Potential Events of Drug Interactions among Elderly Hypertensive

Patients in Surakarta Hospital

Adhi Wardhana Amrullah

, Avianti Eka Dewi Aditya Purwaningsih

Faculty of Health Sciences, Kusuma Husada University of Surakarta, Indonesia

Faculty of Pharmacy, Setia Budi University of Surakarta, Indonesia

Keywords: Elderly, Hypertension, Drug Interactions, Pharmacokinetic, Pharmacodynamics.

Abstract: The use of antihypertensive drugs cannot be separated from the incidence of drug interactions. A study in

2017, showed that of 80 geriatric patients with hypertensive heart disease (HHD), 240 cases of potential drug

interactions were found at Moewardi Hospital. This study aims to determine potential incidence of drug

interactions in elderly hypertensive patients at Surakarta Hospital. This is an observational study using a cross-

sectional method with retrospective data collection of patients in 2018 who were treated at Surakarta Hospital.

The inclusion criteria were elderly patients more than 60 years, diagnosed with hypertension with or without

comorbidities and receiving antihypertensive and non-antihypertensive drugs. Potential drug interactions

were studied theoretically using Medscape.com. The data obtained were analyzed descriptively with cross-

tabulation. The results of study were 86 patients who met the inclusion criteria. The theoretical potential for

drug interactions was found in 98 cases from 505 cases. Pharmacodynamic drug interactions were most

common in the use of bisoprolol with aspirin and furosemide with aspirin in 10 and 8 cases, respectively. The

interaction between Valsartan and Atorvastatin as many as 6 cases with the type of pharmacokinetic

interaction. It can be concluded that there are more pharmacodynamics than pharmacokinetic drug

interactions.

1 INTRODUCTION

Hypertension is a challenge for Indonesia, because

hypertension is a disease that is still often

encountered in health services. The prevalence of

hypertension is still quite high. The results of basic

health research in 2018, the prevalence of

hypertension aged 55-64 years was 55.2%, 65-74

years was 63.2%, and aged over 75 years was 69.5%

(Riskesdas, 2018). At the age of 25 to 44 years the

incidence of hypertension reaches 29%, at the age of

45 to 64 years it reaches 51%, and at the age of more

than 65 years it reaches 65% (Warjiman, et al, 2020).

Hypertension is the most common non-

communicable disease and continues to be a

significant global health risk (Chobanian, et al, 2003).

Currently, hypertension is a major problem in the

world by causing 1.13 billion people to suffer from

this disease and only 16.8% are receiving treatment

(Bloch, 2016). In Indonesia, the prevalence rate of

hypertension in 2013 was 25.8 percent and in 2018 it

increased to 34.1 percent (Riskesdas,2013). Health

data in Central Java in 2018 shows that hypertension

still occupies the largest proportion of all non-

communicable diseases reported at 57.10 percent

(Riskesdas, 2018).

The incidence of hypertension will increase with

age. Increasing age will cause an increase in blood

pressure caused by an increase in arterial thickness

and endothelial tissue dysfunction. This will cause a

build up of collagen in the lining of the blood vessels

which will cause the blood vessels to constrict,

thereby reducing elasticity, becoming inelastic. This

will cause the arteries to become stiff, blood will still

be forced through these narrow blood vessels so that

it will increase blood pressure. WHO estimates that

there will be an increase in the incidence of

hypertension in the proportion of the elderly in the

world from 7% in 2020 to 23% in 2025. Hypertension

in the elderly is related to sodium sensitivity. (WHO,

2015; Sigarlaki, 2006).

Research in 2015 said the prevalence of men was

higher than women, but women had a higher level of

alertness than men (Everett and Zajacova, 2015). But

other studies say that women are more likely to have

hypertension than men. Women are more at risk at the

age of more than 45 years for hypertension, because

before women experience menopause they have the

294

Amrullah, A. and Purwaningsih, A.

Potential Events of Drug Interactions among Elderly Hypertensive Patients in Surakarta Hospital.

DOI: 10.5220/0010760300003235

In Proceedings of the 3rd International Conference on Social Determinants of Health (ICSDH 2021), pages 294-299

ISBN: 978-989-758-542-5

 2022 by SCITEPRESS – Science and Technology Publications, Lda. All rights reser ved

hormone estrogen. This estrogen hormone will play a

role in increasing HDL levels in the blood. At

menopause, women will experience a decrease in the

hormone estrogen, so it will reduce HDL in the blood

and will increase LDL, this will cause atherosclerosis

and increase blood pressure (Wahyuni and Eksanoto,

2013; Anggraini, et al, 2009).

