Drugs Used in Dentistry

ANALGESICS

Pain Control

Pain, as defined by the International Association for the Study of Pain, is "an unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage." It is often pain that brings the patient to the dental office. Conversely, fear of pain is a significant reason for many people to avoid seeking dental care. No matter how successful or how deftly conducted, most dental procedures produce tissue trauma and release potent mediators of inflammation and pain. We now know that unrelieved pain after surgery or trauma has negative physical and psychologic consequences.

The two components of pain are perception and reaction. Perception is the physical component of pain and involves the message of pain that is carried through the nerves eventually to the cortex. Reaction is the psychological component of pain and involves the patient's emotional response to the pain. Although individuals are surprisingly uniform in their perception of pain, they vary greatly in their reaction to it. A decrease in the pain threshold (a greater reaction to pain) has been associated with emotional instability, anxiety, fatigue, youth, certain nationalities, women, and fear and apprehension. The pain threshold is raised by sleep, sympathy, activities, and analgesics.

Fortunately, pain is preventable or controllable in an overwhelming majority of cases. Patients have a right to treatment that includes prevention of pain and adequate relief of pain.

Undertreatment of pain is a significant problem. Numerous clinical surveys have shown that postoperative pain is often inadequately treated because of undermedication, leaving patients to suffer needlessly.

Successful assessment and control of pain depend, in part, on establishing effective communication between the dentist and the patient. Patients should be informed that pain relief is an important part of their health care. Pain is a subjective phenomenon. The patient's self-report is the single most accurate and reliable indicator of the existence and intensity of pain and any resultant distress. Pain is whatever the experiencing person says it is and exists whenever he says it does.

A significant barrier to the effective use of analgesics in managing pain involves several misconceptions regarding pain and its control held by both patients and health care providers.

Misconception 1_Patients who are in pain always have observable signs. Although many patients in acute pain exhibit evidence of anxiety, distress, or decreased function, many do not.

Misconception 2_Obvious pathology, test results, and/or the type of surgery determine the existence and the intensity of pain. Although the ability to identify a pathologic process underlying a patient's pain complaint is a key element in planning and initiating definitive treatment, failure to identify the source of a patient's pain does not necessarily mean than it does not exist.

Misconception 3_Patients should wait as long as possible before taking a pain medication. This abstinence will teach them to have a better tolerance for pain. Pain that is untreated often escalates. Without treatment, sensory input from injured tissue reaches spinal cord neutrons and causes subsequent responses to be enhanced. Aggressive pain prevention and control that occurs before, during, and after a painful event such as dental surgery can yield both short- and long-term benefits. Patients should be encouraged to use analgesics before pain becomes severe and difficult to control.

The most common types of odontogenic pain are characterized as acute pain. Characteristically, acute pain is accompanied by some recognizable evidence of tissue injury or inflammation, and it resolves spontaneously once the underlying cause (inflamed pulp, abscessed tooth, carious lesion) is definitively treated. Few underlying psychologic or behavioral issues affect the dentist's choice of therapies, and, most commonly, a pharmacologic approach to pain management is most appropriate.

In contrast, management of chronic facial pain involves much more complex treatment issues. Chronic pain often lasts months or years beyond the precipitating event, and there is rarely a readily identifiable source, that is, an area of tissue destruction or inflammation. There is often a complicated set of behavioral issues that must be explored and clarified. Pharmacologic approaches to chronic pain are rarely the sole or principal means of managing these disorders.

Peripherally acting analgesics reduce or control pain by directly inhibiting the biochemical mediators of pain at the site of injury. In addition to their analgesic property, the majority of drugs in this class have antiinflammatory and antipyretic activity. In fact, they are often referred to as the NSAIDs or antipyretic analgesics.

Opioids on the other hand, decrease the perception of pain in the CNS. The opioid analgesics act in the CNS at receptors in the spinal cord, rostroventral medulla, and periaqueductal gray matter. These anatomic loci are considered important to the perception of pain.

Analgesic Agents

Analgesic agents can be divided into two groups: the nonopioid, nonnarcotic and the opioid narcotic. An important difference between the nonopioid and the opioid analgesics is their site of action. Nonopioid analgesics act primarily at the peripheral nerve endings, although they also act centrally. Opioids act within the central nervous system.

Another difference between the opioids and the nonopioid analgesic agents is their mechanism of action. The action of the nonopioid analgesic agents is related to their ability to inhibit prostaglandin synthesis. The opioids affect the amount of pain by depressing the CNS (the reaction).

Nonsteroidal antiinflammatory drugs (NSAIDs) act at the site of initiation of noxious impulses. Although it is difficult to separate their antiinflammatory effects from their analgesic effects, nonopioid drugs such as the salicylates and other NSAIDs work predominantly in the periphery by preventing the synthesis and release of inflammatory mediators that sensitize noninceptive receptors to other

algesic mediators, such as bradykinin, and to physical forces. Recent studies suggest that NSAIDs may also have central effects. Acetaminophen has been shown to have analgesic and antipyretic properties, but it lacks significant antiinflammatory effects. Acetaminophen appears to exert its effects both in the CNS and in the periphery.

The peripherally acting or antipyretic analgesics comprise various chemical classes of drugs that have a similar mechanism of action and share clinically important analgesic, antiinflammatory, and antipyretic properties. These analgesics are widely prescribed by dentists and physicians because they can be taken orally, they do not cause central nervous system (CNS) or respiratory depression at therapeutic doses (as do the centrally acting opioid analgesics), and, most important, they are very effective pain relievers.

Aspirin and acetaminophen have been recognized for many years as prototypes for the peripherally acting analgesics. Today, the propionic acid derivatives, led by ibuprofen, have successfully challenged the clinical status of these older drugs and have established a new standard for comparison. Some of the claims made for these agents are greater peak analgesia, longer durations of action, and a lower incidence of side effects. Because the dentist must treat acute pain on a daily basis, the peripherally acting analgesics are of particular importance.

Nonopioid Analgesics

This category comprises various groups of drugs that have a similar mechanism of action and share clinically important analgesic, antiinflammatory, and antipyretic properties. These agents differ from opioid analgesics in the following ways: (1) there is a ceiling effect to the analgesia; (2) they do not product tolerance or physical dependence; (3) they are antipyretic; and (4) they possess both antiinflammatory as well as analgesic properties, except for acetaminophen, which has minimal antiinflammatory activity. Pharmacologic management of mild to moderate pain should begin, unless there is a contraindication, with a nonopioid drug such as acetaminophen, a salicylate, or another NSAID. As a general rule, any analgesic regimen should include a nonopioid drug, even if pain is severe enough to require the addition of an opioid.

Nonopioids are most effective in treating postprocedural pain when given before the procedure ( or immediately following a short procedure), thus preventing the synthesis of prostaglandins that quickly follow the surgical insult. The delayed use of NSAIDs post-procedurally inhibits the subsequent prostaglandin synthesis and provides analgesia, but it does not interfere with the effects of those prostaglandins already produced. Preoperative administration of NSAIDs delays the onset of postoperative pain and lessens its severity and subsequent analgesics requirements.

The NSAIDs all share a qualitatively similar side-effect profile. However, with the exception of a true allergic reaction and the bronchoconstriction response in asthmatics, a patient's inability to tolerate one specific NSAID does not mean the patient will be intolerant of all other NSAIDs. Also, patients may vary in their relative analgesics response to various NSAIDs. Therefore, if a patient does not respond to a particular drug at the maximum therapeutic dose, an alternative NSAID should be considered.

