The prevalence of hypertension increases with advancing age. The management of hypertension especially in the elderly has its own limitations. Verapamil is not recommended in the elderly on account of high incidences of troublesome constipation.  Amlodipine has become very popular with the cardiologists and general physicians.  Survey of literature has not yielded any citation where the troublesome effect of amlodipine on the gastrointestinal tract has been reported.  In an experimental study on isolated rabbit intestine we have demonstrated that amlodipine dose-dependently inhibit the spontaneous activity of the intestinal tract.  With this background the present observational study was planned. A total of 100 hypertensive patients were included in the present study. Fifty patients were on amlodipine alone and 50 patients on combination of amlodipine and atenolol. The main parameter analyzed was the frequency and consistency of stool before and after intake of drug.  The relative risk (RR) of developing constipation was 4.00 with 95% CI 0.8930 to 17.917 in amlodipine alone group.  From this study it can be concluded that the relative risk of developing constipation is 4 times more in patients who are taking amlodipine alone as compared to those patients who are on combination of amlodipine and atenolol

Saha, Lekha

Shekhar Gautam, Chander

ISRN Gastroenterology

English

PubMed

The prevalence of hypertension increases with advancing age. The management of hypertension especially in the elderly has its own limitations. Verapamil is not recommended in the elderly on account of high incidences of troublesome constipation.  Amlodipine has become very popular with the cardiologists and general physicians.  Survey of literature has not yielded any citation where the troublesome effect of amlodipine on the gastrointestinal tract has been reported.  In an experimental study on isolated rabbit intestine we have demonstrated that amlodipine dose-dependently inhibit the spontaneous activity of the intestinal tract.  With this background the present observational study was planned. A total of 100 hypertensive patients were included in the present study. Fifty patients were on amlodipine alone and 50 patients on combination of amlodipine and atenolol. The main parameter analyzed was the frequency and consistency of stool before and after intake of drug.  The relative risk (RR) of developing constipation was 4.00 with 95% CI 0.8930 to 17.917 in amlodipine alone group.  From this study it can be concluded that the relative risk of developing constipation is 4 times more in patients who are taking amlodipine alone as compared to those patients who are on combination of amlodipine and atenolol.</jats:p

