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Pharmacologic considerations in the treatment of the dental patient with autoimmune disease.

According to the American Autoimmune Related Diseases Association (AARDA), approximately 50 million Americans suffer from an autoimmune related disease. Some 80 to 100 autoimmune diseases have been identified, with an additional 40 or more suspected of having an autoimmune origin. In addition, AARDA states that autoimmune disease is one of the top 10 leading causes of death in female children and women in all age groups up to 64 years of age. (1)

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The pharmacologic treatment of autoimmune diseases is, for the most part, aimed at improving the patient's quality of life, since no definitive cure yet exists for these diseases. While the ultimate goal of therapy is complete remission, more research is needed into why immune system self-tolerance mechanisms fail (resulting in the autoimmune process). According to AARDA, such research will lead to an understanding of how to modulate immune system activity, and may ultimately benefit not only patients with autoimmune diseases, but also transplant recipients and patients with cancer, AIDS and infectious diseases. (1)

Thus, patients with autoimmune diseases take multiple medications to reduce inflammation and swelling, relieve pain, facilitate normal function, and, if available, halt the progression of the disease process. However, many of these medications may have significant long-term adverse effects, which may negatively impact patient compliance and quality of life. As a discussion of the pharmacologic treatment of all autoimmune diseases is clearly beyond the scope of this article, we will focus our discussion on the treatment of rheumatoid arthritis (RA), since many drugs used to treat this condition are also used in the treatment of other autoimmune diseases.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of joints--especially of the hands, feet and knees--which may ultimately lead to joint dysfunction and destruction. (2), (3) As a result, in addition to rest, exercise and physical therapy, anti-inflammatory medications are the mainstay of therapy of RA. Since joint pain and swelling associated with RA are the hallmark of inflammatory cytokine activity, medications used in the treatment of RA are selected due to their activity against these inflammatory mediators. (4)

Anti-inflammatory medications used specifically for the treatment of RA-related joint pain and swelling include salicylates such as aspirin, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, and selective COX-2 inhibitors such as celecoxib (Celebrex). While effective in the treatment of the inflammatory symptoms of RA, these drugs have little effect in modifying the course of the disease or limiting joint damage. (4)

The use of aspirin and non-selective NSAIDs is associated with gastrointestinal ulceration, which may limit their long-term effectiveness. As a selective COX-2 inhibitor, Ce-lebrex may cause less gastrointestinal side effects. However, Celebrex has been associated with numerous drug interactions and significant cardiovascular adverse effects, including sudden myocardial infarction and stroke. Patients who are allergic to aspirin may also be allergic to all NSAIDs (including Celebrex) due to cross-sensitivity. (5)

Aspirin and all NSAIDs have anti-platelet activity, which may result in prolonged bleeding. While this effect is irreversible with aspirin (and, thus, continues until new platelets have been produced), the effect of NSAIDs on platelets is reversible and continues only for as long as the drug remains in the bloodstream. Dental patients taking these medications may experience oral aphthous ulcerations, stomatitis and gingival bleeding. (6)

Other anti-inflammatory medications with activity against cytokines that are used specifically to prevent or limit joint damage and slow the progression of the disease are known as disease-modifying antirheumatic drugs (DMARDs). These slow-acting medications include a potpourri of agents from different pharmacologic classes including immunosuppressive agents, specific anti-cytokine agents, antimalarial agents, chelating agents and even gold compounds. As a whole, medications used in the treatment of RA that modify immune function have been associated with significant adverse effects, including increased risk of serious bacterial, fungal and viral infections as well as the development of cancers. (7)

Immunosuppressive agents are used in the treatment of RA as well as for the prevention of organ transplant rejection and cancer chemotherapy. Methotrexate (Rheumatrex[R]) is used in low doses for autoimmune diseases, especially RA. Azathioprine (Imuran[R]) and cyclosporine (Sandimmune[R], Neoral[R])are used in cases of refractory RA. Dental patients taking these medications may experience oral ulcerations, increased risk of infection, delayed wound healing and prolonged bleeding. (5), (6)

Anticytokine agents, such as etanercept (Enbrel[R]) and adalimumab (Humira[R]), antagonize specific pro-inflammatory cytokines such as interleukin-lb and tumor necrosis factor alpha. As a result, they reduce inflammation and reduce joint tissue deterioration and destruction. Dental patients taking these medications may also experience increased risk of infection and prolonged bleeding. (5), (6)

