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CASE REPORT Table of Contents  
Ahead of print publication
Amlodipine-induced gingival hyperplasia: Case reports of two patients


1 Sri Venkateswara Institute of Medical Sciences Sri Padmavathi Medical College for Women, Tirupati, Andhra Pradesh, India
2 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

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Date of Submission25-Mar-2020
Date of Acceptance04-Sep-2020
Date of Web Publication19-Nov-2021
 

  Abstract 


Drugs associated with gingival overgrowth fall into three broad categories – anticonvulsants, immune suppressants and calcium channel blockers. Amlodipine is a third-generation dihydropyridine. The prevalence of amlodipine-induced gingival hyperplasia is 4.2%. We report two patients with the amlodipine-induced gingival hyperplasia.

Keywords: Amlodipine, anticonvulsants, calcium channel blockers, drug-induced gingival overgrowth, gingival hyperplasia, immune suppressants


How to cite this URL:
Lakshmi G S, Tejaswini G, Alekhya B, Manuel MB, Ram R, Kumar V S. Amlodipine-induced gingival hyperplasia: Case reports of two patients. J Clin Sci Res [Epub ahead of print] [cited 2022 Jul 4]. Available from: https://www.jcsr.co.in/preprintarticle.asp?id=330771





  Introduction Top


Kimball[1] reported gingival hyperplasia for the first time in 1939 in a patient following phenytoin use. Drugs associated with gingival overgrowth fall into three broad categories – anticonvulsants, immune suppressants and calcium channel blockers (CCBs).[2],[3] Among CCBs, the dihydropyridines (e.g., nifedipine, felodipine, amlodipine, nitrendipine, nicardipine and manidipine) have a propensity to be more associated with gingival hyperplasia.[4] Amlodipine is a third-generation dihydropyridine. It was patented in 1982 and approved for medical use in 1990.[5] We report two patients with amlodipine-induced gingival hyperplasia.


  Case Reports Top


Patient 1: A 50-year-old man, with hypertension, chronic kidney disease Stage 3 was receiving oral telmisartan 40 mg/day. When blood pressure was not controlled, amlodipine was added. After 3 months, the patient reported the overgrowth of the gums [Figure 1]a. There were no other complaints except for the cosmetic disquiet. Intraoral examination revealed a generalised enlargement of the gingiva extending up to marginal and interdental gingiva. The surface of the gingiva appears lobulated with loss of scalloping. Oral hygiene was poor. We substituted amlodipine with prazosin. After 12 weeks, the gingival hyperplasia had regressed [Figure 1]b. We referred the patient to a dental surgeon for improvement in oral hygiene.
Figure 1: Clinical photograph showing gingival hyperplasia 3 months after the use of amlodipine (a). Clinical photograph of the same patient showing regression of gingical hyperplasia after amlodipine withdrawal (b)

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Patient 2: A 55-year-old man, known to have type 2 diabetes mellitus, hypertension on maintenance haemodialysis for end-stage renal disease presented with complaints of bleeding from gums. The patient had been receiving amlodipine for the past decade. An intraoral examination revealed generalised diffused gingival hyperplasia. The gingival enlargement was painless, lobulated, firm, pink and resilient and had a tendency to bleed. Extensive plaque formation and periodontal disease were also present [Figure 2]. We replaced the amlodipine by an angiotensin-converting enzyme inhibitor and sought a dental surgeon consultation.
Figure 2: Clinical photograph showing gingival hyperplasia after 3-months use of amlodipine

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  Discussion Top


The clinical manifestations of gingival hyperplasia are of a wide spectrum. The appearance ranges from non-inflamed, firm and fibrous gingiva to one that is dominated by oedema, erythema and bleeding. The latter form is especially seen in patients with poor oral hygiene. Although most of the drugs that cause gingival hyperplasia do not directly affect the underlying alveolar bone, the gingival enlargement may increase the accumulation of bacterial biofilm and prevent adequate oral hygiene measures, thus inducing inflammation, periodontitis, bone and tooth loss and halitosis.

In the CCBs-induced gingival enlargement, the increase in the gingival tissue volume is primarily due to a connective tissue response rather than an epithelial cell proliferation.[6] It is characterised by an excessive accumulation of extracellular matrix proteins, such as collagen, amorphous ground substance and of non-collagenous proteins, such as glycosaminoglycans.[7]