Along with the increase in cases of hypertension,

the use of drugs is an important element to achieved

a good quality of life. When drug therapy is given to

a patient, it is necessary to choose which drug to use

first (first therapy). Treatment should be determined

on the basis of appropriate evidence to reduce the risk

of ADRs and drug interactions (Daskalopuolo, et al,

2015).

Drug interactions are a major problem among

patients receiving multidrug therapy. WHO

emphasizes that adverse drug reactions (ADR) and

their effects can be significantly reduced by paying

attention to people at risk for drug interactions

(WHO, 2005). A drug interaction is defined as a

qualitative or quantitative change in the effect of a

drug due to the simultaneous or successive

administration of different drugs. This may result in

changes in the therapeutic effect and safety of one or

both drugs. Drug interactions can occur

pharmacokinetically (change in drug distribution to

its site of action) or pharmacodynamically (change in

target drug response) that require them to receive

multidrug therapy (Osterhoutdt, et al., 2011). The

risk of drug interactions is potentially due to changes

in the pharmacokinetics and pharmacodynamics of

drugs with age (Mallet, et al, 2007). In 2017, a study

by Prakoso showed that of 80 geriatric patients with

hypertensive heart disease (HHD), 240 cases of

potential drug interactions were found at Moewardi

Hospital (Prakoso, 2019). The risk of drug

interactions is very high among geriatrics due to the

many comorbidities.

Based on previous research and the existing

background, we aimed to determine the potential

incidence of drug interactions in elderly hypertensive

patients at the Surakarta City Hospital.

2 MATERIALS AND METHODS

This study is an observational study using a cross-

sectional method with retrospective data collection

obtained from the Surakarta City Hospital. The

sample of this study was geriatric patients who

received antihypertensives through outpatient

installations for the period January 2018 - December

2018. Inclusion criteria were patients aged more than

60 years, diagnosed with hypertension with or

without comorbidities, as well as patients receiving

antihypertensive drugs and other non-

antihypertensive drugs. While the exclusion criteria

were patients who were not yet 60 years old and

patients who did not receive antihypertensives. The

object of research is data taken from medical records

in the form of patient identity, diagnosis and

treatment data including drug name, dose and

frequency of use.

The data collected from medical records were

studied theoretically for potential drug interactions

using the Medscape database interactions checker and

Stockley applications. In the Medscape drug

interaction checker, there are several categories that

are used to indicate the level of potential interaction,

namely, minor (treatment can still be continued),

significant (requires close supervision), and serious

(it is recommended to change to alternative drugs).

The data obtained were then analyzed descriptively

with cross-tabulation. Data is displayed using tables

and figures. Data were collected and entered into a

Microsoft excel 2010 spreadsheet, and analyzed using

SPSS for Windows version 16.0.

3 RESULT

This study obtained samples that match the inclusion

and exclusion criteria as many as 86 patients. Patients

consisted of 47.7% men and 52.3% women, shown in

table 1. These results are in accordance with previous

studies which said that elderly women were more at

risk of developing hypertension than men because

elderly women had reduced estrogen levels which had

an effect on HDL levels in the blood

Table 1. Drug Use Data

Antihypertensive Drug Use Frequency

(Percentage)

Monotheraph

34 (39,5)

Multidru

2 33

(

38,4

)

Multidru

3 17

(

19,8

)

Multidru

(

2,3

)

Antihypertensive monotherapy was often used in

34 cases, while the rest underwent multidrug therapy.

Antihypertensive monotherapy that is often used

comes from the ARB group, namely Candesartan. As

for the combination therapy, the ARB group with

diuretics (Valsartan with furosemide or

spironolactone.

This study found 98 cases of drug interactions

from 501 cases of antihypertensive drug use in 86

Potential Events of Drug Interactions among Elderly Hypertensive Patients in Surakarta Hospital

295

patients. A total of 19.4% of cases found drug

interactions in 86 patients who were obtained. Drug

interactions are more common in pharmacodynamics

than in pharmacokinetics. Pharmacodynamic drug

interactions were 69.39%. Data on the incidence of

drug interactions are shown in table 2. Interactions

that occur with serious severity are 12.2%, while with

minor severity are 21.4%, the rest is completed by

monitoring the incidence of drug interactions.

