Anti-allergic agent

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Anti-allergic agents are medications used to treat allergic reactions. Anti-allergic agents have existed since 3000 B.C in countries such as China and Egypt. It was not until 1933 when antihistamines, the first type of anti-allergic agents, were developed. [1] Common allergic diseases include allergic rhinitis, allergic asthma and atopic dermatitis with varying symptoms, including runny nose, watery eyes, itchiness, coughing, and shortness of breath. More than one-third of the world's population is currently being affected by one or more allergic conditions. [2]

Contents

Commonly used anti-allergic agents include antihistamines, decongestants, corticosteroids, leukotriene pathway modifiers and mast cell stabilizers. Antihistamines and decongestants are generally the first-line treatment in mild to moderate allergic reactions. Corticosteroids are generally indicated for moderate cases. In severe cases, adrenaline is used to reduce swelling and aid breathing. Allergen immunotherapy is an alternative treatment considered in some patients, with a success rate of 80%-90% in reducing symptoms, [3] but requiring a much longer duration of therapy. The choice of medications depends on the disease to be treated, its severity and patient factors.

Allergy

Allergies, also known as type 1 hypersensitivity, are a type of immune response which takes place when our body's protective mechanism defends us against triggers called allergens.

Common causes

An allergic reaction can be caused by direct contact with an allergen. For example, through consuming a certain food, inhalation of pollens or dust mites, or direct contact with a certain material. A family history of allergies also leads to a higher risk of developing allergic diseases. [4]

List of common allergens
AllergenExamples
EnvironmentalAirborne: pollen, pet dander, mould, dust mites, smoke [2]

Skin: plants, cosmetics, cleaning detergents, insect stings, metals such as nickel and chromium

Food Milk, eggs, nuts, shellfish, soy and more [5]
Medications Antibiotics, sulfonamides, NSAIDs, chemotherapy drugs and more. [6]

Mechanism

When a person comes in contact with a specific trigger, their immune system produces antibodies called immunoglobulin E (IgE) molecules that bind to mast cells (immune cells found mainly in the skin, respiratory tract and digestive tract) and triggers the release of histamine and other chemicals that guards our immune system. [3] Histamine increases the level of vascular permeability and increases the swelling and dilation of vessels. This induces allergic symptoms, such as runny nose, sneezing, watery eyes and itching.

Types

Allergic reactions can range from mild to severe. Common allergic diseases include allergic rhinitis, allergic asthma, allergic conjunctivitis and atopic dermatitis. Each condition presents its own set of symptoms. In severe cases, certain allergies can lead to a life-threatening reaction called anaphylaxis. This is a medical emergency that requires immediate treatment, as it can be fatal if not treated properly. [2]

Type of allergic diseaseCommon signs and symptoms
Allergic rhinitis (hay fever) Sneezing, runny or stuffy nose, itching, watery eyes
Allergic asthma Coughing, wheezing, chest tightness, shortness of breath
Allergic conjunctivitis Redness, itching, and swelling of the eyes
Atopic dermatitis (eczema)Itching, redness, and flaking of the skin
Anaphylaxis Flushing, shortness of breath, dizziness, loss of consciousness

Symptoms can vary in severity from person to person. Proper diagnosis and management are crucial as allergies can affect daily activities, sleep quality, work or school performance, and mood, directly impacting an individual's quality of life. [7]

Management

The most effective management of allergies is avoiding allergens to reduce the risk of an allergic reaction. If the allergic reaction continues, medications may be needed to help reduce symptoms.

Common anti-allergic agents

Antihistamines

Antihistamines, specifically H1-antihistamines, are medicines which provide relief for allergic symptoms such as runny nose, sneezing, itching, and watery eyes from seasonal allergies (hay fever). They are usually the first line of medications prescribed by a general practitioner, or a pharmacist for allergies in a community pharmacy. H1-antihistamines are further split into three groups known as the first-generation, second-generation and third-generation antihistamines. Another type of antihistamines known as H2-antihistamines are used to treat gastrointestinal conditions caused by excessive stomach acid. [8]

Mechanism

H-1 antihistamines work by inhibiting histamine from binding to H-1 receptors. Histamine receptors expressed in smooth muscles, vascular endothelial cells, the heart, and the central nervous system. [7] This prevents a range of cellular signaling cascades that lead to vasodilation and increased membrane permeability from happening, thus preventing allergic symptoms.

