analgesics for pain management

8/8/2019 Analgesics for Pain Management

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Pain Management

Need for Pain ControlPain, as defined by the International Association for the Study of Pain, is "an unpleasantsensory and emotional experience arising from actual or potential tissue damage ordescribed in terms of such damage." Fear of pain is a significant reason for many people toavoid seeking dental care. No matter how successful or how deftly conducted, most dentalprocedures produce tissue trauma and release potent mediators of inflammation and pain.

Pain is just one response to the trauma of surgery, however. In addition to the major stress ofsurgical trauma and pain, the substances released from injured tissue evoke "stresshormone" responses in the patient. Such responses promote breakdown of body tissue;

increase metabolic rate, blood clotting, and water retention; impair immune function; andtrigger a "fight or flight" alarm reaction with autonomic features (e.g., rapid pulse) andnegative emotions. Pain itself may lead to shallow breathing and cough suppression in anattempt to "splint" the injured site followed by retained pulmonary secretions and pneumonia.Unrelieved pain also may delay the return of normal gastric and bowel function in thepostoperative patient.

The physiological and psychosocial risks associated with untreated pain are greatest in frailpatients with other illnesses such as heart or lung disease, those undergoing major surgicalprocedures such as aortic surgery, and the very young or very old. Because of advances insurgical and anesthetic techniques, it is now common for such patients to undergo operations

once dismissed as prohibitively risky.

In the past, postoperative pain was thought to be inevitable, a harmless though intensediscomfort that the patient had to tolerate. Now we know that unrelieved pain after surgery ortrauma is often unhealthy; fortunately, it is preventable or controllable in an overwhelmingmajority of cases. Patients have a right to treatment that includes prevention or adequaterelief of pain.

Undertreatment of pain is a significant problem. Numerous clinical surveys have shown thatpostoperative pain is often inadequately treated because of undermedication, leavingpatients to suffer needlessly. Recognition of the widespread inadequacy of pain managementand the detrimental effects of untreated pain has led to corrective efforts in numerous healthcare disciplines involved with pain management.

Health care is both a technical and an ethical enterprise. The ethical obligation to managepain and relieve the patient's suffering is at the core of health care professional'scommitment. While medical treatments often involve risks and burdens, anything harmful tothe patient, including postoperative pain, should be minimized or prevented if possible. Theethical importance of pain management is further increased when additional benefits for thepatient are realizedearlier mobilization, shortened hospital stay, and reduced costs. Ifinadequate pain management results from a clinician's conflict between reducing pain and

avoiding potential side effects and/or legal liability, achieving greater technical competenceand knowledge of risks and benefits can help to reduce such conflicts.


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Pain Classification

Successful treatment of pain conditions with analgesics requires a basic understanding of thetypes of pain. Painful conditions can be divided into two basic categories. Nociceptive pain isa result of mechanical, thermal, or chemical activation of nociceptive afferent receptors.

Nociceptive pain may be either somatic or visceral. Somatic nociception involves pathology inthe skin, muscles, fascia, and bones and is well localized. An example is the pain associatedwith cavity preparation or periodontitis. In both these conditions, inflammatory mediators maysensitize and/or activate nociceptive receptors that result in transduction of the noxiousstimulus into an electrical signal. The electrical signal is then transported toward the brain forinterpretation. Visceral nociceptive pain is poorly localized, may be referred to superficialsomatic regions, and involves pathologic conditions in deep, visceral tissues. An example isangina resulting from myocardial ischemia.

Neuropathic pain is a result of aberrant somatosensory activity either in the peripheralnervous system or the central nervous system (CNS). It is frequently characterized by

paroxysmal shooting or electrical shocklike pains, often on a background of burning orconstricting sensation. Examples of neuropathic pain encountered in the orofacial regioninclude trigeminal neuralgia and postherpetic neuralgia.

Pain may also be characterized as acute or chronic. Acute pain frequently has a knowncause, usually subsides as healing takes place, and has a predictable endpoint. Acute pain isassociated with anxiety and the physiologic "flight or fight" responses of increased pulse andrespiratory rate. Chronic pain is of greater than 3 to 6 months duration. Patients with chronicpain do not usually manifest the physiologic arousal seen with acute pain because the bodyhas adapted to the pain state. However, they may exhibit reactive depression and decreasedfunction.

Pain Assessment

Pain is a complex, subjective response with several quantifiable features, including intensity,time course, quality, impact, and personal meaning. The reporting of pain is a socialtransaction between caregiver and patient. Therefore, successful assessment and control ofpostoperative pain depends in part on establishing a positive relationship between healthcare providers, patients, and (when appropriate) their families. Studies have shown that thepatients provided with information related to physiological coping (instruction in coughing,deep breathing, turning, and ambulation) reported less pain, were given fewer analgesics

postoperatively and had shorter lengths of stay.

Patients should be informed that pain relief is an important part of their health care. Pain is asubjective phenomenon. As such, the care provider must accept that the patient's self-reportis the single most accurate and reliable indicator of the existence and intensity of pain andany resultant distress. This orientation is reflected in a commonly cited definition of pain: Painis whatever the experiencing person says it is and exists whenever he says it does. Self-report measurement tools such as adjective or numerical rating scales or visual analoguescales can assist the patient in quantifying and characterizing the pain.


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In practical use, the visual analog scale is always presented graphically, usually with a 10-cmbaseline and endpoint adjective descriptors. Patients place a mark on the line at a point thatbest represents their pain. The visual analog scale is scored by measuring the distance ofpatient's mark from the zero. For example, numerical rating scales are sometimes presentedverbally, and adjective rating scales are presented as a list of pain descriptors. In a graphic

format, scoring of the numerical and adjective rating scales may be the same as thatdescribed above for the visual analog scale, or they can be scored as numeric integers.

For each of these scales the clinician should request the patient's self-report, not only withthe patient at rest but also during routine activity such as coughing, deep breathing, ormoving (e.g., turning in bed). Complaints of pain must be heeded. The patient should beobserved for behaviors that often indicate pain, such as splinting the operative site, distortedposture, impaired mobility, insomnia, anxiety, attention seeking, and depression. Patientawareness of pain and the ability to control pain are important components of painassessment. If pain behavior is observed or if the patient expresses feelings of inadequatecontrol, a member of the health care team should discuss these with the patient and share

this information with other members of the team. The pain management plan should then berevised as needed.

