**3.2 Oral contraceptives**

*Oral Diseases*

functional outcome [64].

*A case of gingival overgrowth in a patient on amlodipine.*

of the gingival overgrowth.

**3.1 Minocycline**

**3. Other effects of medications on periodontal tissues**

*2.6.3 Verapamil*

**Figure 4.**

interfere with esthetics, mastication, or speech [63]. Management of amlodipine induced gingival overgrowth includes substitution of the drug and controlling the other risk factors with meticulous mechanical and chemical plaque control. Surgical management of the overgrowth is advised in cases to accomplish an esthetic and

Verapamil is an effective preventive agent in both episodic and chronic cluster headache. Gingival overgrowth is an infrequent adverse effect of Verapamil and a prevalence rate of around 4.2% has been reported [33]. Histologically, verapamil induced gingival enlargement shows a highly vascular connective tissue, acanthotic and thickened epithelium with long rete pegs containing dyskeratotic pearls, and varying amounts of subepithelial inflammatory infiltrate which is similar to other group of drugs [65]. The histological appearance is similar to that caused by phenytoin, cyclosporin, and other calcium channel antagonists. Discontinuation of the drug usually results in complete regression

Minocycline, a semi-synthetic broad-spectrum antimicrobial agent, is mainly

used for the treatment of acne, chronic respiratory diseases, and rheumatoid arthritis. It is lipid soluble and therefore can easily penetrate into body fluids, such as saliva and gingival crevicular fluid, and into various body tissues including bone and soft tissues [66]. Minocycline-induced pigmentation of oral mucous membranes including the buccal mucosa, gingiva, palatal area, lips and tongue has been reported [67–69]. The pathophysiology of minocycline staining is not clearly understood. It has been suggested that either a minocycline-metabolite complex or melanin, iron and calcium-containing granules are the source of the pigment [70]. The pigmentation of oral soft tissues appears as distinctive blue-gray or brown in color and occurs as a result of pigmented black bone visible through the thin overlying mucosa without any actual involvement of the soft tissue itself (**Figure 5**) [71]. The pigmentation appears to be related to the duration of minocycline

**62**

A higher prevalence of gingival inflammation, loss of attachment and gingival enlargement in woman taking hormone based oral contraceptives [73, 74]. The gingival inflammation seems to be associated to high concentrations of sex hormones present in oral contraceptives (**Figure 6**) [75]. Oral contraceptives (OCs) enhance periodontal breakdown by reducing the resistance to dental plaque and can induce gingival enlargement in otherwise healthy females [76, 77]. Oral contraceptives have pronounced effects on gingival microvasculature and it has been shown that human gingiva contains receptors for progesterone and estrogen. The dosage and duration of intake are the possible factors which influence the effect of oral contraceptives on the periodontal condition. A continued exposure of oral contraceptives for longer duration results in higher risk of periodontal disease development due to increased production of pro-inflammatory cytokines and prostaglandins as a result of elevated levels of the hormones [78, 79]. However, the currently used combined oral contraceptives showed little influence on the periodontal health, possibly related to their lower concentration of progesterone and estrogen compared to the earlier formulations [74, 80]. A critical review supports the conclusion that there is no impact of modern oral contraceptives on the periodontal and gingival tissues.

**Figure 5.** *Discoloration of the gingiva and teeth in a patient on minocycline therapy.*

**Figure 6.** *Gingival changes in a patient on oral contraceptives.*

Hence, it is concluded that oral contraceptives can no longer be considered to constitute a risk factor for gingivitis or periodontitis [81].

#### **3.3 Bisphosphonates**

Bisphosphonates are used widely in the management of primary and metastatic bone cancer, as well as osteoporosis. Bisphosphonates improve bone mineral density, reduce fracture risk, and reduce hypercalcemia of malignancy. Incidents of osteonecrosis of the jaw have been reported in people on bisphosphonates and undergoing invasive dental treatment procedures, including tooth extractions, dental implants, and surgical and nonsurgical periodontal treatment [82]. The risk for bisphosphonate-induced osteonecrosis may be influenced by the route of administration of the drug, the potency and the duration of use. Jaw osteonecrosis appears more associated with the intravenous use of bisphosphonates. A review showed that 94% of the published cases of osteonecrosis correlated with administration of intravenous, nitrogen-containing bisphosphonates [83].