The oral route of administration is preferred for nonopioids. Some patients, such as young children or patients with intermaxillary fixation following maxillofacial surgery or trauma, are unable to swallow tablets or capsules. For these patients, liquid formulations of acetaminophen or ibuprofen should be considered. For the rare dental patient who is unable to take any medications by mouth, parenteral (ketorolac) or rectal (acetaminophen, aspirin) dosage forms are available.

The nonopioids can be divided into the salicylates (aspirin-like group), acetaminophen, and the nonsteroidal anti-inflammatory agents or drugs (NSAIAs/NSAIDs).

Nonopioid Analgesics

Salicylates NSAIAs Acetaminophen
 

Aspirin

 

Ibuprofen

 

(Tylenol)

Choline salicylate Naproxen  
Sodium salicylate Ketoprofen  
Salsalate Ketorolac  
Magnesium salicylate Diflunsial  

The inhibition of prostaglandin synthesis produced by aspirin is also responsible for its antiinflammatory action, a primary objective in dental pain relief. The prostaglandins are important vasodilating agents that also increase capillary permeability. Therefore, aspirin causes decreased erythema and swelling of the inflamed area.

Aspirin and Related Salicylates

Aspirin has been commercially available since 1899, and, until the late 1970s, no peripherally acting analgesics could claim greater efficacy.

Aspirin belongs to the salicylic acid (salicylate) class of compounds that were originally obtained from botanical sources. The first active substance of this group, salicin, was isolated from the bark of the willow tree. From salicin were synthesized salicylic acid, sodium salicylate, and finally acetylsalicylic acid (aspirin).

Aspirin, the most prominent member of the salicylate group, derives its analgesic, antipyretic, and antiinflammatory action from its ability to inhibit prostaglandin systhesis. Aspirin inhibits the enzyme cyclooxygenase (prostaglandin synthase) by acetylating a serine, which results in inhibition of the production of prostaglandins. A reduction in prostaglandins results in a reduction in painful perception. Many dental patients are advised to take aspirin before the painful stimuli is experienced, such as a "throbbing" pain caused by inflammation.

The antipyretic properties of aspirin are well documented. Antipyresis is best demonstrated in febrile patients, since normal subjects show no marked change in body temperature when therapeutic doses of aspirin are administered.

It is difficult to separate the analgesic and antiinflammatory effects of aspirin, since the vast majority of painful conditions have an inflammatory component. There is little doubt that the cascade of reactions leading to the formation of prostaglandins is integrally involved with the inflammatory response and that aspirin's efficacy in treating inflammation is closely related to its inhibition of prostaglandin synthesis.

Aspirin is rapidly and almost completely absorbed from the stomach and small intestine, producing a peak effect on an empty stomach in 30 minutes. The buffered tablet reaches its peak in about 50 minutes. Addition of a buffer to aspirin facilitates the dispersion and dissolution of the tablet.

Aspirin may be administered rectally when vomiting is present. Since this route is more erratic and unpredictable it should only be used when the oral route is not feasible. An aspirin tablet should never be applied topically to the oral mucosa to treat a toothache. A painful ulceration can occur.

Aspirin is typically used to relieve mild to moderate pain such as a headache or toothache. It is not effective against intense pain because the analgesic potency of aspirin is weaker than that of the opioids.

Aspirin has been reported to have three kinds of adverse effects on the gastrointestinal system. The first is gastric distress. There is evidence suggesting that both local and systemic mechanisms interfere with the ability of gastric mucosal cells to resist penetration by acid. Aspirin's interference with normal cytoprotective mechanisms mediated by prostaglandins in gastric mucosal cells is a primary cause of the gastric distress. A second effect of aspirin is occult gastric bleeding, resulting from cellular and capillary damage along the gastrointestinal tract. The third effect, which is very rare and idiosyncratic, is a sudden acute hemorrhage.

Aspirin significantly increases bleeding time by inhibiting the aggregation of platelets. As little as one 325 mg aspirin tablet can double the normal bleeding time for several days. This protracted inhibition of platelet aggregation correlates with the ability of aspirin to irreversibly acetylate cyclooxygenase. Platelets lack the ability to regenerate this enzyme, and the synthesis of new platelets is required for recovery to occur.

Aspirin in dentistry Aspirin is an effective analgesic for almost any type of acute dental pain. Double-blind, controlled studies of the relief of pain after extraction of third molars have demonstrated that 650 mg of aspirin is substantially more effective than 60 mg of codeine in relieving postoperative pain. In fact, most controlled clinical studies have established that, regardless of the cause of the pain, aspirin (650 mg) provides equal or greater pain relief than codeine (60 mg). A problem with aspirin is that it has a rather flat dose-response curve, with near-maximal analgesia occurring at approximately 650 mg. Increasing the dose to 1000 mg may slightly increase analgesic efficacy and prolong the duration of effect. Clinically, this means that if 650 to 1000 mg of aspirin fails to relieve the discomfort, increasing the dose will be of little help. However, it cannot be overemphasized that at this ceiling dosage, taken every 4 hours, aspirin is a very effective analgesic for most painful dental conditions.

Adverse effects Aspirin has numerous side effects at therapeutic doses, most of which are more annoying than serious. The most commonly reported side effect is nausea. It is important to realize that many surgical procedures or illnesses may cause nausea by themselves and that the analgesic may be blamed unjustly.

Certainly, many dental surgical procedures have the potential for causing nausea because of the swallowing of blood and debris, the use of sedative or anesthetic drugs, and the anxiety associated with dental surgery. However, it is also clear that aspirin can cause gastric irritation that leads to nausea and, occasionally, vomiting. In addition to the effects of aspirin on the gastric mucosa, aspirin causes local irritation directly while the tablet is disintegrating and in contact with the gastric tissues.

The same mechanisms that produce nausea are probably involved in the occult bleeding that develops in over 70% of those who use the drug. This blood loss occurs each time aspirin is ingested, occurs even at low doses, and goes unnoticed unless stool tests for blood are performed. Only in very unusual circumstances is this occult bleeding, which amount to less than 10 mL/day, of any clinical significance. However, aspirin is contraindicated in patients with gastrointestinal ulcers, especially those with peptic ulcers, because the normally innocuous bleeding may lead to severe internal hemorrhaging.

Aspirin significantly increases bleeding time by inhibiting the aggregation of platelets. Although the prolongation of clotting time is tolerated in healthy patients, the possibility exists that aspirin could promote postoperative hemorrhaging, especially if a clot has not fully formed. In two studies of patients undergoing dental impaction surgery, the administration of analgesic doses of aspirin was associated with significantly more postoperative swelling than comparable doses of acetaminophen. In view of these experimental findings, it may be prudent to recommend that aspirin therapy be discontinued before surgical procedures such as tooth extraction and that aspirin not be used prophylactically before any procedure that may involve postoperative bleeding. However, once a clot has been established, there should be little problem caused by the administration of aspirin or related salicylates.

Toxicity caused by aspirin overdose is common. Its symptoms and severity depend on dose. Chronic toxicity caused by salicylates is called salicylism and is characterized by tinnitus, nausea, vomiting, headache, hyperventilation, and mental confusion. Aspirin holds the dubious distinction of being one of the more frequently used drugs for attempted suicides.

The hyperventilation eventually can lead to respiratory alkalosis, which may be followed by a combined respiratory and metabolic acidosis accompanied by dehydration. Acidosis is more prominent as the level of overdose increases. Acidosis is also more likely to occur in children and infants. Impaired vision, hallucinations, delirium, and other CNS effects may be evident, and the situation is considered life threatening.