Both inflammatory and non-inflammatory pathways are proposed to explain the gingival hyperplasia after the use of drugs. The proposed non-inflammatory mechanisms are initiated by the decreased uptake of folic acid, blockage of aldosterone synthesis in the adrenal cortex and consequent feedback increase in adrenocorticotropic hormone level and upregulation of keratinocyte growth factor. The direct toxic effects of concentrated drug in crevicular gingival fluid may initiate the inflammatory process.[8] The risk factors include poor oral hygiene and bacterial dental plaque formation. Age has not been identified as a risk factor for CCBs-induced gingival hyperplasia, as these drugs are usually prescribed to middle-aged and older patients, preventing any attempt to stratify them.[9] Nifedipine increased the conversion of testosterone to 5-dihydrotestosterone.[10] The active androgen metabolite appears to target subpopulations of fibroblasts and induces collagen synthesis or decreases its degradation. Therefore, the drug-induced gingival hyperplasia is reported more in males than in females. There is a lack of a clear correlation between dosage of nifedipine and occurrence of gingival hyperplasia.[11] Some reports on amlodipine suggest that a daily dose of 5 mg or higher could be a risk factor for gingival overgrowth in some patients.[12] Lederman et al.[13] were the first to report its negative oral effects of nifedipine in 1984; subsequent studies showed that its prevalence varied from 14% to 83%.[14],[15] As for verapamil and amlodipine, the prevalence was significantly lower (4.2% and 3.3%, respectively) than that of nifedipine.[12],[16] The most effective treatment of gingival hyperplasia is cessation of the offending medication and a substitution with another class, or substitution with another CCB that has a lower risk of inducing gingival enlargement, such as verapamil[13] and isradipine.[17] In addition, surgical and non-surgical management may be required. As many as 40% of the patients are at risk of recurrence as early as 3–6 months.[18] It appears that the risk of recurrence is higher in patients with poor oral hygiene or lack of dental care.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors are faculty members/Uundergraduate/postgraduate students/residents of Sri Venkateswara Institute of Medical sciences, Tirupati, of which Journal of Clinical and Scientific Research is the official Publication. The article was subject to the journal's standard procedures, with peer review handled independently of these faculty and their research groups.



 
  References Top

1.
Kimball OP. The treatment of epilepsy with sodium diphenyl hydantoinate. J Am Med Assoc 1939;112:1244-5.  Back to cited text no. 1
    
2.
Dongari-Bagtzoglou A, Research, Science and Therapy Committee, American Academy of Periodontology. Drug-associated gingival enlargement. J Periodontol 2004;75:1424-31.  Back to cited text no. 2
    
3.
Garzino-Demo P, Carbone M, Carrozzo M, Broccoletti R, Gandolfo S. An increase in gingival volume induced by drugs (phenytoin, cyclosporine and calcium antagonists). A review of the literature. Minerva Stomatol 1998;47:387-98.  Back to cited text no. 3
    
4.
Srivastava AK, Kundu D, Bandyopadhyay P, Pal AK. Management of amlodipine-induced gingival enlargement: Series of three cases. J Indian Soc Periodontol 2010;14:279-81.  Back to cited text no. 4
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5.
Fischer J, Ganellin CR. Analogue-based drug discovery. John Wiley and Sons; 2006. p. 465.  Back to cited text no. 5
    
6.
Livada R, Shiloah J. Calcium channel blocker-induced gingival enlargement. J Hum Hypertens 2014;28:10-4.  Back to cited text no. 6
    
7.
Marshall RI, Bartold PM. A clinical review of drug-induced gingival overgrowths. Aust Dent J 1999;44:219-32.  Back to cited text no. 7
    
8.
Joshi S, Bansal S. A rare case report of amlodipine-induced gingival enlargement and review of its pathogenesis. Case Rep Dent 2013;2013:138248.  Back to cited text no. 8
    
9.
Ellis JS, Seymour RA, Steele JG, Robertson P, Butler TJ, Thomason JM. Prevalence of gingival overgrowth induced by calcium channel blockers: A community-based study. J Periodontol 1999;70:63-7.  Back to cited text no. 9
    
10.
Sooriyamoorthy M, Gower DB, Eley BM. Androgen metabolism in gingival hyperplasia induced by nifedipine and cyclosporin. J Periodontal Res 1990;25:25-30.  Back to cited text no. 10
    
11.
Barclay S, Thomason JM, Idle JR, Seymour RA. The incidence and severity of nifedipine-induced gingival overgrowth. J Clin Periodontol 1992;19:311-4.  Back to cited text no. 11
    
12.
Jorgensen MG. Prevalence of amlodipine-related gingival hyperplasia. J Periodontol 1997;68:676-8.  Back to cited text no. 12
    
13.
Lederman D, Lumerman H, Reuben S, Freedman PD. Gingival hyperplasia associated with nifedipine therapy. Report of a case. Oral Surg Oral Med Oral Pathol 1984;57:620-2.  Back to cited text no. 13
    
14.
Barak S, Engelberg IS, Hiss J. Gingival hyperplasia caused by nifedipine. Histopathologic findings. J Periodontol 1987;58:639-42.  Back to cited text no. 14
    
15.
Fattore L, Stablein M, Bredfeldt G, Semla T, Moran M, Doherty-Greenberg JM. Gingival hyperplasia: A side effect of nifedipine and diltiazem. Spec Care Dentist 1991;11:107-9.  Back to cited text no. 15
    
16.
Miller CS, Damm DD. Incidence of verapamil-induced gingival hyperplasia in a dental population. J Periodontol 1992;63:453-6.  Back to cited text no. 16
    
17.
Westbrook P, Bednarczyk EM, Carlson M, Sheehan H, Bissada NF. Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine. J Periodontol 1997;68:645-50.  Back to cited text no. 17
    
18.
Ilgenli T, Atilla G, Baylas H. Effectiveness of periodontal therapy in patients with drug-induced gingival overgrowth. Long-term results. J Periodontol 1999;70:967-72.  Back to cited text no. 18
    

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Correspondence Address:
R Ram,
Professor and Head, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_30_20



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