|Year : 2016 | Volume
| Issue : 1 | Page : 32-37
Potential drug-drug interactions among elderly patients on anti-hypertensive medications in two tertiary healthcare facilities in Ekiti State, South-West Nigeria
Joseph Olusesan Fadare1, Adekunle E Ajayi2, Adekunle Olaitan Adeoti2, Olufemi O Desalu3, Abimbola Margaret Obimakinde4, Segun Matthew Agboola5
1 Department of Pharmacology, Ekiti State University, Ado Ekiti, Nigeria
2 Department of Medicine, Ekiti State University, Ado Ekiti, Nigeria
3 Department of Medicine, University of Ilorin, Ilorin, Nigeria
4 Department of Family Medicine, Ekiti State University Teaching Hospital, Ado Ekiti, Nigeria
5 Department of Family Medicine, Federal Teaching Hospital, Ido Ekiti, Nigeria
|Date of Web Publication||6-May-2016|
Joseph Olusesan Fadare
Department of Pharmacology, Ekiti State University, Ado Ekiti
Introduction: Drug-drug interactions remain a major cause of adverse drug reactions with great consequences such as increased morbidity and increased healthcare cost. In elderly patients with systemic hypertension, there is a tendency for them to be prescribed multiple medications and this may expose them to some drug-drug interactions (DDIs) especially in the context of physiological changes of ageing. The objective of this study was to evaluate potential drug-drug interaction among some Nigerian elderly hypertension. Methods: A cross-sectional study involving elderly hypertensive patients attending the general outpatient clinic of two tertiary healthcare facilities located in Ekiti State, South-West Nigeria. The information collected from the patients' medical records included their ages, gender, diagnosis and list of prescribed anti-hypertensive medications. Potential drug-drug interactions were checked for using the Multi-Drug Interaction Checker (Medscape Reference) and Epocrates Drug Interaction Checker (San Mateo CA, USA). Results: A total of 350 elderly patients attended the clinics during the study period of which 208 (59.4%) hypertensive patients were identified and their records used for analysis. The fixed-dose combination drug Moduretic® (Amiloride /Hydrochlorothiazide)-25.7% was the most commonly prescribed antihypertensive followed by Lisinopril (16.6%), Amlodipine (13.2%) and Nifedipine (12.6%). The anti-platelet Acetyl-salicylic acid (ASA) was prescribed for 100 (48.1%) patients and represented 19.8% of all prescribed medications. A total of 231 potential DDIs were found among the patients giving a mean of 1.3 interactions per patient. The most common identified drug pairs with potential interactions were ACE inhibitors - Amiloride, followed by ACE inhibitors - Hydrochlorothiazide, ACE inhibitors - ASA and ARB - Amiloride. Conclusion: Potential drug-drug interactions, though common in this study comprised mainly of minor and moderate types. Notwithstanding, physicians need to be reminded of the potential for interactions when prescribing for elderly patients
Keywords: Anti-hypertensive medications, drug-drug interactions, drug utilization, geriatric patients, polypharmacy
|How to cite this article:|
Fadare JO, Ajayi AE, Adeoti AO, Desalu OO, Obimakinde AM, Agboola SM. Potential drug-drug interactions among elderly patients on anti-hypertensive medications in two tertiary healthcare facilities in Ekiti State, South-West Nigeria. Sahel Med J 2016;19:32-7
|How to cite this URL:|
Fadare JO, Ajayi AE, Adeoti AO, Desalu OO, Obimakinde AM, Agboola SM. Potential drug-drug interactions among elderly patients on anti-hypertensive medications in two tertiary healthcare facilities in Ekiti State, South-West Nigeria. Sahel Med J [serial online] 2016 [cited 2019 Nov 21];19:32-7. Available from: http://www.smjonline.org/text.asp?2016/19/1/32/181896
| Introduction|| |
Systemic hypertension has emerged as a leading cause of morbidity and mortality in many countries in Sub-Saharan Africa. , Some community-based studies conducted in the region showed a higher prevalence of hypertension among the elderly group of the population when compared with the young age group. ,,
Elderly patients are very prone to develop adverse drug reactions (ADRs) due to the peculiarities of their aging process and propensity to have many comorbid conditions. An important factor that may affect the response of elderly patients is their physiological changes with respect to drug disposition . ,, Furthermore , changes due to up- or down-regulation of receptors and those due to disease-drug interactions are other peculiarities related to aging. , Furthermore, enhanced sensitivity to drugs and a decrease in regulatory mechanisms have been reported in the elderly. This may result in adverse reactions such as orthostatic hypotension to anti-hypertensives and a greater risk of respiratory depression when opiates are used among this category of patients. , Many studies have identified drug-drug interactions (DDIs) as major cause of ADRs, especially in elderly patients. ,,, Drug interactions are defined as a drug response that is modified by another drug, food, disease condition or the environment.  DDI has been classified mainly into two - pharmacokinetic and pharmacodynamic.  Pharmacokinetic drug interactions are those due to changes at the level of drug absorption, distribution, metabolism, and excretion. Interaction at these different levels may lead to either a decreased or increased concentration of the drug with corresponding clinical effects. Drug interactions of the pharmaco-dynamic type are usually due to changes in the expected effects of the drugs that is, antagonism or synergism and may lead to either treatment failure or toxic effects. Another way of classifying DDIs is according to their clinical significance, that is, whether or not they affect patient's outcome. DDIs are sometimes beneficial; however, they account for 41% of ADRs. , The ADRs secondary to DDIs may consequently result in increased morbidity, prolonged hospitalizations, and increased healthcare costs. , In elderly patients with systemic hypertension, there is a tendency for prescription of multiple medications, thus exposing them to the risk for adverse DDIs.  