Adverse drug reactions

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Adverse drug reactions

  1. 1. Adverse Drug Reactions Dr. Gyanendra Raj Joshi PharmD, RPh
  2. 2. Terminologies • • • • • Side effect Toxicity Secondary effects Intolerance Idiosyncrasy
  3. 3. Adverse Drug Reaction • WHO definition: – A response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or therapy.
  4. 4. • UK Commission on Human Medicines: – An unwanted or harmful reaction experienced after the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug.
  5. 5. Predisposing factors • • • • • Multiple drug therapy Age Gender Concomitant disease Race and genetic polymorphism
  6. 6. Severity of ADR • • • • Minor Moderate Severe Lethal
  7. 7. Classification • • • • • • • Type A ( Augmented) Type B ( Bizarre) Type C ( Chronic) Type D ( Delayed ) Type E ( End of use ) Type F ( Therapeutic Failure ) Type G ( Genetic /Genomic)
  8. 8. Type A reactions • Exaggerated pharmacological response • Excessive : Anticoagulants • Unwanted : TCAs • Withdrawal : Clonidine • Delayed : Diethylstilbestrol
  9. 9. Mechanisms of Type A reactions 1. Pharmaceutical causes : – Quantity of drug – Quality of drug – Release characters
  10. 10. 2. Pharmacokinetic causes : a. Absorption – Dosage – GI motility – First pass metabolism – Nature of gastric contents – Disease – Concomitant drugs
  11. 11. b. Distribution: – Regional blood flow – Plasma protein binding – Tissue binding c. Elimination : – Reduced elimination – Increased elimination – Drug Metabolism – Drug Excretion
  12. 12. 3. Pharmacodynamic causes
  13. 13. Mechanism of Type B Reactions 1. Pharmaceutical Causes : – Degradation products – Non-drug components (excipients ) – Synthetic by- products 2. Pharmacokinetic Causes : – Bioactivation to reactive metabolites • • • Tacrine: hepatotoxicity Clozapine : agranulocytosis Halothane : hepatotoxicity
  14. 14. 3. Pharmacodynamic causes : a. Immunological b. Genetic c. Teratogenic
  15. 15. Immunological mechanisms Reaction Immunological mechanism Clinical manifestation Drugs Type I IgE mediated •Anaphylaxis Penicillin Type II Humoral (Antibody dependent Cytotoxic) IgG /IgM •Hemolysis •Thrombocytopenia Methyl Dopa Type III Arthus reaction Humoral Immune Complex mediated IgG/IgM •Serum sickness •Acute Glomerulonephritis •SLE •Vasculitis Streptokinase Type IV Delayed Cell mediated injury T cells •Skin eruptions •Steven Johnsons syndrome •Contact dermatitis •Delayed tuberculin test Amoxicillin
  16. 16. Genetic mechanisms • G6PD deficiency • N-acetyltransferase activity
  17. 17. Teratogenic mechanisms • Fertilization and implantation (upto 17 days) • Organogenesis (18-55) • Growth and development (56 onwards ) • • • • • • Thalidomide Phenytoin Warfarin Valproic acid Vit A derivatives Tetracyclines
  18. 18. Pregnancy category of drugs • • • • • A B C D X
  19. 19. Comparison between Type A and Type B Basis Type A Type B Pharmacologically predictable Yes No Dose dependent Yes No Incidence High Low Morbidity High Low Mortality Low High Management Dose adjustment Stop drug
  20. 20. Detecting ADRs • Causal attributes : – Time sequence – Withdrawal or reintroducing – Established pharmacology and toxicology • Degrees of conviction: – – – – – Definite Probable Possible Conditional Doubtful
  21. 21. Pharmacovigilance • Science and activities relating to the detection , assessment , understanding and prevention of adverse effects or any other drug related problems. • Activities : – Post marketing surveillance /ADR monitoring – Dissemination of ADR data – Changes in labeling
  22. 22. Prevention of ADRs • • • • • • • Avoid inappropriate use Rational use of drugs Past medication history Past medical history Drug interactions Correct route and method Lab tests
  23. 23. ???

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