Chpt 3 Adverse Reactions

Therapeutic effects

Clinically desirable actions

Adverse effects

Clinically undesirable reactions

Adverse drug reaction

Undesirable response to drug; potentially harmful; occurs at usual therapeutic doses

Drug Reactions

• Toxic reaction - exaggeration

• Side effect - dose-related

• Idiosyncratic reaction - genetically related

• Drug allergy - immunologic, independent of dose

• Interference with natural defense mechanisms - increased infections

Adverse Reactions

• Exaggerated effect on target tissues

• Effect on nontarget tissues

• Teratogenic effect

• Local effect

• Drug interactions

• Hypersensitivity

• Idiosyncrasy

• Interference with natural defense mechanisms

Exaggerated effect on tissues

An extension of therapeutic effect caused by the overreaction of a sensitive patient or by a dose that is too large for that patient

Effect on Nontarget Tissues

• Caused by the nontherapeutic action of the drug

  • Reactions can occur at usual doses but appear more often at higher doses

  • A reduction in dose usually reduces these adverse reactions

Teratogenic effect

• Terato- = monster

• -genic = producing

• Teratogens are agents that cause congenital malformations and developmental abnormalities if introduced during gestation

• Drugs safe to use during pregnancy

• Penicillin

• Erythromycin

• Acetaminophen

• Local anesthetic lidocaine

Drugs contraindicated during pregnancy

• Tetracycline

• Nonsteroidal anti-inflammatory agents

• Benzodiazepines

• Metronidazole

Most dangerous time?

• Before pregnancy status is known

FDA categories A (safest) - X (highly damaging)

Local Effect

• Local reactions are characterized by local tissue irritation

• Injectable drugs can produce irritation, pain, and tissue necrosis at the site of injection

• Topically applied agents can produce irritation at the site of application

• Drugs taken orally can produce GI symptoms such as nausea or dyspepsia

Drug Interactions

• Toxicity

• Lack of efficacy

Hypersensitivity

Allergic Reaction

Type I

Immediate hypersensitivity; anaphylaxis

• IgE mediated

Type II

Cytotoxic/cytolytic

• IgG or IgM mediated

Type III

Immune complex

• Aggregations of antibodies and antigens

Type IV

Delayed hypersensitivity

• T lymphocytes and macrophages

Allergic Reactions

• Caused when drug is metabolized into a hapten

• Represent less than 5% of all adverse effects

• Penicillin allergy - most likely after injection

Type I - Anaphylactic Shock

• Rhinitis

• Asthma

• Urticaria

• Dermatitis

• Hypotension

• Bronchospasm

• Laryngeal edema

• Cardiac arrhythmias

Type II: Cytotoxic/Cytolytic

Complement-dependent reactions involving either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies

Type III: Immune Complex

Arthus, Serum Sickness

• Aggregate of antibodies and antigens

• Manifested as:

  • Serum sickness

  • Urticarial skin eruptions

  • Arthralgia

  • Arthiritis

  • Lymphadenopathy

  • Fever

Type IV: Delayed Hypersensitivity

• Reactions are mediated by sensitized T lymphocytes and macrophages

• Clinical Manifestations: Idiosyncrasy

• A reaction that is neither the drug’s side effect nor an allergic reaction

• Example: The antimalarial drug primaquine causes severe hemolytic anemia in black males who are deficient in the enzyme glucose-6-phosphate dehydrogenase

Defense mechanisms

A drug’s side effect on the body’s defense mechanisms can result in an adverse reaction

Toxicological Evaluation of Drugs

• Evaluations of the toxic effects of drugs are based on experiments performed with lower animals and clinical trails conducted in humans

• Lethal dose: Dose of drug that kills 50% of the experimental animals - LD50

• Median effective dose: Dose required to produce a specified intensity of effect in 50% of the animals - ED50

Recognizing Adverse Effects

• Patient education

• Communication

  • Determine drugs patient is taking

  • When patient is taking each drug

  • If symptoms occurred after beginning drug theraphy

  • How long after beginning drug therapy that symptoms began

  • Identify drug causing adverse effect

Dental Hygiene Considerations

• Know the difference between side effect, toxic effect, and allergic reaction

• Ask patient for more information

• Allergic to one drug = allergic to drugs in the same chemical class

• Educate patients about possible adverse drug effects and what should be done if they occur

• Ask if patient may be pregnant