INTRODUCTION:

Adverse drug reactions (ADRs) – unintended, harmful events attributed to the use of medicines – occur as a cause of and during a significant proportion of unscheduled hospital admissions. A careful medication history can assist a prescriber in understanding the patient's previous experiences with drug treatment, particularly in identifying previous ADRs that may preclude re-exposure to the drug. Preventing ADRs depends on avoiding treatment in cohorts of patients who are at increased susceptibility or providing treatment under a therapeutic plan that reduces the risk of an adverse effect (eg co-administration of other drugs, monitoring blood test results).

Spontaneous reporting (using the Yellow Card Scheme in the UK) based on the suspicion of an ADR is an important part of pharmacovigilance but, overall, ADRs are vastly underreported across healthcare settings and sectors. If in doubt, it is best to submit a report.¹

Every drug in the therapeutic area poses both benefits and potential threat for causing severe side effects. At times, these side effects are preventable and a timely reporting of same can avoid unwanted health hazards and save millions of lives. An initiative made in the same direction was to design and implement adverse event reporting systems by individual nations and then was adopted by the whole world either unanimously with global organizations or individualizing their own reporting system.² Pharmacovigilance is entirely about monitoring adverse drug reactions (A.D.Rs.) and hence was defined as "The detection in the community of drug effects, usually adverse".

Hypertension is a global public health issue. It is an important public health concern because of its associated morbidity, mortality, and economic impact on the society. Overall prevalence of hypertension in India reported 29.8%. Nearly 1 billion people have high blood pressure (hypertension) globally; out of these, developing countries having two-thirds of patients. Premature deaths worldwide are mostly caused by hypertension and the disease is spontaneously growing with the estimation of 1.56 billion adults will be living with hypertension in 2025. India also facing substantial public health burden on cardiovascular health and health-care systems. Approximately 57% of all stroke deaths and 24% of all coronary heart disease deaths in India are directly by hypertension. Even the WHO also rates hypertension as one of the most important causes of premature deaths worldwide. The present study is conducted to monitor the A.D.Rs. associated with antihypertensive drugs.³

MATERIALS AND METHODS:

All patients coming to the department with blood pressure systolic above 120 mmHg and diastolic above 90 mmHg and prescribed hypertensive will be screened for the study. Those who satisfy the inclusion criteria will be enrolled after taking written informed consent. Diagnosed patients of hypertension above the age of 18 years, and diagnosed with primary hypertension, will be included in the study⁴

The various study tools that will be used are the suspected ADR reporting form issued by Central Drugs Standard Control Organization under Pharmacovigilance Programme of India which will record all the information, such as name, age, sex, weight, other relevant history including pre-existing medical conditions, details of suspected ADRs, and details of suspected medications that the patients might be taking⁵ A.D.RS. reporting form records all the essential information regarding the adverse effects: The onset and severity of the A.D.R. experienced, the impact of A.D.RS. on the treatment and work capacity of the patient, the drug(s) involved, the date of starting the suspected drugs, and the date of reporting of the A.D.RS. Causality assessment will be done using Naranjo's causality assessment scale.

Data management and analysis- Data will be aggregated according to disease profile and other relevant information required for the study. Causality assessment was done using Naranjo's causality assessment scale.₆

For patients on antihypertensive treatment.

1) Inclusion criteria:

The following criteria were included in the study:

· Newly diagnosed patients of hypertension with blood pressure above 120/90 mm Hg

· Patients with age more than 18 years

· Patients of either sex

· Patients having baseline (pre-treatment) biochemical parameters other than blood sugar (i.e., liver function test and kidney function test) within normal range

· Patients having no associated comorbidities

2) Exclusion criteria:

The following criteria were excluded from the study:

· Patients who were unwilling to participate and did not give consent

· in the study Patients who were unable to give interview

· Patients with incomplete medical records

· Patients with chronic liver disease such as cirrhosis, chronic hepatitis, and acute viral hepatitis Terminally ill patients

· Patients with concurrent major psychiatric illness and/or concurrent

· major medical illnesses.

1)Naranjo's causality assessment scale:

The Naranjo's criteria classify the probability that an adverse event is related to drug therapy based on a list of weighted questions, which examine factors such as the temporal association of drug administration and event occurrence, alternative causes for the event, drug levels, dose-response relationships, and previous patient experience with the medication. The ADRs. are assigned to a probability category from the total score as follows:

Definite if the overall score is 9 or greater, probable for a score of 5-8, possible for 1-4, and doubtful if the score is 0.⁷

2)Assessment of severity:

The severity of reported reactions was assessed using Hartwig and Siegel scale and was categorized into mild, moderate, and severe.

ADR severity assessment scale (Modified Hartwig and Siegel)

• Mild:

Level 1: The ADR requires no change in treatment with the suspected drug.OR

Level 2: The ADR requires that the suspected drug be withheld, discontinued or otherwise changed. No antidote or other treatment is required, and there is no increase in lenght of stay.

•Moderate:

Level 3: The ADR requires that the suspected drug be withheld, discontinued or otherwise changed, and/or an antidote or other treatment is required. There is no increase in lenght of stay. OR

Level 4 (a): Any level 3 ADR that increases lenght of stay by at least one day.

Level 4 (b): The ADR is the reason for admission.

• Severe

Level 5: Any level 4 ADR that requires intensive medical care. OR

Level 6: The ADR causes permanent harm to the patient.₈

3)Assessment of preventability:

The preventability of each ADRS was assessed using modified Schumock and Thornton scale and was categorized as definitely preventable, probably preventable, and not preventable. ₉

Questions for assessment of preventability

• Definitely preventable:

1. Was there a history of allergy or previous reactions to the drug?

2. the drug involved inappropriate for the patient's clinical condition?

