#55254: Medication Use in Dentistry

Lidocaine (2%) was the first amide-based local anesthetic created in the 1940s and remains the most popular local anesthetic used in the United States today. The onset of anesthesia is usually less than five minutes, and allergic reactions are a rarity. Lidocaine is available without a vasoconstrictor but is most commonly used with a 1:100,000 concentration of epinephrine. The addition of epinephrine constricts the small blood vessels in the injection area, which decreases the systemic absorption of the local anesthetic and diminishes the potential for systemic toxicity. Decreased vascular perfusion also confines the local anesthetic at the injection site for a longer duration and potentiates the depth and duration of anesthesia. Because epinephrine is a catecholamine and can increase heart rate and blood pressure, its use in cardiac and hypertensive patients should be minimized or, in some circumstances, avoided completely. Lidocaine and all local anesthetics that contain epinephrine also include the preservative sodium bisulfite. This substance is added to delay the oxidation of epinephrine, which would cause its deterioration. Patients with allergies to sulfites may have reactions to this component and should not be administered local anesthetics containing epinephrine and the accompanying preservative [2,3,4].

Lidocaine is compatible with most prescribed medications. However, cimetidine, propranolol, and protease inhibitors (e.g., ritonavir) can decrease the clearance of this local anesthetic [2].

Bupivacaine is a very potent local anesthetic available in 0.5% concentration, as opposed to lidocaine, which is generally produced in a 2% concentration [2]. The onset of anesthesia is approximately 10 minutes; however, the duration of soft tissue anesthesia can extend up to 12 hours [2,7].

Among all local anesthetics, bupivacaine demonstrates the highest ability to bind to proteins within the sodium channels of the neurons that are responsible for the conduction of nerve impulses. This strong affinity extends the time during which the normal inflow and outflow of sodium through these channels is prevented and the usual propagation of the action potential along the neuron is blocked. Bupivacaine is combined with epinephrine in a 1:200,000 concentration [2,3,4].

The extended duration of soft tissue anesthesia makes bupivacaine an excellent anesthetic for surgical cases. Pulpal anesthesia can extend to three hours, so bupivacaine is ideal for lengthy restorative procedures. Some clinicians have used bupivacaine at the conclusion of oral or periodontal surgery to extend the duration of anesthesia and to allow time for prescribed analgesics to become effective before the anesthetic effect dissipates.

This is not the anesthetic of choice for short restorative procedures in adults or for pediatric patients. Pediatric procedures are usually accomplished quickly, which negates the need for prolonged anesthesia. The extended duration of soft tissue anesthesia can also increase the risk of self-inflicted injury from biting anesthetized tissue. Therefore, bupivacaine should be avoided in patients with cognitive impairment or mental disabilities for whom instructions to avoid traumatizing the anesthetized tissues may be difficult to comprehend [4,7]. Similarly, patients with neuromuscular diseases such as Parkinson's disease or multiple sclerosis may be unable to control movements of the oral tissues and teeth even without the influence of a local anesthetic. The induction of a prolonged state of local anesthesia with bupivacaine in these patients could enhance the potential of self-inflicted soft tissue injury. A local anesthetic of short duration would be more appropriate.

Articaine (4%) was developed in Europe in 1969, but it has only been used in the United States since 2000. The original formulation of articaine included the preservative methylparaben, which had been removed from all anesthetic cartridges in North America. The concern with the potential allergic response to methylparaben delayed the distribution of articaine in the United States until another preservative (sodium metabisulfite) was substituted [2,7]. This is the only amide-type local anesthetic with an ester group within its chemical composition. This allows the amide portion to be metabolized in the liver while the ester portion is metabolized by plasma esterases [7,9]. The onset of action is rapid, at one to two minutes for infiltration anesthesia and one to three minutes for a mandibular (inferior alveolar nerve) block. Unlike other local anesthetics, articaine has a sulfur-containing thiophene ring, which confers upon it a higher degree of lipid solubility and a more rapid absorption by the nerve membrane [3]. Some clinicians have claimed that buccal infiltration with articaine on maxillary teeth provides palatal anesthesia without any further independent injection of the palatal tissues [10]. However, controlled studies have offered differing opinions on its ability to do so [11,12,13]. Soft tissue anesthesia extends for three to six hours for articaine with 1:100,000 epinephrine or two to three hours when a 1:200,000 concentration of epinephrine is utilized. Pulpal anesthesia lasts for 75 minutes with the higher epinephrine concentration and for approximately one hour when the lesser concentration is used.

