Adverse Drug Reaction and Monitoring in the society

Awareness to fight against adverse drug reaction and monitoring in the society for National Pharmacovigilance Week 2024.

1. Adverse Drug Reaction and Monitoring Presented by Dr. Sudipta Roy Associate Professor Bengal College of Pharmaceutical Technology, Dubrajpur, 731123

2. Contents Basics of Adverse Drug Reaction Definition of Adverse Drug Reaction Classification of Adverse Drug Reaction Monitoring of Adverse Drug Reaction Prevention and Management of Adverse Drug Reaction Conclusion References Acknowledgement

3. Basics of Adverse Drug Reaction Drug’s pharmacological action Drug’s Dose Dependent H ypoglycemia from insulin

4. Basics of Adverse Drug Reaction A naphylaxis from penicillin Drug Induced Lupus: Source of Image : Vaglio A, Grayson PC, Fenaroli P, Gianfreda D, Boccaletti V, Ghiggeri GM, Moroni G. Drug-induced lupus: Traditional and new concepts. Autoimmunity Reviews. 2018 Sep 1;17(9):912-8.

5. Basics of Adverse Drug Reaction A drenal suppression from long-term corticosteroid use. : Source of Image : https://www.ezmedlearning.com/blog/adrenal-insufficiency-symptoms-treatment-diagnosis

6. Basics of Adverse Drug Reaction Antibiotic Resistance A A ntibiotic Resistance: Antibiotic resistance grows as bacteria adapt to antibiotics, especially when used improperly or excessively. Resistant bacteria thrive while sensitive bacteria are killed, leading to harder-to-treat infections. Key factors include: Selective Pressure : Antibiotics kill non-resistant bacteria, allowing resistant ones to multiply. Incomplete Treatment : Not finishing antibiotics leaves resistant bacteria to grow and spread. Inappropriate Use : Taking antibiotics unnecessarily, like for viral infections, promotes resistance. Normal Flora Disruption : Antibiotics kill beneficial bacteria, allowing resistant bacteria to thrive. Horizontal Gene Transfer : Bacteria share resistance genes through conjugation, transformation, and transduction. Broad-Spectrum Antibiotics : These drugs kill many bacteria, including helpful ones, giving resistant strains an advantage. Cross-Resistance : Bacteria resistant to one antibiotic may resist others too. Biofilm Formation : Some bacteria form biofilms that protect them from antibiotics. Superinfections : Disrupted normal flora can lead to infections by resistant pathogens like C. difficile . Consequences: Harder-to-treat infections Longer illness duration Increased hospitalization Higher mortality rates Prevention: Complete prescribed antibiotic courses Avoid unnecessary antibiotic use Use narrow-spectrum antibiotics when possible Improve infection prevention measures Invest in new antibiotic development Responsible antibiotic use can help curb the rise of resistant bacteria.

7. Basics of Adverse Drug Reaction

8. Basics of Adverse Drug Reaction Monitoring drug safety globally involves coordinated efforts from regulatory agencies, pharmaceutical companies, healthcare providers, and international organizations. Key components include: Pharmacovigilance Systems : These systems track, assess, and prevent adverse drug effects. Regulatory agencies like WHO, FDA, and EMA maintain databases to monitor reports of adverse drug reactions (ADRs). Adverse Drug Reaction Reporting : Spontaneous reporting systems such as FDA's MedWatch and WHO's VigiBase collect ADR reports for analysis to detect safety signals. Global Databases : VigiBase (WHO) and EudraVigilance (EMA) compile ADR data for global surveillance, while FAERS (FDA) supports U.S. post-marketing safety monitoring. Regulatory Oversight : Agencies conduct pre-market evaluations and post-market surveillance to ensure drug safety. Risk Management Plans (RMPs) outline post-market risk mitigation. International Collaboration : WHO and organizations like ICH foster global collaboration to quickly detect and share safety signals. Technology and AI : Machine learning and real-world data (e.g., EHRs) are used to identify ADRs and assess safety in real-world settings. Safety Communication : Agencies like the FDA and EMA issue safety alerts to inform healthcare providers and the public about emerging risks. Education : Ongoing education for healthcare providers and patients helps improve ADR reporting and awareness. Challenges : Varying reporting standards and underreporting, especially in low-resource settings, are key challenges. Recent Trends : COVID-19 vaccine monitoring and the complexities of biologics and biosimilars highlight the need for ongoing vigilance.

