A Pharmacovigilance Study of Antihypertensive Drugs with Reference to ADR Reporting and Patient Awareness in Hypertension.

5. Overview of Hypertension:

• Hypertension, defined as an increase in systolic blood pressure, diastolic blood pressure, or both above normal ranges, is widespread in both industrialised and developing countries, and its prevalence rises with age.
• High blood pressure is also known as hypertension. It can cause serious health problems and increase the risk of heart disease, stroke, and even death

Figure No:1

Table No :1

Blood Pressure Stages
Category	Systolic Blood Pressure (mmHg)	Diastolic Blood Pressure (mmHg)
Normal	<120	< 80
Pre hypertension	120-139	80-89
Hypertension (stage 1)	140-159	90-99
Hypertension (stage 2)	≥ 160	≥100
Hypertension (stage 3)	>180	>110

5. Sphygmomanometer:

A mercury sphygmomanometer is the common device used to monitor blood pressure. Mercury, which has long filled the middle column of traditional sphygmomanometers, is measured in units of mercury.  

5. Antihypertensive Agents:

Antihypertensive drugs are medicines used to treat high blood pressure (hypertension).
They help lower blood pressure and reduce the risk of complications like heart attack, stroke, and kidney disease.

5. Pharmacological Treatment

• Classification of Antihypertensive Drugs

• Non-Pharmacological Treatment

1. Regular Physical Exercise
2. Stress Reduction

5. Telmisartan Drug Profile:

Table No:2

Name	Telmisartan
Chemical Name	2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid.
Molecular Formula	C33H30N4O2
Structure
Molecular Weight	514.62 gm/mol
Description	A white to off - white crystalline powder
Dose	40 mg once a day
Melting Point	261-263°C
Boiling Point	771.9°C
Category/ Therapeutic Class	Antihypertensive
Solubility	Sparingly soluble in dichloromethane, slightly soluble in methanol, practically insoluble in water.
Pharmacological Action	selectively binding to AT1 receptors, preventing vasoconstriction and aldosterone-induced sodium/water retention.

• Many people believe that the tolerability profiles of angiotensin II receptor blockers (ARBs), which are very effective antihypertensive drugs, are comparable to those of placebos. With a half-life of roughly 24 hours, telmisartan has the longest of all the commercially marketed ARBs. This implies that telmisartan should have a prolonged duration of action, guaranteeing blood pressure regulation during the once-daily dosage interval.
• One such characteristic that sets telmisartan apart from other ARBs is its high lipophilicity. This improves intracellular absorption, tissue penetration, and bioavailability. The huge distribution volume of about 500L is indicative of the high lipophilicity. As shown in an animal model, telmisartan's greater lipophilicity than losartan may provide vascular protection.

CH-2: LITERATURE STUDY

5. Telmisartan clinical trials:

1. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-γ-modulating activity
2. Angiotensin type 1 receptor blockers induce peroxisome proliferator activated receptor activity
3. An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes
4. Telmisartan is a dual ARB and PPAR gamma activator that limits weight gain, body fat accumulation, and adipocyte size in rats fed a high fat, high carbohydrate diets
5. Insulin-sensitizing effects of telmisartan: Implications for treating insulin-resistant hypertension and cardiovascular disease.

Long-term treatment is necessary for hypertension. Antihypertensive medications, however, may result in adverse drug reactions (ADRs) that compromise quality of life and compliance. 500 patients taking at least one antihypertensive drug participated in this 12-month prospective observational trial. Pedal edema, dry cough, and dizziness were the most common adverse drug reactions (ADRs) among the 95 ADRs (17.6%), which were mostly caused by calcium channel blockers and ACE inhibitors. Patients on polypharmacy had considerably more adverse drug reactions (ADRs) (p = 0.004), with the majority being categorized as moderate and likely. To enhance safety and maximize the management of hypertension, active pharmacovigilance is crucial.

5. Major Clinical Outcomes Comparing Telmisartan and other ARBs

In this extensive, real-world cohort study that made use of the TriNetX Global Collaborative Network, we assessed cardiovascular outcomes in almost 1.9 million hypertension patients and found 41,598 individuals who were well-matched for each therapy group. When compared to other ARBs, telmisartan use was continuously associated with lower risks of heart failure, stroke, and all-cause mortality. These results, which were seen in important clinical subgroups, imply that telmisartan may provide additional cardiovascular and cerebrovascular advantages over blood pressure management. Our findings support telmisartan as a potentially beneficial treatment choice for hypertension patients at elevated cardiovascular risk, even though additional prospective studies are required to demonstrate causality.

5. ADRs of Antihypertensive Drugs:

• Angiotensin Receptor Blockers and The ADRs observed

CH-3 NEED OF STUDY AND OBJECTIVE

1. 1. High Hypertension Prevalence

One of the most prevalent chronic illnesses in the world, hypertension affects a significant percentage of adults. Because to sedentary lifestyles, stress, obesity, poor diets, smoking, and alcohol consumption, the number of individuals with hypertension is steadily rising.

