Pain management: Part 1: Managing acute and postoperative dental pain

Abstract

Safe and effective management of acute dental pain can be accomplished with nonopioid and opioid analgesics. To formulate regimens properly, it is essential to appreciate basic pharmacological principles and appropriate dosage strategies for each of the available analgesic classes. This article will review the basic pharmacology of analgesic drug classes, including their relative efficacy for dental pain, and will suggest appropriate regimens based on pain intensity. Management of chronic pain will be addressed in the second part of this series.

Figure 1

Synthesis and function of prostanoids. Perturbation of cell membranes can be mediated by diverse endogenous and exogenous stimuli. This triggers activity of phospholipase A₂, releasing arachidonic acid from the phospholipids making up the membrane. Two families of cyclooxygenases (COX-1 and COX-2) convert this fatty acid to a variety of so-called prostanoids that are unique to the particular cell or tissue and include prostaglandins, thromboxanes, and prostacyclin. Each of these prostanoids has specific physiological functions, some of which are listed in the table within this figure. Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective and inhibit both COX-1 and COX-2 families. Celecoxib (Celebrex) is representative of agents that selectively inhibit COX-2; it reduces pain and inflammation with little or no influence on gastric mucosa. However, this selective inhibition may promote greater synthesis of prostanoids derived from COX-1, including thromboxane-mediated effects leading to possible thrombotic events (eg, myocardial infarction, stroke). Arachidonic acid is also a substrate for lipoxygenase that catalyzes the formation of leukotrienes known for their anaphylactoid effects, including bronchospasm and upper airway edema. As NSAIDs inhibit the activity of cyclooxygenases, a greater portion of arachidonic acid can be converted to leukotrienes by lipoxygenase. This may not be tolerated by patients with atopy because they experience pseudoallergic syndromes.

Figure 2

Analgesic efficacy. This graph illustrates a typical dose-response curve for orally administered (PO) analgesics. The dose-response curve for opioids such as morphine demonstrates unlimited efficacy in which greater doses provide greater analgesia. At equipotent doses, all opioids demonstrate a similar dose response. In contrast, nonopioids demonstrate a “ceiling” effect that generally is adequate for relief of mild to moderate pain (pain relief rating of 4–5 in this scale). For ibuprofen, doses greater than 400 mg do not provide further analgesia. For aspirin (ASA) and acetaminophen (APAP), this ceiling effect is achieved at 1000 mg and is somewhat lower than that provided by nonsteroidal anti-inflammatory drugs (NSAIDs).

Figure 3

Molecular structures of morphine, codeine, and derivatives. The top row illustrates molecular structures for morphine and its two derivatives, hydromorphone and oxymorphone. The subtle changes indicated by the asterisks enhance affinity for the opioid receptors, which accounts for greater potency. The bottom row illustrates codeine and its derivatives, which differ from their morphine-derived counterparts only in a methyl substitution (circled). Approximately 60% of an oral dose of codeine-related products is absorbed and may be subjected to varying degrees of demethylation by CYP2D6 to its active metabolite. Framed molecules are those credited with the analgesic effect provided by various codeine-related products. Codeine has little affinity for opioid receptors. Roughly 10% of an absorbed dose is demethylated to morphine, which is credited with its analgesic effect. Hydrocodone and oxycodone have good receptor affinity and provide an analgesic effect. The analgesic effect of hydrocodone is credited to both the parent drug and its active metabolite, hydromorphone, but analgesia provided by oxycodone is almost entirely the result of the parent drug. Very little is demethylated to oxymorphone.

Figure 4

NSAID versus opioid analgesia. The following data were derived from patients who underwent third molar impaction surgery. See text for explanation. (Ibu 400  =  ibuprofen 400 mg; Oxy 5  =  oxycodone 5 mg)