The treatment of aspirin overdose is primarily palliative and supportive. Chronic toxicity usually only requires removal of the drug and eventual dose adjustment. Acute toxicity often requires respiratory support, gastric lavage, maintenance of electrolyte balance (e.g., potassium replacement if necessary), maintenance of plasma pH, and alkalinization of the urine by intravenous (IV) bicarbonate.

Intolerance to salicylates can occur, with symptoms ranging from rhinitis to severe asthma. The reaction is more common in patients with preexisting asthma or nasal polyps. This does not appear to be an immune-mediated reaction. Intolerance occurs to other NSAIDs as well. The incidence of this kind of reaction in asthmatic patients has been reported to be as high as 20%. Patients with a history of asthma, allergic disorders, or nasal polyps should be questioned to be sure that they can tolerate aspirin.

Aspirin is contraindicated in a number of medical conditions. Serious internal bleeding can result from the ingestion of aspirin by a patient with an ulcer condition.

Aspirin is not contraindicated in pregnancy, but it should be used with caution. In the third trimester, aspirin tends to prolong labor by inhibiting the synthesis of prostaglandins involved in initiating uterine contractions. Aspirin has also been reported to increase blood loss at the time of delivery and may cause premature closure of the ductus arteriosus in the fetus. Aspirin should also be avoided in children with influenza or chickenpox (varicella). There are epidemiologic data indicating that aspirin usage during or shortly after these viral diseases increases the risk of developing Reye's syndrome.

Contraindications to the Use of Aspirin and Other Salicylates

Disease state Possible adverse effect of aspirin
 

Ulcer

 

Internal bleeding, possible hemorrhaging

Asthma Asthmatic attack resembling an allergic reaction
Diabetes High doses may cause hyperglycemia or hypoglycemia
Gout Low doses increase plasma urate; high doses lower plasma urate
Influenza Reye's syndrome in children
Hypocoagulation states Excessive bleeding

It is obvious that aspirin is not an innocuous drug. However, there are relatively few instances in which clinically significant side effects occur, and, if reasonable precautions are taken to avoid aspirin when its use is contraindicated, the drug is an extremely effective and safe analgesic.

Acetaminophen

Acetaminophen is the only aniline derivative currently in clinical use. It is widely promoted as the antipyretic analgesic of choice when aspirin cannot be used because of gastric problems or other contraindications.

Acetaminophen has both analgesic and antipyretic activity that is essentially equivalent to that of aspirin. Acetaminophen's mechanism of action also appears to be the same as that of aspirin.

Compared with aspirin, acetaminophen has relatively few important effects on specific organs or systems. The potency and efficacy of acetaminophen as an antipyretic are similar to those of aspirin. At therapeutic doses, acetaminophen has little, if any, effect on the cardiovascular or respiratory systems. Acetaminophen does not inhibit platelet aggregation, cause occult bleeding or gastric irritation, affect uric acid excretion, or have as many drug interactions as aspirin. In overdose, the organ most affected is the liver. Acute renal toxicity may also occur.

The wide publicity given to the adverse effects of aspirin has caused increasing numbers of dentists to substitute acetaminophen for aspirin in the treatment of postoperative dental pain, even though the antiinflammatory effects of acetaminophen are minor. In clinical studies, aspirin and acetaminophen appear to be similar in their effectiveness in relieving pain after the extraction of third molars.

Until recently, acetaminophen was thought to have a plateau for analgesia at about 650 mg, but it is now accepted that acetaminophen does have a linear dose-effect curve for analgesia up to 1000 mg. Based on this finding, some clinicians are recommending the use of 1000 mg of acetaminophen rather than the customary 650 mg dose.

The potential for adverse effects from acetaminophen seems to be singularly confined to the situation in which there is an acute overdose. At therapeutic doses, acetaminophen does not cause nausea, inhibit platelet aggregation, prolong prothrombin time, or produce the other side effects associated with the use of aspirin. Allergy to acetaminophen is rare and is generally manifested as skin eruptions.

Analgesic Alternatives to Aspirin and Acetaminophen

Until the late 1970s, no single-entity oral analgesic had consistently demonstrated grater analgesic efficacy than that of aspirin or acetaminophen. Several new peripherally acting analgesics, most of which had earlier been approved for use as antiinflammatory drugs, have now been evaluated in postoperative dental pain and found to be superior to the standard drugs in peak analgesic effect, duration of effect, or both.

Among the NSAIDs, the propionic acid derivatives constitute the largest group of aspirin alternatives. Ibuprofen, fenoprofen, ketoprofen, and naproxen are approved for use as analgesics. Others, such as flurbiprofen, are currently under review by the Food and Drug Administration (FDA).

Ibuprofen was the first single-entity oral analgesic to be approved by the FDA that showed a greater peak effect than 650 mg. of aspirin. It is also available as a nonprescription drug. The recommended prescription analgesic dose of ibuprofen is 400 mg every 5 to 6 hours. In one study, this dose was more effective than a combination of 650 mg aspirin with 60 mg codeine.

Naproxen is approved for a variety of inflammatory conditions and for the relief of pain. It is available as both the free acid and as the sodium salt, the latter of which is more rapidly absorbed from the gastrointestinal tract and may be preferred form for analgesic use. The recommended analgesic regimen for naproxen is 500 mg initially, followed by 250 mg every 6 to 8 hours. Its longer half-life allows dosing at longer intervals than with ibuprofen.

Fenoprofen is marketed with both analgesic and antiinflammatory indications. The recommended dose of 200 mg every 4 to 6 hours is likely to be superior to 650 mg of aspirin.

Adverse effects The adverse effects of the peripherally acting analgesics are similar to those produced by aspirin; however, they may vary in severity. Gastric irritation (nausea and abdominal pain) is usually the most troublesome adverse effect. Dizziness, gastrointestinal bleeding, fluid retention, and nephrotoxicity have also been reported. Inhibition of platelet aggregation is transient and reversible.

These peripherally acting analgesics should be avoided in most patients whose medical conditions contraindicate the use of aspirin. Of particular concern are patients with gastrointestinal ulcers, coagulation disorders, and aspirin intolerance.

Opioid Analgesics

Opioid analgesics are primarily employed for the relief of pain and consequently find widespread application in dentistry. Opioids also possess therapeutically useful antitussive (cough suppressant) and constipating effects in addition to several undesirable effects, including respiratory depression, urinary retention, sedation, nausea and vomiting, and at times unwanted constipation. Repeated use of opioids for control of pain can lead to analgesic tolerance (loss of analgesic effect), as well as physical and sometimes psychologic dependence. These shortcomings notwithstanding, no other drugs are more efficacious as analgesics than the opioids.

Opioid analgesics are added to nonopioids to manage pain that is moderate to severe or that does not respond to nonopioids alone. Opioids differ from the nonopioids in that they have no ceiling effect. The only dosing limitation is based on side effects. Although opioids are the cornerstone for management of moderate to severe acute pain, they are frequently underutilized and at lower than effective doses as a result of misconceptions and fears regarding their use.

Fear of possible sedation or respiratory depression causes some practitioners to underprescribe and underdose opioids. These adverse events rarely occur when appropriate starting doses are used and then titrated to an effect based on the patient's analgesic response and side effects. Patients vary greatly in their analgesic dose requirements and responses to opioid analgesics.

Fear of addiction on the part of both the practitioner and the patient is a common barrier to the effective use of opioid analgesics. For many, this fear is the result of not being aware of the actual risks associated with opioid analgesics used for the treatment of pain and of confusing addiction with physical dependence, tolerance, or pseudoaddiction. Addiction refers to psychologic dependence, a behavioral pattern of drug use marked by craving, drug-seeking behavior, and compulsive use that may interfere with the person's ability to function in society. Physical dependence, on the other hand, is a pharmacologic property causing the appearance of withdrawal symptoms when the medication is stopped abruptly or following the administration of an antagonist, and tolerance is the requirement for increased doses of a drug to achieve the same effect. Finally, pseudoaddiction is a term used to describe exaggerated behaviors seen in pain patients brought on by inadequate pain relief.

