Allergic Disorders

Allergy is a hypersensitivity disorder of the immune system . Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I(or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever,asthma attacks, food allergies, and reactions to the venom of stinging insects such as wasps and bees.


There are three classes of drugs in this section used to treat immediate hypersensitivity reactions caused by histamine release.

ANTIHISTAMINESAntihistamines are reversible competitive H₁ receptor antagonists that block allergic responses to histamine. They inhibit the constriction of respiratory and vascular smooth muscle, as well as the vasodilatory effects of histamine. H₁ antagonists suppress the edema, wheal, flare and itch components of histamine release. Salivary, lacrimal, and other exocrine gland secretions are also suppressed. H₁ antagonists are metabolized extensively by the liver and are generally eliminated more rapidly by children and more slowly by those with severe liver disease.

First-generation H₁ antagonists (eg, carbinoxamine, chlorpheniramine, cyproheptadine, diphenhydramine) cause both CNS stimulation and depression. CNS stimulation may be caused by a standard dose of these antihistamines; however, it is more likely a side effect of overdose. CNS depression is most often caused by older H₁ antagonists, especially the ethanolamine class of antihistamines (eg, diphenhydramine). Other side effects include GI upset and anticholinergic effects such as dry mouth and urinary retention.

Second-generation ("nonsedating") H₁ antagonists (eg, loratadine, desloratadine, cetirizine, fexofenadine) are more selective for H₁ receptors. They have fewer CNS side effects because they penetrate poorly across the blood-brain barrier. Anticholinergic effects are also insignificant because these drugs have no effect on muscarinic receptors.

MAST CELL STABILIZERS
When given orally, cromolyn acts locally to inhibit the release of histamine and leukotrienes from mast cells. Because cromolyn is poorly absorbed after oral administration, only the GI symptoms of mastocytosis are improved.

LEUKOTRIENE RECEPTOR ANTAGONISTSThe cysteinyl leukotrienes (LTC4, LTD4, LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. Cysteinyl leukotrienes are released from the nasal mucosa after allergen exposure during both early- and late-phase reactions and are associated with symptoms of allergic rhinitis. They bind to cysteinyl leukotriene type-1 (CysLT₁) receptors found in the human airway. Leukotriene receptor antagonists (eg, montelukast) bind with high-affinity and selectivity to the CysLT₁ receptor. By antagonizing CysLT₁ these agents have been found to be useful in the treatment of seasonal and perennial allergic rhinitis. 

Other Sections contain drugs which are useful in treating different types of allergies. 
For dermatitis see Topical steroids and Corticosteroid-responsive disorders sections.
For pruritus see Pruritus and dry skin section.
For ocular inflammation see Ocular allergy/inflammation section.
For asthma see Asthma/COPD section.
For allergic rhinitis see antihistamine/decongestant combinations in Cough and cold section andintranasal products in Rhinitis/rhinorrhea section.


ANAPHYLAXIS:


Epinephrine is a non-selective, direct acting sympathomimetic drug. It is the drug of choice for treating serious acute hypersensitivity reactions, including anaphylaxis to drugs and other allergens. Anaphylactic reactions may occur within minutes after exposure and consist of flushing, syncope, tachycardia, wheezing, dyspnea, pruritus, rashes, urticaria and angioedema.

When given by subcutaneous or intramuscular injection, epinephrine has a rapid onset and short duration of action. This potent vasopressor stimulates both alpha and beta adrenergic receptors. Through its effect on alpha adrenergic receptors, epinephrine acts quickly to counter vasodilation and increased vascular permeability, which can lead to loss of intravascular fluid volume and hypotension during anaphylactic reactions. Through its action on beta receptors, epinephrine promotes relaxation of bronchial smooth muscle, which helps to alleviate wheezing and dyspnea.