ADVANTAGES

The oral route possesses several advantages over other routes of drug administration:

Most adults do not object to taking drugs by mouth. For better or worse, we have become a “pill-popping” society, a fact that makes the prescription of an anxiety-reducing drug before dental treatment all the more palatable to the patient. Many dentists in North America have been trained to provide anxiolysis (minimal sedation) or moderate sedation to their adult patients using oral central nervous system (CNS) depressants. An important exception to the acceptability of orally administered drugs is the young, immature child, who frequently proves unwilling to take any drugs by mouth.

Oral drugs are exceptionally easy for the dentist to administer. In some cases, the drug prescribed for sedation will be taken by the patient at home. In an increasing number of situations, however, it is more prudent for the dentist to administer an oral CNS-depressant drug to the patient personally on arrival in the dental office to better ensure proper dosage and time of administration. In either case, the administration of drugs via the oral route requires only that the dentist have knowledge of the pharmacologic action of the drug administered, its side effects, potential drug-drug interactions, and any contraindications to its administration. No special equipment or personnel is required for the safe use of the oral route (in the adult patient).

The cost of most oral drugs is usually quite low, especially for the small number of doses employed in dentistry. Although there is significant variation in the cost of drugs, the oral form of a drug is usually less expensive than its parenteral counterpart.

Complications are possible whenever drugs are administered, regardless of the route of administration. Drug idiosyncrasy, allergy, and overdose in addition to other adverse actions can and do occur. Drug-related side effects are less likely to develop after enteral drug administration (i.e., oral, rectal) than after parenteral drug administration. In addition, adverse reactions following oral administration are often much less intense than those noted following parenteral administration of the same drug. This is not to imply that serious complications do not occur following oral drug administration. Berger, Green, and Melnick¹ reported cardiac arrest following oral diazepam intoxication, and Gill and Michaelides² described an anaphylactic response to oral penicillin. Other serious adverse reactions to orally prescribed drugs, including suicide, have been reported.^3–5

The convenience of the oral route is a primary reason for its popularity. This technique can be employed with minimal risk if the dentist prescribing the drug(s) is knowledgeable of (1) the pharmacologic actions of the drug; (2) its indications, contraindications, precautions, side effects, and dosage; and (3) the medical history of the patient, especially as it relates to prior drug use, specific contraindications to the use of particular drugs, and prior reactions to the drug to be administered. No special equipment (e.g., needles, syringes) and no additional personnel are required when oral drugs are administered to adult patients.

The aforementioned advantages make the use of orally administered drugs quite compelling. However, there are, as with all routes of drug administration, some distinct disadvantages that effectively limit the clinical use of this route of drug administration.

DISADVANTAGES

Disadvantages associated with the oral route include the following:

When prescribing drugs for oral administration before coming to the dental office, the dentist must rely on the patient to take the drug as prescribed (the proper dose at the proper time). Although most patients will medicate themselves properly, some do not. This potential problem, termed noncompliance, is significant in medicine, especially in relation to long-term drug administration (e.g., antihypertensive drugs). The Council on Patient Information and Education estimates that 35% to 50% of all prescriptions dispensed by physicians are taken incorrectly by patients and that one in five patients never even bother to have the prescription filled. One in seven stops taking the drug too soon. Noncompliance rates among patients older than 65 years are more than 55%.⁶ Although noncompliance is not as critical a problem in the dental situation, the administration of too small or too large a dose, too soon or too late, may significantly alter the drug’s effectiveness during the treatment period. A common form of noncompliance is the taking of a dose larger than that prescribed; the patient’s rationale is “if one (tablet or capsule) is good, then two or more will be better.” This type of thinking leads to oversedation, overdose, and other unwanted and unpleasant complications. Fortunately (in this situation, at least) the erratic and incomplete absorption of orally administered drugs minimizes the development of serious problems from drug overadministration.

On many occasions, I have observed this phenomenon in pediatric dental patients: A parent or guardian administers a tablespoon of drug instead of a teaspoon, or a larger dose than desired, because the child did not take all of the first dose. Significant overdose, with attendant respiratory depression, can develop in this manner if the administered drug is a CNS depressant. The consequences of these actions are formidable, with potential morbidity or mortality as the result. This has led to the enactment of legislation in a number of states restricting the use of oral sedation in patients younger than 13 years of age to dentists who have received appropriate education and training in this patient population.⁷ Oral sedation regulations vary considerably.