Physical dependence and tolerance are involuntary mechanisms that occur in virtually all patients taking opioid analgesics for a prolonged period of time. They are easily managed in the patient with pain. Tolerance is managed with careful upward titration of the dose until adequate pain relief is reobtained. The effects of physical dependence are easily avoided by the gradual tapering of opioids on discontinuation of therapy, as opposed to abrupt withdrawal. Addiction, by contrast, is a voluntary mechanism that rarely occurs in patients taking opioid analgesics for pain. The overwhelming majority of patients taking pain medication stop taking the medication when the pain stops.

Opioid analgesics include both pure agonists, such as codeine and oxycodone, and agonist/antagonists, such as pentazocine and butorphanol. As a general rule, the agonist/antagonists should not be used as first-line therapy. There is no convincing evidence that these drugs offer any advantage over the pure opioid agonists. Agonist/antagonists become less effective at high doses because of the ceiling effect, frequently cause dysphoria, and may cause confusion and hallucinations. In addition, they may cause withdrawal symptoms when given to patients physically dependent on opioid agonists. On occasion, they may be useful in treating individuals unable to tolerate other opioids.

pain.jpg (36860 bytes)

Step-wise process in choosing analgesic medication. Opioid (1) indicates a standard oral opioid in a conventional dose; 2 indicates increasing doses or a change in opioid to increase the analgesic effect. (Based on recommendations of the World Health Organization.)

In 1990, the World Health Organization proposed a stepwise approach for the management of cancer pain. This approach has subsequently come to be recommended for the treatment of noncancer pain as well. The first step, representing mild pain, is to administer a nonopioid drug. In many dental surgical procedures,

NSAIDs alone can achieve excellent pain control. Pain that does not respond adequately to nonopioid agents should be treated with the combination of a nonopioid and an opioid such as codeine, hydrocodone, or oxycodone. Even when insufficient alone to control pain, NSAIDs can reduce the dose of opioid relief. More severe pain, or pain that persists, should be treated with a combination of a nonopioid and a stronger opioid, such as morphine or hydromorphone. At any level, adjuvant agents such as certain anticonvulsants or tricyclic antidepressants may be added when indicated. Common indications in dentistry include the treatment of neuropathic pain and some chronic orofacial pain conditions.

The oral administration of opioid analgesics is preferred whenever possible. It is convenient and inexpensive. Even severe postsurgical pain can be effectively treated with orally administered opioids in the proper doses. For the patient not able to swallow a pill or capsule, numerous liquid formulations of opioids are available (codeine, hydrocodone, oxycodone, and others). Peak drug effects (including side effects) occur 1.5 to 2 hours after the oral administration of most opioids (sustained-release tablets excepted). Therefore, patients may take a second opioid dose safely 2 hours after the first dose if the pain persists and side effects are mild at that time. For patients unable to take medications by mouth, the intravenous, intramuscular, or rectal routes of administration can be considered. Use of the intravenous or intramuscular route to deliver analgesics is almost exclusively limited to inpatient hospital settings. Of the two routes, intravenous administration is preferred. Intravenous bolus administration provides the most rapid and predictable onset of effect. Time to peak effect varies with drug lipid solubility, ranging from 1 to 5 minutes for fentanyl to 15 to 30 minutes for morphine.

As mentioned previously, opioids should almost always be administered with nonopioids for maximum pain relief in dental situations. Many opioids are marketed in combinations with a nonopioid, and it is the latter component that limits the dose. For example, the upper dose limit for acetaminophen is 4000 mg/day. Therefore, for combinations containing 325 mg of acetominophen, the maximum number of tablets/day is 12. For combinations containing 500 mg of acetaminophen, the maximum number of tablets/day is eight. In children under 45 kg, the limit is 90 mg/kg of acetaminophen.

Morphine

Morphine is the prototypic opioid analgesic and the one about which most is known. Morphine is widely used for pain control and can be given by virtually any route of administration.

The CNS effects of morphine are a combination of stimulation and depression and include analgesia, drowsiness, euphoria-dysphoria, respiratory depression, suppression of the cough reflex and pupillary constriction.

The analgesia produced by morphine and its congeners occurs without loss of consciousness. When opioids are administered for relief of pain (or for a cough or diarrhea, for that matter), it must be appreciated that they provide only symptomatic relief without alleviation of the cause of the pain (or cough or diarrhea). The analgesia produced by opioid analgesics is dose dependent and selective in that other sensory modalities (e.g., vision, audition) are unaffected at therapeutic doses. The standard parenteral analgesic dose of morphine, 10 mg/70 kg body weight, is considered a therapeutic dose for relief to severe pain. Greater doses provide greater pain control.

An additional significant feature of opioid analgesics is that they are generally more effective against continous, dull aching pain than against sharp, intermittent pain. Neuropathic pain, such as trigeminal neuralgia, is less responsive to opioids than is nociceptive pain. It is also known that sensitivity to pain and the ability to clear morphine decrease with age, whereas the elimination half-life of morphine does the opposite; thus, the pain relief provided by morphine typically increases with age.

Tolerance and dependence. Tolerance is a decreased effect of drug as a consequence of prior administration of that drug. Accordingly, increasingly greater dose of drug must be administered over time to produce an effect equivalent to that produced on initial administration. Tolerance does not develop uniformly to all opioid effects. In general, tolerance develops to the depressant effects of opioids but not to the stimulant effects. Thus, tolerance develops to opioid-induced analgesia, euphoria, drowsiness, and respiratory depression but not, to any appreciable extent, to opioid effects on the gastrointestinal tract or the pupil.

In the therapeutic setting, the initial indication that tolerance has developed is generally reflected in a shortened duration or reduced analgesic effect. The rate at which tolerance develops is function of the dose and the frequency of administration, as well as perhaps other, nonpharmacologic factors. In general, the greater the opioid dose and the shorter the interval between doses, the more rapid is the development of tolerance. Tolerance, in fact, can develop to such an extent that the lethal dose of the opioid is increased significantly. However, for any individual there always exists an opioid dose capable of producing death by respiratory depression regardless of the extent to which tolerance has developed.

Tolerance becomes apparent during repeated drug administration, whereas dependence is apparent only in the absence of drug. Dependence can be physical or psychologic state produced by repeated administration of a drug, which then makes its continued use necessary to prevent the appearance of a withdrawal or abstinence syndrome. The greater the opioid dose and the longer the duration of administration, the greater is the degree of physical dependence and the more intense is the withdrawal syndrome.

Psychologic dependence is more difficult to define and measure. Psychologic dependence contributes more to drug-seeking behavior than does physical dependence. Addiction is the extreme of compulsive drug use and is associated with significant psychologic dependence, and thus, it is inappropriate to identify as "addicted" a person who becomes physically dependent after repeated opioid administration during hospitalization. All three phenomena_tolerance, physical dependence, and psychologic dependence_are reversible, although psychologic dependence provides a strong drive to drug abuse.

There exists on the part of health professionals and patients alike concern about the use of opioids for pain control, particularly in cases of persistent pain. This so-called "opiophobia" is a reaction to fear of dose escalation (caused by development of tolerance) and subsequent physical dependence (erroneously termed "addiction") associated with treatment for pain that lasts more than a few days. It has been found, for example, that dose escalation for pain control is usually required only at the start of therapy (i.e., when titrating the dose to provide adequate analgesia) and that dose requirements tend to stabilize thereafter for long periods of time.

