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

DH206: PharmacologyChapter 3: Adverse Reactions

Lisa Mayo, RDH, BSDH

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.


Learning Objectives

1. Adverse Reaction Definitions2. Clinical Manifestations of Adverse

Reaction


Objective #1: Adverse Reactions Defined

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

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

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

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

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

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!!

Test Your Knowledge

Patient reports an upset stomach when take ibuprofen

What kind of reaction is this?


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


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


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


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

Objective #2Clinical Manifestations of Adverse Reactions

Clinical Manifestations of Adverse Reactions

1. Effect on fetal development (teratogenic effect)

2. Hypersensitivity (allergic reaction)


Before a drug is used, its risk against its benefits must be assessed

The benefit MUST out-weigh the potential for adverse reactions

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)

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

Don’t worry about DRUG INTERCATIONSTable 3-1, p.28

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


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


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


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


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


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

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

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

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

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

Documents

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