First-generation antihistamines can easily cross the blood-brain barrier into the central nervous system to reach the H-1 receptors within, often causing drowsiness. [7] Second-generation antihistamines selectively bind to the peripheral H-1 receptors outside the blood-brain barrier, therefore they are less likely to cause sedation. First-generation antihistamines usually last around 4–6 hours whilst second-generation antihistamines work for 12–24 hours. [7] Third generation antihistamines are metabolites of the second-generation antihistamines but without cardiac toxicity. [8]

Indications and route of administration

Antihistamines are generally indicated for the alleviation of conditions such as allergic rhinitis, allergic conjunctivitis, or atopic dermatitis. [9] Other indications may include nausea and vomiting. Antihistamines are usually for short-term treatment. Chronic allergies, such as allergic asthma may include health problems which antihistamines alone cannot treat. [9] The routes of administration of antihistamines are usually oral, intranasal, intraocular and topical.

Some examples of antihistamines with their indications and routes of administration
Class of antihistaminesExamplesUsesRoute of administration
First generation Diphenhydramine, Chlorpheniramine, Brompheniramine, Promethazine Allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, itchingOral, topical, intraocular
Second generation Cetirizine, Loratadine, Acrivastine, Azelastine Oral, intranasal
Third generation Levocetirizine, Desloratadine, Fexofenadine Oral
Example of a H-1 antihistamine (Levocetirizine) Levocetirizine.png
Example of a H-1 antihistamine (Levocetirizine)

Side effects

Side effects generally exist more in first-generation antihistamines, for example drowsiness, blurred vision and dry mouth. Other common side effects for all generations include gastrointestinal side effects, headaches and tiredness. [9]

Antihistamines are generally safe to use during pregnancy with second-generation antihistamines being more preferred due to their lack of sedation. [10]

Decongestants

Decongestants are medicines which relieve nasal obstruction due to inflammation in the upper respiratory tract. They are also often used as the first-line therapy for nasal congestion from common cold or allergic rhinitis . [11]

Mechanism

Decongestants work by binding to the alpha-adrenergic receptors in the sympathetic nervous system (controls our body's "fight or flight" response) on the smooth muscle cells situated on the blood vessels in nasal passages. [11] This causes vasoconstriction (narrowing of blood vessels), helps reduce blood flow to the nasal mucosa and decreases swelling. [11] Decongestants help open up nasal passages thus allowing for easier breathing.

Indications and route of administration

Example of oxymetazoline nasal spray Nasal-vasoconstrictor.JPG
Example of oxymetazoline nasal spray

Decongestants are mainly used in conditions like common cold, allergic rhinitis, and sinusitis. They provide temporary relief from symptoms of nasal congestion. Decongestants are available in oral and intranasal forms. Naphazoline and oxymetazoline are common topical (intranasal) decongestants, whilst pseudoephedrine is the most common example of oral decongestant used to reduce nasal congestion. Topical decongestants have a faster onset of action compared with oral ones. [12]

Side effects

Topical decongestants should not be used for longer than a week as prolonged use may result in rhinitis medicamentosa (rebound nasal congestion). [13]

Common side effects for oral decongestants include insomnia, hypertension (elevated blood pressure), and difficulty in urination. [12]

Avoid use during pregnancy as it may cause vasoconstriction of uterine arteries thus reducing fetal blood supply. [14]

Zyrtec-D, an example of combination therapy Zyrtec-D blister pack.png
Zyrtec-D, an example of combination therapy

Combination therapy with antihistamines

Antihistamines and decongestants can be used as a combination to treat nasal congestion, runny nose, and sneezing symptoms caused by common cold and hay fever.

