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.

What Are Allergies?

 Allergies are a reaction by the body's

immune system to harmless

substances that it sees as harmful. 

The allergy causing substances are

called allergens.  It is as if the immune

system is overly-active in response to

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.

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Medical Lecture Notes – All Subjects

USMLE Exam (America) – Practice

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 Alergies occur?

The immune system is the body's natural

defense against infection and other foreign

material. Before the person can has a reaction

to a particular substance, immune system must

first be sensitized to it. This happens in an

earlier contact with the substance. Once

sensitized, the body will react when one has

contact with that substance. Many substances

cause an allergic reaction. The most common

are: pollens, molds, house dust mites, animal

dander, latex, medicines, insect stings and

foods.

Food allergic reactions may be severe or fatal.

Common foods that may cause allergy

symptoms include fish, eggs, milk, nuts, peanuts

and wheat. Food allergies often occur in

children, who may outgrow them.

It is also possible to have an allergic reaction to

sunlight, temperature extremes, water contact

and other elements in your physical

environment.

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)

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 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.

ALLERGIC RHINITIS. Treatment

Immunotherapy, also known as desensitization or

allergy shots, alters the balance of antibody types in the

body, thereby reducing the ability of IgE to cause allergic

reactions. Immunotherapy is preceded by allergy testing

to determine the precise allergens responsible. Injections

involve very small but gradually increasing amounts of

allergen, over several weeks or months, with periodic

boosters. Full benefits may take up to several years to

achieve and are not seen at all in about one in five

patients.

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.

Immunologic Reactions to Drugs &

Drug Allergy

Immediate (Type I) Drug Allergy,

Autoimmune (Type II) Reactions to Drugs,

Serum Sickness & Vasculitic (Type III)

Reactions.

Drug hypersensitivity is defined as an immunemediated response to a drug agent in a sensitized

patient. Drug allergy is restricted specifically to a

reaction mediated by IgE.

Immune-mediated reactions account for 5

to 10 percent of all drug reactions and

constitute true drug hypersensitivity, with

IgE-mediated drug allergies falling into this

category.

Type I reactions (IgE-mediated); Type II

reactions (cytotoxic); Type III reactions

(immune complex); and Type IV reactions

(delayed, cell-mediated).

DRUG HYPERSENSITIVITY

The most important drug-related risk factors

for drug hypersensitivity concern the chemical

properties and molecular weight of the drug.

Larger drugs with greater structural complexity

(e.g., nonhuman proteins) are more likely to be

immunogenic. Heterologous antisera,

streptokinase, and insulin are examples of

complex antigens capable of eliciting

hypersensitivity reactions. Most drugs have a

smaller molecular weight (less than 1,000

daltons), but may still become immunogenic by

coupling with carrier proteins, such as albumin,

to form simple chemical-carrier complexes

(hapten)