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Clinical Pharmacy in Immunoallergology Medical diseases Allergies Allergic Rhinitis ('hay fever') Asthma Chronic Sinusitis Eczema (Atopic Dermatitis) Chronic Hives & Angioedema (swelling) Food Allergies Allergies to Insect Stings Contact Dermatitis Less common conditions including anaphylaxis, drug allergies and immune deficiencies. TERMS Allergen—A substance that provokes an allergic response. Anaphylaxis—Increased sensitivity caused by previous exposure to an allergen that can result in blood vessel dilation (swelling) and smooth muscle contraction. Anaphylaxis can result in sharp blood pressure drops and difficulty breathing. Antibody—A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen. Antigen—A foreign protein to which the body reacts by making antibodies. Mast cells, one of the major players in allergic reactions, capture and display a particular type of antibody, called immunoglobulin type E (IgE) that binds to allergens. Inside mast cells are small chemical-filled packets called granules. Granules contain a variety of potent chemicals, including histamine. Allergic reactions immediate hypersensitivity reactions, which are predominantly mast cellmediated and occur within minutes of contact with allergen; delayed hypersensitivity reactions, mediated by T cells (a type of white blood cells) and occurring hours to days after exposure. Inhaled or ingested allergens usually cause immediate hypersensitivity reactions. Allergens bind to IgE antibodies on the surface of mast cells, which spill the contents of their granules out onto neighboring cells, including blood vessels and nerve cells. Histamine binds to the surfaces of these other cells through special proteins called histamine receptors. Interaction of histamine with receptors on blood vessels causes increased leakiness, leading to the fluid collection, swelling and increased redness. Histamine also stimulates pain receptors, making tissue more sensitive and irritable. Symptoms last from one to several hours following contact. Routes: Allergens enter the body through the airways, the skin, the gastrointestinal tract, and the circulatory system SYMPTOMS Airborne allergens cause the sneezing, runny nose, and itchy, bloodshot eyes of hay fever (allergic rhinitis). Airborne allergens can also affect the lining of the lungs, causing asthma, or the conjunctiva of the eyes, causing conjunctivitis (pink eye). Exposure to cockroach allergans have been associated with the development of asthma. Airborne allergans from household pets are another common source of environmental exposure. SYMPTOMS Allergens in food can cause itching and swelling of the lips and throat, cramps, and diarrhea. When absorbed into the bloodstream, they may cause hives (urticaria) or more severe reactions involving recurrent, noninflammatory swelling of the skin, mucous membranes, organs, and brain (angioedema). Some food allergens may cause anaphylaxis, a potentially lifethreatening condition marked by tissue swelling, airwayconstriction, and drop in blood pressure. Allergies to foods such cow’s milk, eggs, nuts, fish, and legumes (peanuts and soybeans) are common. Allergies to fruits and vegetables may also occur. SYMPTOMS In contact with the skin, allergens can cause reddening, itching, and blistering, called contact dermatitis. Skin reactions can also occur from allergens introduced through the airways or gastrointestinal tract. This type of reaction is known as atopic dermatitis. Dermatitis may arise from an allergic response (such as from poison ivy), or exposure to an irritant causing nonimmune damage to skin cells (such as soap, cold, and chemical agents). SYMPTOMS Injection of allergens, from insect bites and stings or drug administration, can introduce allergens directly into the circulation, where they may cause systemwide responses (including anaphylaxis), as well as the local ones of swelling and irritation at the injection site. The following types of drugs commonly cause allergic reactions: • penicillin or other antibiotics • flu vaccines • tetanus toxoid vaccine • gamma globulin SYMPTOMS (cont’d) Symptoms depend on the specific type of allergic reaction. Allergic rhinitis is characterized by an itchy, runny nose, often with a scratchy or irritated throat due to post-nasal drip. Inflammation of the thin membrane covering the eye (allergic conjunctivitis) causes redness, irritation, and increased tearing in the eyes. Asthma causes wheezing, coughing, and shortness of breath. SYMPTOMS (cont’d) Symptoms