Some examples include:

  1. Pseudoephedrine + Loratadine (Claritin-D®)
  2. Pseudoephedrine + Cetirizine (Zyrtec-D®)
  3. Pseudoephedrine + Fexofenadine (Telfast-D®)

Corticosteroids

The basic structure of steroid Steroid lettering and numbering.svg
The basic structure of steroid

Corticosteroids, specifically glucocorticoids, are anti-inflammatory agents used to treat allergic conditions. Corticosteroids can be classified into mineralocorticoids, which regulate salt and water balances, and glucocorticoids that play a role in glucose homeostasis and regulating the activation of immune cells. The word "glucocorticoid" is derived from "glucose + cortex + steroid", [15] representing its role in the regulation of glucose metabolism, its biosynthesis in the adrenal cortex, and the steroid structure it possesses.

Mechanism

Glucocorticoids bind to glucocorticoid receptors to form a complex which activates the transcription of anti-inflammatory genes in the nucleus (transactivation) and represses the expression of pro-inflammatory factors in the cytosol (transrepression). [16] Ultimately, they decrease the synthesis and release of inflammatory mediators such as mast cells, eosinophils, and cytokines.

Indications

Glucocorticoids have a wide range of therapeutic uses. Since they suppress inflammation and reduce the signs and symptoms such as swelling, redness and itching, they are commonly used to treat allergic conditions including allergic rhinitis, asthma and eczema. Glucocorticoids can be given via different routes of administration, depending on the condition and severity. The most common ones are oral, inhalation, topical and injection.

Some examples of glucocorticoids with their indications and routes of administration
NameUseRoute of administration
Beclomethasone Allergic rhinitisIntranasal
Budesonide, fluticasone Chronic asthmaInhalation
Prednisolone Severe acute asthma attackOral
Hydrocortisone Severe acute asthma attackIntravenous injection
HydrocortisoneEczemaTopical (cream)

Side effects

Common side effects of glucocorticoids include fluid retention, mood changes and weight gain. The side effects are associated with the dosage, type of drug used and the duration of treatment. Systemic corticosteroids are not considered first-line therapy for chronic management due to common and significant risks of adverse reactions. These include osteoporosis, cataracts, depressed immunity and Cushing's syndrome. [17]

Leukotriene pathway modifiers

Leukotrienes are lipid mediators formed from arachidonic acid by the enzyme 5-lipoxygenase, causing constriction of the airway smooth muscle, increased mucus secretion and enhanced immune response, resulting in allergic inflammation. [18] Leukotriene pathway modifiers can be classified into two types: the cysteinyl leukotriene receptor antagonists (including Montelukast and Zafirlukast) that bind to leukotriene receptors to inhibit bronchoconstriction and other effects of leukotrienes, [19] and Zileuton, a 5-lipoxygenase inhibitor which directly prevents the synthesis of leukotrienes. All three leukotriene pathway modifiers are indicated for the treatment of chronic asthma, but only Montelukast is approved to treat allergic rhinitis, [19] with a similar effectiveness as antihistamines, but lower effectiveness than nasal corticosteroids in relieving the symptoms of seasonal allergic rhinitis. [20]

Mast cell stabilizers

Mast cell stabilizers inhibit the release of allergic and inflammatory mediators, helping to prevent and treat allergic conditions. They work by blocking a calcium channel which is essential for mast cell degranulation, [21] inhibiting the release of histamine and other mediators from mast cells. Examples of mast cell stabilizers include cromolyn sodium and nedocromil sodium. They are commonly used in eye drops to treat allergic conjunctivitis, in intranasal formulations for allergic rhinitis and given by inhalation for asthma. Common side effects include irritation, itching, and cough.

Less common anti allergic agents

Adrenaline

Adrenaline (or epinephrine) is the first-line treatment for the life-threatening allergic reaction known as anaphylaxis. [22] The most common anaphylactic reactions are induced by foods, insect stings and medications. [23] Adrenaline is both a hormone and a medication which plays an important role in the body's "fight-or-flight" response (the acute stress response). It is used to treat anaphylaxis as it provides immediate symptomatic relief. It helps open up the airways, maintain heart function and raise blood pressure, reducing or reversing severe symptoms like throat swelling and difficulty in breathing. [23]

Immunotherapy

Allergen immunotherapy is the last line of medications, also known as the closest "cure" for allergies. It is often recommended for patients whose symptoms cannot be controlled by medications, or those who require multiple medications to control their allergies. This immunotherapy involves regular administration of gradually increasing doses of the substance to which the person is allergic over several years. Treatment can be given as an injection, tablet, sprays or sublingual drops. The gradual increase of allergen causes the immune system to become less sensitive to the substance (desensitization), reducing symptoms during future exposures to the allergen, and possibly preventing new allergies.

