Analgesics and Acute Pain Management

Kathleen Ziegler, PharmD

Overview

Pain management is an integral part of dental practice. There are two main types of pain: nociceptive, which is treated with nonopioid and opioid analgesics; or neuropathic, which is treated with adjunctive agents such as anticonvulsant and antidepressant medications. This chapter will focus on oral nonopioid and opioid analgesics. These conventional analgesics either interrupt ascending nociceptive impulses or depress their communication within the central nervous system.

Depending on the dental intervention performed, acute postprocedural pain can be anticipated to be mild, moderate, or severe (Table 1).

In 2016, the ADA House of Delegates adopted a statement on the use of opioids in the treatment of dental pain, which stated, “Dentists should consider nonsteroidal anti-inflammatory analgesics as the first-line therapy for acute pain management.”

Table 1. Anticipated postprocedural pain according to dental intervention
Intervention	Anticipated Postprocedural Pain
Frenectomy Gingivectomy Routine endodontics Scaling/root planing Simple extraction Subgingival restorative procedures	Mild
Implant surgery Quadrant periodontal flap surgery with bony recontouring Surgical endodontics Surgical extraction	Moderate
Complex implant Partial or full bony impaction surgery Periodontal surgery	Severe

1 | Strategy for Dental Pain Management

If pain is anticipated to last 24 to 48 hours following the procedure, patients are advised to take the prescribed medication on a regularly scheduled basis for the 1st two days to prevent pain recurrence when plasma drug levels fall off between doses. The remainder of the medication can be taken “as needed” (i.e., prn) for breakthrough pain.

One algorithm for management of various levels of dental pain was developed by Moore and Hersh. Using the anticipated pain level following a dental procedure, they recommended a stepwise management plan (Table 2).

Other therapeutic strategies include administration of NSAIDs 1 hour prior to the procedure and use of longer-acting local anesthetics (e.g., bupivacaine 0.5% with 1:200,000 epinephrine) during the immediate postoperative period. Also, perioperative administration of a corticosteroid (e.g., dexamethasone) may limit inflammation and decrease pain following third-molar extractions (See Chapter 8: Oral Lesions and Corticosteroids).

Table 2. Analgesic Use According to Pain Level
Anticipated Pain Level	Analgesic Recommendation
Mild	Single-agent ibuprofen 200 to 400 mg as needed
Mild to Moderate	Single-agent ibuprofen 400 to 600 mg fixed interval every 6 hours for 24 hours then Single-agent ibuprofen 400 mg as needed for pain every 4 to 6 hours
Moderate to Severe	Ibuprofen 400 to 600 mg plus acetaminophen 500 mg fixed interval every 6 hours for 24 hours then Ibuprofen 400 mg plus acetaminophen 500 mg as needed for pain every 6 hours
Severe	Ibuprofen 400 to 600 mg plus acetaminophen 650 mg with hydrocodone 10 mg fixed interval every 6 hours for 24 to 48 hours then Ibuprofen 400 to 600 mg plus acetaminophen 500 mg as needed for pain every 6 hours

Adapted from: Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice. J Am Dent Assoc 2013;144(8):898-908.

2 | Nonopioid Analgesics

The nonopioid analgesics include acetaminophen, aspirin and other NSAIDs. The maximum analgesic effect of acetaminophen or aspirin usually occurs with single doses between 650 and 1300 mg. For NSAIDs other than aspirin, the analgesic ceiling may be somewhat higher. One advantage is that tolerance does not develop to the analgesic effects of these drugs.

The anti-inflammatory and analgesic properties of NSAIDs, as well as most of their adverse effects, result from their inhibition of cyclooxygenase (COX), which is a key enzyme in the production of postoperative pain and inflammation due to its ability to convert arachidonic acid to prostaglandins. Prostaglandins are mediators of inflammation, fever, and pain. Aspirin inactivates COX by irreversible acetylation, whereas the newer NSAIDs are reversible competitive inhibitors of COX. Most NSAIDs bind weakly and reversibly to platelet COX, interfering with platelet aggregation only until the drug is cleared from the system; however, because aspirin irreversibly binds platelet COX, platelet function is permanently affected for the life of the platelet (8 to 10 days). Prostaglandins also have a role in GI mucosal protection and play an essential role in renal perfusion; this accounts for the potential of NSAIDs to cause gastrointestinal complications (i.e., bleeding) and nephrotoxicity, respectively.