There is some concern that the use of articaine may result in damage to the nerves being anesthetized, especially the inferior alveolar and lingual nerves of the mandible. A retrospective study in the United States did not duplicate studies from Canada and Denmark that suggested an increase in the incidence of nerve-related injuries after the administration of articaine [14]. Specifically, the international studies indicated an increased risk of paresthesia within tissues previously anesthetized with articaine. Paresthesia is characterized by burning, tingling, or occasional sharp pain, the duration of which can be variable. However, a direct cause and effect relationship has not been established between articaine and paresthesia [15]. It has been suggested that the condition may develop when the needle from an anesthetic syringe contacts a nerve directly, as the problem has not developed when infiltration anesthetic techniques are utilized. It has also been attributed to the use of articaine following the administration of a nerve block injection [16]. Clinicians who use articaine should remain abreast of the research regarding this issue.

Mepivacaine (3%) does not share the vasodilating qualities of other local anesthetics, so its formulation does not contain epinephrine or the associated preservative sodium bisulfite. Thus, dental professionals treating patients with sulfite allergies or for whom epinephrine should be avoided may find mepivacaine suitable for their anesthetic needs, pending no other contraindications [2,3]. It is not an ideal choice for longer procedures, as pulpal anesthesia is only maintained for 20 minutes when mepivacaine is infiltrated or 40 minutes when an inferior alveolar nerve block is used. Soft tissue anesthesia can linger for two to three hours [2,7]. Mepivacaine is best utilized for shorter restorative appointments, pediatric patients, and patients with an increased risk of accidental self-inflicted trauma in anesthetized tissues.

Like many of the other local anesthetics, prilocaine (4%) is often combined with epinephrine to improve its efficacy and extend its duration of action. With the addition of 1:200,000 epinephrine, pulpal anesthesia can last about 1.5 hours, while soft tissue anesthesia can linger for up to 8 hours [4,7,9]. These durations are suitable for procedures of intermediate lengths and for the prolonged anesthesia necessary after surgical procedures.

Without epinephrine, prilocaine is best utilized for shorter procedures. With prilocaine alone, pulpal anesthesia extends about 15 minutes with an infiltration technique and 60 minutes when a nerve block is used [9]. When the same injection techniques are used, soft tissue anesthesia lasts for two or four hours, respectively. Because prilocaine is supplied as a 4% solution, about twice the amount of anesthetic molecules will reach the neurons when compared to lidocaine or mepivacaine. However, one anesthetic cartridge of 4% prilocaine is also more toxic then either lidocaine or mepivacaine, and fewer cartridges of prilocaine may be used before systemic toxicity ensues.

The use of prilocaine has also been linked to the development of methemoglobinemia as a result of its metabolism into o-toluidine. Methemoglobinemia occurs when red blood cells contain more than 1% methemoglobin, with resulting headache, fatigue, and bluish coloring of the skin. Doses of up to 600 mg are generally considered safe, but methemoglobinemia can develop with lower doses in some patients [2,7].

The frequent use of local anesthetics in dentistry should not instill a sense of complacency with their use. These drugs are capable of causing deleterious systemic reactions. Allergic reactions to the amide type of local anesthetics are possible, but rare. Inadvertent intravascular injections can cause seizures and even cardiovascular collapse. Package inserts included with local anesthetics advise clinicians of these potential problems and the need for the dental staff to be adequately trained to treat patients who experience medical emergencies resulting from the use of a local anesthetic.

Vasovagal syncope (fainting) remains the most frequent medical emergency in dental offices. Some of these episodes occur because of the fear and psychogenic response that many patients harbor toward dental treatment, especially injections [2]. This possibility should be considered for patients being administered a local anesthetic.

