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DH206: PharmacologyChapter 3: Adverse Reactions
Lisa Mayo, RDH, BSDH
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
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Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Learning Objectives
1. Adverse Reaction Definitions2. Clinical Manifestations of Adverse
Reaction
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Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Objective #1: Adverse Reactions Defined
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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
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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 categories1) DOSE-RELATED: Side effects, Toxic effects2) NON-DOSE RELATED: Drug allergy, Idiosyncratic rxns
p.26
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Undesirable Effects DefinedDOSE 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
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Undesirable Effects DefinedDOSE 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 poisoningAmt desired effect excessiveConsequences may be life-threatening
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Undesirable Effects DefinedNOT DOSE DEPENDENT
Adverse reactions that are not dose-dependent1. 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
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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!!
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Test Your Knowledge
Patient reports an upset stomach when take ibuprofen
What kind of reaction is this?
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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 interactionsB. allergic reactionsC. adverse reactionsD. toxic reactions
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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 interactionsB. allergic reactionsC. adverse reactionsD. toxic reactions
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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. Toxicityb. Allergyc. Idiosyncrasyd. Adverse effect
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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. Toxicityb. Allergyc. Idiosyncrasyd. Adverse effect
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Objective #2Clinical Manifestations of Adverse Reactions
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Clinical Manifestations of Adverse Reactions
1. Effect on fetal development (teratogenic effect)
2. Hypersensitivity (allergic reaction)
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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
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Clinical Manifestations of Adverse Reactions1. 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)
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Clinical Manifestations of Adverse Reactions1. Effect on Fetal Development
No drug can be considered “safe” in pregnancyDRUGS SAFE IN PREGNANCY
Penicillin
Erythromycin
Acetaminophen
Lidocaine in dental LA
DRUGS CONTRAINDICATED IN PREGNANCY
Tetracycline
NSAIDs
Benzodiazepines (anti-anxiety)
Metronidazole (ABX)
p.26-27
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Don’t worry about DRUG INTERCATIONSTable 3-1, p.28
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Clinical Manifestations of Adverse Reactions2. 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
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Clinical Manifestations of Adverse Reactions2. Hypersensitivity (Allergic Reaction)
4 types of reactions, depending on the type of antibody produced or the cell mediating the reaction
1) Type I2) Type II3) Type III4) Type IV
See Table 3-2,p.28
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Clinical Manifestations of Adverse Reactions2. 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
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Clinical Manifestations of Adverse Reactions2. 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
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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
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Clinical Manifestations of Adverse Reactions2. 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
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NBQ
_____ hypersensitivity reactions are initiated by antigen-activated T-lymphocytes, including CD4+ and CD8+ T cells.
a. Type Ib. Type IIc. Type IIId. Type IV
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NBQ
_____ hypersensitivity reactions are initiated by antigen-activated T-lymphocytes, including CD4+ and CD8+ T cells.
a. Type Ib. Type IIc. Type IIId. Type IV
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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 TRUEb. Both statement are FALSEc. The first statement is TRUE, the second is FALSEd. The first statement is FALSE, the second is TRUE
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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 TRUEb. Both statement are FALSEc. The first statement is TRUE, the second is FALSEd. The first statement is FALSE, the second is TRUE