Table 2: Drug Interaction Events on the Use of

Antihypertensive Drugs

Drug Interaction Frequency

(

Percenta

)

Drug interactions occur

Pharmacodynamics

Pharmacokinetics

Unknown

98 (19,4%)

68 (69,4%)

24 (24,5%)

6 (6,1%)

Dru

interactions do not occu

407

(

80,6%

)

4 DISCUSSION

Hypertension is less common in women than men, in

those younger than 65 years, but is more common in

elderly (65 years and over) women than men. In the

United States, between 2011 and 2014, the prevalence

of hypertension in women and men by age group was

8% versus 11% (20-34 years), 23% versus 23% (35-

44 years), 33% versus 36% (45-54 years), 56% versus

58% (55–64 years), 66% versus 64% (65-74 years),

and 81% versus 73% (≥75 years) (Benjamin, dd,

2017). In the research conducted, it was found that

women had a higher incidence of hypertension than

men.

After menopause in women, there is an increase

in blood pressure which is influenced by the presence

of estrogen and endogenous in the body, where there

will be an increase in arterial stiffness, salt sensitivity,

decreased endothelial nitric oxide production, and

increased blood pressure.

Increased expression of angiotensin II receptors.

This will lead to an increase in blood pressure and

pulse pressure in postmenopausal women which are

higher than men of the same age (old age) (Izumi, et

al, 2007; Lobo, 2008; Steiner, 2003; Son, et al, 2017;

Safar, 2005) Research from Korea says that after the

age of 60, women are more likely to have

hypertension and are less likely to maintain

hypertension control than men of the same age range.

Therefore, a sex-specific approach is recommended

for effective blood pressure management (Choi et al.,

2017).

Hypertension is more common in the elderly

because of increased arteriolar and arteriolar wall

stiffness, decreased baroreceptor sensitivity,

increased responsiveness to sympathetic nerve

stimulation, and changes in renal and sodium

metabolism associated with aging (Pinto, 2007). Most

hypertensive patients underwent multidrug therapy,

only 39.5% of patients underwent monotherapy. This

is in accordance with previous studies regarding the

use of antihypertensive drugs (Busari, et al, 2010,

Adejumo, et al, 2017). The class of antihypertensive

drugs used in this study were ARBs, diuretics, Beta

Blockers, CCBs, and ACE I. This is also in

accordance with previous studies regarding the

classes of antihypertensive drugs that are often used

(Adejumo, et al, 2017; Olanrewaju, et al, 2011). ;

Busari, et al, 2014; Busari, et al, 2010). The pattern of

antihypertensive treatment is in accordance with the

guidelines for managing hypertension by JNC 8.

Diuretics are the first-line drugs for the management

of hypertension according to the guidelines of JNC

VII. Diuretics were prescribed more frequently which

was comparable to studies conducted in several

countries including India and the United States.

Good blood pressure control is usually easier to

achieve with a single drug for patients with mild

hypertension than in patients with moderate to severe

hypertension, who often require multidrug therapy.

The criteria for drug selection consider the patient's

medical condition including the presence of

comorbidities, the level of organ function, and age.

Older patients usually respond to calcium channel

blockers. Patients with DM, chronic kidney disease,

and heart failure usually require ACEI to promote

regression and prevent the development of this type

of comorbidity (Baltazi et al., 2011). Combination

treatment using antihypertensive agents from two

different classes is useful and promising in

controlling blood pressure in hypertensive patients

(Herliany and Wahyuningsih, 2020).

The functions of the organs of metabolism and

excretion of drugs determine the type and amount of

drugs prescribed to individual patients. Measurement

of organ function will help reduce adverse drug

reactions and further organ damage due to

accumulation of toxic drugs. However, drug dose,

drug interactions, and side effects of drug reactions

are not related to the magnitude of blood pressure

control (Alahdal and Elberry, 2012; Karsch, et al,

2013, Abegaz, et al, 2017).

A drug interaction occurs when the effect of one

drug is altered by the presence of another drug.

Changes in the effect of these drugs can occur in

pharmacodynamics (changes in drug effect

ICSDH 2021 - International Conference on Social Determinants of Health

296

independent of concentration) and pharmacokinetics

(changes in drug concentration). In this study, drug

interactions were analyzed with the help of

Medscape. In our study, the most frequent

interactions were pharmacodynamic interactions of

69.4%. This is more common than pharmacokinetic

interactions and interactions with unknown

mechanisms. The results of this study are also in

accordance with previous research, namely

pharmacodynamic interactions are higher than

pharmacokinetic interactions (Patel, et al, 2014;

Subramanian, et al, 2018).

