Pharmacology: Adverse Drug Reactions

Adverse Reactions

• Drugs are used to achieve desired effects but can also produce undesirable or adverse reactions.
• Drugs lack absolute specificity, meaning they may act on unintended targets, leading to adverse reactions.

More than One Action

• Drugs can have both therapeutic (desirable) and adverse (undesirable) effects.
• An adverse effect could, in some cases, be a therapeutic effect in another context.

Adverse Drug Reactions

• Adverse drug reactions are unintended, potentially harmful responses to a drug.
• These responses typically occur at usual therapeutic doses.

Categories of Adverse Drug Reactions

• Toxic reaction: An exaggerated response to the drug's intended action, often dose-related.
• Side effect: A secondary, unintended effect of a drug, not part of the desired action, often dose related and affecting non-target tissues.
• Drug Allergy: An immune response to a drug, not dose-related or predictable; previously exposed patients may exhibit hypersensitivity reactions. Less than 5% of adverse reactions are allergies. Four types of reactions exist (ABCD).
• Idiosyncratic reaction: A reaction that's neither a side effect nor an allergy; genetically-related and unusual.
• Interference with natural defense mechanisms: A drug's impact on the body's natural defenses can result in adverse reactions.
• Teratogenic effects: Agents that cause birth defects, developmental abnormalities during gestation.
• Local effects: Reactions specific to the application site.
• Drug interactions: The alteration of one drug's effect by another drug, food, or disease.

Toxic Reaction

• An extension of the drug's pharmacological effect.
• Dose-related.
• Exaggerated response on target tissues.
• Example: A hypoglycemic agent causing blood sugar to fall too low.

Side Effect

• Not part of the intended therapeutic action.
• Dose-related.
• Drug acts on non-target tissues, causing undesirable effects.
• Example: Ibuprofen causing an upset stomach.

Drug Allergy

• Hypersensitivity response to a previously encountered drug.
• Not dose-related or predictable in this type of reaction.
• Acts as an antigen and reacts with antibodies in sensitized patients.

Type I Drug Allergy

• Anaphylactic shock, a severe, life-threatening event.
• Other symptoms include rhinitis, asthma, urticaria, dermatitis, hypotension, bronchospasm, laryngeal edema, and cardiac arrhythmias.
• Often occurs within minutes of exposure. Can be triggered by local anesthetics and penicillins.

Type II: Cytotoxic/Cytolytic Drug Reaction

• Antigen-antibody complexes attach to circulating blood cells, causing cell death.
• Example: Penicillin-induced hemolytic anemia.

Type III: Immune Complex, Arthus, Serum Sickness

• Clumps of antigen-antibody complexes deposit in the blood vessel walls.
• Symptoms include serum sickness, urticarial skin eruptions, arthralgia, arthritis, lymphadenopathy, and fever.
• Typically occurs 2-3 weeks post exposure.

Type IV: Delayed Hypersensitivity

• Reactions are mediated by sensitized T-lymphocytes and macrophages, not antibodies.
• Symptoms appear 2-3 days later.
• Example: poison oak, cheap jewelry, autoimmune disease.

Idiosyncratic Reaction

• Not a side effect or allergy.
• Genetically related abnormal reaction.
• Example: Eskimos metabolizing drugs faster than others.

Interference with Natural Defense Mechanisms

• Drug's effect on the body's defenses.
• Can result in adverse reactions.
• Example: Prolonged corticosteroid use can decrease infection resistance.

Teratogenic Effect

• Agents causing congenital malformations or developmental abnormalities.
• Exposure during pregnancy can cause birth defects.
• Example: Table 22.1.

Teratogenic Effect (continued)

• No drug is absolutely safe
• Safest drugs to use during pregnancy are: penicillin, erythromycin, and acetaminophen
• Drugs contraindicated during pregnancy are: tetracycline, nonsteroidal anti-inflammatory agents, benzodiazepines, metronidazole, and thalidomine.

Local Effect

• Reactions limited to the application site.
• Injectable drugs can cause pain, irritation, and necrosis.
• Drugs applied topically may also cause irritation.
• Oral medications may cause gastrointestinal symptoms.

Drug Interactions

• The effect of one drug is altered by another drug.
• Types include drug-drug interaction, drug-food interaction, and drug-disease interaction.
• Table 3-1.

Toxicological Evaluation of Drugs

• Evaluating toxic effects of drugs, both on animals and humans.
• Lethal does is the dose that kills 50% of the tested animals.
• Median effective dose is the dose that produces a specific intensity of effect in 50% of the tested animals.
• Therapeutic index.

Recognizing Adverse Effects

• Patient education is critical.
• Crucial to identify drugs being taken and when. The time from beginning therapy to the onset of symptoms is important for assessment.
• Identifying the drug causing the adverse effect is key.

Dental Hygiene Considerations

• Recognizing the difference between side effects, toxic effects, and allergic reactions.
• Asking patients for information and assessing allergy history.
• Educating patients about possible drug effects.
• Assessing possible pregnancy to ensure appropriate medication choices.