Pain is the main complaint that initiates a visit to a dentist or physician. Moreover, pain is almost always present after invasive procedures or surgery. Morphine and other opioid analgesics are the most efficacious analgesic drugs known and are without peer in their ability to control pain. As emphasized earlier, these drugs provide only symptomatic relief of pain without influencing its underlying cause. The opioids, when administered at therapeutic doses to produce analgesia, also produce a drowsiness from which the patient is generally easily aroused, as well as "tranquillization." There is without doubt a significant antianxiety or sedating component in the analgesic effect of opioids. Thus, although nausea and vomiting, respiratory depression, constipation, and tolerance and physical dependence can be drawbacks to their use, the opioids undeniably produce an important combination of desirable effects (e.g., analgesia and sedation) in the suffering patient.

Codeine

As with all opioids analgesics, the analgesic and antitussive actions of codeine (as well as its respiratory depressant and sedative effects) are central in origin. Codeine is frequently classified as a "weak" or "mild" opioid analgesic. That codeine is a mild analgesic incapable of providing an analgesic effect equivalent to morphine is an erroneous, but widely held, impression. Morphine as an analgesic is about 12 times more potent than codeine when both drugs are administered intramuscularly. This ratio simply means that approximately 120 mg of codeine is required to produce an analgesic effect equivalent to 10 mg of morphine. At the present time, however, doses of codeine in excess of 60 mg (orally) are not commonly used and, moreover, are not officially recognized as generally safe and effective by the Food and Drug Administration. Consequently, the impression remains that codeine has limited analgesic efficacy and that a dose of 60 mg of codeine represents an "analgesic ceiling" above which increasing doses will not provide greater analgesic effect.

It should be noted, however, that dental pain associated with inflammation should not be treated with codeine alone because neither codeine nor any of the other opioids has antiinflammatory properties. Rather, aspirin or another nonsteroidal antiinflammatory drug alone or in combination with codeine is appropriate for cases of dental pain involving or arising from inflammation.

Principles of Opioid Analgesic Use

Analgesics should be administered initially on a regular time schedule. For example, if the patient is likely to have pain requiring analgesics for 48 hours after dental surgery, analgesics might be ordered every 4 hours while awake, not as needed (pro re nata or prn), for the first 36 hours. This schedule provides more stable plasma concentrations of the agent with less breakthrough pain. If only prn medications are used, it may take several hours and higher doses to relieve pain, leading to a cycle of undermedication and pain alternating with periods of overmedication and drug toxicity. Later in the postoperative course, as the patient's analgesic dose requirement diminishes, dosing may be switched to an as-needed basis.

Adverse Reactions of Opioids

Unlike many drugs, the adverse reactions of the opioids are not related to a direct damaging effect on hepatic, renal, or hematolgic tissues but rather are an extension of their pharmacologic effects. Like the pharmacologic effects, the adverse reactions of the opioid analgesics are proportional to their analgesic strength.

1. Respiratory depression. The opioid analgesic agonists depress the respiratory center in a dose-related manner. This is usually the cause of death with an overdose.

2. Nausea and emesis. Analgesic doses of opioid analgesics often produce nausea and vomiting. This is due to their direct stimulation of the chemoreceptor trigger zone (CTZ) located in the medulla. This side effect is reduced by discouraging ambulation.

3. Constipation. The opioids produce constipation by producing a tonic contraction of the gastrointestinal tract. Small doses of even weak opioids frequently have this effect and its duration outlasts their analgesic effect. Even with continued administrations tolerance does not develop to this effect.

4. Urinary retention. The opioids increase the smooth muscle tone in the urinary tract, thereby causing urinary retention. They also produce an antidiuretic effect by stimulating the release of antidiuretic hormone (ADH) from the pituitary gland.

5. CNS effects. Occasionally, opioids may produce CNS stimulation exhibited by anxiety, restlessness, or nervousness.

Combinations of Peripherally Acting Analgesics and Opioids

There is a sound scientific basis for combining peripherally acting analgesics with opioids. The peripherally acting drugs combat pain principally by directly interfering with the biochemical mediators that cause sensitization of nerve endings at the site of injury, whereas the opioids alter CNS perception and reaction to pain. The mechanisms of pain relief of these two classes of drugs are distinct, supporting the use of these two types of drugs in combination. In addition to the fact that these combinations seem reasonable, abundant clinical data exists to support the validity of their combined use. However, there is a common misconception that such combinations produce a synergistic phenomenon, that is, an effect greater than the sum of effects expected from both drugs. No evidence currently supports this belief, and, at best, there is purely additive effect when drugs from these two classes of analgesics are combined. Indeed, if any synergism does exist, it is probably with the toxic effects rather than with analgesic efficacy.

Another misconception is that the opioid in the combination is the major contributor to the overall effectiveness of the oral preparation for the treatment of dental pain. Clinical studies indicate quite the opposite, showing that the peripherally acting component is an equal or, more often, greater contributor to the overall efficacy of the combination for most types of pain. When one limits the comparison to those studies evaluating pain of dental etiology, there is no question that the aspirin like drugs provide the bulk of the pain relief, whereas the opioids are of less benefit. When side effects are compared, however, the centrally acting drugs are most often the cause.

The clinical significance of the centrally acting analgesics is that they provide additional analgesia beyond the ceiling effect of the peripherally acting component, and they also contribute a centrally mediated sedative effect. Therefore, the most effective combinations are those that use the optimal amount of an aspirinlike drug combined with the appropriate dose of an opioid analgesic.

Codeine is the most commonly used centrally acting agent in combination analgesics. Its effective oral dose range is 30 to 90 mg, 30 mg providing only minimal analgesia, 60 mg providing a little more analgesia with considerably more nausea and sedation, and 90 mg approaching the dose at which intolerable side effects appear. Codeine is available in combination with aspirin or acetaminophen. For most patients, 600 to 650 mg of the peripherally acting component combined with either 30 or 60 mg of codeine should provide adequate pain relief for almost any acute dental pain.

There are other centrally acting analgesics used in combination, but the vast majority of drug combinations on the market include codeine, oxycodone, hydrocodone, propoxyphene, or pentazocine combined with either aspirin or acetaminophen.

The advent of the NSAIAs has produced a dramatic decrease in the use of the opioids in dental practice. Most dental pain can be better managed by the use of NSAIAs. In the patient in whom NSAIAs are contraindicated, the dentist has a wide range of opioids from which to choose. By beginning with codeine or hydrocodone combinations and progressing to oxycodone combination, almost all dental pain can be managed. Only in rare cases, and for very short periods of time (1 to 2 days), should hydromorphone or meperidine be prescribed for outpatient dental pain.

Dentists should be familiar with several analgesics in both the opioid and nonopioid categories. Different patients vary greatly in their response to, and ability to tolerate, different agents. For this reason, it is important to be familiar with the recommended dose, side-effect profile, and time course of several agents in each category.

Patient should be followed closely, particularly when beginning or changing analgesic regimens. Analgesics are more beneficial if the clinician monitors pain relief and adverse effects frequently and adjusts the regimen as needed to optimize therapy. This monitoring is particularly important when using an agent or combi-nation with which the doctor has little or no experience or when changing from one analgesic to another.

Although pain is a common occurrence in patients seeking or undergoing dental care, it is generally manageable and often avoidable. Accurate assessment, methodical prevention, and aggressive treatment are the tools required to keep pain at a minimum. Rational clinical practice guidelines and equianalgesic charts allow practitioners to determine the appropriate analgesic regimen and dose for each patient.

