Immediate Hypersensitivity Reactions Medication

Medical therapy varies somewhat depending on which type of allergic reaction is being treated. Some of the drugs and their categories are listed here, but refer to the articles on the specific allergic reaction for more detail.

Class Summary

First-line choice to reverse effects of systemic vasodilation and increased vasopermeability observed with anaphylaxis. Although not the first choice for bronchoconstriction, epinephrine can also relieve some symptoms of bronchospasm and rhinitis. In the past, protocols called for subcutaneous or intravenous administration of epinephrine. However, studies have shown that intramuscular epinephrine leads to higher plasma levels than subcutaneous delivery. Intramuscular administration is now preferred over subcutaneous administration.^{[39, 40]}

Predosed autoinjectable epinephrine is now available in 2 forms: EpiPen and Twinject. Two doses of each are available (0.3 mg for EpiPen or Twinject 0.3 and 0.15 mg for EpiPen Jr. or Twinject 0.15). One Twinject pen actually has 2 doses of epinephrine available, which can be administered separately, and also has directions printed on a wraparound label on the pen that can be referred to at the time of use. EpiPen Duopacks contain 2 pens and, therefore, 2 doses. Twinject Two-packs contain 2 pens for a total of 4 doses.

Epinephrine (Adrenalin, Bronitin, EpiPen, Twinject)

Should be administered immediately for anaphylaxis/anaphylactic shock. Multiple preparations allow for delivery SC, IM, IV, or ET. Doses can be repeated q5min prn to maintain blood pressure (and as heart rate allows).

Class Summary

Inhaled bronchodilators are beta-agonists that come in short- and long-acting forms. Short-acting bronchodilators are used to treat acute bronchospasm. Can also be used prophylactically. For example, a patient with a history of asthma exacerbation in the presence of cats can use a short-acting bronchodilator before exposure to cats. Long-acting bronchodilators (eg, salmeterol) can be used twice daily and to help maintain bronchodilation over 12 h. They should only be used in conjunction with inhaled glucocorticoids.

Pirbuterol and formoterol have both short- and long-acting activity. Onset of action is approximately 15 min, but effects last up to 12 h. Of note, when long-acting beta agonists are used alone, concern exists of increased mortality. These medications should be combined with an inhaled corticosteroid and should be reserved for patients with more frequent or moderate to severe symptoms or lung function. Finally, levalbuterol is the R-enantiomer of albuterol and is available in nebulizer and metered dose inhaler (MDI) forms. Advantage of levalbuterol is that it is less likely to cause paradoxical bronchospasm than racemic albuterol.

Previously, MDIs were made using chlorofluorocarbons (CFCs) as the propellant. However, the use of CFCs has been phased out because of environmental concerns. For this reason, companies are now making MDIs with hydrofluoroalkane-134a (HFA), which is not damaging to the ozone layer. Once all previously manufactured CFC MDIs have been distributed, only HFA forms will be available. Importantly, note that, while a spacer should be used with traditional MDIs, spacers may not be necessary for certain HFA inhalers.

Albuterol (ProAir HFA, Ventolin HFA, Proventil HFA)

Sympathomimetic that stimulates beta-2 receptors, leading to bronchodilation. Used for bronchospasm refractory to epinephrine with anaphylaxis. First-line choice for acute bronchospasm associated with asthma.

Salmeterol/fluticasone inhaled (Advair, Symbicort)

Fluticasone inhibits bronchoconstriction mechanisms, may decrease number and activity of inflammatory cells, in turn decreasing airway hyper-responsiveness. Also has vasoconstrictive activity.

Salmeterol relaxes the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, and can relieve bronchospasm. Effect may also facilitate expectoration. Advair is available both as an HFA-propelled MDI and as a dry powder inhaler. Symbicort is only available as an MDI.

Adverse effects are more likely to occur when administered at high or more frequent doses than recommended.

Class Summary

Immunosuppressing agents and, thus, can decrease inflammation. Have particular efficacy in skin eruptions and bronchospasm. Role in anaphylactic shock is limited, although believed to help prevent delayed type of anaphylaxis.

Several different formulations are available; only one is listed. Others include methylprednisolone, dexamethasone, prednisolone (often used in children), and hydrocortisone. Depending on type of corticosteroid, oral, intravenous, and topical forms may be available. In more severe cases of anaphylaxis and asthma, intravenous forms of corticosteroids can be used initially. These can later be switched to oral forms as doses are tapered.

Inhaled corticosteroids are another form of corticosteroids and are key in controlling inflammation of bronchial airways and nasal mucosa. Similarly, topical corticosteroids are useful in treating atopic dermatitis.

Prednisone (Sterapred)

Believed to ameliorate delayed effects of anaphylactic reactions and may limit biphasic anaphylaxis. Doses below are general guidelines for usage; dosing is highly individualized.