9. Case Study of Adverse Drug Reaction Case Study: Hypoglycemia from Insulin Patient Information: Name: John Doe Age: 45 years old Gender: Male Medical History: Type 2 Diabetes Mellitus (T2DM), hypertension, obesity Medications: Metformin 500 mg twice daily Lisinopril 10 mg daily Insulin glargine (long-acting insulin) 40 units at bedtime Background: John Doe, a 45-year-old male with a 10-year history of Type 2 Diabetes Mellitus, has been using oral antidiabetic agents (metformin) to control his blood glucose levels. However, due to increasing HbA1c (9.2%) and poor glycemic control, his physician initiated insulin therapy 3 months ago, adding insulin glargine at bedtime to his regimen. He also suffers from hypertension and obesity. Presentation: John presented to the emergency department with symptoms of dizziness, sweating, confusion, palpitations, and tremors. His wife reported that he was difficult to arouse that morning, and upon checking his glucose with a glucometer, the reading was 42 mg/dL. The family called 911, and paramedics administered a glucose gel before transporting him to the hospital.

10. Case Study of Adverse Drug Reaction C Initial Physical Examination: Vital Signs : BP: 140/85 mmHg HR: 100 bpm RR: 18 breaths per minute Temperature: 98.6°F (37°C) Consciousness : Confused but responsive Physical Findings : Sweaty skin Mild tremor in both hands No focal neurological deficits Laboratory Results: Blood glucose : 38 mg/dL (on arrival) HbA1c : 7.8% Electrolytes : Normal Serum insulin level : Elevated Diagnosis: The patient was diagnosed with hypoglycemia secondary to exogenous insulin use. The likely cause was insulin overdose or improper insulin titration combined with reduced caloric intake the night before. John mentioned that he skipped his usual bedtime snack and exercised more than usual in the evening.

11. Case Study of Adverse Drug Reaction Pathophysiology: Insulin therapy for diabetes, especially long-acting basal insulin like insulin glargine, is designed to provide steady insulin levels throughout the day. However, if the dose is too high, or the patient skips meals or engages in unplanned physical activity, blood sugar can drop to dangerously low levels, leading to hypoglycemia . Hypoglycemia occurs when blood sugar levels fall below 70 mg/dL. The brain relies on glucose as its primary energy source, so when glucose levels fall too low, it can cause neurological symptoms (confusion, seizures, loss of consciousness) and systemic signs (tachycardia, sweating). Treatment: Immediate Management : The patient was given 50 mL of 50% dextrose intravenously to rapidly elevate blood glucose levels. Continuous glucose monitoring was initiated. Monitoring : After the administration of dextrose, his blood glucose stabilized at 110 mg/dL. Neurological symptoms resolved within 15 minutes. Adjustment of Insulin Therapy : After careful review of his insulin dosing, dietary habits, and recent physical activity, the patient’s insulin dose was reduced. The diabetes care team educated John on the importance of: Eating consistent meals and snacks, especially before bed. Adjusting insulin doses if skipping meals or engaging in unplanned exercise. Monitoring blood glucose more frequently, particularly when starting new doses or making lifestyle changes. 4. Follow-Up : John was advised to follow up with his endocrinologist in 1 week for further insulin adjustment. He was prescribed a glucagon injection kit for emergency use at home.

12. Case Study of Adverse Drug Reaction Discussion: This case highlights a common complication of insulin therapy in diabetic patients—hypoglycemia. While insulin is a critical tool in managing diabetes, particularly for patients who cannot achieve adequate glycemic control with oral medications alone, it carries the risk of causing dangerously low blood sugar levels. Several factors contribute to the risk of hypoglycemia in insulin-treated patients, including: Excessive insulin doses : Without proper titration, insulin doses can exceed the patient’s needs, leading to hypoglycemia. Skipping meals : Insulin administration without food intake increases the risk of blood sugar dropping. Physical activity : Exercise increases insulin sensitivity, leading to lower blood sugar levels. Without proper adjustments, this can precipitate hypoglycemia. Alcohol consumption : Drinking alcohol on an empty stomach can inhibit the liver’s ability to release glucose, increasing the risk of hypoglycemia. Patients with diabetes on insulin therapy should be educated about recognizing early symptoms of hypoglycemia (sweating, dizziness, shaking) and treating it quickly with fast-acting carbohydrates (glucose tablets, juice, etc.). Regular glucose monitoring is essential, especially when changes in lifestyle (diet, exercise) or insulin doses occur. Conclusion: This case illustrates the importance of individualized insulin therapy and patient education. Proper dosing, regular glucose monitoring, and awareness of lifestyle factors (meal patterns, physical activity) are critical in preventing hypoglycemic episodes. In John’s case, reducing his insulin dose and reinforcing education on dietary consistency and exercise helped to prevent further hypoglycemic events.

