Pain control is of great importance in dental practice. Pain often brings the patient to the dental office. Conversely, pain can be the factor that keeps the patient from seeking dental care at the appropriate time. Thus dental treatment is often rendered on inflamed, hypersensitive tissues of a patient who suffers from mental fatigue after enduring pain for a length of time.
The dental hygienist must be able to recognize and evaluate a patient’s need for medication to control pain. Because pain is such a complex phenomenon, the entire patient must be considered before the type of medication that may be needed is determined.
The sensation of pain is the means by which the body is made urgently aware of the presence of tissue damage. Pain represents a protective reflex for self-preservation. Just as the hand is quickly removed from a hot object, a painful dental abscess brings the patient to the dental office seeking professional assistance for its resolution. Pain is a diagnostic symptom of an underlying pathologic condition. Although the relief of pain is an immediate objective, only by treatment of the underlying cause is the ultimate resolution achieved.
The two components of pain are perception and reaction. Perception, the physical component of pain, involves the message of pain that is carried through the nerves eventually to the cortex. Reaction, the psychological component of pain, 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 said to be associated with emotional instability, anxiety, fatigue, youth, certain nationalities, female gender, and fear and apprehension. The pain threshold is raised by sleep, sympathy, activities, and analgesics (Figure 5-1). As a result, analgesic therapy must be selected for the individual. A level of discomfort that may not require drug treatment in one person may demand extreme therapy in another. Although some patients undergoing routine exodontia require no postoperative medication, even the strongest analgesics do not completely control postoperative extraction pain in others.
The analgesic agents can be divided into two groups, the nonopioids, also called nonnarcotic analgesics, and the opioids, also called narcotic analgesics.
An important difference between the nonopioid and the opioid analgesics (narcotic analgesics) is their sites of action. Nonopioid analgesics act primarily at the peripheral nerve endings, although their antipyretic effect is mediated centrally. Opioids act primarily within the central nervous system (CNS).
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 (Figure 5-2). The opioids affect the response to pain by depressing the CNS (the reaction). The side effect profiles of the two groups also differ.
The nonopioids can be divided into the salicylates (aspirin-like group), acetaminophen, and the nonsteroidal antiinflammatory drugs (NSAIDs) (Box 5-1). Aspirin, a member of the salicylates, is discussed first.
Since antiquity, extracts of willow bark containing salicin have been used to reduce fever. Over the years, many other salicylates (sa-LI-si-lates) have been synthesized, but aspirin is the most useful salicylate for analgesia. Box 5-2 lists some analgesic and some topical salicylates. Because aspirin is the prototype salicylate, it is discussed.
Acetylsalicylic acid (aspirin, ASA) is broken down into acetic acid (HA) and salicylic acid (SA) (Figure 5-3). Acetic acid imparts the characteristic vinegar odor to a bottle of aspirin. Therefore the degree of breakdown of aspirin can be roughly determined by smelling a bottle of aspirin tablets. (If one thinks “phew” when opening an aspirin bottle, it is time to purchase a new bottle.) In addition, salicylic acid is a strong keratolytic agent (used to remove plantar warts from the bottom of feet) and may cause additional adverse gastrointestinal effects if degraded aspirin is administered orally.
The mechanism of aspirin’s analgesic, antipyretic, antiinflammatory, and antiplatelet effects is related to its ability to inhibit prostaglandin synthesis. Aspirin inhibits the enzyme cyclo-oxygenase (COX I and COX II, prostaglandin synthase) by acetylating serine, which results in inhibition of the production of prostaglandins. Figure 5-4 shows the synthesis of the prostaglandins and leukotrienes from arachidonic acid. Prostaglandins, which are lipids that are synthesized locally by inflammatory stimuli, can sensitize the pain receptors to substances such as bradykinin. Prostaglandins can also lower the pain threshold to painful stimuli, cause inflammation and fever, and affect vascular tone and permeability, resulting in edema.
Therefore a reduction in prostaglandins results in a reduction in pain. Because aspirin blocks the synthesis of prostaglandins by nonselectively blocking cyclooxygenase, it is more effective if given before the painful stimuli are experienced. Because of this mechanism, aspirin is more effective against “throbbing” pain (caused by inflammation and common in dentistry) than against “stabbing” pain (direct effect on nerve endings).
Aspirin is rapidly and almost completely absorbed from the stomach and small intestine, producing its peak effect on an empty stomach in 30 minutes (90 minutes for salicylate). The buffered tablet reaches its peak in about 20 minutes (salicylate). Before a tablet of aspirin can be absorbed, it must be dispersed and dissolved. Addition of a buffer to the tablet facilitates this process. This facilitation is borne out by the somewhat quicker peak of action and higher blood levels attained with buffered aspirin preparations. Buffered aspirin has a higher proportion of the aspirin in the ionized form, which should make absorption slower, but this is offset by the increase in the rate of dissolution, which is facilitated. This difference in absorption has not been shown to translate into a clinically significant quicker effect.
