H1 & H2 receptors drugs
Medication Summary
Most cases of simple acute urticaria can be treated with H1 antihistamine agents. [44] In cases of severe or persistent urticaria, H2 antihistamines may be added and may be given simultaneously orally or intravenously.[38] If the patient with chronic urticaria is refractory to nonsedating antihistamines, doses up to 4 times the recommended maximal dose may be effective. [6] If maximum doses of nonsedating antihistamines are not effective, other therapies should be tried. [45, 46]
In patients with urticaria resistant to the standard dosage of cetirizine or fexofenadine, doubling the daily dose may be effective. In a study of 51 patients treated with cetirizine at a dosage of 10 mg once daily, 18 patients had an inadequate response and were randomized to further treatment with either cetirizine 20 mg once daily or olopatadine 5 mg twice daily. Patients in the increased cetirizine dose group showed significant improvements in the severity of wheal and itching and in quality of life. [47]
Omalizumab (Xolair) was approved by the FDA in March 2014 for chronic idiopathic urticaria (CIU) in adults and children aged 12 years or older who remain symptomatic despite H1 antihistamine treatment. It was originally approved for asthma in 2003. It is a monoclonal antibody that selectively binds to IgE and inhibits binding to IgE receptors on the surface of mast cells and basophils. The efficacy and safety of omalizumab for CIU was demonstrated in two clinical studies that showed omalizumab significantly improved the mean weekly Itch Severity Score (ISS) from baseline by 9.4-9.6 in the 300-mg treatment arm (P <.001-0.0001), 6.4-6.7 in the 150-mg treatment arm (P = .001-0.0012), and 5.9-6.5 in the 75-mg treatment arm (P = .001), compared with a 3.6-5.1 improvement in patients on placebo. [15, 48] Omalizumab treatment is associated with improved quality of life. [49, 50]
Omalizumab is administered as a monthly injection and is effective in approximately 80% of individuals. [23] It is generally very well tolerated and the rate of adverse events is low, but major risk factors include anaphylaxis, among others; thus, it must be administered in a physician’s office. [8, 36]The dosing for use in asthma is based on weight and IgE levels, but omalizumab can be administered in 150- or 300-mg doses and, unfortunately, there are no clinical markers that can predict whether or not it will be effective. Although the evidence supporting its efficacy in treating urticaria is of high quality, the cost of the drug may preclude its use in many patients. [8]
Refractory cases of chronic urticaria may improve with glucocorticoids, but the complications of long-term use generally outweigh the benefits. [8]
Chronic urticaria may benefit from doxepin, a tricyclic antidepressant with potent antihistamine properties. Because of its significant sedative properties, it should be given at bedtime.
Topical therapy with 5% doxepin cream (Zonalon) or capsaicin may also be used in refractory cases.
Cyproheptadine may be useful to suppress recurrent cold urticaria. One study showed that the combination of a leukotriene receptor antagonist and a nonsedating antihistamine was superior to the antihistamine alone in treating chronic idiopathic urticaria. [51]
Cyclosporine has been shown to be effective in cases of refractory chronic urticaria. [52, 53]
Mycophenolate mofetil (CellCept) has also been shown to be effective. [8]
H1-receptor antagonist antihistamines
Class Summary
These agents block the histamine response in sensory nerve endings and blood vessels. They act by competitive inhibition of histamine at the H1 receptor, which mediates wheal and flare reactions, bronchial constriction, mucus secretion, smooth muscle contraction, and edema. Because they have significant anticholinergic activity, especially the older sedating antihistamines, they may cause hypotension, CNS depression, urinary retention, and cardiac arrhythmias, especially in higher therapeutic doses or overdoses.
Hydroxyzine hydrochloride (Atarax, Vistaril)
Hydroxyzine is a sedating peripheral H1 receptor antagonist. It is very effective in urticaria. Hydroxyzine also may suppress histamine activity in the subcortical region of the CNS.
Diphenhydramine (Benadryl, Benylin, Diphen)
Diphenhydramine is a sedating peripheral H1 receptor antagonist. It is used for symptomatic relief of allergic symptoms caused by histamine released in response to allergens.
Cyproheptadine is a sedating H1 antihistamine for symptomatic relief of allergic symptoms caused by histamine released in response to allergens and skin manifestations.
Cetirizine selectively inhibits peripheral histamine H1-receptors and is minimally sedating.
Levocetirizine is a histamine1-receptor antagonist. It is an active enantiomer of cetirizine. Peak plasma levels are reached within 1 hour and the half-life is about 8 hours. Levocetirizine is available as a 5-mg breakable (scored) tablet. It is indicated for seasonal and perennial allergic rhinitis.
Fexofenadine selectively inhibits peripheral histamine H1-receptors and is minimally sedating.
Loratadine (Claritin, Alavert)
Loratadine selectively inhibits peripheral histamine H1-receptors and is minimally sedating.
Desloratadine is a long-acting tricyclic histamine antagonist selective for H1-receptors. It is a major metabolite of loratadine, which, after ingestion, is extensively metabolized to the active metabolite 3-hydroxydesloratadine.
Tricyclic antidepressants (TCAs)
Class Summary
These agents are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin. Some TCAs (eg, doxepin) have antihistamine effects, blocking both the H1 and H2 receptors and have been used in the treatment of allergic reactions, especially urticaria.
Doxepin (Sinequan, Adapin, Zonalon)
Doxepin inhibits histamine and acetylcholine activity and has proven useful in the treatment of allergic dermatologic disorders.
Glucocorticoids
Class Summary
These agents decrease the inflammation associated with urticaria resistant to H1- and H2-receptor antihistamine therapy. They do not inhibit mast cell degranulation. They are often used to treat flares of chronic urticaria or as treatment of histamine-resistant acute urticaria or when angioedema is present. Long-term use is discouraged owing to long-term adverse effects.
Prednisone (Deltasone, Orasone, Meticorten)
Prednisone is used in the treatment of various allergic and inflammatory diseases. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
H2-receptor antagonists
Class Summary
These are reversible, competitive blockers of histamine at H2 receptors, particularly those in gastric parietal cells. The H2 antagonists are highly selective, do not affect H1 receptors, and are not anticholinergic agents. They block the vasodilation mediated by the H2 receptors in blood vessels, possibly leading to less edema formation in urticaria.
The combination of H1 and H2 antagonists may be useful in acute urticaria as well as chronic idiopathic urticaria not responding to H1 antagonists alone. This combination in IV form also may be useful for itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.
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 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.
Cimetidine 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.
Monoclonal Antibody
Class Summary
Monoclonal antibodies directed to IgE binding may reduce release of mediators that provoke an allergic response. These agents may be considered when H1-anagonists 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 H1 antihistamine treatment.
SECTIONSUrticaria
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