The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Agents used in the management of pressure urticaria include antihistamines, leukotriene antagonists, corticosteroids, and nonsteroidal anti-inflammatory drugs (NSAIDs). The benefit of omalizumab has been established in chronic spontaneous urticaria and shows potential for patients with delayed pressure urticaria (DPU). There are many experimental drugs being used.
Antihistamines, 2nd Generation
Antihistamines may be useful in helping control symptoms of chronic urticaria, which frequently coexists with delayed pressure urticaria (DPU). Second-generation antihistamines, also known as less-sedating or low-sedation antihistamines, produce less sedation than traditional H1 blockers because they are less lipid-soluble and only cross the blood-brain barrier in small amounts. They also have longer half-lives, allowing less frequent dosing. Many H1 antagonists are metabolized through the cytochrome P-450 system. Important exceptions include cetirizine, levocetirizine, and fexofenadine.
Levocetirizine is an H1-receptor antagonist and an active enantiomer of cetirizine. Peak plasma levels are reached within 1 hour, and the half-life is approximately 8 hours. Levocetirizine is available as a 5-mg breakable (scored) tablet and a 0.5 mg/mL oral solution. It is indicated for uncomplicated skin manifestations of chronic idiopathic urticaria (CIU).
Fexofenadine is a nonsedating second-generation medication that has fewer adverse effects than first-generation medications. It competes with histamine for H1 receptors in the gastrointestinal (GI) tract, blood vessels, and the respiratory tract, reducing hypersensitivity reactions. Fexofenadine does not sedate. It is available in once-daily and twice-daily preparations.
Loratadine selectively inhibits peripheral histamine H1 receptors.
Desloratadine is a long-acting tricyclic histamine antagonist that is selective for H1 receptors. It is a major metabolite of loratadine, which, after ingestion, is extensively metabolized to the active metabolite 3-hydroxydesloratadine.
Cetirizine selectively inhibits H1 receptor sites in blood vessels, the GI tract, and the respiratory tract, thereby inhibiting the physiologic effects that histamine normally induces at H1 receptor sites. Once-daily dosing is convenient; bedtime dosing may be useful if sedation is a problem.
Antihistamines, 1st Generation
First-generation antihistamines compete with histamine at the tissue-receptor level, preventing it from carrying out its mediator functions in urticaria.
Diphenhydramine is a first-generation antihistamine with anticholinergic effects. It binds to H1 receptors in the central nervous system (CNS) and the body, competitively blocking histamine from binding to these receptors.
Diphenhydramine is employed for symptomatic relief of pruritus caused by release of histamine in inflammatory reactions. It has significant antimuscarinic activity and penetrates the CNS and thus has a pronounced tendency to induce sedation. Approximately half of those treated with conventional doses experience some degree of somnolence. A small percentage of children paradoxically respond to diphenhydramine with agitation.
Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the CNS.
Antihistamines, H2 Blockers
H2 antagonist therapy can be used as an adjunct to H1 antagonist therapy.
Famotidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Ranitidine is a second-generation agent that is effective for the treatment of urticaria. It is tolerated very well, with a rate of sedation that is not significantly different from that seen with placebo.
This agent competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
This agent inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Because of their anti-inflammatory properties, corticosteroids have been used in the management of pressure urticaria, with variable success.
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
This glucosteroid occurs naturally and synthetically. It is used for both acute and chronic asthma. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Monoclonal antibodies directed to immunoglobulin E (IgE) binding may reduce the release of mediators that provoke an allergic response. These agents may be considered when H 1 -receptor antagonists are ineffective.
Omalizumab is a recombinant humanized monoclonal antibody administered by subcutaneous injection every 4 weeks. It selectively binds to IgE and inhibits binding to IgE receptors on the surface of mast cells and basophils. It is indicated for chronic idiopathic urticaria in adults and children aged 12 years or older who remain symptomatic despite anti-H1 antihistamine treatment.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
NSAIDs are the medications most commonly used to control mild to moderate pain and to decrease inflammation. Sulfasalazine, steroids, and immunosuppressive agents are sometimes used, with varying degrees of success. NSAIDs can also be a nonimmunologic trigger of mast cell degranulation and subsequent urticaria.
Ibuprofen is an NSAID with analgesic, anti-inflammatory, and antipyretic properties. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Naproxen inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Agents in this class that antagonize the H1 receptor preventing histamine from causing urticaria. The tricyclic antidepressant doxepin is used in urticaria for its sedative and antihistaminic properties. Oral doxepin may be considered if oral antihistamines are not helpful.
Doxepin is a tricyclic antidepressant that has potent H1-blocking activity, which makes it quite useful for urticaria. However, doxepin has very potent sedative and anticholinergic effects. It can be quite effective if given at bedtime because its sedative effects can make it easier for patients with pruritus to sleep.
Leukotriene Receptor Antagonists
Leukotriene antagonists, alone or in combination, have been found to be efficacious for treating delayed pressure urticaria (DPU). Other forms of chronic urticaria have not demonstrated similar responses to this treatment.
Leukotriene inhibitors can be a helpful addition to therapy in patients with asthma and allergic rhinitis that are not well controlled with H1-receptor blockers and inhaled corticosteroids.
Zafirlukast inhibits effects mediated by leukotriene receptors, the activity of which has been associated with airway edema, smooth muscle contraction, and cellular activity associated with symptoms.
5-Aminosalicylic Acid Derivatives
These agents have anti-inflammatory effects.
Sulfasalazine decreases the inflammatory response and systemically inhibits prostaglandin synthesis.
Some small studies have shown topical corticosteroids to be efficacious in reducing the size of pressure urticaria lesions, as well as the erythema and pruritus associated with them.
Clobetasol propionate is a class I superpotent topical steroid; it suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Clobetasol decreases inflammation by stabilizing lysosomal membranes, inhibiting PMN leukocytes and mast cell degranulation.
What would you like to print?
- Medication Summary
- Antihistamines, 2nd Generation
- Antihistamines, 1st Generation
- Antihistamines, H2 Blockers
- Monoclonal Antibodies
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
- Antidepressants, TCAs
- Leukotriene Receptor Antagonists
- 5-Aminosalicylic Acid Derivatives
- Corticosteroids, Topical
- Show All