of food allergies depend on the tissues most sensitive to the allergen and whether the allergen spread systemically by the circulatory system. Gastrointestinal symptoms may include swelling and tingling in the lips, tongue, palate or throat; nausea; cramping; diarrhea; and gas. Contact dermatitis is marked by reddened, itchy, weepy skin blisters, and an eczema that is slow to heal. It sometimes has a characteritic man-made pattern, such as a glove allergy with clear demarkation on the hands, wrist, and arms where the gloves are worn, or on the earlobes by wearing earrings. Skin reactions Skin reactions include the raised, reddened, and itchy patches called hives that characteristically blanch with pressure and resolve within twenty-four hours. A deeper and more extensive skin reaction, involving more extensive fluid collection and pain, is called angioedema. This usually occurs on the extremities, fingers, toes, and parts of the head,neck,and face. Anaphylaxis Anaphylaxis is marked by airway constriction, blood pressure drop, widespread tissue swelling, heart rhythm abnormalities, and in some cases, loss of consciousness. Other syptoms may include, dizziness, weakness, seizures, coughing,flushing, or cramping. The symptoms may begin within five minutes after exposure to the allergan up to one hour or more later. Mast cells in the tissues and basophils in the blood release mediators that give rise to the clinical symptoms of this IgE-mediated hypersensitivity reaction. Commonly, this is associated with allergies to medications, foods, and insect venoms. Anaphylaxis In some individuals, anaphylaxis can occur with exercise, plasma exchange, hemodialysis, reaction to insulin, radocontrast media used in certain types of medical tests. and rarely during the administration of local anesthetics. The allergic response Treatment Avoiding allergens is the first line of defense to reduce the possibility of an allergic attack. Complete environmental control is often difficult to accomplish, hence therapuetic interventions may become necessary. A large number of prescription and over-the-counter drugs are available for treatment of immediate hypersensitivity reactions. Most of these work by decreasing the ability of histamine to provoke symptoms. Other drugs counteract the effects of histamine by stimulating other systems or reducing immune responses in general. Treatment ANTIHISTAMINES block the histamine receptors on nasal tissue, decreasing the effect of histamine released by mast cells. They may be used after symptoms appear, though they may be even more effective when used preventively, before symptoms appear. Antihistamines are help reduce sneezing, itching, and rhinorrhea. Treatment I generation antihistamines side effect Drowsiness dry mouth, tachycardia, blurred vision, constipation, lower the threshold for seizures. diphenhydramine (Benadryl and generics) chlorpheniramine (Chlor-trimeton and generics) brompheniramine (Dimetane and generics) clemastine (Tavist and generics) These medicatios care should be taken when operating motor vehicles Treatment Newer antihistamines that do not cause drowsiness or pass the blood-brain barrier are available by prescription and include the following: • loratidine (Claritin) • fexofenadine (Allegra) ALLERGIC RHINITIS Allergic rhinitis, more commonly referred to as hay fever, is an inflammation of the nasal passages caused by allergic reaction to airborne substances. Allergic rhinitis (AR) is the most common allergic condition and one of the most common of all minor afflictions. There are two types of allergic rhinitis: seasonal and perennial. Seasonal AR occurs in the spring, summer, and early fall, when airborne plant pollens are at their highest levels. In fact, the term hay fever is really a misnomer, since allergy to grass pollen is only one cause of symptoms for most people. Perennial AR occurs all year and is usually caused by home or workplace airborne pollutants. A person can be affected by one or both types. Symptoms of seasonal AR are worst after being outdoors, while symptoms of perennial AR are worst after spending time indoors. ALLERGIC RHINITIS Causes Allergic rhinitis is a type of immune reaction. Normally, the immune system responds to foreign microorganisms, or particles, like pollen or dust, by producing specific proteins, called antibodies, that are capable of binding to identifying molecules, or antigens, on the foreign particle. This reaction between antibody and antigen sets off a series of reactions designed to protect the body from