Aspirin is widely distributed into most body tissues and fluids. It is poorly bound to plasma proteins. It is hydrolyzed to salicylate in the mucosa of the gastrointestinal tract and on first pass through the liver. The half-life of unhydrolyzed aspirin is about 15 minutes. The half-life of hydrolyzed aspirin is dose-dependent. With small doses, the half-life is 2-3 hours; with higher doses, a half-life of 15-30 hours can be attained. The half-life varies with the dose because a constant amount rather than a constant percentage of the drug is metabolized per hour. This type of metabolism is called zero-order kinetics (see Chapter 2).
Aspirin’s analgesic effect has been repeatedly demonstrated in many clinical trials. In fact, new drugs are often compared in analgesic strength to aspirin. Aspirin typically relieves mild-to-moderate pain such as arthritis, headache or toothache. Aspirin’s effects by dose are illustrated in Figure 5-5.
Because of its easy accessibility and long history of use, aspirin’s worth as an analgesic is often unrecognized by the lay public.
The ability of aspirin to reduce fever (antipyretic effect) results from its inhibition of prostaglandin synthesis in the hypothalamus. Hypothalamic prostaglandin synthesis is caused by elevated blood values of leukocyte pyrogens induced by inflammation. Increased hypothalamic prostaglandin levels produce higher body temperature. Therefore the inhibition of hypothalamic prostaglandin synthesis results in a return to more normal body temperature. Aspirin reduces fever by inducing peripheral vasodilation and sweating. Although it reduces an elevated temperature, it has no effect on normal body temperature. In fact, in toxic doses aspirin causes hyperthermia (see the section on Adverse Reactions).
Aspirin’s antiinflammatory effect is derived from its ability to inhibit prostaglandin synthesis (COX I and COX II). The prostaglandins are potent vasodilating agents that also increase capillary permeability. Therefore aspirin causes decreased erythema and swelling of the inflamed area. This antiinflammatory action is useful in dental patients because inflammation is a significant part of most dental pain. Patients with arthritis may be given large doses of aspirin to provide symptomatic relief of pain and inflammation in the joints.
Although large doses (greater than 3 g/day) of aspirin can produce a uricosuric effect, small doses (less than 1 g/day) produce uric acid retention. Aspirin can also counteract the uricosuric effect of probenecid (proe-BEN-e-sid) (Benemid), which is used to treat gout. Aspirin is no longer used as a uricosuric agent because more effective agents are available to treat gout.
Aspirin irreversibly binds to platelets. Its antiplatelet effect has been shown to be clinically effective for secondary myocardial infarction prevention in adults, the primary prevention of coronary artery disease, and the treatment of an ischemic event or the prevention of a further ischemic event. The effect of aspirin on platelets depends on the dose taken. Depending on the dose, aspirin can inhibit either prostacyclin (inhibits platelet aggregation) or thromboxane A2 (stimulates platelet aggregation). Figure 5-6 demonstrates that inhibition of thromboxane A2 would prevent clotting because thromboxane A2 promotes clotting. Further studies are needed to determine aspirin’s usefulness and dose in preventing clotting events in different patient populations.
In sufficiently high doses, aspirin can have a variety of undesirable effects. Some of aspirin’s side effects can be minimized but not eliminated. Precautions for and contraindications to the administration of aspirin are listed in Table 5-1.
Precautions for and Contraindications to the Administration of Aspirin
|Disease or Condition||Drug Used||Possible Effects of Aspirin|
|Myocardial infarction, atrial fibrillation, valve replacement||Warfarin (Coumadin)||Increases anticoagulant effect of warfarin|
|Peptic ulcer (heartburn), gastroesophageal reflux disease (GERD)||Histamine H2-blockers (e.g., cimetidine)||Gastric irritant effect|
|Gout||Probenecid (Benemid)||Antagonizes uricosuric effect of probenecid|
|Arthritis, cancer, psoriasis||Methotrexate (MTX)||Increases toxicity of methotrexate|
|Rheumatic fever, arthritis||Large doses of aspirin||Do not add more aspirin if patient is taking large doses already|
|Hemophilia||Factor VIII||Gastric bleeding|
|Vitamin K deficiency, alcoholism||Bleeding|
Aspirin’s most common side effect is related to the gastrointestinal tract. It may be simple dyspepsia, nausea, vomiting, or gastric bleeding. These adverse effects result from direct gastric irritation and inhibition of prostaglandins. Because prostaglandins are responsible for inhibition of gastric acid secretion and stimulation of the cytoprotective mucus in the stomach, aspirin counteracts these effects. In high doses, aspirin’s stimulation of the chemoreceptor trigger zone in the CNS can also produce nausea and vomiting. Salicylates may exacerbate preexisting ulcers, gastritis, or hiatal hernia.
