By: Edwin Gruda, PharmD Candidate c/o 2022; Aiśa Mrkulic, PharmD. Candidate c/o 2022
Over-the-Counter (OTC) medications are typically used for mild pain relief. Many patients rely on their OTC medications to treat headaches, fevers, muscle pain, tooth aches and mild arthritis. In March of 2020, the Food and Drug Administration (FDA) approved a new OTC medication by GlaxoSmithKline (GSK) called Advil© Dual Action, which is a combination of ibuprofen 250 mg and acetaminophen 125 mg.¹
Prior to discussing the mechanism of action of ibuprofen/acetaminophen, it is important to understand the transduction of inflammatory intermediates. In other words, what causes pain? Phospholipids of the cell membrane are degraded by an enzyme called Phospholipase A2 to produce arachidonic acid.² Subsequently, arachidonic acid is metabolized by cyclooxygenase-1(COX-1) and cyclooxygenase-2 (COX-2)isoenzymes to yield eicosanoids.² Eicosanoids consist of inflammatory intermediates such as prostaglandins, which induce inflammation, pain, and fever.¹ Cyclooxygenase-3 or COX-3 isoenzymes are particularly expressed in the brain, and its activation induces pain and fever, but not inflammation, unlike those expressed by the activation of COX-1 and COX-2 isoenzymes.³
Ibuprofen is a nonselective COX inhibitor, in that it inhibits the two isoforms of cyclooxygenase, COX-1 and COX-2, preventing the formation of prostaglandins.⁴ Specifically, ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), which helps stop processes that promote inflammation and pain. Although the mechanism of action of acetaminophen is not entirely understood, it is believed to inhibit the COX-3 pathway in the central nervous system, but not peripheral tissues.³ Thus, acetaminophen is generally used for its analgesic effect, as it lacks anti-inflammatory action.
Prior to the approval of GSK’s ibuprofen/acetaminophen combination, many patients have been using ibuprofen and acetaminophen separately to treat their headaches, muscle aches, backaches, arthritis and other joint pain. In essence, GSK’s new combined formulation offers a greater convenience for patients. Many now have the ability to take one combined formulation tablet, rather than two separate tablets. In any case, the desired therapeutic effect can be achieved.
It is not unheard of that a dentist will prescribe narcotic analgesics to patients post-operatively. In fact, it is considered common practice to treat pain which originates from dental procedures with narcotic-containing combination products. Among these heavily-regulated, prescription-only treatments are hydrocodone and acetaminophen (Vicodin®) as well as oxycodone and acetaminophen (Percocet®). According to the American Dental Association (ADA), for dental procedures associated with acute dental pain, NSAIDs remain the first-line therapy for acute pain management.⁵ Moreover, it has been demonstrated that these agents possess an efficacy superior to that of opioid analgesics, which begs the question: Why the apparent reliance on opioid pain relievers coupled with neglect of non-opioid analgesics in dentistry.
The co-administration of an NSAID with non-opioid analgesic, acetaminophen, makes for a that-much-more highly efficacious reduction in mild-to-moderate pain.⁵ It is by way of this combination that a dual-block of the nociceptive pathway is achieved, where the former acts peripherally and the latter, centrally. It is well documented that, “severe tooth decay, extraction of teeth, and root canals” inspire the dispensing of dentist-prescribed opioids by pharmacists.⁶ Ultimately, the question remains: Does GSK’s ibuprofen/acetaminophen suffice as a stand-in for indoctrinated treatment?
For mild to severe pain, evidence-based recommendations put forth by the ADA do not, under any circumstances, welcome the use of opioid pain relievers. Instead, escalating doses of ibuprofen in combination with acetaminophen prevail. Even in the case of pain categorized as ‘severe,’ an opioid-free option exists-namely, 400mg-600mg of ibuprofen with a 500mg acetaminophen add-on.⁶ Both are to be taken every 6 hours for the management of postoperative pain. It should be noted that dentists are permitted to utilize their state’s prescription drug monitoring program (PDMP) to inform their determination of an acute pain management strategy for patients.⁵ In their 2016 statement on the use of opioids in the treatment of dental pain, the ADA House of Delegates encouraged the practice amongst dentists following registration.
