A Study of Adverse Drug Reactions Associated With Antihypertensives in a Tertiary Care Teaching Hospital

Introduction

HTN is treated by a broad range of antihypertensive medications. These medications are usually associated with Adverse Drug Reactions (ADR) that can limit treatment options and reduce patient adherence, which may lead to difficulty in BP control. These drugs cause ADRs or symptoms that makes the patient feel worse, regarding the drug therapy for 'asymptomatic disease'.¹ The adverse effects are regarded as a significant obstacle to the successful treatment of HTN.²

According to World Health Organization (WHO) “An adverse drug reaction (ADR) is any response to a drug which is noxious and unintended and occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease or the modification of physiological function”. ADRs are a major universal problem and are one of the leading causes of mortality and morbidity in health care facilities globally.³

In India there is lack of awareness regarding reporting and monitoring of ADR and thus monitoring of drug safety is one of the major problems in India. To ensure drug safety and quality of life, it is necessary to enhance the awareness regarding the early detection, reporting, management and prevention of ADR.⁴ Around 6% of hospital admissions are estimated to be due to ADRs and about 6-15% of hospitalized patients had experienced serious ADRs.³

When considering ADR, there are number of risk factors which may predispose a patient to adverse responses such as: polypharmacy, extremes of age, gender, concurrent disease, pharmacokinetic variables like renal or hepatic function, pharmaceutical factors such as nature of dosage forms or excipients or dosage forms, race (example: Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency in African middle eastern and South east Asian populations).⁵

Achieving BP control usually requires two or more antihypertensive medications however, increase in the number of antihypertensive medications in a regimen may lead to more adverse effects.⁶ Diuretics have been associated with changes in plasma lipids, glucose intolerance, uremia and electrolyte imbalance. The common ADRs associated with CCB includes: flushing, edema, postural hypotension, headache, constipation. Adverse effects common to all ACE inhibitors include acute renal failure, hyperkalemia, dry cough sometimes accompanied by wheezing, and angioedema. The adverse effects of ARB include hypotension, hyperkalemia, headache, reduced renal function and edema. ADRs associated with the use of beta blockers include bronchospasm, dyspnea, cold extremities, bradycardia, heart failure, heart block and impotence.⁷ As newer drugs are being introduced into the Indian market the need for ADR monitoring is essential more than ever before. Usually ADRs would subside once the offending drug is discontinued or if the dose is reduced, however many results, in permanent damage. Therefore it is necessary to enhance the awareness among the healthcare providers to understand their roles and responsibilities regarding early detection, management, reporting, documenting the further prevention of ADR and thereby ensuring the drug safety and quality of life. The objective of the study was to assess the ADRs associated with antihypertensive medications prescribed in our tertiary care teaching hospital.

Materials and Methods

A prospective observational study was conducted in SSIMS&RC, a tertiary care teaching hospital, Davangere, for a period of 6 months. Before commencement of the study, ethical clearance was obtained from Institutional Ethical Committee. A total of 150 patients were enrolled for the study. All patients admitted above 18 years of age, who were diagnosed with hypertension and were receiving at least one antihypertensive were included in the study. Patients who were not willing to participate in the study, pregnant and lactating women with hypertension were excluded from the study. A suitably relevant patient data collection form was developed containing patient demographics, co-morbidities, past and present medication, HTN complication, BP, electrolyte levels (sodium, potassium and magnesium levels) and other monitoring parameters. Collected data was analysed for ADRs and Naranjo’s adverse drug reaction probability scale was used for the Causality assessment of identified ADRs. The summarized findings were then rearranged and tabulated in a graphical or table form. 

Results

Gender distribution

Among 150 individuals 58.67% (88) of males and 41.34 % (62) females received anti-HTN drugs. Table 1 shows the gender distribution in the study population.

Gender Distribution.

Incidence of Adverse Drug Reaction

Out of 150 patients, 10.66% (16) experienced adverse drug reaction. Table 15 shows the incidence of ADR in the study population.

Incidence of Adverse Drug Reaction.

Adverse Drug Reactions and Suspected Antihypertensives 

Out of 16 patients who experienced ADR, the commonly observed adverse drug reaction was hydrochlorothiazide induced hyponatremia 50% (8).