Interactions that occur are minor as much as

21.4% and there are also interactions that are serious

as much as 12.2%. This is in accordance with other

studies that found serious interactions between 3.6%

and 29.6% (Sivva et al., 2015; Patel et al., 2014;

Chelkeba et al., 2013).

Serious interactions that often occur in the

pharmacodynamics of ramipril and aspirin use in 5

cases, the use of amlodipine with simvastatin with

pharmacokinetic interactions in 3 cases, followed by

the pharmacodynamic interaction between lisinipril

and aspirin in 2 cases. The interaction between

ramipril with aspirin and lisinopril with aspirin is a

pharmacodynamic interaction which occurs by

decreasing the synthesis of renal vasodilating

prostaglandins. Then both will increase its toxicity if

used together, especially in high-dose aspirin. The

interaction between amlodipine and simvastatin will

increase the serum level of simvastatin in the blood.

Administration of this drug will increase the risk of

myopathy or ramdomyolysis, so if it is used it is

necessary to adjust the dose of simvastatin.

The most frequent interactions occurred in the

interaction of bisoprolol with aspirin as many as 10

cases. This interaction is an interaction that can be

completed by monitoring. The effect that occurs from

this interaction is an increase in potassium levels in

the blood. This also occurred in the interaction

between furosemide and aspirin as many as 8 cases

with interactions that occurred where aspirin would

reduce blood potassium levels, while furosemide

would reduce blood potassium levels. So it can be

said that this interaction was completed by

monitoring blood potassium levels in patients

receiving furosemide with aspirin and bisoproplol

with aspirin.

The drug that most often causes interactions with

antihypertensive drugs is the use of aspirin. Aspirin

inhibits the production of prostaglandins and can

reduce the effectiveness of antihypertensives

(Subramanian, et al, 2018). The results above can

provide data on any drugs that interact with

antihypertensive drugs. These data can be used as

data on the prevalence of drug interactions in

antihypertensive patients and can estimate the factors

that influence the incidence of drug interactions. In

addition, the data can also be used to implement or

develop a procedure for handling drug interactions in

hospitals, implementing appropriate interventions

and other research studies can be carried out.

The limitation of this study lies in the software for

analyzing drug interactions with medcape which can

only estimate the potential for drug interactions. Data

on therapeutic success cannot be seen in this study

because the study is still limited to retrospective so

that we cannot know the exact incidence of drug

interactions that arise. Further research is needed on

the potential drug interactions related to the success

of therapy and how interventions can be carried out

to reduce the incidence of existing drug interactions

so as to reduce morbidity and mortality due to drug

interactions.

5 CONCLUSIONS

Based on the results of this study, it can be concluded

that the antihypertensive drugs found with

monotherapy were 39.5%. The potential for serious

drug interactions is 12.2%, while the minor ones are

21.4%. The incidence of drug interactions was more

pharmacodynamic (69.4%) than pharmacokinetic

(24.5%).

REFERENCES

Abegaz, T.M., Tefera, Y.G., Abebe, T.B., 2017.

Antihypertensive drug prescription patterns and their

impact on outcome of blood pressure in Ethiopia: a

hospital-based cross-sectional study. Integrated

Pharmacy Research and Practice. 6 : 29-35

Adejumo, O., Okaka, E., Iyawe, I., 2017. Prescription

pattern of antihypertensive medications and blood

pressure control among hypertensive outpatients at the

University of Benin Teaching Hospital in Benin City,

Nigeria. Malawi Medical Journal. 29 (2).

http://dx.doi.org/10.4314/mmj.v29i2.7

Alahdal AM, Elberry AA. Evaluation of applying drug dose

adjustment by physicians in patients with renal

impairment. Saudi Pharm J. 2012;20(3):217–220.

Anggarini, A, D., Waren, S., Situmorang, E., Asputras, H.,

dan Siahaan, S.S. 2009. Faktor-Faktor yang

berhubungan Dengan Kejadian Hipertensi Pada Pasien

Yang Berobat Di Poliklinik Dewasa Puskesmas

Bangkinang Periode Januari Sampai Juni 2008.

Potential Events of Drug Interactions among Elderly Hypertensive Patients in Surakarta Hospital

297

Fakultas Kesehatan. Universitas Riau. FileofDrsMed-

FKUNRI: 1-41.

