I feel your pain

Non-opioid analgesics useful in the treatment of dental pain include the nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen) and acetaminophen (Tylenol).

by Thomas A. Viola, RPH, CCP

"Yo, what's up, Cuz?"

The voice bellowed from about twenty feet away, tearing through the momentary quiet in our pharmacy like a rock through a plate glass window.

"What can I do for you?" I bellowed back, hoping he would realize that we could converse much more efficiently at closer range and would hold his questions until I was able to join him in the aisle.

"Yo, which one's better, Advil or Relieve?" he said, even louder than before. I surmised then that this was his preferred method of communication.

"Between Advil and Aleve?" I countered.

"Yeah, that's what I said," he yelled, sounding annoyed. "Which one's better?"

"For what?" I asked, matching his tone.

"You always answer a question with a question?" he screamed as he approached the pharmacy counter.

I wanted to fire back, "You mean, like you just did?" But, I caught a glimpse of myself in the mirrored sunglasses perched precariously atop his hat and decided to rein it in. Besides, that response would have been ... you guessed it … yet another question.

"Tell me what kind of pain you're having," I said more softly.

"I got a toothache," he said, still a little too loudly, "and I'm goin' to the game."

He certainly looked the part, dressed from head to toe in every possible form of clothing adorned with the logo of our adopted home team. If anyone would bleed green, I was certain it would be him.

"Ain't nothin' that a few beers with my buddies won't fix, but you know…" he added.

Just as I started to answer, he interrupted and said, "I guess it don't matter. None of these work like the good stuff, right?"

Non-opioid analgesics useful in the treatment of dental pain include the nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen) and acetaminophen (Tylenol). Many patients believe that, since these agents are available without a prescription, they are inferior in their ability to relieve dental pain when compared to the opioid analgesics (such as hydrocodone and oxycodone). However, many studies have concluded that the opposite is true. At regular doses, non-opioid analgesics are as effective as opioid analgesics in relieving dental pain, without the potential for producing serious adverse reactions (such as respiratory depression) and without the potential for dependence and addiction.

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Other articles by Viola

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NSAIDs are similar to aspirin in their antipyretic (fever-reducing), analgesic (pain relieving), and anti-inflammatory activity. These effects are seen in order of increasing dose. For example, ibuprofen has a relatively low maximum dose for its analgesic effect. While doses of up to 400 mg are effective for treating cases of mild to moderate dental pain, higher doses provide no further true analgesic effect. Yet, ibuprofen is still effective for treating cases of moderate to severe dental pain at higher doses, up to 600 mg to 800 mg. How? At these higher doses, ibuprofen also produces its anti-inflammatory effect, and almost all cases of moderate to severe dental pain involve some degree of inflammation.

NSAIDs inhibit the formation of an enzyme, cyclooxygenase-2 (COX-II). This enzyme is responsible for the production of prostaglandins which, in turn, produce pain, fever, and inflammation. Thus, by inhibiting COX-II, NSAIDs produce their therapeutic antipyretic, analgesic, and anti-inflammatory effects. However, NSAIDs also inhibit the formation of another enzyme, cyclooxygenase-1 (COX-I). This enzyme is responsible for the production of prostaglandins which, in turn, produce numerous beneficial effects, such as the production of the gastrointestinal mucous lining, regulation of normal platelet activity, bronchodilation, and maintenance of adequate blood flow to the kidneys. Thus, by inhibiting COX-I, NSAIDs also produce adverse effects such as gastrointestinal upset and mucosal injury, irregular platelet aggregation, bronchospasm, and renal toxicity, especially with long-term use.

NSAIDs produce gastrointestinal mucosal injury through local effects (erosion of the mucosal lining as a result of direct contact with the dosage form after it is swallowed) as well as through systemic effects (as demonstrated when erosion also occurs when the same dose is administered intravenously). This risk may be increased in patients taking selective serotonin reuptake inhibitor (SSRI) antidepressants. The tendency of NSAIDs to produce gastrointestinal adverse effects has spurred the investigation of celecoxib (Celebrex) as a suitable substitute in the treatment of dental pain and has even spawned an effort to make celecoxib available without a prescription.

Celecoxib is classified as a selective COX-II inhibitor, since it inhibits COX-II to a greater extent than COX-I. In theory, this should confer greater therapeutic analgesic, antipyretic, and anti-inflammatory effects and also minimize adverse effects, such as gastrointestinal upset. However, studies have shown that, although celecoxib does produce fewer gastrointestinal adverse effects than traditional NSAIDs with short-term use, this effect is diminished with long-term use. Nevertheless, since NSAIDs are indicated for short-term use in the treatment of dental pain, celecoxib might still seem to have an advantage over traditional NSAIDs in this regard. However, studies have demonstrated that celecoxib is less effective than either ibuprofen or naproxen as an analgesic for dental pain.

