Understanding NSAIDs: essential knowledge for dentists

Dr. Lisa Chan and Barbara Madej, RPh, review the benefits and drawbacks of NSAID use in the dental practice

Introduction

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are a widely used class of medications that effectively manage pain, inflammation, and fever by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. In dental practice, NSAIDs play a crucial role in controlling pain and inflammation associated with common procedures such as extractions, root canals, and periodontal treatments. Their proven efficacy, accessibility, and non-opioid mechanism make them a preferred choice for both acute and chronic dental pain management.

The purpose of this article is to provide dental practitioners with comprehensive knowledge about NSAID use, including their mechanisms, benefits, risks, prescribing guidelines, and considerations for special populations, to ensure safe and effective pain management for patients.

How do NSAIDs work?

NSAIDs work by targeting enzymes in the body called cyclooxygenases (COX-1 and COX-2), which are essential for producing prostaglandins — hormone-like chemicals that promote inflammation, pain, and fever.

There are two main types of COX enzymes in the body: COX-1 and COX-2.¹ Both enzymes are responsible for making prostaglandins, but the effects of these prostaglandins differ based on their origin:

• COX-1 enzymes: These produce prostaglandins that help protect the stomach lining and intestinal tract from digestive acids, as well as thromboxane which regulates blood clotting. While COX-1 inhibitors block inflammation, they also interfere with these protective functions, potentially leading to side effects like stomach ulcers and bleeding.² A common COX-1 enzyme used in dental practices is indomethacin.
• COX-2 enzymes: These primarily produce prostaglandins involved in inflammation and pain. By selectively blocking COX-2, these NSAIDs can reduce inflammation effectively without significantly affecting the protective prostaglandins made by COX-1.^2,3 Celecoxib, etodolac, and meloxicam are common examples of COX-2 NSAIDs.
• Traditional NSAIDs (COX-1 & COX-2): These block both COX-1 and COX-2 enzymes. This dual action reduces inflammation and alleviates pain by decreasing the production of prostaglandins involved in these processes, while also affecting prostaglandins that regulate other bodily functions like stomach lining protection and blood clotting. Many NSAIDs block both COX-1 and COX-2, although one can be better than the other depending on the medication. Some traditional NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, ketorolac, ketoprofen, and nabumetone.

NSAID use in dentistry

NSAIDs are essential in dental pain management due to their effective dual action in alleviating pain and reducing inflammation.^4,5 Acetaminophen is often used in combination with NSAIDs because of its complementary action. While most NSAIDs exert their effects peripherally by reducing inflammation and pain at the site of tissue injury, acetaminophen works centrally, inhibiting prostaglandin synthesis in the central nervous system.6 This complementary action blocks pain signal transmission centrally while NSAIDs address inflammation locally, making their combined use highly effective in managing mild to moderate pain.⁶

Key applications

1. Postoperative pain and inflammation management: NSAIDs are widely used after dental procedures, such as extractions, root canals, and periodontal surgeries, to reduce pain and swelling, promoting faster recovery and enhancing patient outcomes.
2. Adjunctive use in inflammatory conditions: NSAIDs have shown potential as adjuncts to controlling inflammation in dental conditions like periodontitis.⁷ By targeting localized swelling and pain, they may complement conventional periodontal treatments and aid in managing discomfort. However, their use should be carefully weighed against potential risks, highlighting the need for a tailored approach in incorporating NSAIDs into dental care plans.
3. Non-opioid pain management alternative: In light of the opioid crisis, NSAIDs offer a safer, non-addictive alternative for pain management. This makes them particularly beneficial for patients at risk of dependency or those with a history of substance abuse.
4. Patient accessibility and compliance: NSAIDs are widely available both over-the-counter and by prescription, with various formulations (e.g., tablets, capsules, topical gels) that accommodate individual patient preferences. Their familiarity and convenience encourage adherence to pain management regimens, improving treatment outcomes.

