periodontal disease and caries. Following this examination all caries lesions were treated and ill‐fitting dental restorations adjusted. Each patient was also given a detailed case presentation and a dental prophylaxis. The control group patients were not involved in any further dental health programs during the subsequent 6‐year period. Once a year, however, they were recalled to a public dental health clinic for examination and received symptomatic dental treatment. The test group participants, on the other hand, were given a preventive treatment, repeated once every 2–3 months which included (1) instruction and practice in oral hygiene techniques and (2) meticulous prophylaxis.
The patients were re‐examined 3 and 6 years after the baseline examination. At the Follow‐up examinations the parameters studied at the Baseline examination were recorded again. The findings demonstrated that a preventive program which stimulates individuals to adopt proper oral hygiene habits may resolve gingivitis and prevent progression of periodontal disease and caries. Traditional dental care, on the other hand, did not prevent the progression of caries and periodontitis in adults.
The two most common eating disorders, anorexia nervosa and bulimia nervosa, can severely impact oral health. This article will discuss and describe the nature of these disorders and attempt to explain why mostly women suffer from them. In addition, the signs and symptoms of these disorders will be described as they present on medical and oral examination, and recommendations for rehabilitating these patients will be presented.
The oral consequences of opioid drug use are commonly attributed to personal neglect of general health and financial constraint. These factors are compounded by the increasingly recognized range of physical effects exerted by opioid drugs. The dental management of opioid drug dependents is further complicated by a variety of infections and behavioural modifications commonly associated with opioid use. Adequate strategies for the oral care of opioid users need to take cognisance of the broad medical issues for these people along with an appropriate personal approach.
Tobacco is a delivery system for the addictive agent nicotine. The dental profession is encouraged to perform oral examinations that focus on oral cancer detection, but other oral changes occur with tobacco use. The oral mucosa is composed of stratified squamous epithelium and masticatory/keratinized (hard palate, dorsum of the tongue, and keratinized gingival) and lining mucosa (floor of the mouth, ventrolateral surface of the tongue, soft palate complex, labial vestibule, and buccal mucosa). Tobacco use affects the surface epithelium, resulting in changes in the appearance of the tissues. The changes may range from an increase in pigmentation to thickening of the epithelium (white lesion). Tobacco use can also irritate the minor salivary glands on the hard palate and directly increase a person's risk for periodontal disease and oral cancer. This article will review some of the more common oral lesions that are associated with tobacco use-smoker's melanosis, nicotinic stomatitis, periodontal disease, smokeless tobacco keratosis, gingival recession/tooth abrasion, black hairy tongue, and oral cancer.
It is known that morphine has a negative impact on the immune responses. The potent opioids fentanyl and buprenorphine have recently become available as transdermal preparation for the treatment of chronic pain. We analyze the effect of fentanyl and buprenorphine on splenic cellular immune responses in the mouse. The parameters evaluated were lymphoproliferation, natural killer cell activity and interleukin-2 and interferon-gamma production. Drugs were administered acutely at the equianalgesic doses of 0.25 mg/kg for fentanyl and 5 mg/kg for buprenorphine, or delivered continuously with osmotic pumps for 24 h, 3 and 7 days at the rate of 7.5 microg/h per mouse (fentanyl) and 12.5 microg/h per mouse (buprenorphine). After acute administration, a significant decrease of lymphoproliferation is observed in fentanyl-treated animals only. After 24 h of fentanyl administration all the parameters were significantly reduced. After 3 days of fentanyl infusion NK activity had returned to normal values, while all the other parameters were still significantly reduced. In 7 day fentanyl-treated animals immunological tolerance had developed, since no differences with controls were present. In contrast no immune alterations were ever present in buprenorphine-treated animals. No tolerance to the antinociceptive effect of drugs had yet developed. After 1 week of infusion with fentanyl and buprenorphine, new pumps were implanted releasing double amounts of drugs. Neither fentanyl nor buprenorphine-treated animals showed altered immune responses at any time considered. These results indicate that fentanyl and buprenorphine exert different immune effects. Opioid-induced immunosuppression is less relevant in chronic administration than in acute or short-time administration.
Clients in opioid substitution therapy often have considerable unmet health-care needs. The current study aimed to explore health problems related to opioid substitution therapy among clients on methadone and buprenorphine treatment.
A self-complete, cross-sectional survey conducted among 508 patients receiving methadone and buprenorphine treatment at community pharmacies in New South Wales (NSW), Australia.
The most common problems for which participants had ever sought help were dental (29.9%), constipation (25.0%) and headache (24.0%). The most common problems for which participants would currently like help were dental (41.1%), sweating (26.4%) and reduced sexual enjoyment (24.2%). There were no significant differences between those currently on methadone and those currently on buprenorphine for any of the health problems explored, nor differences for gender or treatment duration. Participants on methadone doses 100 mg or above were significantly more likely to want help currently for sedation.
The considerable unmet health care needs among participants in this study suggest that treatment providers should consider improving the detection and response to common health problems related to opioid substitution therapy.
Methamphetamine and its impact on dental care MMSc Author affiliations: Brigham and Women's Hospital (all authors)
- Klasser Gd
- Epstein
Klasser GD, Epstein J. Methamphetamine and its impact on dental care. J Can Dent Assoc. 2005;71(10):759–762. P u b M e d Joji Suzuki, MD jsuzuki2@partners.org Leena Mittal, MD Sook-Bin Woo, DMD, MMSc Author affiliations: Brigham and Women's Hospital (all authors); Harvard Medical School (all authors);
Espoo, Finland: Orion Diagnostica
- Dentobuff
Dentobuff [package insert]. Espoo, Finland: Orion Diagnostica; 2008.
Methamphetamine abuse and dentistry
- Hamamoto Dt
- Nl
Hamamoto DT, Rhodus NL. Methamphetamine abuse and dentistry. Oral Dis. 2009;15(1):27–37.
Clinical practice: office-based treatment of opioiddependent patients
- D A Fiellin
- O' Connor
Fiellin DA, O'Connor PG. Clinical practice: office-based treatment of opioiddependent patients. N Engl J Med. 2002;347(11):817-823. d o i : 1 0
Physical and chemical aspects of saliva as indicators of risk for dental caries in humans
- Leone Cw Oppenheim
- Fg
Leone CW, Oppenheim FG. Physical and chemical aspects of saliva as indicators of risk for dental caries in humans. J Dent Educ. 2001;65(10):1054–1062. P u b M e d
Shortening the Xerostomia Inventory. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
- W M Thomson
- G-J Van Der Putten
- C De Baat
Thomson WM, van der Putten G-J, de Baat C, et al. Shortening the
Xerostomia Inventory. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2011;112(3):322-327. d o i : 1 0