Antianxiety Drugs

Fear and anxiety of dentistry are common. The severity ranges widely, with mild apprehension being reported by as many as 75% of the population and severe anxiety, leading to avoidance of dental treatment, affecting anywhere from 6% to 20%. Although mild fear may have only a minor impact on oral health, true phobia can cause patient to avoid treatment in spite of significant symptoms and to have detrimental consequences for their overall health.

Antianxiety drugs are used in clinical dentistry primarily for premedication of the nervous and apprehensive patient.

The usefulness and effectiveness of any given antianxiety agent will vary, depending on the patient, the clinical surroundings, the "chairside" manner of the dentist, the route of administration, and the properties of the chosen drug.

Benzodiazepines

The benzodiazepines rank as the one of the most widely used drug classes in the history of medicine. This popularity stems from the fact that they are more selective and have a greater margin of safety than drugs used earlier (e.g., barbiturates) for the treatment of anxiety. Currently, there are several dozen benzodiazepines being marketed throughout the world.

Pharmacologic effects The most important pharmacologic effects of the benzodiazepines are on the CNS. The benzodiazepines have clinically useful antianxiety, sedative-hypnotic, anticonvulsant, and skeletal muscle relaxant properties. The clinical effects of these agents in humans are anxiety reduction at low doses and production of drowsiness, and even sleep at higher doses.

The benzodiazepines, particularly diazepam, have anticonvulsant activity (i.e., they increase the seizure threshold). Diazepam has been shown to be an effective anticonvulsant for the prevention of seizures associated with local anesthetic toxicity and for the treatment of status epilepticus.

Many of the gross CNS effects of the benzodiazepines are similar to those of the older sedative-hypnotics, such as the barbiturates. All of the benzodiazepines produce a dose-dependent depression of the CNS. Drowsiness and sedation are common manifestations of this central depressant action and may be considered a side effect in some instances and therapeutically useful in others.

As is true of any sedative drug, the benzodiazepines are respiratory depressants. In normal doses the benzodiazepines have little effect on respiration in the healthy person.

Adverse effects The most common side effect of the benzodiazepines is drowsiness. This may not necessarily be an unwanted side effect, but rather a desirable therapeutic response to anxiety states that cause insomnia. Other side effects that are a result of dose-dependent CNS depression include ataxia, incoordination, dysarthria, confusion, apathy, muscle weakness, dizziness, and somnolence. The elderly (over 65 years) appear to be particularly susceptible, and persons with a history of alcohol or barbiturate abuse particularly resistant, to the CNS depressant properties of the benzodiazepines. The elderly and the young occasionally respond to the benzodiazepines with excitement rather than depression.

Tolerance and psychologic dependence occur rather frequently with the benzodiazepines, but true physical dependence is less common. Nevertheless, the abuse potential of the benzodiazepines is considerable. In cases of physical dependence, the severity of withdrawal depends on the dose of the drug being used and the drug half-life. Rapid discontinuation of the benzodiazepines, especially the short-acting compounds, can lead to symptoms of withdrawal.

The symptoms become more severe with high doses and prolonged treatment. Withdrawal can be minimized by reducing the dosage very gradually (10% or less per day over a course of 10 to 14 days) or by the use of longer-acting compounds.

Despite these problems, one of the major advantages of the benzodiazepines, as compared to other sedatives, is their high margin of safety. Death is rare in cases of overdose and is usually the result of a combination of drugs (especially alcohol) with the benzodiazepines.

The antianxiety agents are important in dentistry for the premedication of the apprehensive patient, the patient exhibiting mild neurosis associated with the mouth, and the uncooperative child. Antianxiety agents, particularly intravenous midazolam and diazepam, are used as adjuncts to local anesthesia.

Perhaps one of the more perplexing questions for the practicing dentist is which oral benzodiazepine to choose from the overexpanding list. There is little doubt of the clinical effectiveness of these drugs in a variety of dental procedures, but there are no unusual characteristics associated with any one benzodiazepine that would make it clearly superior to the others. The major decision to be made in the treatment of the anxious patient is therefore not which drug to use but rather when to administer.

The primary concern of the dentist in using an antianxiety agent should be excessive CNS depression. CNS depression may result from the antianxiety agent alone or its combination with other CNS depressants that the dentist may plan to give or that the patient may already have taken. The antianxiety agents summate with the anesthetics, antipsychotics, antidepressants, opioid analgesics, and sedative-hypnotics. Alcohol may markedly increase the CNS depressant effects of benzodiazepines.

Antianxiety Agents

 

Nonproprietary Name Proprietary Name
 

Benzodiazepines

 
alprazolam  Xanax
chlordiazepoxide Librium
clorazepate  Tranxene
diazepam Valium
halazepam Paxipam
lorazepam Ativan
midazolam Versed
oxazepam  Serax
prazepam Centrax
 

Dephenylmethane antihistamines

 
hydroxyzine hydrochloride Atarax
hydroxyzine pamoate Vistaril
 

Azaspirodecanediones

 
buspirone BuSpar
 

Propanediol carbamates

 
meprobamate Miltown, Equanil
chlormezanone Trancopal

 

Autonomic Nervous System Drugs

It is important that the dentist becomes familiar with the autonomic nervous system (ANS) drugs used in dentistry, such as vasoconstrictors in local anesthetic solutions and drugs used to reduce salivary flow. The dentist should know the oral adverse reactions produced by ANS drugs and should be able to distinguish similar reactions produced by other drugs such as antihypertensives and antipsychotic drugs.

The autonomic nervous system (ANS) and the endocrine system comprise the major regulatory system for controlling homeostatic functions. These two systems collectively regulate and coordinate the cardiovascular, respiratory, gastrointestinal, renal, reproductive, metabolic, and immunologic systems. Accordingly, drugs that alter the activity of either the ANS or the endocrine system often exhibit multiple actions and side effects.

The ANS regulates the function of involuntary structures: smooth muscle, secretory glands, and cardiac muscle. These structures possess intrinsic mechanisms that make it possible for them to function in the absence of innervation, but the ANS contributes a regulatory and coordination function.

The ANS functions largely as an automatic modulating system for many bodily functions including the regulation of blood pressure, heart rate, gastrointestinal tract motility, salivary gland secretions, and bronchial smooth muscle. This system relies on specific neurotransmitters and a variety of receptors to initiate functional responses in the target tissues. The ANS has two divisions, the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS).

These two divisions of the ANS tend to act in opposite directions. The sympathetic division is designed to cope with sudden emergencies, such as, "fight or flight" situations. In contrast, the parasympathetic division is concerned with the conservation of body processes. Working generally in opposite directions, one would increase the heart rate while the other decreases it, one would dilate the pupils and the other would constrict them.

There are four groups of drugs that exert their effects primarily on the ANS.

1. Cholinergic agents or parasympathomimetics mimic the effects of the parasympathetic nervous system.

2. Anticholinergic agents, parasympatholytics, or cholinergic blocking agents block the effects of the parasympathetic nervous system.

3. Adrenergic agents or sympathomimetics mimic the effects of the sympathetic nervous system.

4. Adrenergic or sympathetic blocking agents, or sympatholytics, block the effects of the sympathetic nervous system.

Cholinergic (Parasympathomimetic) Agents

The cholinergic (parasympathomimetic) agents are classified as direct acting and indirect acting depending upon their mechanism of action. The direct-acting agents include the choline-derivatives and pilocarpine.

The indirect-acting parasympathomimetic agents or cholinesterase inhibitors act by inhibiting the cholinesterase. When this enzyme, which normally destroys acetylcholine, is inhibited, the concentration of acetylcholine builds up, resulting in action that resembles PANS stimulation.