Baltatzi M, Savopoulos C, Hatzitolios A. Role of

angiotensin converting enzyme inhibitors and

angiotensin receptor blockers in hypertension of

chronic kidney disease and renoprotection. Study

results. Hippokratia. 2011;15(Suppl 1):27

Benjamin EJ, Blaha MJ, Chiuve SE, et al; American Heart

Association Statistics Committee and Stroke Statistics

Subcommittee. Heart Disease and Stroke Statistics-

2017 Update: A Report From the American Heart

Association. Circulation. 2017;135:e146–e603. doi:

10.1161/CIR.0000000000000485.

Bloch M. J. Worldwode. 2016. Prevalence of hypertension

exceed 1.3 billiom. Journal of the American Society of

Hypertension. 10 :753-754. Doi:10.1016/j.jash.

2016.08.006.

Busari OA, Olanrewaju TO, Desalu OO, Opadijo GO,

Jimoh AK, Agboola SM et al. Impact of knowledge,

attitude and practices on hypertension on compliance

with antihypertensive in a resource-poor setting. TAF

Prev Med Bull 2010;9(2):87-92

Busari OA, Olanrewaju TO, Desalu OO, Opadijo GO,

Jimoh AK, Agboola SM et al. Impact of knowledge,

attitude and practices on hypertension on compliance

with antihypertensive in a resource-poor setting. TAF

Prev Med Bull 2010;9(2):87-92

Busari OA, Oluyombo R, Fasae AJ, Gabriel EO, Ayodele

LM, Agboola SM et al. Prescribing pattern and

utilization of antihypertensive drugs and blood pressure

control in adults patients with systemic hypertension in

a rural tertiary hospital in Nigeria. Am J Inter Med

2014;2(6):144-149Olanrewaju TO, Aderibigbe A,

Chijioke A, Sanya EO, Busari OA, Kolo PI et al.

Descriptive analysis of blod pressure control among

treated hypertensive patients in a tertiary hospital in

Nigeria. Afr J Med Med Sci 2011;40(3):207-212

Chelkeba L, Alemseged F, Bedada W. Assessment of

potential drug-drug interactions among outpatients

receiving cardiovascular medications at Jimma

University specialized hospital, South West

Ethiopia. Int J Basic Clin

Pharmacol. 2013;2:144. [Google Scholar]

Chobanian A. V., Bakris G. L., Black H. R., et al. 2003. The

seventh report of the joint national committee on

prevention, detection, evaluation, and treatment of high

blood pressure. JAMA. 28: 2560 – 2569 . Doi :10

.1001/jama.289.19.2560.)

Choi, H.M., Kim, H.C., Kang, D.R., 2017. Sex differences

in hypertension prevalence and control: Analysis of the

2010-2014 Korea National Health and Nutrition

Examination Survey. PLOS ONE. https:// doi.org /10.

1371/journal.pone. 0178334 May 25, 2017

Daskalopuolo S. S., Rabi D. M., Zarnke K.B., et al. 2014.

The 2015 Canadian Hypertension Education Program

Recommendations for Blood Pressure Measurement,

Diagnosis, Assessment of Risk, Prevention, and

Tratment of Hypertension. Canadioan Journal of

Cardiology. Doi:10.1016/j.cjca.2015.02.016)).

Everett, B., dan Zajacova, A. 2015. Gender Differences in

Hypertension and Hypertension Awareness Among

Young Adult.

http://www.ncbi.nlm.nih.gov/pmc/artivles/PMC48967

34/.

Herliany, Y.S., Wahyuningsih, S.R. 2020. The Profile of

Antihypertensive Drug Prescriptions and Interactions at

Pindad General Hospital. Pharmacology and Clinical

Pharmacy Research. 5 (1). doi:

10.15416/pcpr.v4i3.26172

Indonesian Ministry of Health, Basic Health Research

(RISKESDAS) 2013. Jakarta. Indonesia: Agency for

Health Research and Development; 2013.

Indonesian Ministry of Health, Basic Health Research

(RISKESDAS) 2018. Jakarta. Indonesia: Agency for

Health Research and Development; 2018.

Izumi Y, Matsumoto K, Ozawa Y, Kasamaki Y, Shinndo

A, Ohta M, Jumabay M, Nakayama T, Yokoyama E,

Shimabukuro H, Kawamura H, Cheng Z, Ma Y,

Mahmut M. Effect of age at menopause on blood

pressure in postmenopausal women. Am J Hypertens.