Lekha Saha

Chander Shekhar Gautam

Crossref

International Scholarly Research NetworkISRN GastroenterologyVolume 2011, Article ID 757141, 3 pagesdoi:10.5402/2011/757141Clinical StudyThe Effect of Amlodipine Alone and inCombination with Atenolol on Bowel Habit inPatients with Hypertension: An ObservationLekha Saha1 and Chander Shekhar Gautam21 Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER),Chandigarh 160012, India2 Department of Pharmacology, Government Medical College and Hospital, Chandigarh 160032, IndiaCorrespondence should be addressed to Lekha Saha, lekhasaha@rediﬀmail.comReceived 8 September 2010; Accepted 27 October 2010Academic Editors: F. Azpiroz, J. M. Kim and A. WeimannCopyright © 2011 L. Saha and C. Shekhar Gautam. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.The prevalence of hypertension increases with advancing age. Themanagement of hypertension especially in the elderly has its ownlimitations. Verapamil is not recommended in the elderly on account of high incidences of troublesome constipation. Amlodipinehas become very popular with the cardiologists and general physicians. Survey of literature has not yielded any citation wherethe troublesome eﬀect of amlodipine on the gastrointestinal tract has been reported. In an experimental study on isolated rabbitintestine we have demonstrated that amlodipine dose-dependently inhibit the spontaneous activity of the intestinal tract. With thisbackground the present observational study was planned. A total of 100 hypertensive patients were included in the present study.Fifty patients were on amlodipine alone and 50 patients on combination of amlodipine and atenolol. The main parameter analyzedwas the frequency and consistency of stool before and after intake of drug. The relative risk (RR) of developing constipationwas 4.00 with 95% CI 0.8930 to 17.917 in amlodipine alone group. From this study it can be concluded that the relative risk ofdeveloping constipation is 4 times more in patients who are taking amlodipine alone as compared to those patients who are oncombination of amlodipine and atenolol.1. IntroductionThe prevalence of hypertension increases with advancingage; for example, about 50% of people between the ages of60 and 69 years old have hypertension, and the prevalenceis further increased beyond age 70 [1]. The managementof hypertension especially in the elderly has its own lim-itations. Drugs used in hypertension are calcium channelblockers (CCBs), angiotensin converting enzyme inhibitors(ACEIs), and low-dose diuretics [2]. Verapamil, belongingto papaverine group, is not recommended in the elderlyon account of high incidences of troublesome constipation[2]. Amlodipine, pharmacokinetically the most distinct typeof dihydropyridine (DHP) CCB, has become very popularwith the cardiologists and general physicians in doses of5mg or 10mg once daily [3, 4]. Survey of the literaturehas not yielded any citation where the troublesome eﬀectof amlodipine on the gastrointestinal tract (GIT) has beenreported [5]. We had demonstrated in an experimental studyon isolated rabbit intestine that amlodipine dose depen-dently inhibits the spontaneous activity of the intestinal tract[6]. With this background the present observational studywas planned to demonstrate the experimental observation inthe hypertensive patients’ population coming to the medicalOPD in our hospital. Therefore, the aim of the present studywas to demonstrate the eﬀect of amlodipine alone and incombination with atenolol on the bowel habits in patientswho are taking these drugs.2. Materials and MethodsThis was a noninterventional observational study. Thepresent study was approved by local institutional ethicscommittee. The subject of the present study was the patient2 ISRN Gastroenterologypopulation attending the hypertensive clinic in our institu-tion. Both male and female patients with age 40–70 years,taking amlodipine alone or in combination with atenolol,were screened for this present study. Patients with history ofintake of any other medicines or history of any other diseasesthat can decrease intestinal motility like hypothyroidismwere excluded from the study. Written informed consent wastaken from the patients before being included in the study.A questionnaire-based proforma was filled for each patientwhich includes the frequency and consistency of the stoolbefore and after the drug intake, presence of blood in stooland hard stool, the duration of drug intake, the dose of thedrug, the use of laxatives, physical activity, and diet, andwas filled for each patient. The answers were then compiled,tabulated, and analyzed. The constipation was defined as thehistory of less than 3 spontaneous bowel movements (SBM)per week for a period of at least 6 months [7].3. Statistical AnalysisThe data are expressed as mean ± SD and as absolutenumber of patients whenever applicable. The relative risk ofdeveloping constipation and blood in stool and hard stoolwas calculated in both the patient groups who are takingamlodipine alone or in combination with atenolol by usingFisher’s exact test. The other variables like age, sex, SBM/wk,and duration of treatment were compared by using unpaired“t” test. P < .05 was considered statistically significant.4. ResultsA total of 100 patients who attended the hypertensive clinicin Government Medical College and Hospital, Chandigarh,were included in the study after the screening. Fifty patientswere on amlodipine alone and 50 patients were on combina-tion of amlodipine and atenolol.Table 1 depicted the data of all 100 patients. There wasno significant diﬀerence in the baseline characteristics inboth the groups. The baseline SBM/wk was comparable(8.64 ± 4.4 versus 7.84 ± 2.5) in both the groups (Table 1).The number of patients in the amlodipine group withSBM/wk