Clinical Pharmacy in Clinical Pharmacy in Immunoallergology Immunoallergology Medical diseasesMedical diseases

AllergiesAllergies AllergicAllergic RhinitisRhinitis ('hay fever') ('hay fever') AsthmaAsthma Chronic Sinusitis Chronic Sinusitis Eczema (Atopic Dermatitis) Eczema (Atopic Dermatitis) Chronic Hives & Angioedema (swelling) Chronic Hives & Angioedema (swelling) Food Allergies Food Allergies Allergies to Insect Stings Allergies to Insect Stings Contact Dermatitis Contact Dermatitis Less common conditions including Less common conditions including

anaphylaxis, drug allergies anaphylaxis, drug allergies and immune deficiencies. and immune deficiencies.

What Are Allergies? What Are Allergies?

Allergies are a reaction by the Allergies are a reaction by the body's immune system to body's immune system to harmless substances that it sees harmless substances that it sees as harmful.  The allergy causing as harmful.  The allergy causing substances are called allergens.  substances are called allergens.  It is as if the immune system is It is as if the immune system is overly-active in response to overly-active in response to otherwise innocuous substances.otherwise innocuous substances.

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.

How do How do AlergiesAlergies occur? occur?TheThe immune system is immune system is thethe body's natural body's natural defense against infection and other foreign defense against infection and other foreign material. Before material. Before the personthe person can ha can hass a reaction to a reaction to a particular substance, immune system must a particular substance, immune system must first be sensitized to it.  This happens in an first be sensitized to it.  This happens in an earlier contact with the substance.  Once earlier contact with the substance.  Once sensitized, sensitized, thethe body will react when body will react when one hasone has contact with that substance.  Many substances contact with that substance.  Many substances cause an allergic reaction.  The most common cause an allergic reaction.  The most common are: are: pollens, molds, house dust mites, animal pollens, molds, house dust mites, animal dander, latex, medicines, insect stings and dander, latex, medicines, insect stings and foods.foods.

Food allergic reactions may be severe or fatal.  Food allergic reactions may be severe or fatal.  Common foods that may cause allergy Common foods that may cause allergy symptoms include fish, eggs, milk, nuts, peanuts symptoms include fish, eggs, milk, nuts, peanuts and wheat.  Food allergies often occur in and wheat.  Food allergies often occur in children, who may outgrow them.children, who may outgrow them.

It is also possible to have an allergic reaction to It is also possible to have an allergic reaction to sunlight, temperature extremes, water contact sunlight, temperature extremes, water contact and other elements in your physical and other elements in your physical environment. environment.

Allergic reactions

immediate hypersensitivity reactions, which are predominantly mast cell-mediated 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 thecirculatory system

SYMPTOMSAirborne allergens cause the sneezing, runny nose,and itchy, bloodshot eyes of hay fever (allergic rhinitis).Airborne allergens can also affect the lining of thelungs, causing asthma, or the conjunctiva of the eyes,causing conjunctivitis (pink eye). Exposure to cockroachallergans have been associated with the developmentof asthma. Airborne allergans from householdpets are another common source of environmentalexposure.

SYMPTOMS

Allergens in food can cause itching and swelling of thelips and throat, cramps, and diarrhea. When absorbedinto 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 life-threatening 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 introducedthrough the airways or gastrointestinal tract.This type of reaction is known as atopic dermatitis.Dermatitis may arise from an allergic response (suchas from poison ivy), or exposure to an irritant causingnonimmune 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 system-wide 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 allergicreaction. Allergic rhinitis is characterized by an itchy,runny nose, often with a scratchy or irritated throat dueto post-nasal drip. Inflammation of the thin membranecovering the eye (allergic conjunctivitis) causes redness,irritation, and increased tearing in the eyes. Asthma causeswheezing, 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; andgas. Contact dermatitis is marked by reddened, itchy,weepy skin blisters, and an eczema that is slow to heal. Itsometimes has a characteritic man-made pattern, such asa 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 reactionsinclude the raised, reddened, and itchy patches calledhives that characteristically blanch with pressure andresolve within twenty-four hours. A deeper and moreextensive skin reaction, involving more extensive fluidcollection and pain, is called angioedema. This usuallyoccurs on the extremities, fingers, toes, and parts of thehead,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 afterexposure to the allergan up to one hour or more later.Mast cells in the tissues and basophils in the bloodrelease mediators that give rise to the clinical symptomsof 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

TreatmentAvoiding allergens is the first line of defense to reduce the possibility of an allergic attack.