Predictors of DDIs identified from several studies include polypharmacy, old age, comorbid conditions, and gender difference. ,,,, Since the majority of DDIs are preventable, their timely identification would be necessary to avert the physical and economic burden on patients and their relatives. Although some studies on the pattern of drug utilization and potential DDIs have been conducted among hypertensive patients in Nigeria, no information about the potential interactions between the antihypertensive and co-prescribed anti-platelet drugs among elderly patients with systemic hypertension are found in the literature. , The objectives of this study were to determine the prescribing pattern of anti-hypertensive and anti-platelet drugs among elderly hypertensive Nigerian patients while additional objectives were to find the prevalence of potential DDIs and identify the common DDIs . Our reasons for choosing these two groups of medication are that systemic hypertension is a chronic medical condition with most patients being prescribed antihypertensives and some form of anti-platelet/anticoagulant for primary prevention of complications. Other groups of medications prescribed for the patients such as anti-malarial drugs, antibiotics, and food supplements were not included in the analysis of potential DDIs primarily because the study was focused on antihypertensives and anti-platelets.
| Methods|| |
The study was conducted at the family medicine and general outpatients' clinics of the Ekiti State University Teaching Hospital, Ado-Ekiti and the Federal Medical Centre, Ido-Ekiti, both located in Ekiti State, South-West Nigeria. These healthcare institutions cater for the medical needs of the population of Ekiti and other neighboring states. The general outpatients' clinic of these two tertiary healthcare facilities are usually the first point of contact for patients attending these hospitals, and they are run by 11 consultant family physicians, 30 resident doctors, and 10 medical officers.
Study design and data collection
This is a retrospective cross-sectional study involving elderly patients who are ≥65 years old. The medical records of this group of patients attended at the outpatients' clinic of the two hospitals between March and June 2013 were extracted from the medical records department. The medical records of only those on antihypertensive medications for at least 6 months were selected and included in the study. The medical records of patients on only one medication and those without prescription were excluded from the study. The bio-demographic details of the patients, the antihypertensive and anti-platelet drugs prescribed for patients were extracted from the case files and transcribed into a data collection form. The reason for choosing only these two classes of medication has been ascribed earlier. The data collection form was pretested using the records of ten patients from the medical outpatients department and necessary adjustments made before the commencement of the study. The data collection was carried out by two resident doctors and a consultant in the Family Medicine Department of the two hospitals.
Potential DDIs were checked by using the Multi-drug Interaction Checker (Medscape Reference ® ) and Epocrates Drug Interaction Checker (San Mateo, CA, USA). These instruments have been used and validated in earlier studies conducted in Nigeria and other African Countries. , The antihypertensive and anti-platelet drugs prescribed for each patient were inputted into the two drug interaction checkers, and results recorded in the data collection forms as clinically significant, not clinically significant and the mechanism as pharmacokinetic or pharmacodynamic. , Clinically significant potentially drug interactions are those when the drugs are contra-indicated, with serious interactions necessitating discontinuation of the medication/s and drug combinations requiring close monitoring of either laboratory or clinical parameters. Potential drug interactions that were minor and of no clinical importance were classified as not significant. 
Information from the data collection form was recorded on a spreadsheet and analyzed using IBM SPSS version 19 (IBM Corporation, Armonk, NY, USA). Results are expressed as means, frequencies, and percentages. Analysis of variance was used to compare the means of different groups among the study population. Values of P < 0.05 were considered as significant.
The study received ethical approval from the Hospital Research Ethics Committee prior to commencement of the study.
| Results|| |
A total of 350 elderly patients attended the clinics during the study period of which 208 (59.4%) hypertensive patients were identified and their records were used for analysis. Female patients (106; 51%) constituted a slight majority among the hypertensive elderly patients. The mean age of the patients was 73.2 ± 7.7 years and their age distribution pattern was 65−74 years (125; 60.1%), 75−79 years (38; 18.3%), ≥80 years (45; 21.6%).
The mean number of prescribed drugs (antihypertensive and anti-platelets) was 2.4 ± 0.8. Thirty (15%) had one medication prescribed while 77 (37%), 82 (39%), and 19 (9%) had 2, 3 and 4 medications, respectively. Diuretics 134 (33%), calcium channel blockers 131 (32.3%), and angiotensin converting enzyme inhibitors (ACEIs) 111 (27.3%) were the most common classes of antihypertensive drugs prescribed. Others are beta-blockers 14 (3.4%), angiotensin-receptor blockers (ARBs) 8 (2%), and centrally acting antihypertensives 8 (2%). The fixed-dose combination drug Moduretic ® (amiloride/hydrochlorothiazide) -25.7% was the most commonly prescribed antihypertensive followed by lisinopril (16.6%), amlodipine (13.2%), and nifedipine (12.6%). The anti-platelet acetylsalicylic acid (ASA) was prescribed for 100 (48.1%) patients and represented 19.8% of all prescribed medications. No other anti-platelet or anticoagulant was prescribed for the patients.