less than 3 was 8 whereas in combination group(amlodipine + atenolol) it was 2 (P = .045, Fisher’sexact test, significant). The relative risk (RR) of developingconstipation was 4.00 with 95% CI 0.8930 to 17.917 inamlodipine alone group. However, there was no significantdiﬀerence in SBM/wk in both the groups before and aftertreatment (P > .05). The majority of the patients in boththe groups were on amlodipine 10 mg daily dose (28(56%)patients in amlodipine group and 29(58%) patients incombination group) (Table 1). The duration of treatmentwith amlodipine was also comparable in both the groups(16.75 ± 2.5 months versus 14.025 ± 2.58 months). Thenumber of patients with blood in stool was 5 in amlodipinegroup while there was none in the combination group (P =.028, significant). Straining/hard stool was seen in 10 patientsin the amlodipine group and 3 patients in the combinationgroup (P = .035, significant) (Table 1). The risk (RR =3.33 with 95% CI 0.9748 to11.399) of developing hard stoolTable 1: Eﬀects of amlodipine alone and in combination withatenolol on bowel habit in patients with hypertension. SBM:spontaneous bowel movement. Results are expressed as mean± SDand absolute number.ParametersAmlodipine(n = 50)Amlodipine+ atenolol(n = 50)Age (Yrs) (M± SD) 54.14± 11.32 54.36± 10.27Male : Female 23 : 27 21 : 29SBM/wk (M± SD)Before treatment 8.64± 4.4 7.84± 2.5After treatment 8.0± 4.7 7.44± 2.64No of patients with SBM/wk < 3 8∗ 2No. of patients with blood in stool 5∗∗ 0No. of patients with straining/hardstool10∗∗∗ 3Duration of treatment (Months)(M± SD) 16.75± 2.5 14.025± 2.6Dose of amlodipineNo. of patients taking 5mg OD 22 21No. of patients taking 10mg OD 28 29No. of patients taking isabgual 5 4∗P = .045, Fisher’s exact test, RR = 4.00.∗∗P = .028, Fisher’s exact test.∗∗∗P = .035, Fisher’s exact test, RR = 3.33.was more in amlodipine group. The number of patientstaking laxatives was 5 in amlodipine alone group and 4 incombination group (P > .05).5. DiscussionSo from the present observation, it can be said that amlodip-ine alone associated with increased incidence of constipation(RR = 4.00) and hard stool (RR = 3.333) and when atenololwas combined, the incidence of constipation and hard stoolwas less (P < .05). Like our previous animal study, thisobservational study also demonstrated that amlodipine canreduce the peristaltic activity of the intestine when usedalone. From this observation and previous animal study,we can hypothesized that when amlodipine is used alone itcould reduce the peristaltic activity of the intestine whichmay be due to the release of catecholamines (like nifedipine)[5], and subsequent interaction of this catecholamines withthe adrenergic receptors present in the gastrointestinal tractmay lead to constipation. However, when amlodipine wascombined with atenolol, the released catecholamine wasunable to produce an eﬀect as β-adrenergic receptor inthe GIT was blocked by atenolol. The Indian populations,especially the advancing age group, are very much concernedabout their bowel evacuation. Such hypertensive patientswho suﬀer constipation on account of the drug can also havethe mental stress which can further facilitate the release ofcatecholamines and may have deleterious eﬀect on the bowelhabits. Hence, in an elderly patient having concomitantISRN Gastroenterology 3compromisedGIT and hypertension warrants a judicious useof amlodipine. Further study is in progress.Conflict of InterestsThe authors declare that they have no conflict of interests.References[1] A. V. Chobanian, G. L. Bakris, H. R. Black et al., “Seventh reportof the joint national committee on prevention, detection, evalu-ation, and treatment of high blood pressure,” Hypertension, vol.42, no. 6, pp. 1206–1252, 2003.[2] D. A. Weiner, “Calcium channel blockers,” Medical Clinics ofNorth America, vol. 72, no. 1, pp. 83–115, 1988.[3] D. Murdoch and R. C. Heel, “Amlodipine. A review ofits pharmacodynamic and pharmacokinetic properties, andtherapeutic use in cardiovascular disease,” Drugs, vol. 41, no.3, pp. 478–505, 1991.[4] E. Agabiti-Rosei, M. L. Muiesan, D. Rizzoni et al., “Cardio-vascular structural changes and calcium antagonist therapy inpatients with hypertension,” Journal of Cardiovascular Pharma-cology, vol. 24, supplement, pp. S37–S43, 1994.[5] K. Egstrup and P. E. Andersen Jr., “Transient myocardialischemia during nifedipine therapy in stable angina pectoris,and its relation to coronary collateral flow and comparison withmetoprolol,” American Journal of Cardiology, vol. 71, no. 2, pp.177–183, 1993.[6] C. S. Gautam, S. Malhotra, and N. K. Goel, “Intestinal motility:the eﬀect of amlodipine on isolated rabbit intestine,” IndianJournal of Pharmacology, vol. 30, no. 1, p. 54, 1998.[7] M. J. Kreek, “Constipation syndromes,” in A PharmacologicalApproach to Gastrointestinal Disorders, J. H. Lewis, Ed., pp. 179–208, Williams & Wilkins, Baltimore, Md, USA, 1994.Submit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

The Effect of Amlodipine Alone and in Combination with Atenolol on Bowel Habit in Patients with Hypertension: An Observation

Amlodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease,”

and treatment of high blood pressure,” Hypertension,

Calcium channel blockers,”

Cardiovascular structural changes and calcium antagonist therapy in patients with hypertension,”

Constipation syndromes,”

Intestinal motility: the eﬀect of amlodipine on isolated rabbit intestine,”

Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, anditsrelationtocoronarycollateralﬂowandcomparisonwith metoprolol,”

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The Effect of Amlodipine Alone and in Combination with Atenolol on Bowel Habit in Patients with Hypertension: An Observation

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