Class Summary

Type 1 histamine-receptor blockers act to block action of histamine on H1 receptor after its release from mast cells and basophils. Most effective when used prophylactically. Sedating first-generation and nonsedating second-generation H1 antihistamines are available. Typically, sedating antihistamines have more adverse anticholinergic effects. Sedating antihistamines include diphenhydramine, hydroxyzine, cyproheptadine, chlorpheniramine, and brompheniramine. Nonsedating antihistamines include cetirizine (cause drowsiness in 15% people), fexofenadine, loratadine, and desloratadine. Desloratadine and fexofenadine may also help decrease nasal congestion. Liquid forms are more rapidly absorbed orally and should be used for immediate treatment of an allergic reaction if intravenous access is not available.

Diphenhydramine (Benadryl, Dihydrex injection, Belix)

Most widely available antihistamine (available OTC). Sedating antihistamines may be necessary to control more severe allergic reactions because they are very potent. Dosing interval of diphenhydramine is 4-6 h. Nonsedating antihistamines are all now available in a 24-h formulation but can only be administered PO.

Azelastine (Astelin)

An effective antihistamine delivered via the intranasal route. Mechanism is similar to oral antihistamines. Systemic absorption occurs and may cause sedation, headache, and nasal burning.

Forms complex with histamine for H1-receptor sites in blood vessels, GI tract, and respiratory tract.

Use prn or qd. Use alone or in combination with other medications. Unlike oral antihistamines, has some effect on nasal congestion. Helpful for vasomotor rhinitis. Some patients experience a bitter taste. Systemic absorption may occur, resulting in sedation (reported in approximately 11% of patients).

Cetirizine (Zyrtec)

Selectively inhibits histamine H1 receptor sites in blood vessels, GI tract, and respiratory tract, which in turn inhibits 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.

Class Summary

Can be administered in addition to H1-receptor blockers for additional control of urticaria and angioedema. Examples include ranitidine, famotidine, and cimetidine. Cimetidine has been studied more extensively for this indication than other members of this class.

Ranitidine (Zantac)

Multiple formulations are available. Cimetidine was first to be widely used but tends to have more drug interactions than other H2-receptor blockers. If no response to H1-receptor antagonist alone, coadministration with an H2-receptor antagonist can help relieve symptoms of itching and flushing in anaphylaxis, pruritus, and urticaria. Cimetidine plus an H1 blocker blocks cardiovascular effects of histamine.

Class Summary

Leukotrienes are synthesized by degranulated mast cells and basophils and likely contribute significantly to symptoms of allergic reactions. Three leukotriene inhibitors are now available in the United States. Montelukast and zafirlukast act as leukotriene D4-receptor blockers, whereas zileuton acts to inhibit production of leukotrienes B4, C4, D4, and E4. Disadvantages of the latter medication are its qid dosing and the need to monitor liver enzymes. However, a sustained release formulation is now available, permitting q12 h dosing; zileuton’s ability to inhibit synthesis of leukotrienes C4 and B4 as well as D4 may lead to increased use of this leukotriene modulator for certain indications.

Montelukast (Singulair)

Leukotriene inhibitors can be a helpful addition to asthma and allergic rhinitis not well controlled with H1-receptor blockers and inhaled corticosteroids.

Class Summary

Tacrolimus is a calcineurin inhibitor initially used in oral form as an immunosuppressant for transplantation patients. It has since been developed in topical form (Protopic) and can be used to treat atopic dermatitis that does not respond well to topical corticosteroids. A similar topical agent, pimecrolimus (Elidel), became available in the past few years and is indicated for mild atopic dermatitis. Systemic calcineurin inhibitors have been shown to cause immunosuppression and certain malignancies such as lymphoma. In January 2006, the FDA issued a black box warning for topical tacrolimus and pimecrolimus for these reasons.^[37] To date, studies have not shown significant systemic absorption, systemic immunosuppression, or increased risk of malignancy with the topical formulations. Trials are currently underway to assess possible benefit of inhaled tacrolimus for asthma.

Tacrolimus ointment (Protopic)

Reduces itching and inflammation by suppressing release of cytokines from T cells. Can be used in patients as young as 2 y. More expensive than topical corticosteroids.

Class Summary

Omalizumab (Xolair) is a monoclonal anti-IgE antibody indicated for refractory asthma. Has been shown to greatly improve severity of asthma in patients and can be used to help patients dependent on oral steroids to be weaned from steroids. Omalizumab has also been shown to decrease allergic response to peanuts in patients with severe peanut allergy.^[41] This could be helpful in preventing anaphylaxis from accidental peanut exposure in patients who normally would not tolerate even the slightest exposure to peanut allergen, but it only has FDA approval for asthma at this time. Patients should undergo a full allergy evaluation prior to starting omalizumab, if needed, because it interferes with prick skin test and RAST results.

Omalizumab (Xolair)

Binds to IgE and thereby prevents IgE from binding to mast cells and basophils.