The U.S. Food and Drug Administration (FDA) has assigned risk categories to all medications for their potential to cause birth defects in the developing fetus. While these categories can be a guide to the choice of a local anesthetic for pregnant patients, it would be prudent to consult with the patient's obstetrician prior to the use of any local anesthetic. All clinicians should have a thorough knowledge of the patient's current medical history before the initiation of any dental treatment, the injection of any local anesthetic, or the dispensation of any prescribed medication.

State laws vary as to the degree of staff training and the type of emergency supplies that are necessary to address medical emergencies in the dental setting. Many states require dental offices to have an automated external defibrillator (AED) and for staff to be trained in its proper use. All dental offices should have periodic mock emergency drills in which each staff member is assigned a role to assume during a real medical emergency. The ability to use portable oxygen tanks and to retrieve and use the appropriate supplies from a medical emergency kit should be a part of the training for medical emergencies. The staff has the responsibility of treating the patient until emergency medical services arrive.

Acetaminophen was first approved for use by the FDA in 1951, and it is both an analgesic and antipyretic (fever reducer). It is used in dentistry for the treatment of mild-to-moderate pain and can be dispensed by itself or in combination with narcotic medications such as codeine, hydrocodone, or oxycodone. This analgesic works by decreasing the synthesis of prostaglandins, chemical mediators of inflammation and pain, in the central nervous system and by peripherally blocking the generation of pain impulses. Because the primary metabolism of acetaminophen occurs in the liver, patients with impaired liver function can have difficulty metabolizing this medication properly and can cause further damage to the hepatocytes (liver cells) by ingesting even small doses. The use of alcohol can exacerbate the hepatotoxic potential of acetaminophen, and therefore it should not be consumed concurrently with this medication. Concomitant use of carbamazepine, isoniazid, and rifampin can increase the hepatotoxic potential of acetaminophen [4,7].

However, acetaminophen does have advantages over some other analgesics. It is better tolerated in some patients, with fewer gastrointestinal side effects compared to nonsteroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is also safe to take with antihypertensive drugs, unlike long-term NSAID use, which decreases the efficacy of these medications.

Opioids are a class of analgesic medications prescribed for the relief of mild-to-severe pain. In dentistry, oral or periodontal surgery, orthognathic surgery, endodontic procedures, and oral and maxillofacial trauma are among the situations for which opioid analgesics may be prescribed. The acute pain associated with these procedures and problems is generally of a short duration, with a commensurate schedule for the administration of these medications. However, even short-term use of opioid analgesics can cause complications such as respiratory depression, constipation, dizziness, and sedation [23]. Physical dependence, tolerance, and withdrawal symptoms may develop with extended use. Due diligence must be utilized when these medications are prescribed because of the potential for addiction. Opioid analgesics act by mimicking the naturally occurring endogenous opioid peptides or endorphins in the brain [23].

Aside from physicians, dentists are the most frequent prescribers of immediate-release opioids (e.g., codeine, hydrocodone, oxycodone). While most patients use these for the analgesic purpose for which they are intended, abuse of prescribed opioid medications heavily contributed to the second wave of the opioid crisis in the United States that began between 2010 to 2013. However, increased education, awareness campaigns, and regulatory efforts have proven to reduce opioid prescribing rates among dentists. One study showed that 60% of dentists reduced their opioid prescribing rates by 30% to 83% between 2016 and 2019. However, 3.4% of dentists consistently prescribed at high rates. It is essential that all clinicians prescribe opioid medications in a responsible fashion [26].

A web-based survey of dentists was conducted to assess their pain management prescribing practices and risk-mitigation strategies, including risk screening, prescription drug monitoring program (PDMP) use, and patient education [27]. Of the 822 dentists who completed the survey, a minority reported prescribing opioids alone or in combination with an NSAID or acetaminophen (11% and 18%, respectively). The respondents also reported that 50% or more of their patients required acute pain management, yet most dentists reported infrequent PDMP use and patient counseling regarding risks, storage, and disposal of opioids. Higher levels of opioid prescribing were associated with less consistent risk mitigation implementation and patient education [27]. In a separate survey of 87 dental practitioners, 75.8% reported prescribing opioids; 44% reported regularly screening patients for current prescription drug misuse; 5.8% reported requesting prior medical records; 38% reported ever accessing a PDMP; and 4.7% consistently used a PDMP [28].