The clinician should document the patient's preferred tool for pain assessment and the goalfor postoperative pain control as expressed by a score on a pain scale in the patient's chartas part of the pain history. Simply to record patient responses to the questions "how is yourpain?" invites misunderstanding or denial and hinders quantification. Pain should beassessed and documented: 1) preoperatively; 2) routinely at regular intervals postoperatively,as determined by the operation and severity of the pain (e.g., every 2 hours while awake for 1day after surgery); 3) with each new report of pain; and 4) at a suitable interval after eachanalgesic intervention (e.g., 30 minutes after parenteral drug therapy and 1 hour after oralanalgesics). Most important, the team should evaluate immediately each instance ofunexpected intense pain, particularly if sudden or associated with oliguria or altered vitalsigns such as hypotension, tachycardia, or fever, and consider new diagnoses such aswound dehiscence, infection, or deep venous thrombosis.

Occasionally, apparent discrepancies between behaviors and a patient's self-report of painmay occur. For example, patients may describe pain as an 8 out of 10 on a pain scale whilesmiling and walking freely or as 2 out of 10 while tachycardic, splinting, and sweating.Discrepancies between behavior and a patient's self-report may result from excellent copingskills. The patient who uses distraction and relaxation techniques may engage in diversionary

activities while still experiencing severe pain. Patients may deny severe pain for a variety ofreasons, including fear of inadequate pain control or perception that stoicism is expected orrewarded. Similarly, patients managed with as-needed analgesia may perceive thatmedication will be given only if the pain score is very high. Patients who perceive staff asinattentive to their concerns may use pain as a way to get help for other reasons.

When discussing pain assessment and control with patients, members of the health careteam should emphasize the importance of a factual report, thereby avoiding both stoicismand exaggeration. Patients with anxiety or other concerns should rate their mood andemotional distress separately from their pain by using similar scales. When discrepanciesbetween behaviors and self-report of pain occur, clinicians should address these differences

with the patient. The team and the patient should then renegotiate the pain managementplan.


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Patients unable to communicate effectively with staff require special consideration for painassessment, e.g., neonates and children, developmentally delayed persons, psychoticpatients, patient with dementia, and non-English speaking patients. Children and cognitivelyimpaired patients require simpler or modified pain measurement scales and assessmentapproaches. The staff should work with both the patient and parent or guardian pre- and

postoperatively. Staff should endeavor to find a translator for the non-English speakingpatient, at least once, to determine a convenient way to assess pain. Members of the healthcare team should attend to the preferences and needs of patients whose education orcultural tradition may impede effective communication. Certain cultures have strong beliefsabout pain and its management, and these patients may hesitate to complain aboutunrelieved pain. Such beliefs and preferences should be determined and respected, if at allpossible.

Misconceptions About Pain and Analgesics

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 provides.

Misconception 1- Patients who are in pain always have observable signs. Although manypatients in acute pain exhibit evidence of anxiety, distress, decreased function, many do not.Such overt pain behaviors also may not be seen at all in patients attempting to adapt to, andcope with, persistent pain. It is important to remember that, to treat the pain effectively, theclinician must first believe the patient's complaint of pain.

Misconception 2- Obvious pathology, test results, and/or the type of surgery determine theexistence and the intensity of pain. Although the ability to identify a pathologic processunderlying a patient's pain complaint is a key element in planning and initiating definitivetreatment, failure to identify the source of a patient's pain does not necessarily mean that itdoes not exist.

Misconceptions 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 untreatedoften escalates. Without treatment, sensory input from injured tissue reaches spinal cordneurons and causes subsequent responses to be enhanced. Pain receptors in the peripheryalso become more sensitive after injury. Studies have demonstrated long-lasting changes incells within the spinal cord pain pathways after brief painful stimuli. These physiologic studiesconfirm long-standing clinical impressions that established pain is more difficult to suppress.

Aggressive pain prevention and control that occurs before, during, and after a painful eventsuch as dental surgery can yield both short- and long-term benefits. Prevention of pain oftenrequires a lower analgesic dose than does treatment. This lower dose can also result indecreased side effects. Patients should be encouraged to use analgesics before painbecomes severe and difficult to control.

Pharmacologic Management

Pharmacologic management of mild to moderate postoperative pain should begin unlessthere is a contraindication with an NSAID. Moderately severe to severe pain normally shouldbe treated initially with an opioid analgesic. After many relatively noninvasive surgical

procedure, NSAIDs alone can achieve excellent pain control.


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NSAIDs decrease levels of inflammatory mediators generated at the site of tissue injury.Even when insufficient alone to control pain, NSAIDs have a significant opioid dose-sparingeffect upon postoperative pain and can be useful in reducing opioid side effects. Theconcurrent use of opioids and NSAIDs often provides more effective analgesia than either ofthe drug classes alone. Although it is likely that NSAIDs also act within the central nervous

system, in contrast to opioids they do not cause sedation or respiratory depression, nor dothey interfere with bowel or bladder function. Acetaminophen does not affect plateletaggregation, nor does it provide peripheral antiinflammatory activity. Some evidence existsthat two salicylates do not affect platelet aggregation profoundly; these are salsalate andcholine magnesium trisalicylate. All other NSAIDs appear to produce a risk of plateletdysfunction that may impair blood clotting and carry a small risk of gastrointestinal bleeding.

Opioid analgesics are the cornerstone of pharmacological postoperative pain management,especially for more extensive surgical procedures that cause moderate to severe pain. Otheragents such as NSAIDs or single injections of local anesthetics may control mild to moderatepain after relatively minor procedures or reduce opioid dose requirements after more

extensive operations when this is a goal. Even in the absence of preemptive efforts targetedat postoperative analgesia adequate postoperative pain control can usually be achieved withopioid analgesics. When increasing doses of opioids are ineffective in controllingpostoperative pain a prompt search for residual pathology is indicated and other diagnosessuch as neuropathic pain should be considered.

Opioid tolerance or physiological dependence is unusual in short-term postoperative use inopioid naive patients. Likewise, psychologic dependence and addiction are extremely unlikelyto develop after patients without prior drug abuse histories use opioids for acute pain. Properuse of opioids involves selecting a particular drug and route of administration and judging: 1)suitable initial dose; 2) frequency of administration; 3) optimal doses of nonopioid analgesics,if these are also to be given; 4) incidence and severity of side effects; and 5) whether theanalgesic will be given in an inpatient or ambulatory setting. Titration to achieve the desiredtherapeutic effect in the immediate postoperative period and to maintain that effect over timeshould be emphasized.