Pharmacokinetics and pharmacodynamics

NSAIDs are well-absorbed after oral administration, typically reaching peak plasma concentrations within hours.⁹ Once in the bloodstream, they bind extensively to plasma proteins, primarily albumin, and are metabolized in the liver by enzymes like cytochrome P450 (e.g. CYP2C9, CYP3A4).⁹ These processes yield inactive metabolites that undergo further processing, often through glucuronidation, to enhance water solubility, facilitating excretion primarily via urine and, to a lesser extent, bile in the feces.¹⁰

The plasma half-life of NSAIDs closely determines their onset and duration of action.¹¹ Short-acting NSAIDs, including aspirin, diclofenac, and ibuprofen, are effective for rapid relief of acute pain or inflammation due to their half-lives of less than 6 hours. Long-acting options like naproxen and celecoxib, with half-lives exceeding 10 hours, are better suited for managing chronic conditions such as arthritis, maintaining therapeutic levels over extended periods. Choosing between short- and long-acting NSAIDs depends on the clinical need for immediate relief versus sustained control of chronic symptoms.

Patient response to NSAIDs is influenced by pharmacokinetic profiles, genetic variations (e.g., CYP2C9 activity), and individual factors like age, organ function, and comorbidities.¹¹ Personalized treatment strategies and clear communication are essential for optimizing outcomes, ensuring proper adherence to dosing schedules, and tailoring therapy to meet patient-specific needs.

Risks and side effects of NSAIDs

NSAIDs are effective medications but can cause a range of side effects, from mild to severe.^12,13 Common mild side effects include:⁴

• Nausea, vomiting, bloating, and heartburn
• Dizziness, headache, and drowsiness
• Tinnitus (ringing in the ears)
• Diarrhea, constipation, and stomach discomfort

More serious complications may include:”4

• Gastrointestinal (GI) toxicity: ulcers, bleeding, or perforation
• Cardiovascular issues: hypertension, heart attack, and stroke
• Kidney damage (nephrotoxicity) and liver damage (hepatotoxicity)
• Thrombocytopenia, hyperkalemia, and anemia
• Rare hypersensitivity reactions like Stevens-Johnson Syndrome

These risks underscore the importance of careful patient selection and ongoing monitoring during NSAID use.

Contraindications and special considerations

NSAIDs are contraindicated in specific situations, including:

• Patients undergoing coronary artery bypass graft (CABG) surgery for perioperative pain
• Individuals with known hypersensitivity to NSAIDs or aspirin
• Patients with a history of asthma, urticaria, or allergic reactions triggered by NSAIDs

Special caution is required for:

• Older adults
• Patients with a history of peptic ulcer disease (PUD) or GI bleeding

Prescription NSAIDs carry black box warnings for cardiovascular thrombotic events and GI risks. Similarly, prescription acetaminophen warns against hepatotoxicity, particularly at doses exceeding 4,000 mg/day, which can cause acute liver failure. In cases where NSAIDs are contraindicated, consider alternatives like acetaminophen or acetaminophen-based opiate combinations (e.g., Tylenol #3).

Risks with prolonged use

Chronic NSAID use increases the risk of severe complications, especially in older populations. These include:

• Peptic ulcer disease14 and acute kidney injury (AKI)15
• Serious cardiovascular events (e.g., stroke, myocardial infarction)16
• Worsening pre-existing conditions such as hypertension and heart failure

The inhibition of prostaglandin production — vital for protecting the GI mucosa and maintaining kidney function — can lead to gastrointestinal damage, reduced renal perfusion, and impaired drug clearance. Patients with moderate to severe renal issues or those on dialysis should be closely monitored, as NSAIDs can exacerbate renal dysfunction and increase the risk of AKI.¹⁵

Patient education

Educating patients on the safe use of NSAIDs is crucial. Key points to emphasize include:

• Use the lowest effective dose for the shortest duration.
• Avoid combining prescription and OTC NSAIDs to reduce adverse effects.
• Carefully review OTC medication labels to prevent duplicate or excessive dosing.

Patients should be informed about potential side effects and encouraged to report symptoms promptly. Clear communication helps minimize risks and maximize treatment effectiveness.

NSAID interactions with other medications

NSAIDs commonly interact with other medications, leading to adverse effects.^3,17

Common drug interactions

• Other NSAIDs or aspirin: Co-administration increases the risk of gastrointestinal ulcers, bleeding, hypertension, and hyperkalemia.
• Corticosteroids (e.g. prednisone, methylprednisolone): Combination heightens the likelihood of GI bleeding, fluid retention, and hypertension.
• Anticoagulants (e.g. warfarin, rivaroxaban, dabigatran, apixaban, edoxaban): Combination significantly elevates the risk of serious bleeding.
• Methotrexate, lithium, phenytoin, and calcium channel blockers: Some NSAIDs, such as celecoxib, can increase blood levels of these drugs, raising the risk of nephrotoxicity.¹⁸
• Oral antidiabetic drugs: NSAIDs may increase the risk of hypoglycemia.
• Antifungals (e.g. fluconazole): Can elevate celecoxib levels, amplifying side effects.
• Quinolone antibiotics (e.g. ciprofloxacin, levofloxacin): May enhance the risk of central nervous system stimulation and seizures when combined with NSAIDs.

