Heterogeneity of the gingival response depends on several variables, including the drug in question, plaque-induced inflammatory changes in the gingival tissues, genetic factors, and other factors known to influence drug pharmacokinetics and pharmacodynamics (Charles et al., 2012). It has been reported that good oral hygiene practices can mitigate the degree of gingival enlargement associated with drugs (Khzam, Bailey, Yie, & Bakr, 2016). The enlargement is generally greater in inflamed tissue because less active or quiescent fibroblasts in non- inflamed gingiva do not respond to circulating systemic drugs, whereas inflammatory mediators and endogenous growth factors cause fibroblasts in inflamed tissue to be active and exhibit an exaggerated response to drug therapy. Researchers have described drug-specific pathogenic processes for gingival enlargement (Zoheir, & Hughes, 2020). For example, cyclosporine A increases production of collagen and protein by fibroblasts, which results in formation of extracellular collagen and matrix and reduction in the activity of the enzyme collagenase. In addition, increased levels of cytokines, such as interleukin-6, and reduced levels of gamma-interferon may promote fibroblast synthesis of collagen (Murai et al., 2011). Phenytoin-induced gingival overgrowth has been attributed to activity of hormones in the gingiva (Agrawal, 2015). Although the presentation of drug-specific gingival overgrowth may be similar, the etiology of these conditions can be different on a molecular level. Nifedipine is a commonly prescribed calcium channel blocker that has been implicated in causing gingival enlargement. Other calcium channel blockers, such as amlodipine, diltiazem, felodipine, nitrendipine, and verapamil, may also precipitate this condition (Aral, Dilber, Aral, Sarica, & Sivrikoz, 2015). Researchers have linked the pathogenesis of nifedipine-linked gingival hyperplasia to the inhibition of apoptosis (planned cell death) with consequent epithelial hyperplasia (Cohen & Bhattacharyya, 2008; Trackman & Kantarci, 2015; Zoheir, &
Hughes, 2020). In addition, gingival enlargement has been attributed to nifedipine’s inhibition of both the adherence- and macrophage-induced death of fibroblasts (Fujimori, Maeda, Saeki, Morisaki, & Kamisaki, 2001; Trackman & Kantarci, 2015, Zoheir, & Hughes, 2020). Gingival enlargement induced by oral contraceptives is common and has long been reported (Domingues et al., 2012; Pearlman, 1974; Sumanth, Bhat, & Bhat, 2007). Both estrogen and progesterone, which are used in oral contraceptives, are known to increase gingival exudate, edema, and inflammation. It has been shown that women who take oral contraceptives exhibit greater periodontal destruction than a control group of comparable age and oral hygiene (Domingues et al., 2012). Although it does not prevent gingival enlargement, practicing good oral hygiene can limit response severity (Kalmar, 2016). The exact role played by bacterial plaque in drug-induced gingival enlargement is unclear, but good oral hygiene and professional plaque removal have been shown to decrease the amount of gingival enlargement. One study involving transplant patients exhibiting cyclosporine A-related gingival enlargement reported that a strict plaque control program lowered inflammatory infiltrate and changed connective tissue composition (Aimetti, Romano, Marsico, & Navone, 2008; Zoheir, & Hughes, 2020). Treatment for drug-induced gingival enlargement should be tailored to the patient and the causative medication as well as the clinical presentation of each particular case (Kalmar, 2016; Mohan et al., 2013). Initially, the clinician should consider discontinuing the offending agent or changing medication. Although cessation or substitution of the drug may lead to regression, surgical removal of the excess tissue (i.e., gingivectomy) may be necessary in certain individuals. Consider periodontal surgery if gingival enlargement persists despite drug substitution and good plaque control (Aral et al., 2015; Cohen & Bhattacharyya, 2008).
DRUG-RELATED MUCOSAL DISORDERS
Disorders of the mucosal tissues can result from various drug- related effects, ranging from direct burns to disturbances of the immune system and opportunistic infection. Oral mucositis Oral mucositis is inflammation and ulceration of the mouth mucosa with pseudomembrane formation. Incidence and prevalence data for this condition are believed to be underreported and inconsistent because of the lack of consistency in diagnostic criteria for mucositis (Villa and Sonis, 2015; Blakaj, Bonomi, Gamez, & Blakaj, 2019). Two major etiological mechanisms are implicated in mucositis: direct toxicity associated with treatment and myelosuppression resulting from therapy. The pathogenic mechanism involves chemotherapy and radiotherapy causing reduction of cell renewal in the basal epithelial layers, with insufficient replacement of desquamated cells (Blakaj, Bonomi, Gamez, & Blakaj, 2019). Mucositis is considered an inevitable but transient side effect of antineoplastic therapies (Grenon, 2013) or radiation in head and neck oncology (de Barros da Cunha et al., 2015). It is characterized by squamous epithelial atrophy, vascular damage, and an inflammatory infiltrate concentrated at the basement region. Ulceration follows epithelial atrophy. Its severity can range from a minor erythema, edema, or allodynia to large and painful ulcers that affect eating, swallowing, and talking. Four grades (I, II, III, and IV) are used to score mucositis. Grades III and IV mucositis are painful and characterized by ulcerative lesions, which are covered by fibrinous-inflammatory (pseudomembranous) exudate (Blakaj, Bonomi, Gamez, & Blakaj, 2019). In its early stages, chemotherapy-induced mucositis can appear clinically as erythema 4 to 5 days after the start of treatment. Ulcers may develop 7 to 10 days after chemotherapy and
often cause marked discomfort. The movable tissues of the buccal mucosa and the tongue’s lateral and ventral surfaces are the most common sites of chemotherapy-induced mucositis, whereas the hard palate and gingiva are less common. Often, these findings are resolved within 2 weeks of initial presentation (Villa & Sonis, 2015; Blakaj, Bonomi, Gamez, & Blakaj 2019). The frequency and severity of mucositis depend on several factors, including the type and dose of chemotherapeutic agents and patient-specific factors such as age, as well as nutritional, buccodental, and hematological status (Villa & Sonis, 2015; Blakaj, Bonomi, Gamez, & Blakaj 2019). Combination therapy with cytotoxic drugs can influence known side effects and increase the toxicity to the patient. The Consensus Development Panel of the National Institutes of Health (NIH) concluded that drug intervention cannot effectively prevent mucositis, an opinion that still holds (Chaveli-López & Bagán-Sebastián, 2016; NIH, 1989). Consequently, management of chemotherapy-related mucositis is still limited to reducing its severity. Good gingival status and good oral hygiene during chemotherapy can lower the incidence and severity of mucositis (Villa & Sonis, 2015; Blakaj, Bonomi, Gamez, & Blakaj, 2019). In addition, several interventions have been proposed to reduce mucosal exposure to chemotherapeutic drugs. For example, ice chips held in the mouth can constrict blood vessels and thereby reduce exposure of mucosal tissues to the chemotherapy agent. A Cochrane analysis that evaluated the effectiveness of prophylactic agents for oral mucositis in patients receiving treatment for cancer found that ice chips prevented mucositis
EliteLearning.com/Dental
Book Code: DFL3024
Page 135
Powered by FlippingBook