Mechanics of Action

Opioids produce analgesia by binding to opioid receptors both within and outside the centralnervous system. Opioid analgesics are classified as full agonists, partial agonists, or mixedagonist-antagonists depending on the manner in which they interact with opioid receptors.

Full agonists produce a maximal response within the cells to which they bind; partial agonistsproduce a lesser response, regardless of their concentration; and mixed agonist-antagonistsactivate one type of opioid receptor while simultaneously blocking another type.

Several types and subtypes of such receptors exist. The most important receptor type forclinical analgesia is named "mu" because of its affinity for morphine. Other commonly usedmu opioid agonists include hydromorphone, codeine, oxycodone and hydrocodone,methadone, levorphanol, and fentanyl. All mu opioid agonists have the potential to causeconstipation, urinary retention, sedation, and respiratory depression and frequently alsoproduce nausea or confusion. Mixed agonist antagonists in clinical use include pentazocine[Talwin], butorphanol tartrate [Stadol], and nalbuphine hydrochloride [Nubain]; each of these

blocks is neutral at the mu opioid receptor while simultaneously activating a different type ofopioid receptor termed "kappa.' Patients receiving mu opioid agonists should not be given a


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mixed agonist-antagonist because doing so may precipitate a withdrawal syndrome andincrease pain. Mixed agonist-antagonists and partial agonists may exhibit a ceiling effect notonly with respect to respiratory depression but also in regard to their analgesic activity. In theawake patient, there is a clinical ceiling analgesic effect even with morphine because sideeffects such as respiratory depression limit the dose that may be safely given. However, this

does not limit the ability of clinicians to effectively increase the drug dose when the painfulstimulus increases and respiratory status is monitored.

Meperidine [Demerol], a mu opioid analgesic, is commonly used for postoperative paincontrol. Meperidine is commonly underdosed and administered too infrequently even byphysicians aware of its pharmacokinetics. The common postoperative meperidine order of 75mg parenterally every 4 hours as needed often is inadequate for several reasons. Meperidineproduces clinical analgesia for only 2.5-3.5 hours, and a dose of 75 mg every 4 hours isequivalent to only 5-7.5 mg of morphine. Therefore, to obtain postoperative analgesia equalto that from 10 mg of morphine sulfate every 4 hours, a clinician would have to use 100-150mg of meperidine every 3 hours.

Because of its unique toxicity, meperidine is often contraindicated in patients with impairedrenal function and those receiving antidepressants of the monamine oxidase inhibitor class.Normeperidine (6-N-desmethylmeperidine) is a toxic meperidine metabolite excreted throughthe kidney. In patients with normal renal function, normeperidine has a half-life of 15 to 20hours; this time is extended greatly in elderly individuals and patients with impaired renalfunction. Normeperidine is a cerebral irritant that can cause effects ranging from dysphoriaand irritable mood to convulsions. These effects have been observed even in young,otherwise healthy patients given sufficiently high doses of normeperidine postoperatively.Therefore, meperidine should be reserved for very brief courses in otherwise healthy patientswho have demonstrated an unusual reaction (e.g., local histamine release at the infusionsite) or allergic response during treatment with other opioids such as morphine orhydromorphone.

Dosage and Frequency

Titration of opioids should be based on the patient's analgesic response and side effects.Remember that patients vary greatly in their analgesic dose requirements and responses toopioid analgesics. Relative potency estimates provide a rational basis for selecting theappropriate starting dose to initiate analgesic therapy, changing the route of administration(e.g., from parenteral to oral), or when switching to another opioid. Dosage conversion

factors based on relative potency estimates may differ somewhat between individual patients.When estimating the initial postoperative dose of an opioid analgesic, a clinician shouldconsider whether patients have been receiving opioid analgesics preoperatively. In suchpatients, supplemental postoperative doses should be adjusted above the preoperativebaseline requirement unless the operation itself is likely to remove the painful stimulus.

An "as-needed" order for opioid administration can result in prolonged delays while the nurseunlocks the controlled substances cabinet and prepares the drug for administration and untilthe drug takes effect. These delays can be eliminated by administering analgesics on aregular time schedule initially. For example, if the patient is likely to have pain requiring opioidanalgesics for 48 hours following surgery, morphine could be ordered every 4 hours by the

clock (not "as needed") for 36 hours. Once the duration of analgesic action is determined fora patient, the dosage frequency should be adjusted to prevent pain from recurring.


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Depending on patient preferences, the orders may be written so that the patient can refusean analgesic if not in pain or forego it if asleep. However, as in dosing with other drugs thatrequire a steady blood level to remain effective, interruption of an around-the-clock dosageschedule during the hours of sleep may cause the patient to be suddenly awakened byintense pain as blood analgesic levels decline.

It may be acceptable late in the postoperative course to give the same drug every 4 hours asrequested. Switching from an around-the-clock to an as-needed dosage schedule later in thepatient's course is one way to provide pain relief while minimizing the risk of adverse effectsas the patient's analgesic dose requirement diminishes. As part of this schedule, a patient'spain should be assessed at regular intervals to determine the efficacy of the drugintervention, the presence of side effects, or the need for dosage adjustment or supplementaldoses for breakthrough pain. Effective use of opioid analgesics should facilitate routinepostoperative activitiese.g., coughing and deep breathing exercises, ambulation, andphysical therapy. The opioid should be withheld if the patient is sedated when awake orwhenever there is respiratory depression (usually fewer than 10 breaths per minute).

Routes of Administration

Opioids may be administered by a variety of routes; oral dosing is usually the mostconvenient and least expensive route of administration. It is appropriate as soon as thepatient can tolerate oral intake and is the mainstay of pain management in the ambulatorysurgical population.

Preoperative intravenous or epidural access may be appropriate for postoperativemanagement of severe pain, even when the oral route is available. Relatively few side effectswill occur ordinarily, providing that these modalities are carefully managed by clinicians withappropriate expertise. Using potent analgesics or invasive techniques postoperatively, at atime when the patient's level of consciousness and physical function are returning to normal,requires careful titration and patient assessment.