Bisphosphonates inhibit bone resorption by acting on osteoclasts to reduce their activity or to increase the rate of apoptosis [84]. The inhibitory effect on osteoclast function, bone formation coupled with resorption results in an overall reduction in the rate of bone remodeling [85]. Moreover, bisphosphonates may antagonize the action of several matrix metalloproteinase involved in breakdown of structural components of periodontal connective tissue [86]. In view of the antiresorptive properties of bisphosphonates and the ability to inhibit cytokines of periodontal tissue destruction, there has been interest in the possible use of bisphosphonates as an adjunct to scaling and root planning in the management of periodontitis [87, 88]. Although bisphosphonates claim its effectiveness in controlling periodontal destruction, clinical use warrants further evidence. A systematic review concluded that bisphosphonates may be used topically as an adjunct to scaling and root planing [89].

#### **3.4 Statins**

Statins, or inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), are a group of drugs, used mainly to treat hyperlipidemia. In addition to their cholesterol lowering properties they also have strong anti-inflammatory properties and may stimulate bone growth [90]. Statins have anabolic effects on the bone by augmenting bone morphogenetic protein-2 expression and thereby contributing towards the differentiation and activity of osteoblasts [91]. Due to their activity on bone formation statins have been considered as potential agents in improving periodontal treatment outcomes [92]. Limited data is available on the impact of stains on periodontal tissues suggesting a reduction in periodontal destruction and tooth loss [93]. Experimental studies on rats support the potential protective effect of statins on periodontal bone loss. Although these basic data are interesting, further research could extrapolate the use of statins as a potential adjunctive therapeutic agent in periodontal disease and bone regeneration.

#### **3.5 Anti-platelet drugs**

Anti-platelet drugs are widely used for the treatment of established cardiovascular disease, the prevention of atherothrombotic events and the treatment of myocardial infarction. The most commonly prescribed antiplatelets drugs are aspirin

**65**

**Author details**

**4. Conclusion**

the causative agents.

**Conflict of interest**

None declared.

Sukumaran Anil1

Elna Paul Chalisserry3

Sciences, Thiruvalla, Kerala

\*, Seham H.S.A. Alyafei1

Pukyong National University, Busan, South Korea

\*Address all correspondence to: drsanil@gmail.com

provided the original work is properly cited.

1 Department of Dentistry, Hamad Medical Corporation, Doha, Qatar

2 Department of Periodontology and Implantology, Pushpagiri College of Dental

3 Interdisciplinary Program of Biomedical, Electrical and Mechanical Engineering,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Annie Kitty George2

and

*Adverse Effects of Medications on Periodontal Tissues DOI: http://dx.doi.org/10.5772/intechopen.92166*

and clopidogrel which are often used in combination. Both of these drugs have been reported to cause increased gingival bleeding. Patients on these medications carry a risk of an increased tendency to bleeding during or following periodontal surgery

Several systemic factors are known to contribute to periodontal diseases or conditions and among those are the intake of drugs. The gingival overgrowth associated with medications occur as a side effect of systemic medications. These medications include the anti-seizure drug phenytoin, the immune suppressor cyclosporin A, and certain anti-hypertensive dihydropyridine calcium-channelblockers, most notably nifedipine. It is crucial that health professionals understand the complications that medications can have on the oral health of their patients. In order to properly diagnose and treat patients, a complete medical history including prescription medications, over the counter drugs and dietary supplements must be recorded which will enable the healthcare team to identify

and this risk is far greater when the drugs are used in combination [94].

and clopidogrel which are often used in combination. Both of these drugs have been reported to cause increased gingival bleeding. Patients on these medications carry a risk of an increased tendency to bleeding during or following periodontal surgery and this risk is far greater when the drugs are used in combination [94].