Adverse Drug Reactions and Suspected Antihypertensives.

Causality Assessment by Naranjo Scale

In the reported ADRs 10.66% (16) which were assessed based on Naranjo’s probability scale, 62.5% (10) were classified as probable and 37.5% (6) were classified as possible.

Discussion

Increased life expectancy and high global prevalence of HTN and its complication render the treatment of this condition a lifelong personnel and social burden. The increasing prevalence of HTN along with world’s ageing population places an increasing burden on health care system. Antihypertensives play an important role in improving, preserving and restoring health. Prescribing pattern helps to assess whether the current usage is rational or in concordance with current treatment guidelines for HTN.

Diuretics, Angiotensin receptor blockers, Calcium channel blockers and Angiotensin converting enzyme inhbitors are constantly the most commonly prescribed antihypertensive agents in both younger and older patients with hypertension as recommended by JNC.⁸ These are the commonly prescribed drugs in several other studies.

This study was carried out in a tertiary care teaching hospital for a period of six months. During the study period, ADR identification and ADR reporting were done. A total of 150 cases of patients above the age of 18, diagnosed with hypertension and who were receiving antihypertensives were prospectively monitored during the study. Out of the 150 patients, 88 (58.67%) patients were males and 62 (41.33%) were females, which was in concordance with the study that was carried out by Yadav et al. where a male preponderance was observed this may be due to more number of male hypertensive patients coming to medical OPD.⁸

During the study period, a total of 16 ADRs (10.66%) were observed in which a male predominance was seen which was in concordance with the study conducted by Neupane et al. ¹ ADRs identified included hydrochlorothiazide induced hyponatremia(50%) and hypoglycemia(6.25%), amlodipine induced palpitation(6.25%) and flushing(6.25%), felodipine induced flushing(6.25%), furosemide induced hyperuricemia(6.25%), spironolactone induced hyperkalemia(6.25%), Ramipril induced hypotension(6.25%) and carvedilol induced dizziness(6.25%), out of which the major ADR identified was hydrochlorothiazide induced hyponatremia(50%) which was in concordance with Becker et al. where hydrochlorothiazide induced hyponatremia(80%) was most commonly seen, which may be related to electrolytes or fluid imbalance caused by diuretics, due to sodium ions depletion.^9,1

The Naranjo’s adverse drug reaction probability scale was used for the Causality assessment for the reported ADRs. The Causality assessment scales were used to classify the probability of adverse reaction with WHO assessment. According to the Naranjo’s scale adverse drug reactions identified were classified as probable 10 (62.5%) and possible 6 (37.5%) whish was in concordance with the study conducted by Isah et al. ¹⁰

Conclusion

During the study, 150 patients given with antihypertensive were observed, in which 58.67% (88) were males and 41.34 % (62) were females. Out of 150 patients observed 16 patients experienced ADR. During the study, diuretics were found to be the most frequently associated class of drug which caused ADRs and after following up those 16 patients’ symptoms and laboratory values like BP and electrolyte levels (sodium, potassium and magnesium levels) it was concluded that hydrochlorothiazide induced hyponatremia was the frequently observed ADR. Naranjo’s adverse drug reaction probability scale was used for the Causality assessment of identified ADRs and it was observed that more than half of the reported ADRs were classified as probable (62.5%) and remaining were classified possible (37.5%).

It can be concluded that adverse drug reaction is a significant limitation to the success of therapy. The implementation of pharmacovigilance programs in the hospitals is essential to ensure safe pharmacotherapy and to improve patient compliance. As the study was related to ADR profile of antihypertensive agents, it will be helpful in enhancing patient compliance with the therapy by selecting medicines of lesser ADRs profile thereby, reducing unnecessary economic burden to the patients due to unwanted effects of the therapy. The study also suggest that the implementation of ADR monitoring in patients administered with antihypertensive in the hospital settings is essential, so that the harmful effect caused by different antihypertensive can be identified, documented and prevented.

Acknowledgement

We would like to express our gratitude to our Principal, HOD and Faculties of Pharmacy Practice Department, Bapuji Pharmacy College for their continuous support and encouragement.

Conflict of Interest

There was no conflict of interest between the authors