ADR by Mukesh Jaiswal & Somya Verma


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This presentation is about brief description of Adverse Reaction occurred during Clinical Trials.

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ADR by Mukesh Jaiswal & Somya Verma

  2. 2.   Most drugs produce several effects, but usually only one effect—the therapeutic effect—is wanted for the treatment of a disorder. The other effects may be regarded as unwanted certain antihistamines cause drowsiness as well as control the symptoms of allergies. When an overthe-counter sleep aid containing an antihistamine is taken, drowsiness is considered a therapeutic effect. But when an antihistamine is taken to control allergy symptoms during the daytime, drowsiness is considered an annoying, unwanted effect.
  3. 3.    adverse drug reaction is technically more appropriate for drug effects that are unwanted, unpleasant, noxious, or potentially harmful. An adverse drug reaction (abbreviated ADR) is an expression that describes harm associated with the use of given medications at a normal dose. The study of ADRs is the concern of the field known as pharmacovigilance.
  4. 4. •  Classification ADRs may be classified by e.g. cause and severity. Cause Type A: Augmented pharmacologic effects - dose dependent and predictable Type B: Bizarre effects (or idiosyncratic) - dose independent and unpredictable Type C: Chronic effects(dose related & time related) Type D: Delayed effects(time related) Type E: End-of-treatment effects(withdrawal) Type F: Failure of therapy(failure)
  5. 5. Seriousness and Severity 1. 2. 3. 4. 5. The American Food and Drug Administration defines a serious adverse event as one when the patient outcome is one of the following: Death Life-Threatening Hospitalization (initial or prolonged) Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life. Congenital Anomaly
  6. 6. • The terms "severe" and "serious" when applied to adverse events are technically very different. • A headache is severe, if it causes intense pain. There are scales that help us assess the severity. On the other hand, a headache can hardly ever be serious, unless it also satisfies the criteria for seriousness. • Overall Drug Risk While no official scale exists yet to communicate overall drug risk, the iGuard Drug Risk Rating System is a five colour rating scale 1. Red (High Risk) 2. Orange (Elevated Risk) 3. Yellow (Guarded Risk) 4. Blue (General Risk) 5. Green (Low Risk)
  7. 7. • Location Adverse effects may be local, i.e. limited to a certain location, or systemic, where a medication has caused adverse effects throughout the systemic circulation. For instance, some ocular antihypertensive cause systemic effects, although they are administered locally as eye drops, since a fraction escapes to the systemic circulation • Mechanisms As research better explains the biochemistry of drug use, fewer ADRs are Type B and more are Type A. Common mechanisms are: 1) Abnormal pharmacokinetics due to genetic factors co morbid disease states 2) Synergistic effects between either a drug and a disease & two drugs
  8. 8. • Abnormal pharmacokinetics Comorbid disease states Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states • Genetic factors Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation.Pharmacogenomics is the study of the inherited basis for abnormal drug reactions. 1. Phase I reactions . Inheriting abnormal alleles of cytochrome P450 can alter drug metabolism. . Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolism of drugs such as succinylcholine
  9. 9. 2. Phase II reactions . Inheriting abnormal N-acetyltransferase which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as isoniazid, hydralazine, and procainamide. . Inheriting abnormal thiopurine Smethyltransferase may affect the metabolism of the thiopurine drugs mercaptopurine and azathioprine • Interactions with other drugs The risk of drug interactions is increased with polypharmacy. 1. Protein binding These interactions are usually transient and mild until a new steady state is achieved. These are mainly for drugs without much first-pass liver metabolism. The principal plasma proteins for drug binding are • albumin • α1-acid glycoprotein • lipoproteins
  10. 10. • Cytochrome P450 Patients have abnormal metabolism by cytochrome P450 due to either inheriting abnormal alleles or due to drug interactions. • Synergistic effect • Monitoring bodies Many countries have official bodies that monitor drug safety and reactions. On an international level, the WHO runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies.
  11. 11. ADR EXAMPLE Abortion, miscarriage or uterine hemorrhage misoprostol (Cytotec), a laborinducing drug (this is a case where the adverse effect has been used legally and illegally for performing abortions) Addiction many sedatives and analgesics such as diazepam, morphine, etc. Birth defects Thalidomide and Accutane Bleeding of the intestine aspirin therapy Cardiovascular disease COX-2 inhibitors (i.e. Vioxx)
  12. 12. Deafness and kidney failure gentamicin (an antibiotic) Death, following sedation Propofol (Diprivan) Dementia heart bypass surgery Depression or hepatic injury interferon Diabetes antipsychotic medications Diarrhea orlistat (Xenical) Erectile dysfunction many drugs, such as antidepressants
  13. 13. Fever vaccination (in the past, imperfectly manufactured vaccines, such as BCG and poliomyelitis, have caused the very disease they intended to fight). Glaucoma corticosteroid-based eye drops Hair loss and anemia chemotherapy against cancer, leukemia, etc. Headache spinal anesthesia Hypertension ephedrine users, which prompted FDA to remove the status of dietary supplement of ephedra extracts Insomnia stimulants, etc.
  14. 14. • MANAGEMENT Management includes withdrawal of the drug if possible and specific treatment of its effects. Suspected adverse drug reactions should be reported. • Severity - Mild - symptomatic treatment, alter dose, no change of drug - Moderate - change in drug therapy - Severe - unexpected untoward leading to possible debility, or death
  15. 15. An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is serious and should be reported to FDA when the patient outcome is: Death Report if you suspect that the death was an outcome of the adverse event, and include the date if known. Life-threatening Report if suspected that the patient was at substantial risk of dying at the time of the adverse event, or use or continued use of the device or other medical product might have resulted in the death of the patient. 
  16. 16. Congenital Anomaly/Birth Defect Report if you suspect that exposure to a medical product prior to conception or during pregnancy may have resulted in an adverse outcome in the child. Required Intervention to Prevent Permanent Impairment or Damage (Devices) Report if you believe that medical or surgical intervention was necessary to preclude permanent impairment of a body function, or prevent permanent damage to a body structure, either situation suspected to be due to the use of a medical product.
  17. 17. Hospitalization (initial or prolonged) Report if admission to the hospital or prolongation of hospitalization was a result of the adverse event.Emergency room visits that do not result in admission to the hospital should be evaluated for one of the other serious outcomes (e.g., life-threatening; required intervention to prevent permanent impairment or damage; other serious medically important event). Disability or Permanent Damage Report if the adverse event resulted in a substantial disruption of a person's ability to conduct normal life functions, i.e., the adverse event resulted in a significant, persistent or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities and/or quality of life.
  18. 18. Other Serious (Important Medical Events) Report when the event does not fit the other outcomes, but the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes. Examples include allergic brochospasm (a serious problem with breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood disorders) or seizures/convulsions that do not result in hospitalization. The development of drug dependence or drug abuse would also be examples of important medical events.
  19. 19. THANKS !