2007;20:1045–1050.doi:10.1016/ j.amjhyper. 2007.04.

019.

Karsch-Völk M, Schmid E, Wagenpfeil S, Linde K,

Heemann U, Schneider A. Kidney function and clinical

recommendations of drug dose adjustment in geriatric

patients. BMC Geriatr. 2013;13(1):1

Lobo RA. Metabolic syndrome after menopause and the

role of hormones. Maturitas. 2008;60:10–18. doi:

10.1016/j.maturitas.2008.02.008.

Mallet, L., Spinewine, A., Huang, A. 2007. The Challenge

of Managing Drug Interactions in Elderly People.

Lancet 370: 185-191

Osterhoudt K. C., and Penning J. C. Goodman and Gilmans

the Pharmacological Basis of Therapeutics, Brunton L.

L., Chabner A. B., and Knollmann C.B. (Eds) (2011)

Drug toxicity and poisoning, McGreaw-Hill, New

York, USA.

Patel PS, Rana DA, Suthar JV, Malhotra SD, Patel VJ. A

study of potential adverse drug-drug interactions

among prescribed drugs in medicine outpatient

department of a tertiary care teaching hospital. J Basic

Clin Pharm. 2014;5:44–8. [PMC free

article] [PubMed] [Google Scholar]

Pinto E. Blood pressure and aging. Postgrad Med J

2007;83(976):109- 114

Prakoso, A. 2019. Interaksi Obat Potensial Pada Pasien

Geriatri Rawat Inap Dengan Penyakit Hypertensive

Heart Disease RSUD Dr. Moewardi Surakarta Tahun

2017. Skripsi. Universitas Muhammadiyah Surakarta.

Safar ME. Systolic hypertension in the elderly: Arterial

wall mechanical properties and the renin-angiotensin-

aldosterone system. Journal of Hypertension. 2005.

doi:10.1097/01.hjh.0000163130.39149.fe

Sigarlaki, H.J.O. 2006. Karakteristik dan Faktor

Berhubungan dengan Hipertensi di Desa Bocor

Kecamatan Bulus Pesantren, Kabupaten Kebumen,

Jawa Tengah, Tahu 2006. Makara Kesehatan. 10

(2):78-88.

ICSDH 2021 - International Conference on Social Determinants of Health

298

Sivva D, Mateti UV, Neerati VM, Thiruthopu NS, Martha

S. Assessment of drug-drug interactions in hypertensive

patients at a superspeciality hospital. Avicenna J

Med. 2015;5:29–35. [PMC free

article] [PubMed] [Google Scholar]

Son WM, Sung KD, Cho JM, Park SY. Combined exercise

reduces arterial stiffness, blood pressure, and blood

markers for cardiovascular risk in postmenopausal

women with hypertension. Menopause. 2017;24:262–

268. doi: 10.1097/GME.0000000000000765.

Steiner M, Dunn E, Born L. Hormones and mood: from

menarche to menopause and beyond. J Affect Disord.

2003;74:67–83.

Subramanian, A., Adhimoolam, M, Kannan, S., 2018.

Study of drug–Drug interactions among the

hypertensive patients in a tertiary care teaching

hospital. Perspectives in Clinical Research. 9 (1): 9-14.

doi:10.4103/picr.PICR_145_16: 10.4103/picr. PICR_

145_16

Wahyuni dan Eksanoto, D. 2013. Hubungan Tingkat

Pendidikan dan Jenis Kelamin dengan Kejadian

Hipertensi di Kelurahan Jagalan di Wilayah Kerja

Puskesmas Pucang Sawit Surakarta. Jurnal Ilmu

Keperawatan Indonesia. 1 (1): 79-85.

Warjiman, Er, U. E., Yohana, G., Hapsari, dan Dwi, F.

(2020). Skrining dan edukasi penderita hipertensi.

Jurnal Suaka Insan Mengabdi (JSIM). 2 (1): 15-26.

Weber MA, Neutel JM, Cheung DG. Hypertension in the

aged: a pathophysiologic basis for treatment. Am J

Cardiol 198963(16)25-32

WHO.2015. Question and Answer on Hypertension.

https://www.who.int/news-room/q-a-

detail/noncommunicable-diseases-hypertension.

Diakses tanggal 23 Juni 2021.

World Health Organization. WHO Drug Information

(2005) Geneva: World Health Organization 19:3-4).

Potential Events of Drug Interactions among Elderly Hypertensive Patients in Surakarta Hospital

299