Case: Antihistamines
An 8-year-old girl is brought in by her mother for evaluation of allergies. Each year in the spring the child develops a runny nose; itchy, watery eyes; and sneezing. She has been treated in the past with diphenhydramine, but the child‘s teacher says that she is very drowsy during school. She has no other medical problems and is on no chronic medications. Her examination is unremarkable today. You diagnose her with seasonal allergic rhinitis and prescribe fexofenadine.
What is the mechanism of action of antihistamine medications?
What are the common side effects of antihistamine medications?
What is the pharmacologic basis of switching to fexofenadine?
Answers to case: Antihistamines
Summary: An 8-year-old girl with seasonal allergic rhinitis is switched to fex-ofenadine because of the sedation caused by diphenhydramine.
Mechanism of action of antihistamines: Competitive antagonist of histamine receptors.
Common side effects: Sedation, dizziness, nausea, constipation, diarrhea, loss of appetite, anticholinergic effects — dry mouth, dry eyes, blurred vision, urinary retention.
Rationale for switching to fexofenadine: Less central nervous system (CNS) penetration and less sedating than earlier antihistamines.
Clinical correlation
Histamine is found in many tissues throughout the body. Most histamine is stored in mast cells and basophils. Histamine is released primarily from mast cells via the process of degranulation. Degranulation occurs when immunoglobulin E (IgE) fixates to mast cells, and there is a subsequent exposure to a specific antigen. Complement activation may also induce degranulation. When released, histamine becomes bound to specific membrane-bound histamine receptors. The therapeutic uses of antihistamine medications primarily involve the H1 and H2-receptor subtypes. H1 receptors are located in the brain, heart, bronchi, gastrointestinal (GI) tract, and vascular smooth muscle. Their activation increases phospholipase C activity, causing increases in diacylglycerol and intracellular calcium. Activation of H: receptors in the brain increases wakefulness. In blood vessels, activation causes vasodilation and increased permeability. H1-receptor antagonists are competitive inhibitors at this receptor site. H1-receptor antagonists are frequently used for the treatment of allergic rhinitis, urticaria, and hives. Some are used as prophylaxis for motion sickness and as sleep aids. Older, first-generation, antihistamines cross the blood-brain barrier, contributing to their potentially use-limiting side effect of sedation and can also have significant anticholinergic effects (dry mouth, dry eyes, blurred vision, urinary retention). They must be used with caution in the elderly and in combination with other sedating medications, because the effects can be additive. Newer, second-generation antihistamines have significantly less penetration into the CNS and reduced anticholinergic activity. This results in a lower incidence of sedation and fewer anticholinergic side effects. H2-receptor activity is coupled to cyclic adenosine monophosphate (cAMP). Activation of H2 receptors in gastric parietal cells causes an increase in gastric acid production. Medications that are competitive antagonists of H2 receptors are used to reduce gastric acid secretion. These are used clinically in the management of peptic ulcer disease, gastroesophageal reflux disease, heartburn, and acid hypersecretory syndromes.
Approach to pharmacology of histamine and antihistamines
Objectives
1. Know the synthesis and mechanism of action of histamine.
2. Know the mechanism of action, uses, and adverse effects of antihistamine medications.
Definitions
Allergic rhinitis: An antigen-mediated allergic reaction that causes nasal congestion, sneezing, itchy eyes, and bronchoconstriction; also called hay fever.
Continuation: Case: Antihistamines. Class
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