When to avoid NSAIDs

Long-term use of NSAIDs should also be avoided in patients with hypertension and congestive heart failure. NSAIDs may produce sodium and water retention, which may exacerbate these conditions. In addition, NSAIDs decrease the production of prostaglandins necessary for adequate renal perfusion and function, which is often compromised in patients with cardiovascular disease. This is usually not a concern in the short-term use of NSAIDs, such as in the treatment of dental pain, except in patients with documented renal dysfunction.

NSAIDs reduce the production of a specific prostaglandin, thromboxane A2, which normally causes platelet aggregation. Thus, NSAIDs have antiplatelet effects. This has given rise to speculation that NSAIDs might also be useful in the prevention of thrombotic events, such as heart attacks and strokes. However, the antiplatelet effects of NSAIDs are reversible and are lost when the drug is cleared from the body. Only aspirin has been proven effective in preventing such thrombotic events, since its antiplatelet effects are irreversible and persist for the life of the platelet, long after aspirin has been cleared from the body. Although NSAIDs may cause an increased risk of bleeding due to their antiplatelet effects, this is usually not a concern for patients undergoing minor dental surgical procedures.

The use of NSAIDs should be avoided in patients taking antiplatelet agents (such as Plavix and Effient) and anticoagulant agents (such as Coumadin and Pradaxa). This is not due to the antiplatelet effects of NSAIDs but, rather, their propensity for causing gastrointestinal mucosal injury, which may result in a greater risk of internal bleeding in patients taking these antithrombotic agents. Interestingly, aspirin is often prescribed in combination with these antithrombotic drugs since it exerts its antiplatelet effects at doses low enough to avoid gastrointestinal side effects. Once again, the tendency of NSAIDs to produce these gastrointestinal side effects has spurred the investigation of celecoxib as a suitable substitute in patients taking antithrombotic drugs. However, studies have shown that selective inhibition of COX-II may result in increased platelet aggregation and an increased risk of serious thrombotic events.

Ironically, recent studies have shown that ibuprofen competitively inhibits the cardioprotective antiplatelet effects of low-dose aspirin when both agents are used together. However, since aspirin exerts its antiplatelet effects immediately after absorption, this interaction can be avoided by delaying the administration of ibuprofen by two hours until after the aspirin has been absorbed. The use of ibuprofen and other NSAIDs should be avoided in patients taking lithium and methotrexate, since NSAIDs may increase the blood levels of both drugs and produce serious adverse effects.

NSAIDs decrease the production of prostaglandins necessary for maintaining proper fetal circulation during pregnancy and for uterine contraction during delivery. Their use should be avoided during pregnancy, especially during the third trimester. NSAIDs may increase the production of leukotrienes. These inflammatory substances may produce a variety of symptoms of allergic response, including bronchospasm. Thus, it might be advisable to avoid the use of NSAIDs in patients with severe respiratory disease.

While the question is obviously quite common, there is no definitive evidence to support the conclusion that one NSAID is superior to another in its ability to relieve dental pain. However, there is considerable evidence to support the conclusion that the preoperative use of NSAIDs decreases the intensity of postoperative dental pain. This prophylactic dosing of NSAIDs to prevent future pain is further enhanced by the addition of acetaminophen. Several studies have demonstrated that the combination of acetaminophen and an NSAID was more effective in the prophylaxis and treatment of dental pain than either acetaminophen or the NSAID alone. Although there is, as yet, no nonprescription analgesic product that combines acetaminophen with an NSAID, there is considerable evidence that such a combination would offer superior analgesia. Acetaminophen and NSAIDs have similar, but different, mechanisms of action, and a combination of the two ingredients would offer a synergistic approach to pain relief.

As he stood there weighing his options, I imagined him at the game, surrounded by his buddies, as he attempted to converse with the players on the field from where he was seated in the stands. I couldn't help but wonder if I should also mention the proven efficacy of NSAIDs in relieving headaches. RDH

THOMAS A. VIOLA, RPH, CCP, In addition to his daily practice of the profession of pharmacy, Thomas A. Viola, RPh, CCP, also serves the professions of dentistry, dental hygiene, and dental assisting as an educator, published writer, and professional speaker. As an educator, Viola is a member of the faculty of seven dental hygiene and dental assisting programs, as well as several national board exam review courses. Visit Viola's website: www.tomviola.com.

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