3. Was the dose, route or frequency of administration inappropriate for the patient's age, weight or disease state?

4. Was a toxic serum drug concentration (or laboratory monitoring test) documented?

5. Was there a known treatment for the Adverse Drug Reaction? ₁₀

• Probabaly preventable:

6.Was required Therapeutic drug monitoring or other necessary laboratory tests not performed?

7.Was a drug interaction involved in the ADR?

8.Was poor compliance involved in the ADR?

9.Were preventative measures not prescribed or administered to the patient?₁₁

• Not preventable:

If all above criteria not fulfilled ₁₂

RESULT:

Total number of 10 prescriptions were collected as per inclusion and exclusion criterion and 15 ADRs were also collected and analysed. In this study out of patients, 8(85.72%) were male and 2 (14.28%) were female.

Fig 1. Gender Distribution of Patients developing ADR to antihypertensive drug

Males have shown higher prevalence of essential hypertension compared to female. There is highly significant association between essential hypertension and sex. There is highly significant association between essential hypertension and age. Among the 10 prescriptions of antihypertensive drugs. In this study it was observed that 14 (%) ADRs were developed for different types of antihypertensive drugs during the period from April 2022 to June 2022. The distribution of ADRs in male was 85.72% while in female, it was 14.28%, which is statically significant.

Gender	Number of patients (%)
Male	8 (85.72%)
Female	2 (14.28%)
Total	10

Amlodipine was found to be the commonest drug associated with ADRs (n = 14). In this study ADRS to antihypertensive drugs associated with central nervous system (n=3, 21.42%) were found to be the most frequent (dizziness, vertigo, depression). Other systems associated with ADRs were musculoskeletal system (n=5, 35.71%) [rash, itching, fatigue, mouth, swelling of hands and feets], respiratory system (n= 2, 14.28%) [wheezing and breathlessness], gastrointestinal system (n = 1, 7.14%) (constipation], cardiovascular system (n=3, 21.42%).(hypotension, bradycardia, fainting).

Fig 2. Distribution of ADRs to antihypertensive drugs affecting various systems

According to WHO causality assessment scale most of the ADRs were "probable" 8(57.14%) followed by"possible" 2 (14.28%), certain 4 (28.57%)).

Fig 3. Distribution of ADRs according to WHO casuality assessment

According to Hartwig and Siegel scale of severity assessment, the most of the adrs were mild 10(71.42%) and moderate 4 (28.57%) .and In this outpatient-based study there were absence of serious adverse reactions as there were no deaths, hospitalizations, disabilities, or life-threatening events that required intervention to prevent permanent damage.

Fig 4. Distribution of ADRs according to Hartwig and Siegel scale

According to Schumock and Thornton scale of preventability assessment all ADR are definitely preventable.

DISCUSSION:

In this study 85.72% patients were male, and 14.28% patients were female, and it was found that essential hypertension was more prevalent in male than females. The hypothetical cause of higher number of me patients is due to the elevated levels of androgen (such a testosterone) as they play a significant role in elevation of blood pressure.

It was found that common age group of patients with essential hypertension was 51 to 60 years. Plasma renin falls by 17% each decade which may be the possible reason of essential hypertension in advance age, this finding has already introduced a searching question whether this renin is a friend or foe for human beings. This study was similar to a study done by Tiwari et al, which also showed that the commonest age group affected was 51 to 60 yrs.

In the present study amlodipine was the most commonly used drug as monotherapy of patients. CCBs have very less or no metabolic effects which is beneficial for diabetic hypertensive patients and also it is cheap. These could be the reasons for it to be the most commonly prescribed drug. Drug utilization study of antihypertensive drugs by Maduram et al, and John et al, also showed amlodipine as the most frequently prescribed drug. The antihypertensive effect of CCBs are independent of sodium intake or concurrent use of NSAIDS which is not the case with ACE inhibitors. In patients having hypertension with coexisting nephropathy, CCBS remarkably reduce the blood pressure. CCBs are the most preferred drugs in case of hypertensive patients with coexisting diabetes mellitus. They also have additional natriuretic effect and thus it rules out the need for adding a diuretic. One of the important factors which affects patient compliance and drug adherence is the occurrence of adverse drug reactions.

CONCLUSION:

This prospective observational study was conducted to find out and assess the incidence and causality, severity and preventability of ADR related to Antihypertensive drugs. In this study the ADRs were found probable" 8(57.14%) followed by "possible" 2 (14.28%), certain 4 (28.57%)). According to hartwig and Siegel scale of severity assessment, the most of the adrs were mild 10(71.42%) and moderate 4 (28.57%). and there is absence of serious ADR as there is no death, prolonged hospitalization or life threatening events. According to Schumock and Thornton scale of preventability assessment all ADR are definitely preventable.

This study also found that amlodipine was responsible for most of the ADRs and among all the ADRS reported Dizziness was the commonest followed by vertigo, depression, swelling of hands and feet’s, fatigue, Hypotension, dry mouth, breathlessness, bradycardia, rash, muscle cramps, , constipation , wheezing , irritation all over the body. The results of this study would be useful for the physicians in rational Selection of drug therapy for treatment of hypertensive patients.

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Received on 08.07.2022 Modified on 26.10.2022

Asian J. Research Chem. 2023; 16(1):39-42.

DOI: 10.52711/0974-4150.2023.00007