Drug dosage, frequency, side effects, and risks differ even more noticeably between theintravenous and epidural routes than between the oral and intravenous routes. Clinicians notfamiliar with epidural opioid doses and pharmacokinetics must review the literature carefullybefore using that route. In addition, side effects (e.g., confusion, respiratory depression,hypotension, urinary retention, or pruritus) associated with opioids can be greater withintravenous and epidural administration and require ongoing assessment and monitoring.

Other potential problems that dictate expert vigilance and follow-up during epidural analgesiainclude abscess development or anesthesia of a nerve root at the site of catheter tip. Theseroutes of administration are best limited to specially trained staff who are knowledgeable andskilled in the management of patients receiving intravenous or epidural opioids typicallyunder the direction of an acute or postoperative pain treatment service.

Patient controlled analgesia is a safe method for postoperative pain management that manypatients prefer to intermittent injections. Systemic PCA usually connotes intravenous drugadministration, but it also can be subcutaneous or intramuscular. Few studies of the use ofPCA drug delivery to the epidural space exist. A typical intravenous PCA prescriptionapplicable to many contexts relies on a series of "loading" doses: for example, 3-5 mg of

morphine, repeated every 5 minutes until the initial postoperative pain (if present) diminishes.A low-dose basal infusion (0.5-1 mg/hr) at night allows uninterrupted sleep. On-demand


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doses typically add l mg of morphine every 6 minutes, with a total hourly limit of 10 mg. Oncethe patient is able to take oral medications, an around-the-clock schedule of an oral opioidsuch as a codeine-acetaminophen combination is provided, and the basal infusion rate isdiscontinued. By observing the number of "on-demand" doses self-administered by thepatient, the clinician can assess the adequacy of the oral medication and titrate it further,

change to a stronger compound such as oxycodone with acetaminophen, or discontinue thePCA pump.

Intravenous administration is the preferred route for postoperative opioid therapy when thepatient cannot take oral medications. When intravenous access is problematic, sublingualand rectal routes should be considered as alternatives to traditional intramuscular orsubcutaneous injections. All routes other than intravenous require a lag time for absorption ofthe drug into the circulation. In addition, repeated injections with associated pain and traumamay deter some patients, especially children, from requesting pain medication. Continuousadministration of low doses of opioids intravenously or transdermally and intermittent deliveryacross the buccal mucosa are relatively new but apparently effective methods to administer

opioids postoperatively. Further experience is needed to define the clinical roles of theseinnovative methods in relation to more well-established methods.

Opioids and local anesthetic agents interact favorably. Continuous administration into theepidural space of low concentrations of opioids in dilute solutions of local anesthetic providesexcellent analgesia, while reducing the potential risks (e.g., respiratory depression or motorblock) associated with equianalgesic concentrations of either agent administered singly. In aless technologically demanding approach, systemically administered opioids given pre-,intra-, or postoperatively augment the duration and effectiveness of local anesthetics givenspinally or epidurally. Local anesthetics alone may be applied intermittently to specific nervesto interrupt pain pathways. For example, injecting local anesthetics around the intercostalnerves after thoracotomy significantly improves pulmonary function. Catheters for continuousor repeated intermittent dosing of local anesthetic also have been employed postoperativelyin the pleural space or adjacent to nerves such as the brachial plexus or cervical sympatheticganglia. However, a clinical role for interpleural or perineural local anesthetics in thepostoperative setting has not yet been defined.

Nonpharmacologic Management

Nonpharmacologic interventions can be classified as either cognitive-behavioral interventionsor physical agents. Cognitive and behaviorally based approaches include several ways to

help patients understand more about their pain and take an active part in its assessment andcontrol. The goals of interventions classified as cognitive-behavioral therapies are to changepatients' perceptions of pain, alter pain behavior, and provide patients with a greater sense ofcontrol over pain. The goals of interventions classified as physical agents or modalities are toprovide comfort, correct physical dysfunction, alter physiological responses and reduce fearsassociated with pain-related immobility or activity restriction. Nonpharmacologic approachesare intended to supplement, not substitute for, the pharmacologic or invasive techniquesdescribed above.

Nonpharmacologic interventions are appropriate for the patient who: 1) finds suchinterventions appealing; 2) expresses anxiety or fear, as long as the anxiety is not

incapacitating or due to a medical or psychiatric condition that has a more specific treatment;3) may benefit from avoiding or reducing drug therapy (e.g., history of adverse reactions, fear


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of or physiological reason to avoid over sedation); 4) is likely to experience and need to copewith a prolonged interval of postoperative pain, particularly if punctuated by recurrentepisodes of intense treatment- or procedure-related pain; or 5) has incomplete pain relieffollowing appropriate pharmacologic interventions. Cognitive-behavioral approaches includepreparatory information, simple relaxation, imagery, hypnosis, and biofeedback. Physical

therapeutic agents and modalities include application of superficial heat or cold, massage,exercise, immobility, and electroanalgesia such as TENS therapy.

Giving a patient a detailed description of all medical procedures, expected postoperativediscomfort, and instruction aimed at decreasing treatment- and mobility-related pain candecrease self-reported pain, analgesic use, and postoperative length of stay. Patients shouldreceive sufficient procedural and sensory information to satisfy their interest and enable themto assess, evaluate, and communicate postoperative pain. In addition, all preoperativepatients should receive instruction emphasizing the importance of coughing, deep breathing,turning, and walking, along with suggestions on how to decrease physical discomforts fromsuch activities. When fear or anxiety occur, it is important to assess psychological coping

skills and provide practical suggestions for managing pain and maintaining a positive outlook.Patients who appear anxious or fearful before surgery, and others who express an interest incognitive-behavioral strategies, should be assisted in selecting an intervention (e.g., simplerelaxation or imagery) and taught how to use it. In some patients, particularly those with highlevels of anxiety, too much information, or too many demanding decisions can exacerbatefear and pain. Psychiatric evaluation is appropriate for patients who manifest disabling ordisruptive anxiety symptoms such as emotional instability, restlessness, inability to sleep, anddulled thinking.

Relaxation is the most widely evaluated cognitive-behavioral approach to postoperative painmanagement. Relaxation strategies, including simple relaxation, imagery, hypnosis,biofeedback, and music-assisted relaxation have all shown some degree of effectiveness inreducing pain. Relaxation strategies and imagery techniques need not be complex to beeffective. Relatively simple approaches such as the brief jaw relaxation have been successfulin decreasing self-reported pain and analgesic use. These strategies take only a few minutesto teach but require periodic reinforcement through encouragement and coaching. Supportivefamily members or audiotapes often can sustain patient skills. A relaxation strategy that canbe used informally is music distraction. Both patients' personally preferred music and "easylistening" music have significantly decreased postoperative pain in clinical studies. Patientswho need repeated coaching may benefit from the use of a commercially prepared relaxationor music-assisted relaxation audiotape.