Patient risk factors

Special caution is necessary for patients with the following conditions, as NSAID use must be carefully monitored to prevent exacerbation:¹⁹

• Chronic gastrointestinal issues (e.g., stomach ulcers, GERD, Crohn’s disease, ulcerative colitis, gastrointestinal bleeding).
• Kidney or liver disease.
• Cardiovascular conditions (e.g., heart failure, uncontrolled high blood pressure, history of stroke or heart attack).
• Diabetes, bleeding disorders, or poorly managed chronic illnesses.

Best practices for safe NSAID use

1. Patient evaluation: Thoroughly review the patient’s medical history to identify potential risks or contraindications.
2. Appropriate NSAID selection: Choose the safest option based on the patient’s health status, and prescribe the lowest effective dose for the shortest duration.
3. Monitoring: Regularly assess kidney and liver function, particularly in long-term NSAID users.
4. Patient education: Inform patients about:
   1. Risks of overuse or combining NSAIDs with other medications.
   2. The importance of adhering to dosing instructions.
   3. Recognizing early signs of adverse effects (e.g., gastrointestinal bleeding, swelling, unusual fatigue).
5. Reevaluation: Periodically reassess the need for NSAIDs and consider alternative therapies where appropriate.

By understanding and mitigating potential interactions, healthcare providers can enhance patient safety and reduce the risks associated with NSAID therapy in dental practice.

Special considerations for pediatric, geriatric, and perinatal patients

Pediatrics

Prescribing NSAIDs for children requires careful attention to their unique needs.²⁰

• Dosing and formulation: Always calculate doses based on weight to avoid toxicity, and choose age-appropriate formulations for ease of use.
• Precautions: Use NSAIDs cautiously in children with asthma or kidney problems, as these conditions can worsen with their use.
• Aspirin contraindication: Avoid aspirin in children under 18 due to the risk of Reye’s Syndrome, a rare but serious condition.
• Safer options: Ibuprofen is a well-studied and reliable choice for children when used at the right dose.

Geriatrics

For older adults, NSAIDs can be effective, but they come with increased risks due to age-related changes in the body.^21,22

• Risks: For geriatric patients, increased sensitivity to NSAIDs, slower metabolism, and a higher likelihood of adverse effects, such as gastrointestinal bleeding, renal impairment, and cardiovascular complications, necessitate a more cautious approach.
• Strategies: Start with the lowest effective dose, limit how long the medication is used, and monitor regularly for any side effects.

Pregnant and breastfeeding patients

NSAIDs require extra caution during pregnancy and breastfeeding to protect both mother and child.²³

• Pregnancy:
  • In 2020, the FDA updated the prescribing information for prescription NSAIDs to highlight the risk of kidney problems in unborn babies, which can lead to low amniotic fluid levels (oligohydramnios). The updated guidance advises avoiding NSAIDs in pregnant women starting at 20 weeks of pregnancy, a change from the previous recommendation of 30 weeks.
  • Avoid NSAIDs in the third trimester, as they can lead to serious complications for the baby, including renal injury, oligohydramnios, ductus arteriosus constriction, persistent pulmonary hypertension, necrotizing enterocolitis, and intracranial hemorrhage.
• Breastfeeding:
  • NSAIDs generally result in low infant exposure through breastmilk and are considered safe, with ibuprofen and naproxen preferred over aspirin due to their more favorable risk profiles.

“NSAIDS are a cornerstone of care that, when used thoughtfully, can profoundly impact a patient’s comfort and recovery.”

Best practices for NSAID prescribing

Effective dental pain management involves tailoring analgesics to the expected level of pain. These evidence-based guidelines offer a structured approach to prescribing based on pain severity:⁴

Anticipated pain level: mild

For patients experiencing mild pain, a non-prescription NSAID is often sufficient:

• Oral analgesic option: Ibuprofen 200–400 mg as needed for pain, every 4 to 6 hours.

