African Health Sciences Vol 12 Issue 4 December 2012576

Amlodipine-induced gingival hyperplasia in chronic renal failure: acase report

*Aldemir NM1, Begenik H2, Emre H2, Erdur FM2, Soyoral Y2

1. Department of Internal Medicine, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey2. Department of Nephrology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey

AbstractAmlodipine is a dihydropyridine calcium channel blocker that is used in the management of both hypertension and angina.Amlodipine induced side effects are headache, dizziness, edema, flushing, palpitations, and rarely gingival hyperplasia. Theexact reason of amlodipine-induced gingival hyperplasia is not known. We presented a case with chronic renal failure (CRF)that developed gingival hyperplasia due to amlodipine use, which improved after ceasing the drug.Keywords: Amlodipine, gingival hyperplasia, chronic renal failureAfrican Health Sciences 2012; (4): 576 - 578 http://dx.doi.org/10.4314/ahs.v12i4.30

*Corresponding author:Mehmet Naci AldemirSanlurfa Education and Research Hospital,Internal Medicine DepartmentSanlurfa, TurkeyTel: +90 414 318 60 00E- mail: aldemirmn@gmail.com

IntroductionAmlodipine is a long-acting calcium channel blockerbelonging to dihydropyridine group, which is usedfor the treatment of hypertension and angina.Pharmacokinetic profile characteristic of this group,which would also have an increased oralbioavailability and extended clearance time. A singleintravenous dose of 10 mg resulted in an absolutebioavailability of 64% and a calculated eliminationhalf-life of 34 hours1. Side effects of amlodipineusage involve headache, dizziness, edema, flushing,palpitation and rarely gingival hyperplasia2. Wepresented here a case with stage-3 chronic renal failure(CRF), which developed gingival hyperplasia due toamlodipine use.

Case reportA 39-year-old male patient, who had been underfollow up because of the diagnosis of stage-3chronic renal failure and hypertension for one year,appealed to the dentist with the complaint of gingivalhyperplasia. The patient who was planned surgerywas referred to the nephrology policlinic to be givenpreoperative recommendations for renal failure. Itwas revealed that the patient admitted to ourpoliclinic had used amlodipine 10 mg 1x1 andcarvedilol 6,25 mg 2x1 for approximately 1 yearand that the patients complaint of gingival

hyperplasia had begun 2 months after the use ofthese drugs and had gradually worsened. Since thegingival hyperplasia was assumed to be due toamlodipine, the medications were ceased and thepatient was prescribed angiotensin receptor blockers.During follow up, a remarkable improvement ofthe patients gingival hyperplasia was observed. Thepatients figures of during the use of amlodipineand 3 months after discontinuation have beenshowed in figures 1 and 2.

Figure 1: Amlodipine induced gingivalhyperplasia

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Figure 2: Regression of gingival hyperplasiaduring 3 months after discontinuation ofamlodipine.

DiscussionThe drugs causing gingival hyperplasia can bediscussed as three major groups: Anticonvulsants(phenytoin), immunosuppressive agents(cyclosporine A) and calcium channel blockers3.Among calcium channel blockers, the ones causinggingival hyperplasia in order of frequency arenifedipine (6.3%)4, verapamil (4.1%)5 and amlodipinewith lower rates (1.3% to 3.3%)3,4,6.

Amlodipine is a long-acting calcium channelblocker agent from dihydropyridine group, whichis used for the treatment of hypertension and angina.The side effects developed due to the use ofamlodipine are headache, dizziness, edema, flushing,palpitation, and rarely gingival hyperplasia2.

Amlodipine-associated gingival hyperplasiawas first reported in 19932. The majority of the casesin the literature were published in the journals ofdentistry. Gingival hyperplasia arises approximately2 to 3 months after the use of amlodipine7. In ourpatient, it began to occur after 2 months, the patientcontinued to take the drug since the patient did notknow that it might be related to the drug and thepatient appealed to the dentist at first.In the literature, there are three prevalence studiesalong with case reports regarding amlodipine-induced gingival hyperplasia. Gingival hyperplasia dueto the use of amlodipine was found in 5 (3.3%) of150 patients in the study performed by Jorgensen etal. in 19973, in 3 (1.7%) of 181 patients in the studyconducted by Ellis et al. in 19994, and in 4 (1.3%) of301 patients in the study performed by Ono et al. in20106. To our knowledge, our reported case is the

first case with CRF in the literature to develophyperplasia due to amlodipine.

Although the exact reason of drug-inducedgingival hyperplasia is not known, some well-knownrisk factors are gingival inflammation resulted frompoor oral hygiene, presence of dental plaques, thedose and duration of the drug used8,9. The underlyingmechanism remains to be fully understood.However, two main inflammatory and non-inflammatory pathways have already been suggested.The proposed non-inflammatory mechanismsinclude defective collagenase activity due todecreased uptake of folic acid, blockage ofaldosterone synthesis in adrenal cortex andconsequent feedback increase in ACTH level, andupregulation of keratinocyte growth factor (KGF).Alternatively, inflammation may develop as a resultof direct toxic effects of concentrated drug increvicular gingival fluid (CGF) and/or bacterialplaques. This inflammation could lead to theupregulation of several cytokine factors such as TGF-110. Consequent gingival hyperplasia causes not onlyesthetic problems but also difficulty speaking andmastication, impairs oral hygiene and leads tomalnutrition8,9. Our patient did not have the habitof regular tooth brushing (only once a week) andgingival hyperplasia evolved resulted in nutritionaland speaking problems. Another factor having animpact on the development of gingival hyperplasiais gender. It occurs three times more often in menthan in women11. Our patient was a man with chronicrenal failure. It is not known whether chronic renalfailure is associated with adverse effects ofamlodipine.

The primary treatment of drug-inducedgingival hyperplasia involves ceasing the drug,prescribing another drug from a different groupinstead, and a good oral care. In case of establishingthese things, gingival hyperplasia often improves.Usually, surgical approach is not needed. In thesituations requiring surgery, gingivectomy orperiodontal flap is performed12. Gingival hyperplasianormally begins at the interdental papillae and isfrequently found in the anterior segment of the labialsurfaces13. A gingival specimen was obtained forhistological examination, of which the findings werethe epithelium with irregular elongation and fusionof rete ridges and bundles of collagen fibers in thesubepithelial connective tissue6. However, a biopsyhas not been made may be deficiency of for ourcase report.

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Our patient appealed to his dentist and wasreferred to our policlinic for preoperative evaluationbecause of coexisting CRF. His medication wasceased since the development of gingival hyperplasiawas assumed to be associated with amlodipine andit regressed within 3 months without surgicalintervention. Therefore, it is of importance that thedentists should consider the drugs in the etiology ofthese disorders because most of these patients appealto the dentists.

ConclusionWhen prescribing amlodipine, it should be consideredthat amlodipine potentially causes gingivalhyperplasia. The patients should be recommendedpay attention to oral hygiene and appeal to a healthcarecenter in case gingival hyperplasia develops.

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