Other cognitive-behavioral strategies require greater professional involvement; these includecomplex imagery, hypnosis, biofeedback, and combined therapies. Such strategies arecommonly applied when patients have chronic pain even before surgery.

Examples of Nonpharmacologic Interventions for Postoperative Pain

Cognitive-Behavioral Physical Agents

education/instruction

application of heat or coldrelaxation massage, exercise, and immobilization


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imagery transcutaneous electrical nerve stimulation

music distraction

biofeedback

Although some data suggest that the use of complex imagery may reduce pain, thatbiofeedback may lessen pain and operative site muscle tension, and that interventions whichcombine imagery and relaxation may decrease pain, each requires specialized training and,for biofeedback, the use of special equipment. Findings from studies of hypnosis for controlof postoperative pain are inconsistent. Insufficient research to demonstrate effectiveness inreducing postoperative pain and the need for special training or equipment preclude therecommendation of complex imagery biofeedback, or hypnosis for routine postoperative paincontrol. This is not to say that patients who have a high level of preoperative anxiety, whosepain is severe and enduring, or who suffer recurrent episodes of procedure-related pain willnot benefit from these strategies. However, for such patients a more comprehensive painmanagement program must include active involvement of professionals skilled in cognitive-

behavioral therapy and psychological assessment.

In addition to cognitive-behavioral interventions, several physical therapeutic methods can beused to manage pain. Commonly used physical agents include applications of heat and coldmassage, exercise, and rest or immobilization. Applications of heat or cold are used to alterpain threshold, reduce muscle spasm, and decrease congestion in an injured area.Applications of cold are used initially to decrease tissue injury response. Later, heat is usedto facilitate clearance of tissue toxins and accumulated fluids. Massage and exercise areused to stretch and regain muscle and tendon length. Immobilization is used following manymusculoskeletal procedures to provide rest and maintain the alignment necessary for proper

healing. With the exception of applications of cold and immobilization, these interventionstypically are not used following surgery unless complications occur or an extendedpostoperative course is expected. When physical modalities are used, it is often for aphysiological goal other than pain relief. Of these modalities only cryotherapy (application ofcold) has been evaluated in the literature. There is insufficient evidence to suggest thatcryotherapy alone is effective in reducing postoperative pain. Cryotherapy is different fromcryoanalgesia (application of a cryoprobe to specific peripheral nerves), which has proveneffective for post-thoracotomy pain

TENS therapy is one physical modality for which there is some support. TENS therapy hasbeen effective in reducing self-reported pain and analgesic use following abdominal surgery,

orthopedic surgery, thoracic surgery, mixed surgical procedures, and cesarean section.TENS therapy also has improved physical mobility following thoracic and orthopedic surgery.Both TENS therapy and sham TENS therapy (that is, application of electrodes withouttransmission of electric current) significantly reduced analgesic use and subjective reports ofpain. No significant differences were found between TENS therapy and sham-TENS. Eventhough these findings suggest a placebo effect underlies the reduction of perceived pain andanalgesic use during TENS therapy, beneficial effects do, in fact, result. The physicalmodalities of acupuncture and electroacupuncture also have been clinically evaluated inpostoperative patients, with conflicting findings; no clear analgesic effect has beendemonstrated.

How each patient's postoperative pain management program is designed and implementedwill vary according to the type of medical facility and services available to support a pain


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management program. At the least, clinicians should be introduced to these methods so theyrecognize the benefits of cognitive-behavioral and physical interventions, know theindications for their use, and are able to provide information and counseling to patients. Inaddition, patients should have access to written information about available therapies, whyand when to use them, and sources for self-management materials or professional

consultations.

Catastrophic postoperative events are rarely, if ever, masked by any of the approaches topostoperative pain control previously described. Any sudden or unexplained change in painintensity requires immediate evaluation by the surgeon. Likewise, a sudden increase inanxiety may signal cardiac or pulmonary decompensation and requires prompt medical orsurgical assessment.

Dental Surgery

The most common forms of dental surgery are brief and relatively noninvasive procedures

often performed on an outpatient basis. A patient's anxiety is frequently disproportionate tothe safety of the procedure; such a patient may benefit from behavioral or pharmacologic(anxiolytic) therapy. Mild pain associated with most forms of uncomplicated dental care suchas simple tooth extractions, endodontic therapy, or scaling of the periodontal area or of apreviously asymptomatic tooth is well managed by oral administration of an NSAID such asaspirin or ibuprofen. Preoperative administration of ibuprofen appears to delay the onset ofpostoperative pain and lessen its severity. For patients unable to tolerate aspirin or ibuprofen,acetaminophen can provide an acceptable analgesic effect.

Dental procedures such as surgical removal of bony impactions and osseous periodontalsurgery are more traumatic and typically produce intense and prolonged postoperative pain.The onset of such pain can be delayed by preoperative treatment with ibuprofen and/orapplication of a long-acting local anesthetic such as bupivacaine during the procedure.

Rarely, an intravascular or intraneural injection of local anesthetic in this context leads tobruising, bleeding, or systemic symptoms such as fainting, allergic reaction, or persistent paindue to direct nerve injury. When postoperative pain

does emerge, it often requires the addition of an opioid to the nonsteroidal regimen. Codeineis frequently prescribed at a dosage of 30-60 mg every 4-6 hours. Increased analgesiabutalso an increased number of opioid side effects such as nausea, constipation, sedation, and

respiratory depressionfollow dosage increases above this level. Alternative opioids includepropoxyphene or oxycodone administered in doses that are equainalgesic to 30-60 mg ofcodeine.

Some operations on the oral cavity preclude the patient's taking oral medicationspostoperatively (e.g., wiring the mouth closed after an operation on a mandibular fracture).Alternative therapy should be based on the severity of the surgical procedure and expectedpain associated with it, as well as the surroundings in which it will be managed. Formulationsof NSAIDs such as rectal suppositories (indomethacin) or intramuscular injection (ketorolac)are now commonly available. Opioids may be administered by a variety of routes(intravenous, intramuscular, subcutaneous injection, transdermal, rectal) and schedules,

including a patient controlled schedule. Cost-efficacy analyses of parenteral opioidadministration for oral surgery are not sufficient to permit any clear recommendations. Pain


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that does not respond to these measures should prompt a search for infection, osteitis,peripheral nerve injury, or the emergence of psychological and behavioral changesconsistent with the development of chronic pain syndrome.