Complete environmental control is often difficult toaccomplish, hence therapuetic interventions maybecome necessary. A large number of prescription andover-the-counter drugs are available for treatment ofimmediate hypersensitivity reactions. Most of thesework by decreasing the ability of histamine to provokesymptoms. Other drugs counteract the effects of histamineby stimulating other systems or reducing immuneresponses in general.

TreatmentANTIHISTAMINES 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.

TreatmentI generation antihistamines side effect

Drowsinessdry 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)

Treatment MAST CELL STABILIZERS

Cromolyn sodium prevents the release of mast cell granules, thereby preventing the release of histamine and other chemicals contained in them. It acts as a preventive treatment if it is begun several weeks before the onset of the allergy season.

It can also be used for year round allergy prevention. Cromolyn sodium is available as a nasal spray for allergic rhinitis and in aerosol (a suspension of particles in gas) form for asthma.

Treatment LEUKOTRIENE MODIFIERS

These medications are useful for individuals with aspirin sensitivity,sinusitis,

poliposis, urticaria. Examples include zafirlukast (Accolate), montelukast (Singulair), and zileuton (Zyflo).

When zileuton is used, care must be taken to measure liver enzymes.

ALLERGIC RHINITISAllergic rhinitis, more commonly referred to as hay

fever, is an inflammation of the nasal passages caused byallergic 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

CausesAllergic 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. Afew 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. TreatmentAvoidance 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.

DRUGSANTIHISTAMINES. Antihistamines block the histaminereceptors on nasal tissue, decreasing the effect ofhistamine release by mast cells. They may be used aftersymptoms appear, though they may be even more effectivewhen used preventively, before symptoms appear. Awide 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. TreatmentNewer 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. TreatmentTopical 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.

ALLERGIC RHINITIS. Treatment

Immunotherapy, also known as desensitization or

allergy shots, alters the balance of antibody types in thebody, thereby reducing the ability of IgE to cause allergicreactions. Immunotherapy is preceded by allergy testingto determine the precise allergens responsible. Injectionsinvolve very small but gradually increasing amounts ofallergen, over several weeks or months, with periodicboosters. Full benefits may take up to several years toachieve and are not seen at all in about one in fivepatients.

Treatment of anaphylaxisThe 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.

Immunologic Reactions to Drugs & Immunologic Reactions to Drugs & Drug Allergy Drug Allergy

Immediate (Type I) Drug Allergy,Immediate (Type I) Drug Allergy,

Autoimmune (Type II) Reactions to Drugs, Autoimmune (Type II) Reactions to Drugs,

SSerum Sickness & Vasculitic (Type III) erum Sickness & Vasculitic (Type III) Reactions. Reactions.

Drug hypersensitivityDrug hypersensitivity is defined as an immune- is defined as an immune-mediated response to a drug agent in a sensitized mediated response to a drug agent in a sensitized patient. patient. Drug allergyDrug allergy is restricted specifically to a is restricted specifically to a

reaction mediated by IgE.reaction mediated by IgE. Immune-mediated reactions account for 5 Immune-mediated reactions account for 5 to 10 percent of all drug reactions and to 10 percent of all drug reactions and constitute true drug hypersensitivity, with constitute true drug hypersensitivity, with IgE-mediated drug allergies falling into this IgE-mediated drug allergies falling into this category. category. Type I reactions (IgE-mediated); Type II Type I reactions (IgE-mediated); Type II reactions (cytotoxic); Type III reactions reactions (cytotoxic); Type III reactions (immune complex); and Type IV reactions (immune complex); and Type IV reactions (delayed, cell-mediated). (delayed, cell-mediated).

DRUG HYPERSENSITIVITYDRUG HYPERSENSITIVITY

The most important drug-related risk The most important drug-related risk factors for drug hypersensitivity concern the factors for drug hypersensitivity concern the chemical properties and molecular weight of the chemical properties and molecular weight of the drug. Larger drugs with greater structural drug. Larger drugs with greater structural complexity (e.g., nonhuman proteins) are more complexity (e.g., nonhuman proteins) are more likely to be immunogenic. Heterologous antisera, likely to be immunogenic. Heterologous antisera, streptokinase, and insulin are examples of streptokinase, and insulin are examples of complex antigens capable of eliciting complex antigens capable of eliciting hypersensitivity reactions. Most drugs have a hypersensitivity reactions. Most drugs have a smaller molecular weight (less than 1,000 smaller molecular weight (less than 1,000 daltons), but may still become immunogenic by daltons), but may still become immunogenic by coupling with carrier proteins, such as albumin, coupling with carrier proteins, such as albumin, to form simple chemical-carrier complexes to form simple chemical-carrier complexes (hapten). (hapten).