Amlodipine-Induced Gingival Hyperplasia in a Great Dane
A 3 yr old, 70 kg (154 lbs) female spayed Great Dane developed gingival hyperplasia after treatment of systemic hypertension with amlodipine 7.5 mg q 12 hr for 16 mo. Physical examination was unremarkable except for systemic hypertension and severe gingival hyperplasia. Amlodipine was replaced with hydralazine (0.72 mg/kg [0.32 mg/lb]). Nine months later, gingival hyperplasia was nearly resolved and hypertension was well controlled. Calcium channel blockers such as amlodipine are a rare cause of gingival hyperplasia in the canine patient. Recognition of this side effect is important because a full recovery can be achieved when the offending agent is removed.
Introduction
Gingival hyperplasia is a well known but rare side effect in human medicine of prolonged administration of calcium channel blocking drugs (e.g., amlodipine), but has rarely been documented in veterinary literature.1–3 By contrast, this complication is well reported and more common with cyclosporine. It is estimated that the veterinary use of cyclosporine is associated with ∼3% incidence of gingival hyperplasia; once the drug is removed, the gingiva return to normal within a few weeks to months.4 There also appears to be a higher prevalence of gingival hyperplasia with cyclosporine usage in boxers, Great Danes, collies, Doberman pinschers, and Dalmations.5
Case Report
A 70 kg, 3 yr old female spayed Great Dane was evaluated on July 19, 2006 because of sudden onset of fasciculationsa. The dog was bright, alert, and responsive. The only abnormality noted was tachycardia (144 beats/min) and hypertension (direct blood pressure was 201/109 mm Hg, mean, 126 mm Hg)b. Electrocardiography showed only tachycardia. Funduscopic examination was normal. Normal diagnostic studies were complete blood count, chemistry panel, chest and abdominal radiographs, echocardiogram, and abdominal ultrasound. The dog's blood pressure remained elevated in a hospital setting over the next 24 hr. After she was sedated with 1 cc of acepromazinec and 1 cc of butorphanold IV, her blood pressure remained at 200 mm Hg, and her tachycardia resolved. The dog was sent home on 12.5 mg of atenolole q 12 hr with plans for a recheck in 5 days.
Six days later, her heart rate was 124 beats/min and her Dopplerf blood pressure was 300 mm Hg. Her atenolole dose was increased to 25 mg q 12 hr.
Two weeks after initial evaluation, her heart rate was 88 beats/min and her blood pressure was >300 mm Hg by Dopplerf. She was started on amlodipineg 7.5 mg q 12 hr and continued on 25 mg of atenolole q 12 hr. Two weeks later, her blood pressure was controlled (140 mm Hg). On her yearly recheck, July 12, 2007, her blood pressure was 288 mm Hg by Dopplerf. Her clinical examination was normal.
On November 12, 2007, the patient presented for re-evaluation with a recent history of blood seen on her rawhide treats. She had a heart rate of 160 beats/min with a blood pressure of >300 mm Hg by Dopplerf, and was noted to have severe hyperplasia of the gingiva in the vicinity of her upper and lower canines and incisors (Figure 1). Her medications were amlodipineg 7.5 mg q 12 hr and atenolole 25 mg q 12 hr. She was also receiving Sentinelh heartworm protection. Because of the gingival hyperplasia and her inadequately controlled blood pressure, amlodipine was discontinued, and she was begun on hydralazinei 50 mg/day.
Citation: Journal of the American Animal Hospital Association 47, 5; 10.5326/JAAHA-MS-5565
The owners reported gradual improvement of the gingival hyperplasia over the next several months. Eight months after the previous visit, her blood pressure was stabilized at 120 mm Hg and her gingiva were nearly normalized. The large gingival masses seen over her upper canines were almost completely resolved and her incisors were easily visible (Figure 2).
Citation: Journal of the American Animal Hospital Association 47, 5; 10.5326/JAAHA-MS-5565
Discussion
There are multiple causes of gingival hyperplasia. Acute pathology, such as gingivitis, periodontal abscesses, or chronic disease, such as dental plaque accumulation, can result in this condition. Gingival hyperplasia has been attributed to phenytoin and cyclosporine, as well as calcium channel blockers in research animals to oxodipine.2,3,5
Until recently, the only published research on gingival hyperplasia due to calcium channel blockers was in rats and beagles.1–3,6,7 A recent article by Thomason et al. documented gingival hyperplasia in 7 of 82 dogs treated with amlodipine for degenerative valvular disease from 2004 to 2008.8 Gingival hyperplasia began to resolve 2–8 wk after discontinuation of the calcium channel blocker, with complete resolution in 3–6 mo.8 The cause of drug-induced gingival hyperplasia is unknown. It was hypothesized in human medicine that calcium channel blockers cause hyperplasia due to upregulation of circulating androgens, which are transformed into testosterone, resulting in stimulation of the androgen-sensitive gingiva.1,9 Another hypothesis involved blocking of the calcium-dependent enzyme, transglutaminase, which is involved in apoptosis. Transglutaminase appears to be more active in gingival tissue; therefore, blocking this enzyme could allow for increased gingival growth.5,6
Calcium channel blocker induced gingival hyperplasia is rare. This side effect is not well documented in veterinary literature and its underlying pathophysiology remains unknown; however, it is important for clinicians to recognize this side effect, as it is usually reversible.
Gingival hyperplasia in a 3 yr old Great Dane on 7.5 mg amilodine q 12 hr for 16 mo. Mandibular incisors cannot be seen due to the gingival hyperplasia, and the maxillary canines are partly engulfed.
Nine months after discontinuation of amlodipine, the gingiva are nearly normal.
Contributor Notes
