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CALCIUM CHANNEL BLOCKERS AS A ETHIOLOGICAL FACTOR FOR
GASTROESOPHAGEAL REFLUX DISEASE
Ismoilova M.I., Mirzajonova Sh.A.
Ferghana State Public Health Medical Institute
Ferghana, Republic of Uzbekistan
Abstract:
Gastroesophageal reflux disease is the most common visceral manifestation of
chronic calcium channel blockers use, resulting in impaired esophageal clearance and
retention of ingested food. Progression of gastroesophageal reflux disease and the damaging
effect of due to esophageal dysmotility is clearly understood . Nifedipine is a widely
prescribed calcium antagonist in a significant percentage of ischaemic heart disease patients
in order to inhibit coronal vasospasm. We describe the case of severe exacerbation of
gastroesophageal reflux disease in a 76-year-old female with Gastroesophageal refluxe
disease who was treated with oral nifedipine for Ischaemic heart disease.
Key Words:
Esophagus, Ischaemic heart disease, Nifedipine, Gastroesophageal reflux
disease.
Introduction
Gastrointestinal dysmotility is not uncommon in patients suffering from
gastroesophageal reflux disease, with a reported incidence even up to 80% [1]. Esophagus
stands for the most frequently invaded organ in cases of gastrointestinal involvement, with
gastroesophageal reflux disease (GERD) [2]. The main mechanisms of nifedipine that cause
gastroesophageal reflux disease is impaired efficacy of peristalsis and clearance, reduction
of the pressure of the lower esophageal sphincter (LES), high incidence of hiatal hernias due
to the gradual shortening of the organ, and delay of gastric emptying [3].
Concerning Ischaemic heart disease and Gastroesophageal reflux disease, their firm
association is well established. Patients suffering from ischaemic heart disease and taking
nifedipine are likely to develop Gastroesophageal reflux disease . [4].
These patients who are suffering from Gastroesophageal reflux disease and taking
nifedipine for their ischaemic heart disease should avoid treatment with any drug that could
enhance GERD development. Recent studies suggest that calcium channel blockers (CCBs),
and particularly nifedipine, increase the risk of GERD by significantly reducing the tone of
the LES, increasing esophageal exposure to gastric acid and reducing the amplitude and
duration of esophageal peristalsis [6–8]. According to these findings, the administration of
CCBs should be avoided, if possible, in patients with GERD. We report a very interesting
case of gastroesophageal reflux disease developing in a 76-year-old female suffering from
ischaemic heart disease and taking nifedipine , after a 6-month period of receiving oral
nifedipine for treating ischaemic heart disease. Our case underlines for the first time the
urgent need of considering the potential effect of CCBs as an exaggerator of
gastroesophageal reflux disease in patients with nifedipine-derived GERD, through
enhancing esophageal acid reflux due to progression of esophageal LES dysmotility.
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Case Report
Our patient was a 76-year-old never-smoker female who presented to the emergency
department complaining of retrosternal discomfort, after a chocking episode which had
awakened her during the night. Physical examination revealed limited thickness of the
fingers, presence of ulcers in the oral cavity, palmar telangiectasias and slightly audible
crackle sounds bilaterally in the lower respiratory fields. Her vital signs were as follows:
blood pressure 160/95 mm Hg, heart rate 70 bpm, temperature 36.3°C, respiration rate
20/min and SatO2 97%.. Electrocardiogram reveal ischaemic heart disease. Blood tests at
admission demonstrated leukocytosis (4,800/mm3), slight thrombocytosis (280,000/mm3),
C-reactive protein levels of 1.8 mg/dl and serum lactic dehydrogenase of 412 IU/l. The
rheumatological patient’s medical history included presence of Sjögren’s syndrome,
rheumatoid arthritis and GERD (under anti-secretory treatment). In addition, she reported
that approximately 6 months before she had been diagnosed with ischaemic heart disease
and arterial hypertension and since then she had been receiving oral nifedipine (40 mg) daily.
The patient mentioned that after the initiation of treatment with nifedipine, arterial
hypertension was controlled and she did not experience any other ischaemic heart disease
symptoms; nevertheless, she reported exacerbation of GERD symptoms, despite receiving
anti-secretory treatment with proton pump inhibitors.
The initial management of our patient in the emergency department consisted of intravenous
administration of hydrocortisone and omeprazole. After 2 h, the patient’s clinical condition
had improved, The patient was referred to the Department of Gastrointestinal Medicine for
further hospitalization and was discharged after 9 days in excellent clinical condition. It was
decided that nifedipine treatment for ischaemic heart disease should be replaced with
diltiazem, which has proven to affect less esophageal dysmotility and lower sphincter
pressure, compared to other CCBs [9]. Moreover, the daily dose of anti-secretory therapy
with omeprazole was doubled. Nearly 12 months after her admission to the emergency
department, the patient has not experienced similar severe GERD symptoms or respiratory
complications, with both arterial hypertension and ischaemic heart disesa efficiently
controlled.
Discussion
CCBs, which are considered to be the gold standard in confronting ischaemic heart disease,
have proven to be associated with impaired esophageal motility by various studies, with
nifedipine so far dominating the researchers’ interest. This adverse effect is mediated by the
inhibition of calcium influx into the smooth muscle cells, which is essential for adequate
contraction and thus maintenance of efficient pressure of the LES, in order to prevent
gastroesophageal reflux [10]. Moreover, CCBs tend to increase esophageal exposure to
gastric acid and to reduce the amplitude and duration of esophageal peristalsis [6–8],
implying the existence of multiple effects of these drugs on esophageal motility. These
findings are collected , which suggested that over the 10-year period of the study, treatment
with CCBs was an independent factor for GERD-related physician visits [11]. Consequently,
it is evident that CCBs should be prescribed with extreme caution in patients with
potentially life-threatening GERD, such as patients with systemic sclerosis, particularly in
cases of pre-existing lung invasion of the disease, as chronic aspiration may lead to rapid
progression of lung fibrosis.