The direct-acting agents as well as indirect-acting agents are used primarily in the treatment of glaucoma and, occasionally, to treat myasthenia gravis, a disease resulting in muscle weakness. The urinary retention that occurs after surgery is also treated with the choline esters.

Anticholinergic (Parasympatholytic) Agents

The anticholinergic agents prevent the action of acetylcholine at the postganglionic parasympathetic endings by completely blocking the receptor sight. These agents are used in preoperative medication, treatment of gastrointestinal disorders, ophthalmologic examination, reduction of Parkinson-like movements, motion sickness medication, over-the-counter sleepaids, and in dentistry to produce a dry field before some dental procedures.

Neuromuscular Blocking Drugs

Neuromuscular blocking drugs are agents that affect transmission between the mortar nerve endings and the nicotinic receptors on the skeletal muscle. They include known depolarizing blockers and depolarizing agents.

Adrenergic Drugs

Vasoconstrictors are widely used in conjunction with local anesthetic solutions. The vasoconstrictor most commonly employed in dentistry is l-epinephrine, with levonordefrin (the l isomer of nordefrin) being employed somewhat less frequently, usually with mepivacaine. Norepinephrine is only rarely used for this purpose.

The table below lists the concentrations and amounts of adrenergic vasoconstrictors contained in commercially available dental local anesthetic cartridges. The maximum recommended strength of the vasoconstrictor is 1:100,000 epinephrine equivalency for routine nerve block anesthesia. When local tissue hemostasis is required for surgical procedures, such as periodontal surgery, the dentist may additionally choose to infiltrate the area with local anesthetic solution containing up to 1:50,000 epinephrine.

Vasoconstrictors serve several useful purposes when employed with local anesthetic solutions. First, they prolonged the duration of local anesthesia severalfold and may improve the frequency of successful nerve block. Second, toxicity of the local anesthetic may be minimized by delaying and reducing the peak blood concentration of the anesthetic agent. Third, when anesthetic solutions are given by infiltration, vasoconstrictors tend to reduce blood loss associated with surgical procedures.

With a working knowledge of the ANS and the role it plays in the normal function of the various organs, it is possible to predict what effects a drug with a known mechnism of action would have.

Concentrations and Amounts of Adrenergic Vasoconstrictors in Dental Local Anesthetic Cartridges

 

Vasoconstrictor

 

Dilution

Amount per dental cartridge           (mg/1.8 mL)
Epinephrine hydrochloride 1:200,000 9
Epinephrine hydrochloride 1:100,000 18
Epinephrine hydrochloride 1:50,000 36
Levonordefrin hydrochloride 1:20,000 90

  

Effect of Epinephrine on the Duration of Local Anesthesia

Local Anesthetic Vasoconstrictor Duration - Mean (min) Duration - Maximum (min)
 

Lidocaine 2%

 

None

 

44

 

100

Lidocaine 2% Epinephrine 1:1,000,000 57 130
Lidocaine 2% Epinephrine 1:750,000 67 145
Lidocaine 2% Epinephrine 1:250,000 90 175
Lidocaine 2% Epinephrine 1:50,000 88 210

Adverse effects Almost all adverse effects of the adrenergic amines are dose related. Toxic reactions can result from the administration of too large a dose, accidental intravascular injection, impaired uptake of the drug, a heightened sensitivity or number of adrenergic receptors, or therapeutic doses given to a patient with preexisting cardiovascular disease. Relatively small amounts of epinephrine can cause potentially grave effects in the highly susceptible patient. In general, however, serous complications may be expected with doses of epinephrine above 0.5 mg, and fatalities are likely to occur with doses of 4 mg. or more. Correct dosage calculations, careful reading of labels, and a complete medical history can help reduce accidents.

Most serious of the toxic effects of epinephrine are cardiac disturbances, with increased stimulation of the heart leading to myocardial ischemia, possible heart attack, and arrhythmias, including ventricular fibrillation.

Adrenergic Blocking Drugs

Agents that suppress functions of the sympathetic nervous system, as well as those that block the actions of exogenous adrenergic amines, have a number of important implications for the practice of dentistry. Usually, these drugs are used in major cardiovascular disease, signaling the dentist's need to pay heed to potential risks associated with the condition. Drug therapy with any of these blocking drugs results in a patient whose autonomic capability for maintaining homeostasis has been altered. These changes may alter responses to sympathetic drugs and may lead to characteristic adverse effects.

A consideration for patients being treated with adrenergic blocking drugs is the patient's position during and after dental procedures. Suddenly standing upright after being in a supine position in the dental chair is very apt to cause syncope.

This is particularly true for the antihypertensive drugs more prone to cause orthostatic hypotension. Accidents ranging from broken teeth and restorations to fractured mandibles and worse have resulted from falls. Contemporary practice standards require the monitoring of blood pressure in dental patients. Such monitoring is particularly important in hypertensive patients.

Increasingly, incidents are occurring in which dentists are not informed of patients receiving medication from another practitioner in which there is a change in drug therapy or dosage. With the drugs that interrupt sympathetic function, this lack of knowledge can have serious consequences. Patients taking MAO inhibitors must not be given drugs that have indirect sympathomimetic activity or are inactivated by MAO. Occasionally, the dentist may find reason to use the vasoconstrictor phenylephrine. Because it causes even a minor release of norepinephrine from adrenergic nerves and is subject to metabolism by MAO, phenylephrine must be avoided in patients taking MAO inhibitors. Epinephrine and levonordefrin, which are most commonly found in local anesthetic solutions, are contraindicated. Nonetheless, the avoidance of hemostatic preparations containing high concentrations of epinephrine is recommended. Opioids and other CNS depressants should be used cautiously and usually at lower doses in patients who are taking MAO inhibitors. Meperidine is absolutely contraindicated.

Local Anesthetics

Local anesthetics are agents that reversibly block nerve conduction when applied to a circumscribed area of the body. Although numerous substances of diverse chemical structure are capable of producing local anesthesia, most drugs of proven clinical usefulness (identified by the suffix "caine") share a fundamental configuration with the first true local anesthetic, cocaine.

Local anesthetics block the sensation of pain by interfering with the propagation of peripheral nerve impulses. Both the generation and the conduction of action potentials are inhibited.

Vasoconstrictors are often added to local anesthetic solutions to impede systemic absorption of the anesthetic agent. Epinephrine in concentrations of 4 to 20 mg/mL (1:250,000 to 1:50,000) is most commonly used for this purpose. Localization of the anesthetic solution in the area of the injection by epinephrine is often highly beneficial. The duration of local anesthesia may be prolonged severalfold, and even the success rate and intensity of nerve block may be improved. Systemic toxicity may be reduced because less anesthetic may be needed, and drug metabolism is more likely to keep pace with drug absorption. During surgery, hemostasis afforded by the infiltration of a local anesthetic solution containing epinephrine may also be advantageous.

Modern local anesthetic solutions are quite safe when employed by competent personnel. Most toxic effects of a serious nature are related to excessive blood concentrations caused by inadvertent intravascular injection or the administration of large quantities of drug. Convulsions, respiratory depression, and cardiovascular collapse represent the greatest hazards to health. Such reactions can usually be prevented by observing three precautions: (1) administer the smallest dose that will provide effective anesthesia; (2) employ proper injection techniques, including aspiration; and (3) use a vasoconstrictor-containing solution when not contraindicated by patient history or operative need. If an adverse response occurs despite these procedures, immediate therapy must be administered. The patient should be placed in the supine position, and oxygen should be given. This procedure is often all that is needed for mild toxic reactions, epinephrine responses, or syncopal attacks.

