1. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 3 Adverse Reactions

2. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Side Effects  Predictable  Dose-related  Acts on nontarget organs  Examples include stomachache, headache, nausea, vomiting, local effects 2

3. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Toxic Reactions  Predictable  Dose-related  Acts on target organs  Extension of the drug’s pharmacologic effects  Examples include hypoglycemia with an oral hypoglycemic agent or insulin 3

4. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Allergic Reactions  Not predictable  Not dose-related 4

5. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Allergic Reactions  Type 1 Mediated by immunoglobulin E (IgE) antibodies Mediated by immunoglobulin E (IgE) antibodies Anaphylactic shock or immediate hypersensitivity reactions Anaphylactic shock or immediate hypersensitivity reactions  Type 2 Complement-dependent reactions involving IgG or IgM antibodies Complement-dependent reactions involving IgG or IgM antibodies Examples include penicillin-induced hemolytic anemia Examples include penicillin-induced hemolytic anemia 5

6. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Allergic Reactions  Type III Mediated by IgG Mediated by IgG It is manifested as serum sickness It is manifested as serum sickness  Type IV Delayed hypersensitivity reaction Delayed hypersensitivity reaction Mediated by T lymphocytes and macrophages Mediated by T lymphocytes and macrophages Examples include allergic contact dermatitis Examples include allergic contact dermatitis 6

7. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Reactions  Idiosyncratic Reactions  This is a reaction that is neither a side effect or an allergic reaction.  Some are genetically determined abnormal reactions.  Some are due to an immunologic mechanism. 7

8. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Toxicologic Evaluation of Drugs  Therapeutic Index (TI = LD50) ED50 ED50  An approximate statement of the relative safety of the drug expressed as the ratio of the lethal or toxic dose to the therapeutic dose of a drug  LD50: Minimum dose causing death in 50% of a sample population  ED50: Dose required to produce a specified intensity of effect in 50% of a sample population 8

9. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Testing  Phase I Trials  Determines the biologic effects, safe dose range in humans, and toxic effects of the drug  Phase II Trials  The main purpose of this phase is to test for drug effectiveness and adverse effects  Phase III Trials  Patients with the actual drug indication receive the drug. The drug is evaluated for safety and efficacy  Phase IV Trials  Postmarketing surveillance 9