At usual therapeutic doses, aspirin irreversibly interferes with the clotting mechanism by reducing platelet adhesiveness caused by interfering with adenosine diphosphate (ADP) release. The bleeding time is prolonged, and each platelet is affected until new platelets are formed (4-7 days). Replacement of all of the affected platelets is not required to produce normal clotting. After about 20% of the platelets have been replaced with newly formed platelets, clotting will return to normal by about 36 hours. Therefore with lower doses of aspirin, 1.5 days should be enough to obtain normal clotting. With large doses of aspirin, the half-life is prolonged. Aspirin inhibits the production of prothrombin, resulting in hypoprothrombinemia. Three other mechanisms—the local irritant effects on the stomach, the decrease in platelet stickiness, and the loss of protective mucosa—magnify adverse effects on the stomach. Salicylate-induced gastric bleeding is painless. With a small loss of blood, aspirin does not produce significant bleeding. Salicylates may exacerbate preexisting conditions such as ulcers, gastritis, hiatal hernia, and gastrointestinal esophageal reflux disease (GERD).
In children and adolescents with either chickenpox or influenza, the use of aspirin has been epidemiologically associated with Reye’s (pronounced “rize”) syndrome. In place of aspirin, acetaminophen is used in pediatrics for both its analgesic and its antipyretic actions. Reye’s syndrome is associated with hepatotoxicity and encephalopathy, commonly fatal.
Rarely, aspirin can produce hepatotoxicity. Renal papillary necrosis and interstitial nephritis leading to dialysis is associated with use of certain analgesics. It may be caused by the concomitant administration of aspirin and acetaminophen.
Although animal studies have shown that aspirin can cause birth defects, human studies have demonstrated only a slight positive correlation between long-term aspirin ingestion and congenital abnormalities. With aspirin abuse, increased risk of stillbirth, neonatal death, and decreased birth weight occur. With near-term, high-dose administration of aspirin, gestation can be prolonged, parturition delayed, and risk of hemorrhage in the newborn and mother increased. Even premature closure of the patent ductus arteriosus (hole in the fetal heart) has been reported. Although salicylates are excreted in the breast milk, usual occasional therapeutic doses of aspirin do not present a problem for the healthy nursing infant.
The incidence of true aspirin allergy is less than 1% (0.2-0.4%). Many patients with “allergy to aspirin” in their charts, on questioning, actually have stomach problems rather than true allergy. In the patient’s chart, it is important to differentiate aspirin’s adverse reactions from its hypersensitivity reactions. Adequate questioning of patients who “claim” to be allergic to aspirin is needed; patients with true aspirin hypersensitivity cannot be given any of the NSAIDs because of some cross-hypersensitivity. Allergic reactions can vary from rash, wheezing, urticaria, and angioneurotic edema to anaphylactic shock. When a true aspirin allergy exists, any aspirin-containing products or NSAIDs should be avoided.
Persons with asthma are more likely to have a hypersensitivity reaction to aspirin, with the incidence ranging from 5% to 15%. The aspirin hypersensitivity triad, consisting of aspirin hypersensitivity, asthma, and nasal polyps—often occur together. This reaction is thought to be the result of the shunting of the products of arachidonic acid from the production of prostaglandins to the leukotrienes and is thought to be a potential mechanism for this hypersensitivity. These patients exhibit cross-hypersensitivity involving aspirin and other agents, including the NSAIDs, and they should not be given any NSAIDs.
An overdose of aspirin can have harmful effects and even cause death.
When the blood level of salicylates reaches a certain point, a toxic reaction, referred to as salicylism, occurs. It is characterized by tinnitus (ringing in the ears), headache, nausea, vomiting, dizziness, and dimness of vision. Hyperthermia and electrolyte imbalance can also occur. With higher blood levels, stimulation of respiration leads to hyperventilation, which produces respiratory alkalosis. Compensatory alkalosis results in renal loss of bicarbonate, sodium, and potassium. Both respiratory acidosis and metabolic acidosis ensue. The cause of death from aspirin poisoning is usually acidosis and electrolyte imbalance.
Children are the primary victims of accidental poisoning. The lethal dose of aspirin for a child is 4 g, and the lethal dose of aspirin for an adult is 10-30 g. The education of parents regarding the potential for poisoning and proper storage and childproof containers for over-the-counter (OTC) aspirin have significantly reduced accidental poisonings in children.
Treatment of aspirin poisoning includes removing excess drug in the stomach by inducing emesis or administering activated charcoal to absorb the aspirin. Other symptoms are treated symptomatically. For example, hyperthermia is treated with cooling baths or “blankets,” acidosis with sodium bicarbonate, hypokalemia with potassium, and hypoglycemia with intravenous (IV) glucose. Box 5-3 lists the patient instructions for aspirin.