Tetracyclines are generally not used in the treatment of acute orofacial infections or for prophylaxis of bacterial endocarditis. Instead, formulations of tetracycline are used as pharmacologic adjuncts in the definitive treatment of periodontal disease.

The decision to use antibiotics as adjunctive treatment for periodontal disease depends upon the patient's medical history and the extent of the periodontal disease. Patients should be informed that these medications are not substitutes for good oral hygiene, recall appointments, root planing and curettage, or periodontal surgery. The most common tetracyclines used in the treatment of periodontal disease are tetracycline, doxycycline, and minocycline. The benefits accrued through these medications extend beyond their bacteriostatic effect. They reduce inflammation and reduce matrix metalloproteinases such as collagenase, a protein that is associated with periodontal pathogens that damages connective tissue and bone [17].

Tetracycline can be administered systemically or locally. Doxycycline is also available in different formulations developed for various delivery systems. A systemic but subantimicrobial dose of doxycycline (20 mg) may be used as an adjunctive treatment for periodontal disease. At a dose of 20 mg, the therapeutic benefit is anticollegenase and anti-inflammatory rather than antibacterial, allowing the medication to be used daily for several months without the risk of developing resistance [40]. Doxycycline is also available in a controlled-release 10% gel formulation applied into periodontal pockets. This application is active for more than 21 days, and it is completely bioabsorbable, so no removal is required [7,31].

Minocycline is most frequently administered via a local subgingival delivery system. It is supplied in unit dose cartridges, with 1 mg of minocycline base per cartridge. The minocycline dose is incorporated into a bioresorbable polymer, which is then placed into the periodontal pocket, where the therapeutic minocycline concentrations are maintained for 21 days [7,31].

Each clinician must decide which tetracycline, if any, is appropriate for their patients. Periodontal disease can be refractory to conventional forms of definitive treatment with or without adjunctive pharmacotherapeutic support, and referral to a periodontist may be required.

One of the most notable side effects of tetracycline and its derivatives is irreversible staining of the developing permanent teeth. Therefore, tetracyclines should not be taken by women who are pregnant or nursing or children 8 years of age or younger [7]. As with the other antibiotics, drug interactions include an increase in the anticoagulant effect of warfarin and decreased efficacy of oral contraceptives.

Polyene antifungal medications such as nystatin act by combining with ergosterol, an important and unique constituent of the fungal cell membrane, to cause porosities in the membrane. This results in an outflow of the potassium ion and ultimately the death of the fungal organism [7]. Nystatin is most commonly prescribed as an oral suspension, dissolvable troches, or a topical ointment.

Typically, the adult dose of the oral suspension of nystatin for the treatment of oral candidiasis is 400,000–600,000 units four times every day [7,19]. A swish-and-swallow protocol is utilized, as fungal organisms that have extended toward the esophagus can be treated as the oral suspension is swallowed. This regimen is followed for an average of 7 to 10 days. Nystatin is also available as a dissolvable troche that contains 200,000–400,000 units of the drug, usually taken four to five times daily [7,19]. Patients using this formulation should be advised to remove any oral prosthesis to allow adequate contact between the oral mucosa and the dissolving troche. The ability of the nystatin troche to work properly depends on an adequate salivary medium, so any medication or condition that diminishes salivary gland output can decrease the efficacy of this formulation.

A topical ointment formulation of nystatin can be used to treat the mucocutaneous candidal infection angular cheilitis, which occurs at the corners of the mouth. The oral suspension and troche formulations will have inadequate access and contact time with this area. The topical version of nystatin can be combined with triamcinolone, a synthetic corticosteroid, to reduce the inflammation associated with this condition.