Anticipated pain level: mild to moderate

For mild-to-moderate pain, a fixed dosing schedule initially ensures better pain control, followed by as-needed administration:

• Oral analgesic option: Ibuprofen 400–600 mg on a fixed interval, every 6 hours for the first 24 hours. Then, ibuprofen 400 mg as needed for pain, every 4 to 6 hours.

For patients requiring longer-term pain management, meloxicam can be considered as an option due to its once-daily dosing and favorable safety profile when used appropriately.

• Meloxicam dosage:²⁴ Start with 7.5 mg orally once daily, and adjust based on individual response. The maximum recommended daily dose is 15 mg. In patients undergoing hemodialysis, the dose should not exceed 7.5 mg/day. To minimize gastrointestinal upset, it can be administered with food. Use the lowest effective dose for the shortest duration to align with treatment goals.

Anticipated pain level: moderate to severe

For moderate-to-severe pain, combining an NSAID with acetaminophen offers enhanced analgesic efficacy:

• Oral analgesic option: Ibuprofen 400–600 mg plus acetaminophen 500 mg on a fixed interval, every 6 hours for the first 24 hours. Then, ibuprofen 400 mg plus acetaminophen 500 mg as needed for pain, every 6 hours.

Anticipated pain level: severe

For severe pain, a combination of an NSAID, acetaminophen, and an opioid is recommended initially, with a step-down approach as pain diminishes:

• Oral analgesic option: Ibuprofen 400–600 mg plus acetaminophen 650 mg with hydrocodone 10 mg on a fixed interval, every 6 hours for 24 to 48 hours. Then, ibuprofen 400–600 mg plus acetaminophen 500 mg as needed for pain, every 6 hours.

After prescribing NSAIDs, careful monitoring is essential to ensure patient safety and prevent adverse effects.²⁵ Key considerations include assessing kidney function through renal studies and liver health with liver function tests. Coagulation studies, such as prothrombin time and international normalized ratio (INR), are particularly important in patients on anticoagulants. A complete blood count (CBC) can help detect signs of anemia or other blood-related issues, as well as symptoms of gastrointestinal bleeding. Patients should also be advised to monitor for warning signs of bleeding, such as nosebleeds, unusual bruising, blood in the stool or urine, or feelings of dizziness.²⁶

Additionally, regular monitoring of blood pressure is necessary, as NSAIDs can contribute to hypertension, especially in patients with pre-existing cardiovascular conditions. These measures help identify potential complications early and ensure the safe, effective use of NSAIDs.

Case studies and clinical scenarios

The importance of thorough medication review and patient history cannot be overstated, as highlighted by the experiences of this paper’s co-authors.

Dr. Lisa Chan shared a harrowing case from her husband who is a hospitalist. A patient was prescribed ibuprofen by their dentist to manage dental pain. Soon after, they were rushed to the emergency room with severe gastrointestinal bleeding, requiring two pints of blood. The cause? The patient had already been taking celecoxib, another NSAID, prescribed by their physician.

Similarly, over many years in pharmacy practice, Barbara Madej, RPh, encountered situations where combining NSAIDs with selective serotonin reuptake inhibitors (SSRIs)—such as citalopram, sertraline, fluoxetine, or paroxetine — significantly increased the risk of upper gastrointestinal bleeding. In these scenarios, careful consideration of the risks and benefits is crucial. When such combinations are unavoidable, co-prescribing a proton pump inhibitor (PPI) can help mitigate the risk of serious complications.

These examples highlight the critical importance of reviewing patient histories and checking for drug interactions before prescribing NSAIDs. A simple review of current medications using new, dentistry-specific technology such as the MedAssent DDS Digital Drug Handbook could have prevented the severe, avoidable outcomes in these cases.

Conclusion

NSAIDs are more than just a tool for managing dental pain — they are a cornerstone of care that, when used thoughtfully, can profoundly impact a patient’s comfort and recovery. Yet, their power comes with responsibility. As dental professionals, the choices we make in prescribing NSAIDs can mean the difference between relief and harm, between trust and fear.

Each patient brings a unique story, a medical history that demands our attention and respect. By taking the time to review drug interactions, anticipate risks, and educate our patients, we reinforce the trust they place in us that forms the foundation of excellent care.