Chapter 32: Drug Therapy to Decrease Histamine Effects and Allergic Response

Histamine and Its Role in the Immune Response

Histamine is a key chemical mediator in the immune and inflammatory response, synthesized and stored in most body tissues. It is especially concentrated in tissues exposed to the environment, such as the eyes, nose, lungs, and gastrointestinal tract.

• Definition: Histamine is a biogenic amine involved in local immune responses, regulating physiological functions in the gut, and acting as a neurotransmitter in the central nervous system (CNS).

• Release Mechanism: Discharged from mast cells and basophils in response to specific stimuli.

• Action: Binds to histamine receptors on target organs, producing reactions specific to the muscle groups involved.

• Location: Found in the CNS and peripheral tissues.

• Example: Histamine release causes symptoms such as itching, sneezing, and nasal congestion during allergic reactions.

Hypersensitivity Reactions

Hypersensitivity reactions are exaggerated responses by the immune system that produce tissue injury and may cause serious disease. The mechanisms are similar to those of natural immunity and may involve specific antibodies, sensitized T lymphocytes, or both.

• Definition: Hypersensitivity refers to an excessive or inappropriate immune response to an antigen.

• Mechanism: Can be antibody-mediated or cell-mediated.

• Example: Allergic rhinitis, contact dermatitis, and anaphylaxis are clinical manifestations of hypersensitivity.

Types of Hypersensitivity Reactions

Hypersensitivity reactions are classified into four types based on their mechanisms and clinical manifestations.

• Type I (Immediate Hypersensitivity): IgE-induced response, occurs on second exposure to antigen, can cause anaphylaxis.

• Type II (Cytotoxic): Mediated by IgG or IgM, causes direct damage to cell surfaces. Examples include blood transfusion reactions and hemolytic disease of the newborn.

• Type III (Immune Complex): Mediated by IgG or IgM, forms antigen–antibody complexes leading to acute inflammatory reactions in tissues. Example: serum sickness.

• Type IV (Delayed Hypersensitivity): Cell-mediated response involving sensitized T lymphocytes. Examples: tuberculin test, contact dermatitis, graft rejection.

Clinical Manifestations of Allergic Reactions

Allergic reactions can present in various forms depending on the type of hypersensitivity and the organ system involved.

• Allergic Rhinitis: Inflammation of nasal mucosa caused by type I reaction to inhaled allergens. Symptoms include nasal congestion, itching, sneezing, cough, watery drainage, and itching of throat, eyes, and ears.

• Types: Seasonal (hay fever, response to airborne pollens) and perennial (response to nonseasonal allergens such as dust mites, molds, animal dander).

• Allergic Contact Dermatitis: Type IV reaction due to direct contact with antigens.

• Allergic Food Reactions: Immune response to ingestion of proteins (e.g., shellfish, peanuts, milk, eggs). May trigger anaphylaxis, especially in children.

• Allergic Drug Reactions: Any drug can induce an immunologic response, potentially causing multiple hypersensitivity states.

• Pseudoallergic Drug Reactions: Resemble immune responses but do not involve antibodies or sensitized T lymphocytes. Anaphylactoid reactions may occur on first exposure and are life-threatening.

Antihistamines: Classification and Mechanism

Antihistamines are medications that antagonize the action of histamine, reducing or preventing its physiological effects at receptor sites.

• First-Generation H1 Receptor Antagonists: Prototype: diphenhydramine. Prevent/reduce most effects of histamine, inhibit smooth muscle constriction, decrease capillary permeability, salivation, and tear formation. High incidence of drowsiness and anticholinergic effects; limited role.

• Second-Generation H1 Receptor Antagonists: Prototype: cetirizine. Faster onset, superior potency, selectivity, and efficacy. Do not readily enter the brain, reducing sedation. Used for allergic rhinitis and urticaria.

• Third-Generation H1 Receptor Antagonists: Prototype: fexofenadine. Bind preferentially to peripheral H1 receptors, do not enter the brain, further reducing adverse effects like drowsiness. Effective for allergic conditions.

Pharmacokinetics and Drug Therapy Considerations

Understanding the pharmacokinetics, action, use, adverse effects, and contraindications of antihistamines is essential for safe and effective therapy.

• Pharmacokinetics: Refers to the absorption, distribution, metabolism, and excretion of drugs.

• Action: Antihistamines block histamine receptors, preventing histamine-mediated symptoms.

• Use: Symptomatic relief of allergic rhinitis, anaphylaxis, allergic conjunctivitis, drug allergies, blood transfusion reactions, dermatologic conditions.

• Adverse Effects: Drowsiness, anticholinergic effects, rare severe reactions.

• Contraindications: Vary by drug; may include certain medical conditions or drug interactions.

Antihistamine Indications and Use in Special Populations

Antihistamines relieve symptoms but do not address the underlying hypersensitivity. Their use must be tailored to specific populations.

• Indications: Allergic rhinitis, anaphylaxis, allergic conjunctivitis, drug allergies, pseudoallergies, blood/blood product transfusion, dermatologic conditions.

• Special Populations: Children, older adults, patients with abnormal kidney function, hepatic impairment, critical illness, and those receiving home care may require dose adjustments or monitoring.

Nursing Implications

Nurses play a critical role in the safe administration and monitoring of antihistamine therapy.

• Preventing Interactions: Assess for potential drug-drug or drug-disease interactions.

• Administering Medication: Follow proper dosing and administration guidelines.

• Assessing for Adverse Effects: Monitor for drowsiness, anticholinergic effects, and allergic reactions.

• Assessing for Therapeutic Effects: Evaluate symptom relief and improvement in allergic conditions.

• Patient Teaching: Educate patients about medication use, potential side effects, and when to seek medical attention.

Additional info:

• Antihistamines are not curative for hypersensitivity reactions but are essential for symptom management.

• Children may outgrow certain food allergies, but there is no known preventative for allergic reactions.

• Pseudoallergic reactions can be life-threatening and may occur on first exposure to a drug.