Nystatin formulations have high sugar content, so oral hygiene should be meticulous for the duration of its administration. Patients with diabetes should consult with their physician prior to its use. Because the oral suspension is not absorbed from the gastrointestinal mucosa, nystatin is not intended to be used for systemic fungal infections and usually will not interact with other medications. Side effects are generally mild and involve the gastrointestinal tract. A systemic antifungal agent should be considered if empiric therapy with nystatin does not resolve the initial fungal infection, as resistance to oral fungal organisms is a growing problem.

The successful treatment of oral candidiasis must also include the treatment of any oral prostheses in addition to the oral cavity. The acrylic of partial or complete dentures, orthodontic appliances, and night guards contain numerous microscopic porosities in which fungal organisms may reside. Without the elimination of this reservoir of fungal contaminants, a cycle of re-inoculation of the oral tissue can occur. The acrylic and metallic components of prostheses can vary considerably, so any substance designed to treat fungal organisms on appliances should follow manufacturers' guidelines.

Azole antifungal agents are used for systemic fungal infections in addition to localized treatment of oropharyngeal candidiasis. These agents interact with enzymes necessary for the conversion of lanosterol to ergosterol. When this important fungal cell membrane constituent is lacking, increased fungal cell permeability causes the death of the fungal organism. Azole antifungals used in dentistry include fluconazole, ketoconazole, and clotrimazole [7,18,19].

The most common oral lesion of viral origin, recurrent herpes labialis, is caused by a reactivation of the herpes simplex virus-1 (HSV-1), which can lie dormant for years in a regional nerve ganglion. Illness, sunlight, emotional stress, and immunosuppression are among the most common factors to trigger a reactivation of HSV-1 from dormancy. The classic presentation of herpes labialis is the development of small, fluid-filled vesicles laden with viral particles, usually at the mucocutaneous junction of the skin and lips. The vesicles fuse to form larger lesions that ulcerate, crust, and heal within two weeks in healthy patients. Patients with herpes can experience mild discomfort and malaise, but systemic involvement is rare. Immunosuppressed patients, such as those with HIV/AIDS, may experience a more virulent course, longer healing times, systemic involvement, and overlapping recurrent episodes of successive outbreaks with a lack of complete healing.

Unlike antibiotic or antifungal medications, which target the cell wall or cell membrane, acyclovir becomes incorporated into the viral DNA and prevents further viral replication. Acyclovir and its derivatives are highly selective for viral DNA, so collateral damage to the host mammalian cells is spared [30]. The bioavailability of oral acyclovir is low, ranging from 10% to 20% [7]. While oral and topical formulations are prescribed most frequently, intravenous acyclovir is also available for patients whose immunosuppression is conducive to a longer and more virulent HSV-1 course. The topical form of acyclovir decreases viral shedding and can be applied directly to the lesion with a special applicator. Patients should be advised to avoid direct contact between the fingertips and the viral lesions. Viral inoculation of the finger can result in the development of recurrent herpetic outbreaks of the finger known as herpetic whitlow. Oral acyclovir is taken in either 200- or 400-mg doses three to five times per day [7]. The duration of treatment is determined by the extent of viral involvement. The medication may also be used to suppress future outbreaks.

Possible side effects of oral acyclovir include abdominal cramping, nausea, and vomiting. Simultaneous use of the antiviral medication zidovudine, which is used to treat HIV/AIDS patients, or probenecid, used to treat gout, can lead to adverse central nervous system effects [7].

Oral acyclovir may also be used to treat oral hairy leukoplakia, characterized by bilateral lesions on the lateral surfaces of the tongue. These corrugated white lesions are painless and fixed to the underlying tissue and arise as a result of reactivation of the Epstein-Barr virus in immunosuppressed patients. These lesions will regress with acyclovir therapy but often return upon its cessation.

Acyclovir can also be used for the treatment of the oral and cutaneous lesions caused by the reactivation of varicella zoster virus, also known as shingles [7]. Varicella zoster virus is the etiologic agent of chickenpox in children and young adults, and after this initial infection, the virus migrates to a cranial nerve or dorsal root ganglia, where it remains dormant until reactivation (often decades later). Immunosuppression, physical conditions or trauma, and emotional stress can prompt the reactivation of varicella zoster virus, causing shingles. Shingles lesions are usually found on the skin of the back, stomach, chest, or buttocks, but some may be facial or intraoral. In the oral and maxillofacial complex, lesions follow the distribution of the divisions of the facial and the trigeminal nerves and have a protracted course compared to recurrent herpes labialis.