The mechanism of action of acetaminophen is less clear compared with NSAIDs; however, it is thought to involve inhibition of prostaglandin synthesis within the central nervous system.

3 | Opioid Analgesics

Opioid analgesics can be categorized as full agonists, partial agonists, or mixed agonist/antagonists. Full agonists are generally used for treatment of moderate-to-severe acute or chronic pain. Unlike NSAIDs, most opioids have no ceiling for their analgesic effectiveness, except that imposed by development of adverse effects.

The precise mechanism of the analgesic action of opioids is unknown. However, specific central nervous system opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of these drugs.

Risks of these drugs include nausea and vomiting, drowsiness, respiratory depression, potential addiction, abuse, and misuse.

| Suggested Reading

• American Dental Association. Statement on the Use of Opioids in the Treatment of Dental Pain. 2016. https://www.ada.org/en/press-room/news-releases/2018-archives/february/american-dental-association-statement-on-opioids. Accessed August 3, 2018.

• Becker DE. Pain management: Part 1: Managing acute and postoperative dental pain. Anesth Prog 2010;57(2):67-78.

• Ganzberg S, Fricton J. Analgesics: Opioids and Nonopioids. In: ADA/PDR Guide to Dental Therapeutics, Ciancio SG, editor. 5th ed. Chicago: American Dental Association and Physician’s Desk Reference, Inc., pp 63-133, 2009.

• Hersh EV, Kane WT, O’Neil MG, et al. Prescribing recommendations for the treatment of acute pain in dentistry. Compend Contin Educ Dent 2011;32(3):22, 24-30.

• Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice. J Am Dent Assoc 2013;144(8):898-908.

• Drugs for pain. Treat Guidel Med Lett 2013;11(128):31-42.

Drug Monograph

The following table lists some of the opioids and non-opioids analgesics commonly used in dentistry. The monographs below highlight a 4 days prescription, however, prescribers are encouraged to use their clinical judgment; the length of treatment might vary depending on the procedure performed and the patient’s anticipated level of pain.

NOTE: The sample prescriptions in this handbook represent a general recommendation. Clinicians are responsible to adjust the prescription dose, frequency and length of treatment based on the procedure performed, the medicine prescribed, and the patient conditions such as age, weight, metabolism, liver and renal function.

Non-Opioids list:

Acetaminophen

Tablets: 325 mg, 500 mg, 650 mg · Chewable tablets: 80 mg, 160 mg Liquid: 32 mg/mL, 100 mg/mL

	• Dental pain management
	• Take 2 tablets (2x 325 mg) every 6 hours for 4 days as needed (32 tablets) maximum dose 4,000 mg/day manufacturers recommend 3,000 mg/day
BLACK BOX WARNING – Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death especially at doses that exceed 4,000 mg per day, and often involving more than one acetaminophen-containing product.
	• Active and severe hepatic disease •Hypersensitivity to acetaminophen •Severe hepatic impairment
	• Recent alcohol consumption increases risk of hepatic injury
	• Concurrent use of acetaminophen and isoniazid may result in an increased risk of hepatotoxicity • Concurrent use of acetaminophen and imatinib may result in increased acetaminophen levels • Concurrent use of acetaminophen and warfarin may result in an increased risk of bleeding
	Common Reactions: • Pruritus • Constipation, nausea, vomiting • Headache, insomnia • Agitation • Atelectasis	Less common reactions: • Generalized, acute exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis • Liver failure • Pneumonitis
	• Pregnancy Category C • Lactation: amounts of acetaminophen secreted in milk are much less than doses usually given to infants • Elderly patients: no specific dosage adjustment is necessary • Renal failure: severe renal impairment (CrCl of 30 mL/min or less) increases risk of hepatic injury; dose reductions may be required • Hepatic disease: active hepatic disease or hepatic impairment increases risk of hepatic injury; dose reductions may be required • Recommend patient to keep hydrated and well-nourished while on medication to avoid hepatic injury
	• Peak serum time: 0.5 to 1 hr • Half-life: 2 to 3 hours (adults) • Extensively metabolized in the liver • Excretion: less than 5% excreted unchanged in urine