Oral Sedation in Children. As of April 2008, the American Dental Association (ADA) was aware of three states having enteral sedation permits specific to administration to minors (e.g., Louisiana has a permit entitled “restricted” that allows the dentist to administer to adults only). Three other states mention within their enteral sedation permit language stating, “additional training requirements to administer to children.” Three other states have language within their enteral sedation laws that require the dentist to have a parenteral “conscious” sedation permit to administer enteral to children.⁷

Oral Sedation in Adults. The ADA is aware of two states having oral sedation permits specific to adults. This does not take into account those other states that require the dentist to obtain a parenteral sedation permit to administer to children. For example, Idaho has a limited permit and comprehensive permit. The comprehensive (IV sedation) permit is required to administer to children; therefore one could argue that the limited is an adult-only permit.⁷

Oral Sedation, in General to Any Patient. Absent occasional references to PALS (pediatric advanced life support) for dentists treating pediatric patients, the ADA is aware of 14 states that have fairly straightforward options for enteral permits that do not mention additional training for administration to pediatric or minor patients.⁷

The dentist prescribing oral drugs for the management of anxiety must never forget that these drugs are CNS depressants and that excessive CNS depression (e.g., oversedation or general anesthesia) is always possible. To minimize concern over patient noncompliance, the dentist should (1) tell the patient, or the parent or guardian, exactly how much of the drug to take and at what time to take it; (2) write these instructions down and give them to the patient; (3) make sure that the prescription is clearly marked with these same instructions; (4) prescribe only the dose the patient is to take (this is warranted even though prescriptions for larger numbers of tablets or capsules are less expensive per item than are single doses); and (5) record the instructions given to the patient and the drug and its dose in the patient’s chart.

When the patient or parent (guardian) of a child is believed to be unreliable, the patient should be requested to appear in the dental office 1 hour before the scheduled treatment, where the drug may be administered to the patient by the dentist in a controlled manner.

A significant disadvantage of the oral route is its relatively long latent period (the period following administration before a clinical effect is observed). Most orally administered drugs have a latent period of approximately 30 minutes. At this time (30 minutes), the blood (plasma) level of the drug is at the minimum (therapeutic) level required for clinical activity to be observed. Absorption of oral drugs occurs primarily from the small intestine with some absorption from the stomach (alcohol and aspirin are exceptions where significant absorption occurs from the stomach). Drug absorption into the cardiovascular system continues, and the blood level of the drug increases until a maximum level is reached. With most oral drugs, peak blood levels occur approximately 60 minutes following ingestion or 30 minutes following the onset of clinical activity. Peak blood level is equated clinically with maximal drug action (i.e., most intense analgesia or sedation).

In addition to a long latent period, most oral drugs are absorbed erratically and incompletely from the GI tract, which makes consistent clinical results difficult to achieve. A number of factors act to influence absorption of drugs from the GI tract as follows:

RATIONALE FOR USE

When the advantages and disadvantages of the oral route are compared, it becomes obvious that a number of significant disadvantages are associated with the use of this technique. These combine to produce a route of drug administration in which the administrator has little control over the ultimate clinical action of the drug.

This lack of control over drug action is a potential problem every time a drug is administered orally. This is particularly so when the drug is a CNS depressant, as are those used in stress reduction. The potential for oversedation, respiratory depression, and loss of consciousness must always be considered when administration of an oral drug for anxiety relief is contemplated.

Despite the negative factors associated with oral sedation, there is considerable need in dentistry for orally administered drugs for stress reduction. The primary use of the oral route is in the management of anxiety before the dental procedure. However, because of the lack of control over the ultimate drug action, it is strongly suggested that only minimal to moderate sedation be sought via the oral route. Minimal sedation may prove adequate to reduce anxieties that develop before the dental appointment, but may prove inadequate in diminishing the fears occurring once the patient enters the dental office and commences treatment. It is possible to produce moderate to deep sedation with the oral route. However, the clinician must always keep in mind the lack of control over drug action and the wide range of individual responses to a given drug dose. The possibility of overdose, respiratory depression, impaired consciousness, or unconsciousness is increased as the degree of CNS depression increases. Persons untrained in the management of the unconscious airway ought not attempt to achieve deep sedation by the oral route. In addition, the dentist prescribing or administering oral drugs must possess a thorough knowledge of the drug’s actions, contraindications, side effects, and precautions. The dentist must also be capable of prompt recognition and management of any adverse reaction that might develop (e.g., unconsciousness). This is the concept of “rescue” from a level of sedation beyond what is intended. If deep sedation is required, a more controllable technique of sedation (i.e., inhalation or IV) should be considered.

What then represents the rational use of the oral route in a typical dental practice? From the standpoint of safety, it is important that the clinician never seek to achieve a level of sedation beyond which he or she is comfortable (has been trained to use) and is capable of recognizing and managing any undesirable side effects that might develop. For these reasons, the rational use of oral sedation includes only minimal sedation or, in selected situations, moderate sedation. Deep sedation should be restricted to more controllable techniques.

The most common use of oral sedation is for the relief of anxiety in the hours immediately preceding a dental appointment. An antianxiety or sedative-hypnotic drug is used to reduce anxiety so that the patient will appear in the dental office for the scheduled appointment. More controllable techniques may be used at this time for intraoperative sedation. When using oral drugs for this purpose, the clinician must remember to remind the patient of the absolute prohibition against driving a motor vehicle or operating hazardous machinery. If the patient has taken the drug at home, he or she should be advised against driving a car and should be accompanied to the office by (driven by) a responsible adult. For medicolegal purposes, this should also be noted in the patient’s chart.