The dosage and the route of administration of acyclovir for shingles is commensurate with the severity of the outbreak, with some cases in need of intravenous acyclovir. These patients are usually managed by a physician.

Valacyclovir is an ester of acyclovir and is converted to acyclovir in the liver and gastrointestinal tract. It is only available in an oral formulation and is predominantly used to treat infections caused by the herpes simplex viruses, with limited activity against Epstein-Barr virus. It has much higher bioavailability (55%) compared to acyclovir [7].

The adverse drug interactions and gastrointestinal side effects of valacyclovir are similar to those of acyclovir. Caution should be exercised if this medication is used in immunocompromised patients, as rare but serious adverse incidents, such as thrombocytopenic purpura or hemolytic uremic syndrome, can occur [7]. Consult a physician if this medication is to be used for patients who are immunosuppressed, as an alternative antiviral medication may be required.

Diazepam was the second benzodiazepine medication ever developed, first becoming available in 1963. Today, it is one of the core medications in the World Health Organization's Model List of Essential Medicines [21]. The bioavailability after oral administration is 90%, and peak plasma levels occur 15 minutes to 2.5 hours after oral administration, allowing for a rapid onset of action. When used as an anxiolytic medication before dental treatment, it may be taken both the night prior and one hour before the appointment. The dose depends upon the degree of anxiety, the patient's weight, concurrent use of other medications, and pertinent factors in the patient's medical history. The degree of sedation varies among individuals, so patients should not drive to or from their dental appointments if this drug is used. Diazepam has a lengthy half-life of 44 to 48 hours; the half-life of its active major metabolite, desmethyldiazepam, is 100 hours [7]. This extended half-life results in a protracted period of varying degrees of sedation, and any activity that would endanger the patient during this interval (e.g., operating heavy machinery) should be avoided.

Among the most common medical conditions that preclude the use of diazepam for sedation are severe respiratory disorders, alcohol or drug dependence, liver disorders, and renal disorders [7]. Hepatic pathologies such as hepatitis and cirrhosis impede the metabolism of diazepam and can allow accrual of the drug, causing excessive sedation and potential toxic accumulation. Similarly, renal impairment can decrease the excretion of diazepam and allow serum drug levels to remain high. Gastrointestinal side effects, such as nausea, vomiting, and constipation, can occur. Possible adverse central nervous system effects include amnesia, confusion, excessive sedation, and paradoxical excitement [7].

Diazepam has the potential for many adverse interactions with other medications, including some medications prescribed for oral health issues. Diazepam increases the depressive effect of narcotic analgesics and can exacerbate respiratory depression [7]. Simultaneous use of ketoconazole can decrease the elimination of diazepam and prolong its effect [22]. Patients who consume alcoholic beverages while taking diazepam can experience advanced sedation and hypotension. Before diazepam is administered for anxiolytic purposes, patients should be informed of its potential side effects and adverse medication interactions.

Triazolam, also a benzodiazepine drug, has been available in the United States since 1982. Triazolam has a rapid onset of action and a significantly shorter half-life (two to five hours) compared to diazepam. Therefore, there is a decreased potential for protracted sedation with this medication. Triazolam can be administered sublingually the night before a dental appointment to promote good sleep and one hour before the appointment for anxiolytic purposes, although this use is off label. The usual dose is 0.25 mg, with a maximum cumulative dose of 0.5 mg/day [7]. Unlike diazepam, triazolam has no active metabolites and does not cause extended sedation. In fact, the sedative effect of an initial dose of triazolam may not be sufficient for longer appointments. However, extreme caution must be used in the administration of additional doses of this medication. At least 90 minutes should elapse before even the lowest second dose (0.125 mg) is provided [7]. Given the variability in action among patients based on the degree of anxiety, weight, and medical history, excess sedation can occur in some patients even before the maximum cumulative dose is reached. The lowest possible initial and cumulative doses necessary to attain the desired sedative effect should be used.