Convulsions are usually self-limiting and require no treatment other than supporting ventilation and protecting the patient from bodily harm. Pharmacologic intervention is necessary, however, when seizures are so intense or prolonged that hypoxia threatens to ensue. The most satisfactory method of seizure control for the dentist is the intravenous administration of a rapidly acting benzodiazepine.

Local anesthetics are generally regarded as safe for use throughout pregnancy, and retrospective studies of women receiving local anesthesia for emergency procedures in the first trimester have supported this view.

It would be difficult to overstate the profound influence of local anesthesia on the practice of dentistry. Many of the complex restorative procedures routinely performed on conscious patients would be inconceivable without effective pain control. By eliminating most nociceptive sensations associated with dental care, local anesthetics improve patient acceptance of dental treatment and, as a result, contribute significantly to oral health. Because local anesthetics are so frequently employed and, for many practitioners, represent the only drugs administered parenterally, the toxicity as well as efficacy of these agents is of particular interest and concern.

Without question, local anesthesia is often considerably safer in dentistry than in medicine. Dosage employed for infiltration and nerve block in the oral cavity are often less than one-tenth those used for compound nerve block or for epidural injection. Recipients of dental anesthesia are in better systemic health than some medical patients and usually undergo only minor operative stress.

Selection of a local anesthetic for dental application must include considerations of efficiency, safety, and individual patient and operative needs. Indeed, 2% lidocaine hydrochloride with 1:100,000 epinephrine remains unsurpassed as dental anesthetic for routine use.

Anesthetics in Surface Application

Topical anesthetics are used in the oral cavity for a variety of purposes. Formulations marketed as pressurized sprays produce widespread surface anesthesia appropriate for making impressions or intraoral radiographs. Such preparations are potentially hazardous, however, and only products with metered valve dispenser to help prevent inadvertent overdose should be employed. Topical liquids, which avoid the possibility of aerosol inspiration, may also be used for anesthetic coverage of large surface areas. Nonaqueous topical preparations are suitable for most other procedures.

Benzocaine Poorly soluble in aqueous fluid, benzocaine tends to remain at the site of application and is not readily absorbed into the systemic circulation. Because of its low toxic potential, benzocaine is especially useful for anesthesia of large surface area within the oral cavity.

Tetracaine hydrochloride has approximately 10 times the toxicity and potency of procaine. Tetracaine is one of the most effective topical anesthetics, but the drug's toxic potential after surface application should dictate caution in its use.

Sources: Yagiela JA, Neidle EA, Dowd FJ: Pharmacologic and therapeutics for dentistry, ed 4, St. Louis, 1998, Mosby-Year Books, Inc.

Requa-Clark BS, Holroyd SV: Applied pharmacology for the dental hygienist, ed 3, St. Louis, 1995, Mosby-Year Books, Inc.

Recently-Approved Dental Drugs

The FDA has approved four new drugs of dental interest. See the table below.

New Dental Drugs

Brand Name Generic Name Use Manufacturer
 

Aphthasol

 

Amlexanox

 

Tx of aphthous ulcers

 

Block

Denavir Penciclovir Recurrent herpes labialis SmithKline- Beecham
       
DentiPatch Lidocaine patch Local anesthetic Noven
Viractin Tetracaine Cold sore pain killer Schering

 

Amlexanox (Aphthasol) is a locally applied anti-inflammatory indicated for the treatment of signs and symptoms of canker sores (minor aphthous ulcers). It is supplied as a 5 percent paste, and is available only by prescription. The suggested dosage is the application of a small amount directly to ulcers 4 times daily following oral hygiene, after meals, and before going to bed. The only adverse effects reported with amlexanox are a stinging or burning sensation at the site of application.

Penciclover (Denavir) is a topical antiviral agent indicated for the treatment of recurrent herpes labialis (cold sores) in adults. It is supplied as a 1 percent cream in 2 g tubes, and is available only by prescription. The suggested dosage is the application of a small amount at the first sign or symptom of a cold sore( e.g., tingling, swelling), and then every 2 hours, during waking hours, for 4 days.

Lidocaine transoral mucosal dental delivery system (Dentipatch) is a preparation of lidocaine available in a transoral patch to provide local anesthesia of the oral mucosa prior to oral injections and soft-tissue dental procedures. The recommended dose is one patch applied to a selected area of the oral mucosa. The onset of anesthesia is 2 minutes after patch application, with a duration of 45 minutes. The manufacturer, Noven Pharmaceuticals, claims that Dentipatch is safe, with "negligible systemic absorption" of lidocaine. The agent is "clinically proven to prevent injection pain from 25 gauge needles that are inserted to the level of the bone."

Tetracaine 2 percent (Viractin) is an over-the-counter preparation promoted as a cold sore and fever blister pain killer, available in 0.25 oz. cream and gel forms. The 2 percent tetracaine penetrates the skin to attack the source of pain. This product is marketed by Schering-Plough Health Care Products.

Source: Wynn RL. Drugs approved by the FDA in 1996. Gen Dest 1996; 45:224-227.

References

1. Barsan WG, Jastremski MS, Syverud SA, eds: Emergency drug therapy, Philadelphia 1991, WB. Saunders.

2. Bennett CR: Conscious-sedation in dental practice, ed 2, St. Louis 1978, CV Mosby.

3. Cousins MJ, Bridenbaugh PO, eds: Neural blockade in clinical anesthesia and management of pain, ed 2, Philadelphia, 1988, JB Lippincott.

4. Covino BG, Vassallo HG: Local anesthetics_mechanisms of action and clinical use, New York, 1976, Grune & Stratton.

5. de Jong RH: Local anesthetics, St. Louis, 1994, Mosby-Year Book.

6. Dionne RA, Phero JC: Management of pain and anxiety in dental practice. New York, 1991, Elsevier Science.

7. Dray A, Urban L, Dickenson A: Pharmacology of chronic pain. Trends Pharmacol Sci 15:190-197, 1994.

8. Gebhart GF, Hammond DL, Jensen TS, eds: Proceedings of the 7th World Congress on Pain, Seattle, 1994 IASP Press.

9. Hardman JG, Limbird LE, eds: Goodman & Gilman's the pharmacological basis of therapeu tics, ed 9, New York, 1996, McGraw-Hill.

10. Hargreaves KM, Dubner R: Mechanisms of pain and analgesia. In Dionne RA, Phero JC, eds: Management of pain and anxiety in dental practice, New York, 1991, Elsevier Science.

11. Kalsner S, ed: Trends in autonomic pharmacology, vol 2, Baltimore, 1982. Urban & Schwarzenberg.

12. Malamed SF: Sedation: a guide to patient management, ed 3, St. Louis, 1995, Mosby-Year Book.

13. Malamed SF: Medical emergencies in the dental office, ed 4, St. Louis 1993, Mosby-Year Book.

14. McCarthy FM, ed: Medical emergencies in dentistry, Philadelphia 1982, WB Saunders.

15. Milgrom P, ed al: Treating fearful patients. A patient management handbook, Reston, VA, 1985, Reston.

16.Murray MD, Brater DC: Renal toxicity of nonsteroidal anti-inflammatory drugs, Annu Rev Pharmacol Toxicol 33:435-465, 1993.

17.Omoigui S: The pain drugs handbook, St. Louis, 1995, Mosby-Year Book.

18. Pasternak GW:Pharmacological mechanisms of opioid analgesics, Clin Neuropharmacol 16:1- 18, 1993.

19.Strichartz GR, Berde CB: Local anesthetics. In Miller RD, ed: Anesthesia, ed 4, New York, 1994. Churchill Livingstone.