Furthermore, the organization advocates for the pursuit of, “continuing education [CE] in addictive diseases and pain management” as they pertain to opioid prescribing by aspiring dental professionals and dentists alike.⁷ On the matter of PDMP, pharmacists may be the key to routine use of the tool by dentists. Dentists have admitted to only consulting the database when having perceived patients to be at a high-risk for misuse, as evidenced by a 2018 survey of over 700 dentists nationwide.⁸ Slightly less than half of all survey-takers reported habitual use of PDMP.⁸ It would be wise of the dental professionals to be vigilant and consider the words of one of their very own, Michael Ellis, DDS. The clinical associate professor in oral and maxillofacial surgery at Texas A&M University’s College of Dentistry warned dental students of the delicateness that comes with opioid prescribing, “you don’t want to give them a problem they don’t have.”⁸
Evidently, the ADA is no stranger to the abuse potential associated with medication-combinations of oral analgesics. Our nation’s ongoing opioid epidemic has remained a long-standing concern of healthcare providers belonging to every health field, including dentistry. It is with those in possession of prescribing power, regardless of how limited their scope, that share the responsibility to curb opioid access. Through exercising their professional judgment, dentists will prove valuable in the fight against opioid diversion and misuses; however, it is not without invoking patient education efforts of their own that an observable betterment of our nation’s public health will ensue.
When accompanied by a working relationship between pharmacists and local dentists, patients stand a chance against the evils of misusing opioid pain relievers. Pharmacists, the community’s most accessible healthcare providers, are ranked time and time again among some of the most trusted professions.⁹ Nearly 9-in-10 Americans are fortunate enough to live within 5 miles of a community pharmacy or pharmacist.¹⁰ Consequently, it is understandable that these healthcare professionals, once wrongfully pigeon-holed to their dispensing roles, now honorably bare the greater responsibility of fulfilling medication education needs. It is essential that their fellow healthcare heroes acknowledge them for their value and their drug expertise during these trying times. Now more than ever, inter-professional collaboration represents a necessary good. If our public health is to be safeguarded, promising FDA approvals alone will not suffice. Responsibility rests on the shoulders of practitioners to shape common practice in favor of patients.
1. FDA approves GSK’s Advil Dual Action with Acetaminophen for over-the-counter use in the United States. GSK website. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-advil-dual-action-with-acetaminophen-for-over-the-counter-use-in-the-united-states/.Published March 2, 2020. Accessed September 25, 2020.
2. Hanna VS, Hafez EAA. Synopsis of arachidonic acid metabolism: A review. J Adv Res.2018;11:23-32. Published 2018 Mar 13. doi:10.1016/j.jare.2018.03.005
3. COX-3: the Acetaminophen Target Finally Revealed. R& D Systemswebsite.www.rndsystems.com/resources/articles/cox-3-acetaminophen-target-finally-revealed.Accessed September 25, 2020.
4. Zarghi A, Arfaei S. Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships. Iran J Pharm Res. 2011;10(4):655-683.Accessed September 25, 2020.
5. ADA Statement on the Use of Opioids in the Treatment of Dental Pain. American Dental Association’s website. https://www.ada.org/en/member-center/oral-health-topics/oral-analgesics-for-acute-dental-pain. Published October 2016. Updated September 15, 2020.Accessed September 23, 2020.
6. American Dental Association Announces New Policy to Combat Opioid Epidemic. American Dental Association’s website. https://www.ada.org/en/press-room/news-releases/2018-archives/march/american-dental-association-announces-new-policy-to-combat-opioid-epidemic. Published March 26, 2018. Accessed September 23, 2020.
7. ADA Policy on Opioid Prescribing. American Dental Association’s website. https://www.ada.org/en/member-center/oral-health-topics/oral-analgesics-for-acute-dental-pain. Published October 2018. Updated September 15, 2020. Accessed September23, 2020
8. Fuentes J. Opioids and Dentistry. Texas A&M College of Dentistry’s Dentistry Insider. https://dentistryinsider.tamhsc.edu/opioids-and-dentistry/. Published August, 28, 2018.Accessed September, 23, 2020.
9. Crossley K. Public Perceives Pharmacists as Some of the Most Trusted Professionals. Pharmacy Times website. https://www.pharmacytimes.com/publications/career/2019/careerswinter19/public-perceives-pharmacists-as-some-of-the-most-trusted-professionals. Published March 18,2019. Accessed September 23, 2020
10. Get to Know Your Pharmacist. Center for Disease Control and Prevention (CDC) website. https://www.cdc.gov/features/pharmacist-month/index.html. Updated October 18, 2018. Accessed September 23, 2020.