infection. Sometimes, this same series of reactions is triggered by harmless, everyday substances. This is the condition known as allergy, and the offending substance is called an allergen. Virtually any type of tree or grass may cause AR. A few types of weeds that tend to cause the most trouble for people include the following: • ragweed • sagebrush • lamb’s-quarters • plantain • pigweed • dock/sorrel This illustration depicts excessive mucus production in the nose after inhalation of airborne pollen ALLERGIC RHINITIS. Symptoms Inflammation causes itching, sneezing, runny nose, redness, and tenderness. Sinus swelling can constrict the eustachian tube that connects the inner ear to the throat, causing a congested feeling and “ear popping.” The drip of mucus from the sinuses down the back of the throat, combined with increased sensitivity, can also lead to throat irritation and redness. AR usually also causes redness, itching, and watery eyes. Fatigue and headache are also common. ALLERGIC RHINITIS. Treatment Avoidance of the allergens is the best treatment, but this is often not possible. When it is not possible to avoid one or more allergens, there are two major forms of medical treatment, drugs and immunotherapy. DRUGS ANTIHISTAMINES. Antihistamines block the histamine receptors on nasal tissue, decreasing the effect of histamine release by mast cells. They may be used after symptoms appear, though they may be even more effective when used preventively, before symptoms appear. A wide variety of antihistamines are available. ALLERGIC RHINITIS. Treatment Older antihistamines often produce drowsiness as a major side effect. Such antihistamines include the following: • diphenhydramine (Benadryl and generics) • chlorpheniramine (Chlor-trimeton and generics) • brompheniramine (Dimetane and generics) • clemastine (Tavist and generics). ALLERGIC RHINITIS. Treatment Newer antihistamines that do not cause drowsiness are available by prescription and include the following: • astemizole (Hismanal) • loratidine (Claritin) • fexofenadine (Allegra) • azelastin HCl (Astelin). – Hismanal has the potential to cause serious heart arrhythmias when taken with the antibiotic erythromycin, the antifungal drugs ketoconazole and itraconazole, or the antimalarial drug quinine. ALLERGIC RHINITIS. Treatment Decongestants constrict blood vessels to counteract the effects of histamine. Nasal sprays are available that can be applied directly to the nasal lining and oral systemic preparations are available. Decongestants are stimulants and may cause increased heart rate and bloodpressure, headaches, and agitation. Use of topical decongestants for longer than several days can cause loss of effectiveness and rebound congestion, in which nasal passages become more severely swollen than before treatment. ALLERGIC RHINITIS. Treatment Topical corticosteroids reduce mucous membrane inflammation and are available by prescription. Allergies tend to become worse as the season progresses because the immune system becomes sensitized to particular antigens and can produce a faster, stronger response. Topical corticosteroids are especially effective at reducing this seasonal sensitization because they work more slowly and last longer than most other medication types. As a result, they are best started before allergy season begins. Side effects are usually mild, but may include headaches, nosebleeds, and unpleasant taste sensations. ALLERGIC RHINITIS. Treatment MAST CELL STABILIZERS Cromolyn sodium prevents the release of mast cell granules, thereby preventing release of histamine and the other chemicals contained in them. It acts as a preventive treatment if it is begun severalweeks before the onset of the allergy season. It can be used for perennial AR as well. Treatment of anaphylaxis The emergency condition of anaphylaxis is treated with injection of adrenaline (epinephrine). Paticular care should be taken to assess the affected individual’s airway status, and he or she should be placed in a recumbent pose and vital signs determined. If a reaction resulted from insect sting or an injection, a tourniquet may need to be placed proximal to the area where the agent penetrated the skin. This should then be released at intervals of ten minutes at a time, for one to two minutes duration. Oxygen may be given, as well as intravenous replacement fluids. Antihistamines may be used for skin rash, and aminophylline for bronchial constriction. If the upper airway is obstructed, placement of a breathing tube or tracheostomy tube may be needed.