Analgesics for Pain Management

ANALGESICS

Pain Control

Pain, as defined by the International Association for the Study of Pain, is "an unpleasantsensory 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 tissuetrauma and release potent mediators of inflammation and pain. We now know that unrelievedpain after surgery or trauma has negative physical and psychologic consequences.

The two components of pain are perception and reaction. Perception is the physicalcomponent of pain and involves the message of pain that is carried through the nerveseventually to the cortex. Reaction is the psychological component of pain and involves thepatient's emotional response to the pain. Although individuals are surprisingly uniform in theirperception 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 raisedby 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 thatpostoperative pain is often inadequately treated because of undermedication, leavingpatients to suffer needlessly.

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

A significant barrier to the effective use of analgesics in managing pain involves severalmisconceptions regarding pain and its control held by both patients and health careproviders.


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Misconception 1- Patients who are in pain always have observable signs. Although manypatients in acute pain exhibit evidence of anxiety, distress, or decreased function, many donot.

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 processunderlying a patient's pain complaint is a key element in planning and initiating definitivetreatment, failure to identify the source of a patient's pain does not necessarily mean than itdoes 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 untreatedoften escalates. Without treatment, sensory input from injured tissue reaches spinal cordneutrons and causes subsequent responses to be enhanced. Aggressive pain preventionand control that occurs before, during, and after a painful event such as dental surgery canyield 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 injuryor inflammation, and it resolves spontaneously once the underlying cause (inflamed pulp,abscessed tooth, carious lesion) is definitively treated. Few underlying psychologic orbehavioral issues affect the dentist's choice of therapies, and, most commonly, apharmacologic approach to pain management is most appropriate.

In contrast, management of chronic facial pain involves much more complex treatmentissues. Chronic pain often lasts months or years beyond the precipitating event, and there israrely 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 ofmanaging these disorders.

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

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

Analgesic Agents

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


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Another difference between the opioids and the nonopioid analgesic agents is theirmechanism of action. The action of the nonopioid analgesic agents is related to their ability toinhibit 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 theperiphery by preventing the synthesis and release of inflammatory mediators that sensitizenoninceptive receptors to other algesic mediators, such as bradykinin, and to physical forces.Recent studies suggest that NSAIDs may also have central effects. Acetaminophen has beenshown to have analgesic and antipyretic properties, but it lacks significant antiinflammatoryeffects. 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 drugsthat have a similar mechanism of action and share clinically important analgesic,

antiinflammatory, and antipyretic properties. These analgesics are widely prescribed bydentists and physicians because they can be taken orally, they do not cause central nervoussystem (CNS) or respiratory depression at therapeutic doses (as do the centrally actingopioid analgesics), and, most important, they are very effective pain relievers.

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

Nonopioid Analgesics

This category comprises various groups of drugs that have a similar mechanism of actionand share clinically important analgesic, antiinflammatory, and antipyretic properties. Theseagents differ from opioid analgesics in the following ways: (1) there is a ceiling effect to theanalgesia; (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 foracetaminophen, which has minimal antiinflammatory activity. Pharmacologic management of

mild to moderate pain should begin, unless there is a contraindication, with a nonopioid drugsuch as acetaminophen, a salicylate, or another NSAID. As a general rule, any analgesicregimen should include a nonopioid drug, even if pain is severe enough to require theaddition of an opioid.

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

subsequent analgesics requirements.


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The NSAIDs all share a qualitatively similar side-effect profile. However, with the exception ofa true allergic reaction and the bronchoconstriction response in asthmatics, a patient'sinability to tolerate one specific NSAID does not mean the patient will be intolerant of all otherNSAIDs. 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 youngchildren or patients with intermaxillary fixation following maxillofacial surgery or trauma, areunable to swallow tablets or capsules. For these patients, liquid formulations ofacetaminophen or ibuprofen should be considered. For the rare dental patient who is unableto 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, andthe 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 itsantiinflammatory action, a primary objective in dental pain relief. The prostaglandins areimportant vasodilating agents that also increase capillary permeability. Therefore, aspirincauses 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 peripherallyacting analgesics could claim greater efficacy.

Aspirin belongs to the salicylic acid (salicylate) class of compounds that were originallyobtained from botanical sources. The first active substance of this group, salicin, was isolatedfrom the bark of the willow tree. From salicin were synthesized salicylic acid, sodiumsalicylate, 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 inhibitsthe enzyme cyclooxygenase (prostaglandin synthase) by acetylating a serine, which results

in inhibition of the production of prostaglandins. A reduction in prostaglandins results in a


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reduction in painful perception. Many dental patients are advised to take aspirin before thepainful stimuli is experienced, such as a "throbbing" pain caused by inflammation.

The antipyretic properties of aspirin are well documented. Antipyresis is best demonstrated infebrile 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 vastmajority of painful conditions have an inflammatory component. There is little doubt that thecascade of reactions leading to the formation of prostaglandins is integrally involved with theinflammatory response and that aspirin's efficacy in treating inflammation is closely related toits 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 itspeak 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 moreerratic and unpredictable it should only be used when the oral route is not feasible. An aspirintablet should never be applied topically to the oral mucosa to treat a toothache. A painfululceration can occur.

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

Aspirin has been reported to have three kinds of adverse effects on the gastrointestinalsystem. The first is gastric distress. There is evidence suggesting that both local andsystemic mechanisms interfere with the ability of gastric mucosal cells to resist penetration byacid. Aspirin's interference with normal cytoprotective mechanisms mediated byprostaglandins in gastric mucosal cells is a primary cause of the gastric distress. A secondeffect of aspirin is occult gastric bleeding, resulting from cellular and capillary damage alongthe gastrointestinal tract. The third effect, which is very rare and idiosyncratic, is a suddenacute 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. Thisprotracted inhibition of platelet aggregation correlates with the ability of aspirin to irreversiblyacetylate cyclooxygenase. Platelets lack the ability to regenerate this enzyme, and thesynthesis 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 havedemonstrated that 650 mg of aspirin is substantially more effective than 60 mg of codeine inrelieving 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 reliefthan 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 1000mg may slightly increase analgesic efficacy and prolong the duration of effect. Clinically, this


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potassium replacement if necessary), maintenance of plasma pH, and alkalinization of theurine 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 highas 20%. Patients with a history of asthma, allergic disorders, or nasal polyps should bequestioned to be sure that they can tolerate aspirin.