A second use for oral sedation is one that is often overlooked by a busy clinician. As noted earlier (see Chapter 4), not only do patients with fears of dentistry or surgery become apprehensive immediately before their appointment, often their anxieties start to build the day before the scheduled appointment. These persons might be unable to sleep the night before the appointment as they anticipate their upcoming “ordeal” and will be fatigued when they appear in the dental office the next day, a factor leading to a lowering of the pain reaction threshold. An antianxiety or hypnotic drug taken 1 hour before sleep (1 hr hs) the night before the appointment can help ensure a restful night’s sleep and a more stress-tolerant patient during treatment.

Other uses of the oral route in dentistry include the administration of drugs to inhibit salivary secretions (antisialagogues), drugs to prevent or to manage nausea (antiemetics), and antibiotics.

DRUGS

A large number of drugs may be administered orally in the management of anxiety. The overwhelming majority of these are classified as either antianxiety or sedative-hypnotic drugs. Other drug groups that may be used for this purpose are histamine blockers and opioids.

Before we discuss these drugs, a word is in order regarding the appropriate dosages to be used. The clinician must use as much information as is available to make an informed decision regarding the appropriate dose to administer, particularly when using the oral route. Information available to the clinician includes the patient’s medical history, age, weight, and previous drug reactions. In addition, the clinician must determine the degree of anxiety present and the level of sedation sought. After consideration of these factors, a drug dose is determined.

A source of information regarding recommended dosages of drugs is the drug package insert or publications such as Facts and Comparisons,¹³ Physicians’ Desk Reference,¹⁴ or Mosby’s Dental Drug Reference, eighth edition.¹⁵ Online sources of drug information, such as ePocrates.com¹⁶ or Mosby’s MD Consult¹⁷ are readily available for downloading onto a desktop computer or hand-held device. An advantage of online drug data resources is that they are updated on a regular basis.

A common problem associated with the use of recommended doses is that they often lead to inadequate anxiety reduction in the dental or surgical setting. There is a reasonable explanation for this: The package insert recommends a certain dose of a drug to induce sedation or sleep in a nonstress situation, such as the home environment. The dose of a drug that would effectively relax an apprehensive individual at home will probably prove ineffective when the stresses of the dental office environment are added. For this reason, the doses recommended for oral sedation in this chapter and in many textbooks of pediatric dentistry may be somewhat higher than those in the package inserts.^18,19

Many antianxiety and sedative-hypnotic drugs for oral administration are produced in three dosage forms. When a dosage is chosen for stress reduction in dental practice, these three dosage forms correlate with the normal distribution (“bell-shaped”) curve (Figure 7-1). The middle dosage form represents the “average” dose, producing clinically effective results (in nonstress situations) in approximately 70% of persons receiving it. The larger dosage form is for persons in whom the average dose proves to be ineffective or who have a greater degree of anxiety. The smaller dosage form is for persons in whom the average dose provides too intense a clinical effect, for persons with a lesser degree of anxiety, for elderly patients, or for debilitated patients. It must be remembered that the added stresses associated with dental or surgical treatment will increase the percentage of patients requiring larger than “usual” doses for management of their treatment-related fears.

Figure 7-1 Normal distribution curve (“bell-shaped” curve). Persons will respond to drug dosages in dissimilar ways. Approximately 2.5% of persons will be extremely resistant to a “usual dose,” and 2.5% will be quite sensitive to the same dose.

(Data from Bennett CR: Jorgensen Memorial Lecture: Drug interactions, Anesth Prog 30(4):106-112, 1983.)

Although titration (individualization of drug dosages) is not possible with orally administered drugs—a significant impediment to their safe use—it is possible in situations in which oral drugs are to be used over multiple appointments to titrate by appointment. This concept was introduced to me by Dr. Ronald Johnson, then chairman of the Department of Pediatric Dentistry at the University of Southern California.²⁰ Quite simply, titration by appointment means that the dentist will assess the efficacy of sedation achieved at the first appointment with a given drug dosage and, if necessary, increase or decrease the dosage of drug(s) administered at subsequent appointments. Therefore over a period of two to three visits, the appropriate dosage for that patient can be achieved (titrated). Titration by appointment is discussed more fully in the chapter on pediatric sedation (see Chapter 35).

In the remainder of this chapter, drugs that are administered orally for minimal to moderate sedation are reviewed. Drugs are discussed by their therapeutic category as follows:

ANTIANXIETY DRUGS

Antianxiety drugs are used to manage mild to moderate daytime anxiety and tension. Drugs in this group share a similar CNS-depressant action: At therapeutic dosages they produce the level defined as minimal sedation usually without impairing the patient’s mental alertness or psychomotor performance. Groups of drugs that are commonly categorized as antianxiety drugs are as follows:

For the management of mild to moderate levels of anxiety, the benzodiazepine antianxiety drugs are preferred. Benzodiazepine antianxiety drugs have a wide therapeutic dosage range and thus are less likely to produce undesirable side effects.

Although termed antianxiety drugs, a more appropriate name for these drugs might be sedative-antianxiety drugs because all drugs in this group possess sedative properties and antianxiety actions.

The antianxiety drugs have, in the past, been known by other names, such as minor tranquilizers, anxiolytics, ataractics, anxiolytic sedatives, and psychosedatives. The general category “antianxiety drugs” has become accepted for this group of drugs.

Pharmacology