Antimalarial agents used for the treatment of RA include chloroquine (Aralen[R]) and hydroxychloroquine (Plaquenil[R]). These medications impair antigen-antibody reactions and slow the destruction of joint tissue. Dental patients taking these medications may exhibit blue-black pigmentation to the oral mucosa and significant ocular adverse effects, including retinopathy. (5), (6)

Chelating agents, such as penicillamine (Cuprimine[R]) and gold compounds, such as auranofin (Ridaura[R]) are used to decrease inflammation and to slow the destruction of joint tissue. These medications are associated with significant toxicities and numerous oral adverse effects. Dental patients taking these medications may experience prolonged bleeding, glossitis and aphthous stomatitis. (5), (6)

Corticosteroids are potent anti-inflammatory agents. In addition, they suppress immune function and, so, are frequently used to control acute symptoms of RA. However, long-term use of corticosteroids is generally avoided due to numerous adverse effects that may affect patients' quality of life. Dental patients taking these medications may experience adrenal suppression, osteoporosis, weight gain, diabetes, increased risk of infection, delayed wound healing, peptic ulcer, psychological changes, insomnia and abnormal fat distribution. (4)

Since many of the medications used to treat RA have unique, although sometimes unknown, mechanisms of action, patients with severe RA are often prescribed therapies that consist of a combination of NSAIDs, corticosteroids and DMARDs. (4) While arguably more effective than monotherapy, combination therapy with these medications may also increase the likelihood of similar adverse effects.

Patients with autoimmune diseases may experience relief of symptoms by taking multiple medications aimed at reducing inflammation, swelling, and pain and the progression of their disease. However, many of these medications may have significant long-term adverse effects, which may negatively impact patient compliance and quality of life. In addition, several of the medications used in the treatment of autoimmune diseases are also used routinely in dentistry in the treatment of post-therapeutic pain and inflammation. Thus, it is important to take a complete and accurate medical history to assess the impact of autoimmune diseases and their treatment on dental therapy and patient management.

Patients with autoimmune diseases take multiple medications to reduce inflammation and swelling, relieve pain, facilitate normal function, and, if available, halt the progression of the disease process.

In addition to his profession of pharmacy, Thomas Viola, RPh, CCP, also serves the professions of dentistry, dental hygiene and dental assisting as an educator, published writer and professional speaker. He is a member of the faculty of seven dental hygiene and dental assisting programs, as well as national board exam review courses, serves as a contributor to several dental professional journals, and serves as a contributor to Mosby's Dental Drug Reference. He has presented hundreds of continuing education courses, nationally and internationally, in the areas of dental pharmacology and local anesthesia. Visit his website at www.thomasviola.com.

References

(1.) American Autoimmune Related Diseases Association, Inc. Autoimmune statistics. Available at: https://www.aarda.org/autoimmune_statistics.php. Accessed Mar. 6, 2014.

(2.) Vadasz Z, Haj T, Kessel A, Toubi E. Age-related autoimmunity. BMC Med. 2013 Apr 4; 11: 94.

(3.) Salinas GE, Braza F, Brouard S, et al. The role of B lymphocytes in the progression from autoimmunity to autoimmune disease. Immunol. 2013; 146(1): 34-45.

(4.) Little JW, Falace D, Miller C, Rhodus NL. Little and Falace's dental management of the medically compromised patient, 8th ed. Mosby, 2013.

(5.) Wynn RL, MeiIler TF, Crossley HL. Drug information handbook in dentistry, 18th ed. Hudson: Lexi-Comp Inc., 2012.

(6.) Pickett FA, Terezhalmy GT. Dental drug reference with clinical implications, 2nd ed. Baltimore: Lippincott Williams & Wilkins, 2008.

(7.) Walsh MM. Persons with autoimmune diseases, In: Darby ML, Walsh MM. Dental hygiene theory and practice, 3rd ed. St. Louis: Saunders Elsevier; 2010: 919-32.

By Thomas Viola, RPh, CCP
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Title Annotation:pharmacology
Author:Viola, Thomas
Publication:Access
Geographic Code:1USA
Date:Apr 1, 2014
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