Aspirin is contraindicated in a number of medical conditions. Serious internal bleeding canresult 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 thirdtrimester, aspirin tends to prolong labor by inhibiting the synthesis of prostaglandins involvedin 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 areepidemiologic data indicating that aspirin usage during or shortly after these viral diseasesincreases 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 allergicreaction

DiabetesHigh doses may cause hyperglycemia orhypoglycemia

GoutLow doses increase plasma urate; high doseslower 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 fewinstances in which clinically significant side effects occur, and, if reasonable precautions aretaken to avoid aspirin when its use is contraindicated, the drug is an extremely effective andsafe analgesic.

Acetaminophen

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


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

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 thoseof aspirin. At therapeutic doses, acetaminophen has little, if any, effect on the cardiovascularor respiratory systems. Acetaminophen does not inhibit platelet aggregation, cause occultbleeding or gastric irritation, affect uric acid excretion, or have as many drug interactions asaspirin. 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 ofdentists 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 afterthe 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 analgesiaup to 1000 mg. Based on this finding, some clinicians are recommending the use of 1000 mgof acetaminophen rather than the customary 650 mg dose.

The potential for adverse effects from acetaminophen seems to be singularly confined to thesituation in which there is an acute overdose. At therapeutic doses, acetaminophen does notcause nausea, inhibit platelet aggregation, prolong prothrombin time, or produce the otherside effects associated with the use of aspirin. Allergy to acetaminophen is rare and isgenerally manifested as skin eruptions.

Analgesic Alternatives to Aspirin and Acetaminophen

Until the late 1970s, no single-entity oral analgesic had consistently demonstrated grateranalgesic efficacy than that of aspirin or acetaminophen. Several new peripherally actinganalgesics, most of which had earlier been approved for use as antiinflammatory drugs, havenow been evaluated in postoperative dental pain and found to be superior to the standarddrugs 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 asanalgesics. Others, such as flurbiprofen, are currently under review by the Food and DrugAdministration (FDA).

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

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 rapidlyabsorbed from the gastrointestinal tract and may be preferred form for analgesic use. The


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recommended analgesic regimen for naproxen is 500 mg initially, followed by 250 mg every 6to 8 hours. Its longer half-life allows dosing at longer intervals than with ibuprofen.

Fenoprofen is marketed with both analgesic and antiinflammatory indications. Therecommended 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 thoseproduced by aspirin; however, they may vary in severity. Gastric irritation (nausea andabdominal pain) is usually the most troublesome adverse effect. Dizziness, gastrointestinalbleeding, fluid retention, and nephrotoxicity have also been reported. Inhibition of plateletaggregation is transient and reversible.

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

Opioid Analgesics

Opioid analgesics are primarily employed for the relief of pain and consequently findwidespread 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 attimes unwanted constipation. Repeated use of opioids for control of pain can lead toanalgesic tolerance (loss of analgesic effect), as well as physical and sometimes psychologicdependence. These shortcomings notwithstanding, no other drugs are more efficacious asanalgesics than the opioids.

Opioid analgesics are added to nonopioids to manage pain that is moderate to severe or thatdoes not respond to nonopioids alone. Opioids differ from the nonopioids in that they have noceiling effect. The only dosing limitation is based on side effects. Although opioids are thecornerstone for management of moderate to severe acute pain, they are frequentlyunderutilized and at lower than effective doses as a result of misconceptions and fearsregarding their use.

Fear of possible sedation or respiratory depression causes some practitioners tounderprescribe and underdose opioids. These adverse events rarely occur when appropriatestarting 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 andresponses to opioid analgesics.

Fear of addiction on the part of both the practitioner and the patient is a common barrier tothe effective use of opioid analgesics. For many, this fear is the result of not being aware ofthe actual risks associated with opioid analgesics used for the treatment of pain and ofconfusing addiction with physical dependence, tolerance, or pseudoaddiction. Addictionrefers topsychologic 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 functionin society. Physical dependence, on the other hand, is a pharmacologic property causing theappearance 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


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drug to achieve the same effect. Finally,pseudoaddiction is a term used to describeexaggerated behaviors seen in pain patients brought on by inadequate pain relief.

Physical dependence and tolerance are involuntary mechanisms that occur in virtually allpatients 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 untiladequate pain relief is reobtained. The effects of physical dependence are easily avoided bythe gradual tapering of opioids on discontinuation of therapy, as opposed to abruptwithdrawal. Addiction, by contrast, is a voluntary mechanism that rarely occurs in patientstaking opioid analgesics for pain. The overwhelming majority of patients taking painmedication stop taking the medication when the pain stops.

Opioid analgesics include both pure agonists, such as codeine and oxycodone, andagonist/antagonists, such as pentazocine and butorphanol. As a general rule, theagonist/antagonists should not be used as first-line therapy. There is no convincing evidencethat 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 withdrawalsymptoms when given to patients physically dependent on opioid agonists. On occasion, theymay be useful in treating individuals unable to tolerate other opioids.

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

NSAIDs alone can achieve excellent pain control. Pain that does not respond adequately tononopioid agents should be treated with the combination of a nonopioid and an opioid suchas 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, shouldbe treated with a combination of a nonopioid and a stronger opioid, such as morphine orhydromorphone. At any level, adjuvant agents such as certain anticonvulsants or tricyclicantidepressants may be added when indicated. Common indications in dentistry include thetreatment of neuropathic pain and some chronic orofacial pain conditions.

The oral administration of opioid analgesics is preferred whenever possible. It is convenientand 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 oraladministration of most opioids (sustained-release tablets excepted). Therefore, patients maytake a second opioid dose safely 2 hours after the first dose if the pain persists and sideeffects are mild at that time. For patients unable to take medications by mouth, theintravenous, intramuscular, or rectal routes of administration can be considered. Use of theintravenous or intramuscular route to deliver analgesics is almost exclusively limited toinpatient 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.