13. Adverse Drug Reaction Adverse drug reactions (ADRs) refer to any unintended, harmful effects that occur when a medication is administered at normal doses for the prevention, diagnosis, or treatment of disease. ADRs can range from mild side effects to severe, life-threatening conditions. They are an important public health concern and a leading cause of morbidity and mortality.

14. Classification of Adverse Drug reaction Adverse Drug Reaction Type A (Augmented) Reactions Type B (Bizarre) Reactions Unpredictable Related to individual patient susceptibility. Not dose-dependent. Examples: anaphylaxis from penicillin, drug-induced lupus. Predictable Related to the drug’s pharmacological action. Often dose-dependent. Examples: hypoglycemia from insulin, bleeding from anticoagulants.

15. Classification of Adverse Drug reaction Adverse Drug Reaction Type C (Chronic) Reactions Type D (Delayed) Reactions Effects appear after some time. Examples: secondary cancers after chemotherapy. Associated with long-term use of the drug. Examples: adrenal suppression from long-term corticosteroid use.

16. Classification of Adverse Drug reaction Adverse Drug Reaction Type E (End of Use) Reactions Type F (Failure) Reactions Effects appear after some time. Examples: secondary cancers after chemotherapy. Associated with long-term use of the drug. Examples: adrenal suppression from long-term corticosteroid use.

17. Classification of Adverse Drug reaction Adverse Drug Reaction Type E (End of Use) Reactions Type F (Failure) Reactions The drug fails to produce the expected therapeutic effect. Example: antibiotic resistance. Occur when the drug is stopped. Example: withdrawal symptoms after stopping opioids.

18. Monitoring of Adverse Drug Reactions Monitoring ADRs is critical to improving patient safety and outcomes. Effective monitoring can help identify reactions early, adjust dosages, and guide therapy changes.

19. Methods for monitoring ADRs Spontaneous Reporting Systems (SRS): Healthcare providers, patients, and manufacturers report ADRs to regulatory agencies (e.g., FDA’s MedWatch, WHO’s VigiBase). Helps in identifying rare ADRs that were not detected in clinical trials. Pharmacovigilance Programs: Formal systems designed to collect, assess, and respond to ADRs. National and international programs, like the WHO Pharmacovigilance Programme, monitor drug safety globally. Electronic Health Records (EHR) Surveillance: EHR systems can track ADRs in real time, providing data on the incidence of reactions across large populations. Causality Assessment Tools: Tools like the Naranjo Scale help healthcare providers assess whether a particular reaction is due to a specific drug. Therapeutic Drug Monitoring (TDM): Involves measuring drug levels in the blood to ensure they stay within a therapeutic range, minimizing the risk of ADRs. Used for drugs with narrow therapeutic windows, like digoxin or lithium. Clinical Trial Monitoring: ADRs are closely monitored during clinical trials through strict protocols. However, many ADRs are only discovered post-marketing when drugs are used in the general population.

20. Prevention and Management of ADRs Patient Education : Ensure patients are informed about potential side effects and signs to look out for. Dose Adjustment : Careful consideration of dosing in populations like children, the elderly, or those with kidney or liver dysfunction. Medication Reviews : Regular reviews, especially in patients on multiple medications, to assess for interactions. Pharmacogenomics : Tailoring medication based on genetic profiles to minimize the risk of ADRs.

21. Conclusion Effective ADR monitoring and management can prevent harm and improve patient outcomes significantly.

22. References World Health Organization. "Pharmacovigilance." WHO. U.S. Food and Drug Administration. "FAERS Public Dashboard." FDA. European Medicines Agency. "EudraVigilance." EMA. International Council for Harmonisation. "Pharmacovigilance." ICH. Edwards IR, Aronson JK. "Adverse drug reactions: definitions, diagnosis, and management." The Lancet . 2000;356(9237):1255-1259.

23. Acknowledgment I am acknowledging to Principal and Management, Organizing team of Pharmacist Day, National Pharmacovigilance Week celebration to fight against Adverse Drug Reaction in the society to present my awareness talks to all.

24. Thank You….

25. Question and Answer?