1. 2. Serious Public Health Issue

Because it is a major risk factor for major cardiovascular problems such stroke, myocardial infarction, renal problems, and heart failure, hypertension is regarded as a major public health concern. Increased morbidity and mortality can result from uncontrolled blood pressure.

1. 3. Growing Patient Population

Due to urbanization, population aging, inactivity, and dietary changes, the incidence and prevalence of hypertension are rising both worldwide and in India.

1. 4. The Requirement for Extended Therapy

Antihypertensive medications are typically needed to treat hypertension for the rest of one's life. Long-term and continuous medication therapy raises the risk of drug interactions, adverse drug responses, and problems with patient compliance.

1. 5. The Value of Tracking Adverse Drug Reactions
      Despite their effectiveness, antihypertensive drugs have a number of adverse drug reactions (ADRs), including headache, dizziness, hypotension, exhaustion, and edema.
   6. To guarantee patient safety, increase treatment compliance, and improve therapeutic results, it is critical to monitor these reactions.
   7. Widespread Amlodipine Use

Amlodipine's efficacy and easy once-daily dosage make it one of the most often recommended hypertension medications. However, it is crucial for pharmacovigilance evaluation because it is often linked to adverse drug reactions (ADRs) such peripheral edema, flushing, dizziness, and palpitations.

1. 8. Lack of ADR Reporting Awareness

There is inadequate awareness among healthcare professionals and patients regarding ADR reporting and pharmacovigilance practices. Underreporting of ADRs remains a major challenge in ensuring medication safety.

1. 9. Importance of Pharmacovigilance

Pharmacovigilance helps in the detection, assessment, prevention, and reporting of adverse drug reactions. Conducting studies on hypertension can contribute to improving pharmacovigilance systems and promoting rational use of medicines.

1. 10. Common Symptoms of Hypertension

Many patients with hypertension remain asymptomatic; however, some may experience                                symptoms such as:

• Headache
• Dizziness
• Fatigue
• Blurred vision
• Chest pain
• Shortness of breath
• Palpitations
• Nosebleeds

5. Objectives of the Study

• General Objective

1. To evaluate adverse drug reactions associated with antihypertensive drugs with special reference to amlodipine and to assess pharmacovigilance practices among patients and healthcare professionals.

• Specific Objectives

1. To study the pattern and frequency of adverse drug reactions associated with antihypertensive drugs.
2. To identify and evaluate adverse drug reactions specifically associated with amlodipine.
3. To assess the awareness and knowledge of pharmacovigilance among healthcare professionals.
4. To evaluate the occurrence and reporting of adverse drug reactions among patients receiving antihypertensive therapy.
5. To analyze adverse drug reactions using standard assessment tools such as the Naranjo ADR Probability Scale.

CH-4 MATERIALS AND METHODS

5. Study Design

In order to assess the adverse drug reactions (ADRs) linked to antihypertensive medications in actual clinical practice, the current study was planned as an observational, cross-sectional pharmacovigilance study. Particularly in chronic illnesses like hypertension where long-term drug usage is widespread, pharmacovigilance is essential to assuring drug safety after marketing.
This study used a survey-based methodology, using structured questions created with Google Forms to gather information from patients and healthcare professionals. In addition to identifying frequently prescribed antihypertensive medications, the study sought to evaluate the frequency, type, and reporting of adverse drug reactions (ADRs) linked to these treatments.

Based on replies received during the survey, common medications like telmisartan and    other antihypertensive classes were given particular attention. The design made data entry simple.

5. Study Population

Patients and healthcare professionals made up the two main segments of the study population. Pharmacists made up the majority of healthcare professionals, and they were selected as the key responders because of their accessibility and direct involvement in patient interactions and medicine distribution. Pharmacists are an essential source of pharmacovigilance data since they are crucial in identifying and reporting adverse drug reactions.
Patients with a diagnosis of hypertension who were receiving antihypertensive medication were included in the second group. Real-world information about medication use, adverse effects, and treatment compliance was given by these patients. In order to ensure practical exposure and accurate data collection, the study was carried out in and around local regions, including community pharmacies and hospital settings.

5. Inclusion Criteria

• Patients diagnosed with hypertension and currently receiving antihypertensive drug therapy.

• Healthcare professionals, especially pharmacists, involved in dispensing or monitoring medications.

• Participants willing to provide informed responses through the questionnaire.

• Complete and properly filled Google Form responses.

5. Exclusion Criteria

• Individuals not diagnosed with hypertension

• Patients not receiving any antihypertensive treatment

• Incomplete, duplicate, or inconsistent responses in Google Forms

• Participants unwilling to share information or lacking basic knowledge of the subject

5. Hospital Visit

In order to have firsthand experience with adverse drug reaction monitoring and reporting systems in a clinical context, a hospital visit was undertaken as part of the pharmacovigilance study.
Interactions with medical experts, such as pharmacists and hospital employees, were conducted throughout the visit in order to comprehend the procedure for recognizing, recording, and reporting adverse drug reactions (ADRs). The visit gave insights into how antihypertensive medications are prescribed in the real world and how medical professionals contribute to drug safety. Data was gathered about regularly prescribed drugs, including telmisartan and other antihypertensive medicines.