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As mentioned previously, opioids should almost always be administered with nonopioids formaximum pain relief in dental situations. Many opioids are marketed in combinations with anonopioid, and it is the latter component that limits the dose. For example, the upper doselimit for acetaminophen is 4000 mg/day. Therefore, for combinations containing 325 mg ofacetominophen, 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 ofadministration.

The CNS effects of morphine are a combination of stimulation and depression and includeanalgesia, drowsiness, euphoria-dysphoria, respiratory depression, suppression of the coughreflex and pupillary constriction.

The analgesia produced by morphine and its congeners occurs without loss ofconsciousness. 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 withoutalleviation of the cause of the pain (or cough or diarrhea). The analgesia produced by opioidanalgesics is dose dependent and selective in that other sensory modalities (e.g., vision,audition) are unaffected at therapeutic doses. The standard parenteral analgesic dose ofmorphine, 10 mg/70 kg body weight, is considered a therapeutic dose for relief to severepain. Greater doses provide greater pain control.

An additional significant feature of opioid analgesics is that they are generally more effectiveagainst 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 alsoknown that sensitivity to pain and the ability to clear morphine decrease with age, whereasthe elimination half-life of morphine does the opposite; thus, the pain relief provided bymorphine 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 beadministered over time to produce an effect equivalent to that produced on initialadministration. 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 respiratorydepression but not, to any appreciable extent, to opioid effects on the gastrointestinal tract orthe pupil.

In the therapeutic setting, the initial indication that tolerance has developed is generallyreflected in a shortened duration or reduced analgesic effect. The rate at which tolerancedevelops 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 theinterval between doses, the more rapid is the development of tolerance. Tolerance, in fact,


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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 byrespiratory 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 stateproduced by repeated administration of a drug, which then makes its continued usenecessary to prevent the appearance of a withdrawal or abstinence syndrome. The greaterthe opioid dose and the longer the duration of administration, the greater is the degree ofphysical dependence and the more intense is the withdrawal syndrome.

Psychologic dependence is more difficult to define and measure. Psychologic dependencecontributes more to drug-seeking behavior than does physical dependence. Addiction is theextreme of compulsive drug use and is associated with significant psychologic dependence,and thus, it is inappropriate to identify as "addicted" a person who becomes physicallydependent after repeated opioid administration during hospitalization. All three phenomena-

tolerance, physical dependence, and psychologic dependence- are reversible, althoughpsychologic dependence provides a strong drive to drug abuse.

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

Pain is the main complaint that initiates a visit to a dentist or physician. Moreover, pain isalmost always present after invasive procedures or surgery. Morphine and other opioidanalgesics are the most efficacious analgesic drugs known and are without peer in theirability to control pain. As emphasized earlier, these drugs provide only symptomatic relief ofpain without influencing its underlying cause. The opioids, when administered at therapeuticdoses to produce analgesia, also produce a drowsiness from which the patient is generallyeasily aroused, as well as "tranquillization." There is without doubt a significant antianxiety orsedating 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 ofdesirable 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 itsrespiratory depressant and sedative effects) are central in origin. Codeine is frequentlyclassified as a "weak" or "mild" opioid analgesic. That codeine is a mild analgesic incapableof 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 bothdrugs 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 thepresent time, however, doses of codeine in excess of 60 mg (orally) are not commonly used


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and, moreover, are not officially recognized as generally safe and effective by the Food andDrug Administration. Consequently, the impression remains that codeine has limitedanalgesic 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 betreated with codeine alone because neither codeine nor any of the other opioids hasantiinflammatory properties. Rather, aspirin or another nonsteroidal antiinflammatory drugalone or in combination with codeine is appropriate for cases of dental pain involving orarising from inflammation.

Principles of Opioid Analgesic Use

Analgesics should be administered initially on a regular time schedule. For example, if thepatient is likely to have pain requiring analgesics for 48 hours after dental surgery, analgesicsmight 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 lessbreakthrough pain. If only prn medications are used, it may take several hours and higherdoses to relieve pain, leading to a cycle of undermedication and pain alternating with periodsof overmedication and drug toxicity. Later in the postoperative course, as the patient'sanalgesic 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 damagingeffect on hepatic, renal, or hematologic tissues but rather are an extension of theirpharmacologic effects. Like the pharmacologic effects, the adverse reactions of the opioidanalgesics are proportional to their analgesic strength.

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

2. Nausea and emesis. Analgesic doses of opioid analgesics often produce nausea andvomiting. 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 itsduration outlasts their analgesic effect. Even with continued administrations tolerance doesnot 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 therelease 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


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There is a sound scientific basis for combining peripherally acting analgesics with opioids.The peripherally acting drugs combat pain principally by directly interfering with thebiochemical mediators that cause sensitization of nerve endings at the site of injury, whereasthe opioids alter CNS perception and reaction to pain. The mechanisms of pain relief of thesetwo 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, abundantclinical data exists to support the validity of their combined use. However, there is a commonmisconception that such combinations produce a synergistic phenomenon, that is, an effectgreater than the sum of effects expected from both drugs. No evidence currently supportsthis belief, and, at best, there is purely additive effect when drugs from these two classes ofanalgesics are combined. Indeed, if any synergism does exist, it is probably with the toxiceffects rather than with analgesic efficacy.

The clinical significance of the centrally acting analgesics is that they provide additionalanalgesia beyond the ceiling effect of the peripherally acting component, and they alsocontribute a centrally mediated sedative effect. Therefore, the most effective combinations

are those that use the optimal amount of an aspirinlike drug combined with the appropriatedose of an opioid analgesic.

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

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

The advent of the NSAIAs has produced a dramatic decrease in the use of the opioids indental practice. Most dental pain can be better managed by the use of NSAIAs. In the patientin whom NSAIAs are contraindicated, the dentist has a wide range of opioids from which tochoose. By beginning with codeine or hydrocodone combinations and progressing tooxycodone combination, almost all dental pain can be managed. Only in rare cases, and forvery 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 nonopioidcategories. Different patients vary greatly in their response to, and ability to tolerate, differentagents. For this reason, it is important to be familiar with the recommended dose, side-effectprofile, and time course of several agents in each category.

Patient should be followed closely, particularly when beginning or changing analgesicregimens. Analgesics are more beneficial if the clinician monitors pain relief and adverseeffects frequently and adjusts the regimen as needed to optimize therapy. This monitoring isparticularly important when using an agent or combination with which the doctor has little or

no experience or when changing from one analgesic to another.


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

analgesics for pain management

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