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It is reasonable to assume that treating patients with esophageal dysmotility with CCBs, e.g.
for hypertension or angina pectoris, may resemble a serious risk factor of further impairment
of GERD and GERD-related diseases, such as chronic inflammation of the respiratory tract.
In patients with esophageal sclerosis, this vicious circle of aspiration and lung inflammation,
apart from further enhancing fibrosis, is associated with an increased probability of sleep
apnea, another life-threatening condition, which is consistent with the feeling of chocking
that awakened our patient during the night [13]. Also, the absence of long-term beneficial
effect of CCBs in progressive gastroesophageal reflux disease further highlights the
importance of their cautious prescription in patients with esophageal dysmotility. On the
other hand, it is suggested that not all CCBs have to the same extent the adverse effects
described above; it appears that diltiazem affects less esophageal dysmotility and lower
sphincter pressure, compared to other CCBs [9]. Diltiazem was an attracting alternative,
providing minimal damaging effect on GERD and the concomitant aspiration risk.
Nevertheless, its administration was accompanied by doubling of the daily proton pump
inhibitor dose.
Up to now, there are no solid data that can shed light on this therapeutic challenge. So far,
the skepticism regarding the use of CCBs in patients with gastroesophageal reflux disease
mainly focuses on investigating the consequences of their administration in esophagus
function itself. Although the up-to-date findings are undoubtedly impressive, the final effect
of CCBs on GERD-related disorders remains unknown. Consequently, further prospective
studies should be conducted in order to assess the short- and long-term effects of CCBs in
patients with disease complicated by esophageal dysmotility, GERD and serious GERD-
related conditions, such as interstitial lung disease.
Conclusions
CCBs have been proven to be associated with a higher risk of developing gastroesophageal
reflux. We report a case of rapid progression and exacerbation of gastroesophageal reflux
symptoms in a 76-year-old non-smoker female with ischaemic heart disesa , after a 6-month
period of receiving oral nifedipine. The patient finally addressed the emergency department
with symptoms of gastroesophageal reflux disease. After 9 days of hospitalization the
patient was discharged in excellent clinical condition and nifedipine was switched to
diltiazem, along with increasing the daily dose of anti-secretory therapy. Nearly 12 months
later, the patient has not experienced similarly severe GERD symptoms and seems to
tolerate the new therapeutic approach well. Our case report highlights the necessity of
further investigation of the long-term effects of CCBs in GERD-related complications,
particularly those imposing a significant risk of mortality.
References
1 Jaovisidha K, Csuka ME, Almagro UA, Soegrel K: Severe gastrointestinal involvement in
systemic sclerosis: report of five cases and review of the literature. Semin Arthritis Rheum
2004;34:689–702.
2 Abu-Shakra M, Guillemin F, Lee P: Exaggerated fibrosis in patients with systemic
sclerosis (scleroderma) following radiation therapy. J Rheumatol 1993;20:1601–1603.
3 Ebert EC: Esophageal disease in scleroderma. J Clin Gastroenterol 2006;40:769–775.
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
4 Mouthon L, Bérezné A, Guillevin L, Valeyre D: Therapeutic options for systemic sclerosis
related interstitial lung diseases. Respir Med 2010;104(suppl 1):S59–S69.
5 Bryan C, Knight C, Black CM, et al: Prediction of five-year survival following
presentation with scleroderma: development of a simple model using three disease factors at
first visit. Arthritis Rheum 1999;42:2660–2665.
6 Kovac J, Preiksaitis H, Sims S: Functional and molecular analysis of L-type calcium
channels in human esophagus and lower esophageal sphincter smooth muscle. Am J Physiol
Gastrointest Liver Physiol 2005;289:998–1006.
7 Ishikawa H, Iwakiri K, Sugiura T, Kobayashi M: Effect of nifedipine administration (10
mg) on esophageal acid exposure time. J Gastroenterol 2000;35:43–46.
8 Yoshida K, Furuta K, Adachi K, et al: Effects of anti-hypertensive drugs on esophageal
div contraction. World J Gastroenterol 2010;16:987–991.
9 Hughes J, Lockhart J, Joyce A: Do calcium antagonists contribute to gastro-oesophageal
reflux disease and concomitant noncardiac chest pain? Br J Clin Pharmacol 2007;64:83–89.
10 Hamada A, Isii J, Doi K, et al: Increased risk of exacerbating gastrointestinal disease
among elderly patients following treatment with calcium channel blockers. J Clin Pharm
Ther 2008;33:619–624.
11 Freindenberg F, Hanlon A, Vanar V, et al: Trends in gastroesophageal reflux disease as
measured by the National Ambulatory Medical Care Survey. Dig Dis Sci 2010;55:1911–
1917.
12 Domenighetti G, Saglini V: Short- and long-term hemodynamic effects of oral nifedipine
in patients with pulmonary hypertension secondary to COPD and lung fibrosis. Deleterious
effects in patients with restrictive disease. Chest 1992;102:708–714.
13 Prado G, Allen R, Trevisiani V, et al: Sleep disruption in systemic sclerosis (scleroderma)
patients: clinical and polysomnographic findings. Sleep Med 2002;3:341–345.