Possible side effects of triazolam use include nausea, vomiting, drowsiness, dizziness, and in some cases, psychiatric disturbances [7]. Many medications have problematic interactions with triazolam, including drugs regularly used in dental care. Azole antifungal medications such as ketoconazole and antibiotics such as erythromycin can increase the blood plasma levels and effects of triazolam. Simultaneous use of narcotic analgesics and triazolam can cause enhanced respiratory depression. Hepatic impairment can decrease the metabolism of triazolam, while renal problems can decrease its excretion, both of which can cause increased plasma drug levels and enhanced sedation.

Lorazepam has poor solubility in lipids, and its more hydrophilic nature accounts for its onset of action after oral administration. It has a half-life of approximately 10 to 20 hours in adults, which makes its duration of action shorter than diazepam but longer than triazolam [7,22]. Compared with other members of the benzodiazepine group, lorazepam can produce better amnesic effects, but the extended length of sedation may be undesirable for patients. It can be administered the night before a dental appointment to promote sleep and two hours before the dental appointment to reduce anxiety. As with all anxiolytic medications, a responsible driver should transport the sedated patient to and from the dental appointment.

Interactions between lorazepam and other medications prescribed for oral health concerns can occur. As described for the other benzodiazepines, the concomitant use of narcotic analgesics can enhance respiratory depression. The potential drug interactions associated with lorazepam are numerous and beyond the scope of dental practice. If questions regarding appropriate use arise, a physician should be consulted. When lorazepam is used as a short-term anxiolytic for dental treatment, the side effects are usually confined to gastrointestinal upset. However, patients must be monitored carefully, as excessive sedation may occur with anxiolytic doses.

Nitrous oxide was first used in dentistry in the 1840s to minimize the discomfort patients experienced during the extraction of teeth [24]. While this formulation was comprised entirely of nitrous oxide without oxygen, it is the forerunner of the modern nitrous oxide/oxygen systems used today.

Also known as "laughing gas" or "sweet air," nitrous oxide/oxygen is used for its anesthetic and analgesic effects. Whether used alone or combined with an oral anxiolytic medication, state regulations exist defining the degree of training and certification required for the dentist and staff involved in administering this medication [25].

The American Dental Association asserts that because sedation and general anesthesia are a continuum, it is not always possible to predict how an individual patient will respond. Hence, practitioners intending to produce a given level of sedation should be able to diagnose and manage the physiologic consequences (rescue) for patients whose level of sedation becomes deeper than initially intended.

(https://www.ada.org/-/media/project/ada-organization/ada/ada-org/files/resources/research/ada_sedation_use_guidelines.pdf Last Accessed: August 22, 2024)

Strength of Recommendation/Level of Evidence: Strong recommendation, moderate quality of evidence

Unlike the first uses of pure nitrous oxide, conventional dental use of this gas today is combined with varying percentages of oxygen. A typical mixture is 30% nitrous oxide and 70% oxygen, with other proportionate combinations also used. This combination of gases rapidly diffuses into the bloodstream and is eliminated at the end of the session when pure oxygen is inhaled for five minutes; it is not metabolized by the body and is secreted essentially unchanged via the lungs. There are no known significant drug interactions, although there is some evidence that nitrous oxide may increase the risk of methotrexate-associated toxicity. Common side effects are postprocedural nausea and vomiting. Absolute contraindications to nitrous oxide use include emphysema, pneumothorax, middle ear surgery, air embolus, elevated intracranial pressure, and methionine synthase pathway enzyme deficiencies. Renal, hepatic, and neurologic problems may be noted, and fertility issues can develop in women exposed to multiple doses of nitrous oxide [5,7].

To protect staff, scavenger systems are available to recover nitrous oxide that escapes from the system. All components of these delivery systems should be inspected on a regular basis, as chronic exposure to nitrous oxide can be hazardous. During the administration of nitrous oxide/oxygen, patients should only speak when there is an issue relative to their dental treatment in order to minimize the amount of nitrous oxide exhaled into the room. Properly fitted inhalation masks should be worn by the patient to decrease the amount of nitrous oxide leaked into the office.