One hundred and seventy-eight patients had two or more medications prescribed. Ninety-nine patients were identified with at least one potential DDIs giving a prevalence of 47.6% among the elderly hypertensive patients. A total of 231 potential DDIs were found among the patients giving a mean of 1.3 interactions per patient. The results of the cross tabulation of the number of interactions with some variables (age, sex, and number of prescribed drugs) showed statistically significant difference with number of prescribed drugs only (P < 0.001). The most common identified drug pairs with potential interactions were ACEIs-amiloride, followed by ACEIs-hydrochlorothiazide, ACEIs-ASA, and ARB-amiloride. The list of identified potential DDIs, its clinical manifestation and grading is as shown in [Table 1].
| Discussion|| |
This study reflects the high prevalence of hypertension among elderly patients and also highlights some important potential DDIs in this group. The prevalence rate of hypertension (59.4%) found among elderly patients in this study is slightly higher than 51.5% reported by Ejim et al. in a study among middle-aged and the elderly in Nigeria.  In contrast, a community-based study in South-East Nigeria conducted by Ulasi et al. found over 80% of participants aged >70 years to be hypertensive as compared to 40% among patients aged 30-39 years. 
The mean number of potential DDIs found in this study was 1.3 with over half of the patients with ≥2 medications having a combination with the potential for interaction. The prevalence of DDI among elderly patients with systemic hypertension in this study was 55.6% and it is comparatively <90.6% reported from a Croatian study on the incidence of potential DDIs among elderly patients with systemic hypertension.  Carter et al. found between 55-84% of Medicaid patients on antihypertensives having at least one potential DDI while a similar work among Palestinian hypertensive patients showed more than half with a potential DDI. , Studies conducted in India and Nepal among cardiac inpatients revealed an incidence rate of 30.7% and 21.3%, respectively. , The variation in the prevalence of DDI might be attributed to the study design, physicians prescribing pattern, differences in available medications, and difference in comorbidities among patients in the above-cited studies.
The most common potential DDIs found in this study were ACEI-ASA, ACEI-amiloride, and ACEI/hydrochlorothiazide. In a recent Nigerian study among hypertensive patients, ACEI-nonsteroidal anti-inflammatory drugs (53.3%) and ACEI-amiloride/hydrochlorothiazide (22.6%) were the most common potential DDIs.  In a cross-sectional study among elderly patients in some Finnish nursing homes, potassium-sparing diuretics were the most common identified agents causing DDIs.  Anti-platelets, anticoagulants, diuretics, and ACEIs have been identified as potential causes of DDIs in many other studies. ,, In this study, no anticoagulant was prescribed and this may be due to relatively stable state of the patients, the problem of monitoring and potential adverse reaction (warfarin), and cost issues (dipyridamole and clopidogrel). In a population-based study among elderly Brazilian patients, the combination of ACEI and a diuretic was the most common cause of potential DDI (56.7%).  Regarding the severity of the interactions, 59.1% and 40.9% of the identified DDIs among our patients were of moderate and mild class, respectively; a similar study from Pakistan had about 63.6% and 23% in the moderate and severe category, respectively. 
The most common clinical outcome of the identified potential DDIs in this study were the risk of hyperkalemia, hypotension, decreased drug efficacy, renal impairment, and heart conduction problems. In a study by Tulner et al., up to a quarter of patients with potential DDIs were found to have adverse effects and reduced efficacy of their treatment. 
The positive association between the number of prescribed drugs and potential interactions (P < 0.001) found in this study reflects findings from similar studies. ,,, However, in contrast to the recently cited studies, there was no positive association between the sex of the patients and their age.
| Conclusion|| |
Potential DDIs, though common in this study, is comprised mainly of minor and moderate types. Physicians need to be reminded of the potential for serious interactions when prescribing for patients, especially the elderly. The introduction of interaction detection software in hospital pharmacies would assist in the reduction of interactions with serious clinical importance.
One of the limitations of this study is the theoretical nature of these interactions, as the interactions may not be experienced in our practice settings. However, the need for prescribers to be aware of potential DDIs and take proactive measures are major points in favor of this study. Another limitation is the category of patients and medications included in this study; it could lead to underestimation of potential DDIs. Limiting the study to only antihypertensive and anti-platelet drugs alone would enable practitioners to focus on potential DDIs with clinical significance among patients taking these medications. The relatively high prevalence of hypertension among the elderly bracket, the physiological changes due to the aging process, and the potential for ADRs is in support of this study. The two-centered nature of the study, relatively large sample size, and use of validated interaction screening tools are also additional strengths of the study.
The authors appreciate the staff of the Medical Records Unit of the two participating centers for assisting in the retrieval of patient's medical records.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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