1. DH206: Pharmacology Chapter 3: Adverse Reactions Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. Learning Objectives 1. Adverse Reaction Definitions 2. Clinical Manifestations of Adverse Reaction

3. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Objective #1: Adverse Reactions Defined

4. Drug Effects On The Body  Drugs act on the body to accomplish a desired effect, but they lack absolute specificity  They don’t know what their target is – lack of specificity  Reason for undesirable effects  No drug is side effect FREE

5. Drug Effects On The Body  All drugs produce more than one effect in the body  Therapeutic effects: clinically desirable effects, intended pharmacological effect at target organ  Contraindications: situation or circumstance when a drug should NOT be used  Adverse effects: undesirable rxn 2 categories 1) DOSE-RELATED: Side effects, Toxic effects 2) NON-DOSE RELATED: Drug allergy, Idiosyncratic rxns p.26

6. Undesirable Effects Defined DOSE DEPENDENT 1) Side effect Additional drug actions at therapeutic levels Not part of desired therapeutic outcome Dose-related & predictable Clinically evident at non-target organ sites Ex: dry moiuth caused by antihistamines Ex: minoxidil(Loniten, Rogaine) developed as an antihypertensive – found to have side effect of growing hair

7. Undesirable Effects Defined DOSE DEPENDENT 2) Toxic reaction: The amount of the desired effect is excessive Predictable, dose dependent, may be clinically evident at non-target organ sites Implies drug poisoning Amt desired effect excessive Consequences may be life-threatening

8. Undesirable Effects Defined NOT DOSE DEPENDENT  Adverse reactions that are not dose-dependent 1. Drug allergy Occurs when the drug is acting like an antigen & body produced antibodies to the drug Unpredictable, immunologic response Ex: penicillin (10% population) 2. Idiosyncratic reaction Unexplained, uncharacteristic response to a drug Caused by genetic factors

9. Adverse Reactions Example  Example: Aspirin  Toxicity: hyperthermia, tinnitus  Allergic: hives, rash, difficulty breathing  Side effect: GI upset/pain ASK THE PATIENT IS THEY HAVE A TRUE ALLERGY TO ASPIRIN OR AN ADVERSE REACTION!!

10. Test Your Knowledge Patient reports an upset stomach when take ibuprofen What kind of reaction is this?

11. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Board Questions A recall patient reveal a recent history of taking Premarin. She states that she has gained weight, and the dental hygienist discovers that the patient’s blood pressure is much higher than during previous visits. These symptoms may be the result of A. drug interactions B. allergic reactions C. adverse reactions D. toxic reactions

12. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Board Questions A recall patient reveal a recent history of taking Premarin. She states that she has gained weight, and the dental hygienist discovers that the patient’s blood pressure is much higher than during previous visits. These symptoms may be the result of A. drug interactions B. allergic reactions C. adverse reactions D. toxic reactions

13. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following terms describes the development of constipation after a patient started taking acetaminophen with codeine after a tooth extraction? a. Toxicity b. Allergy c. Idiosyncrasy d. Adverse effect

14. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following terms describes the development of constipation after a patient started taking acetaminophen with codeine after a tooth extraction? a. Toxicity b. Allergy c. Idiosyncrasy d. Adverse effect

15. Objective #2 Clinical Manifestations of Adverse Reactions

16. Clinical Manifestations of Adverse Reactions 1. Effect on fetal development (teratogenic effect) 2. Hypersensitivity (allergic reaction)

17. Clinical Manifestations of Adverse Reactions  Before a drug is used, its risk against its benefits must be assessed  The benefit MUST out-weigh the potential for adverse reactions

18. Clinical Manifestations of Adverse Reactions 1. Effect on Fetal Development  Relationship between drugs & congenital abnormalities well established  Ex: thalidomide (sedative) now ONLY used in tx major aphthous stomatitis in HIV-patients  FDA: 5 pregnancy drug categories  They are A, B, C, D, and X (from least to most risky)

19. Clinical Manifestations of Adverse Reactions 1. Effect on Fetal Development  No drug can be considered “safe” in pregnancy DRUGS SAFE IN PREGNANCY Penicillin Erythromycin Acetaminophen Lidocaine in dental LA DRUGS CONTRAINDICATED IN PREGNANCY Tetracycline NSAIDs Benzodiazepines (anti-anxiety) Metronidazole (ABX) p.26-27

20. Don’t worry about DRUG INTERCATIONS Table 3-1, p.28

21. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction)  When the immune system responds to a drug  An ingested drug may be metabolized to a reactive metabolite known as a hapten (NBQ)  Hapten acts as an antigen - then antibody produced  Subsequent exposure to the drug: antibodies will react with the drug as an antigen & elicit a life-threatning rxn

22. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction) 4 types of reactions, depending on the type of antibody produced or the cell mediating the reaction 1) Type I 2) Type II 3) Type III 4) Type IV See Table 3-2,p.28

23. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction) Type I (Immediate)  Mediated by IgE antibodies  When a drug antigen binds to IgE antibody - histamine, leukotrienes, and prostaglandins are released - produce vasodilation, edema, inflammation  Effects: asthma, rhinitis, dermatitis, anaphylaxis (hypotension, bronchospasm, laryngeal edema, cardiac arrhythmias)  These reactions occur quickly after drug exposure - they are known as immediate hypersensitivity reactions

24. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction) Type II (Cytotoxic/Cytolytic)  Complement-dependent reactions involving IgG or IgM  Antigen-antibody complex fixes to RBC = results in lysis  Ex: penicillin-induced hemolytic anemia

25. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction) Type III (Arthus/Serum Sickness)  Mediated by IgG antibodies  The drug antigen-antibody complex fixes complement and deposits in the vascular endothelium  Effects: serum sickness (fever, skin eruptions, lymphadenopathy, arthritis, arthralgia)  Can be caused by penicillins or sulfonamides

26. Clinical Manifestations of Adverse Reactions 2. Hypersensitivity (Allergic Reaction) Type IV (Delayed Hypersensitivity)  Mediated by sensitized T-lymphocytes & Macrophages  When the cells contact the antigen, an inflammatory reaction is produced by lymphokines, neutrophils, and macrophages  Ex: contact dermatitis caused by topical application of drugs

27. NBQ _____ hypersensitivity reactions are initiated by antigen- activated T-lymphocytes, including CD4+ and CD8+ T cells. a. Type I b. Type II c. Type III d. Type IV

28. NBQ _____ hypersensitivity reactions are initiated by antigen- activated T-lymphocytes, including CD4+ and CD8+ T cells. a. Type I b. Type II c. Type III d. Type IV

29. NBQ Type II hypersensitivity reactions result from the binding of antigen to antigen-specific IgE bound to its Fc receptor, principally on mast cells. Type III hypersensitivity reactions are caused by small soluble immune complexes formed by soluble protein antigens binding to the IgG made against them. a. Both statements are TRUE b. Both statement are FALSE c. The first statement is TRUE, the second is FALSE d. The first statement is FALSE, the second is TRUE

30. NBQ Type II hypersensitivity reactions result from the binding of antigen to antigen-specific IgE bound to its Fc receptor, principally on mast cells. Type III hypersensitivity reactions are caused by small soluble immune complexes formed by soluble protein antigens binding to the IgG made against them. a. Both statements are TRUE b. Both statement are FALSE c. The first statement is TRUE, the second is FALSE d. The first statement is FALSE, the second is TRUE