5. Data Collection Method

Structured questionnaires created with Google Forms were used to gather data for this investigation. To measure adverse drug reactions (ADRs) and pharmacovigilance awareness, two distinct questionnaires were created for patients and healthcare professionals.
The antihypertensive medication therapy used to treat hypertension was the main topic of the study. Both multiple-choice and open-ended questions about drug use, adverse effects, frequently prescribed drugs, and ADR reporting procedures were included in the surveys.
Pharmacists, as well as other medical professionals and patients, were the main recipients of the Google Forms. Since pharmacists are crucial to the normal practice of administering medications and monitoring side effects reported by patients, they were explicitly targeted.

Telmisartan was shown to be one of the most frequently given antihypertensive medications among the research population based on the responses gathered.
Responses were gathered over a predetermined period of time after the forms were distributed online. For additional interpretation, the gathered data was then assembled, arranged, and examined using basic statistical techniques.
Pharmacists provided the majority of the responses, which yielded insightful information on prescription trends. Based on the information gathered, telmisartan was discovered to be one of the most frequently given antihypertensive medications.

5. ADR Monitoring Form

In the current investigation, information about potential adverse drug reactions linked to antihypertensive medications used to treat hypertension was carefully gathered using an Adverse Drug Reaction (ADR) monitoring form.
Essential information such as patient demographics (age, gender), suspected drug, dosage, mode of administration, length of therapy, description of adverse response, onset and duration of reaction, and any concurrent drugs were all included in the ADR form. Information about rechallenge was also taken into consideration, if it was accessible.
The form was created using standard pharmacovigilance reporting standards to guarantee consistency and precision in data gathering. It assisted in the organized documentation of ADRs, which was then utilized for the Naranjo ADR Probability Scale's causality assessment.

5. ADR Assessment Method

The reported adverse drug reactions (ADRs) were evaluated using the Naranjo ADR Probability Scale, a widely accepted and standardized tool for causality assessment.

The Naranjo Scale consists of a structured questionnaire with multiple parameters such as temporal association of drug administration, alternative causes, drug levels, dose-response relationship, and previous patient experience with the drug.

Based on the total score obtained, ADRs were classified into the following categories:

• Definite ADR (score ≥ 9)

• Probable ADR (score 5–8)

• Possible ADR (score 1–4)

• Doubtful ADR (score ≤ 0)

This method provided a systematic approach to determine the likelihood that a drug caused a particular adverse effect, thereby improving the reliability of the study findings.

5. Data Analysis

The collected data from Google Forms was compiled and organized systematically using spreadsheet tools. Every response was thoroughly examined and classified according to factors like medication use, prescription frequency, adverse drug reaction incidence, and pharmacovigilance awareness.
The data was analysed using simple statistical methods, primarily focusing on frequency distribution and percentage analysis. This method made it easier to spot trends like the most often prescribed antihypertensive medications, frequently reported adverse drug reactions, and the degree of awareness among medical professionals.
To improve comprehension and clarity, the data analysis was displayed utilizing visual aids such tables, pie charts, and bar graphs. These visual aids made it simpler to analyse the data and come to insightful conclusions.

• The overall methodology adopted in the present study is summarized in the following flowchart

Selection of Topic

⬇

Literature Review (Pharmacovigilance & Antihypertensive Drugs)

⬇

Selection of Drug Class (Antihypertensive Drugs)

⬇

Selection of Drug (telmisartan as Focus Drug)

⬇

Design of Data Collection Tools (Google Forms)

⬇

Preparation of Questionnaires

(For Pharmacists, Healthcare Professionals & Patients)

⬇

Distribution of Google Forms

⬇

Data Collection

(Responses from Pharmacists and Patients)

⬇

Identification of ADRs

⬇

ADR Assessment

(Using Naranjo Scale)

⬇

Data Compilation & Tabulation

⬇

Data Analysis (Graphs & Tables)

⬇

Interpretation of Results

⬇

Conclusion & Report Writing

CH-5 RESULTS AND DISCUSSIONS

5. Introduction

A total of 100 responses were collected, including 50 responses from pharmacists and 50 responses from patients. The data was collected using structured questionnaires to evaluate drug usage patterns, awareness of adverse drug reactions (ADRs), and reporting practices associated with antihypertensive drugs used in the management of Hypertension.

• Pharmacist-Based Analysis (n = 50)

5.2.1 Profession

Result: All respondents belonged to the pharmacy profession.

Discussion: Inclusion of pharmacists ensures reliability of data, as they are directly involved in dispensing antihypertensive drugs and interacting with patients.

5.2.2 Name of Medical Store

Result: Responses were collected from multiple community pharmacies across different locations.

Discussion: Data from different stores improves the diversity and generalizability of the study findings.

5.2.3 Most Commonly Sold Antihypertensive Drug

Result: Telmisartan was found to be the most commonly sold antihypertensive drug.

Discussion: This indicates its widespread use in the treatment of Hypertension, likely due to its efficacy and tolerability.