Future developments

Research led by Professor Billy K C Chow from the School of Biological Sciences, Faculty of Sciences, the University of Hong Kong has been conducted into the use of small novel MRGPRX2 antagonists as some cases of allergies are refractive to currently available treatments. [24] MRGPRX2 receptors are discovered to be responsible for producing inflammatory allergic reactions. The absence of this drug on the current market also emphasises its importance in future use.

Related Research Articles

<span class="mw-page-title-main">Allergy</span> Immune system response to a substance that most people tolerate well

Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.

An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies.

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Allergic rhinitis</span> Nasal inflammation due to allergens in the air

Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, itchy, and watery eyes, and swelling around the eyes. The fluid from the nose is usually clear. Symptom onset is often within minutes following allergen exposure, and can affect sleep and the ability to work or study. Some people may develop symptoms only during specific times of the year, often as a result of pollen exposure. Many people with allergic rhinitis also have asthma, allergic conjunctivitis, or atopic dermatitis.

<span class="mw-page-title-main">Immunoglobulin E</span> Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Rhinitis</span> Irritation and inflammation of the mucous membrane inside the nose

Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Type I hypersensitivity</span> Type of allergic reaction

Type I hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I is distinct from type II, type III and type IV hypersensitivities. The relevance of the Gell and Coombs classification of allergic reactions has been questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice.

<span class="mw-page-title-main">Nasal spray</span> Spray that delivers medications locally in the nasal cavities or systemically

Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for systemic therapy because it provides an agreeable alternative to injection or pills. Substances can be assimilated extremely quickly and directly through the nose. Many pharmaceutical drugs exist as nasal sprays for systemic administration. Other applications include hormone replacement therapy, treatment of Alzheimer's disease and Parkinson's disease. Nasal sprays are seen as a more efficient way of transporting drugs with potential use in crossing the blood–brain barrier.

<span class="mw-page-title-main">Allergic conjunctivitis</span> Medical condition

Allergic conjunctivitis (AC) is inflammation of the conjunctiva due to allergy. Although allergens differ among patients, the most common cause is hay fever. Symptoms consist of redness, edema (swelling) of the conjunctiva, itching, and increased lacrimation. If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis (ARC).

<span class="mw-page-title-main">Aspirin-exacerbated respiratory disease</span> Chronic inflammatory disease affecting the sinuses and lungs

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated respiratory disease (N-ERD) or historically aspirin-induced asthma and Samter's Triad, is a long-term disease defined by three simultaneous symptoms: asthma, chronic rhinosinusitis with nasal polyps, and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease.

<span class="mw-page-title-main">Post-nasal drip</span> Medical condition

Post-nasal drip (PND), also known as upper airway cough syndrome (UACS), occurs when excessive mucus is produced by the nasal mucosa. The excess mucus accumulates in the back of the nose, and eventually in the throat once it drips down the back of the throat. It can be caused by rhinitis, sinusitis, gastroesophageal reflux disease (GERD), or by a disorder of swallowing. Other causes can be allergy, cold, flu, and side effects from medications.

<span class="mw-page-title-main">Fluticasone propionate</span> Medication

Fluticasone propionate, sold under the brand names Flovent and Flonase among others, is a steroid medication. When inhaled it is used for the long term management of asthma and COPD. In the nose it is used for hay fever and nasal polyps. It can also be used for mouth ulcers. It works by decreasing inflammation.

<span class="mw-page-title-main">Levocetirizine</span> Antihistamine drug

Levocetirizine, sold under the brand name Xyzal, among others, is a second-generation antihistamine used for the treatment of allergic rhinitis and long-term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.

<span class="mw-page-title-main">Ketotifen</span> Antihistamine medication

Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives). Ketotifen is available in ophthalmic and oral forms: the ophthalmic form relieves eye itchiness and irritation associated with seasonal allergies, while the oral form helps prevent systemic conditions such as asthma attacks and allergic reactions. In addition to treating allergies, ketotifen has shown efficacy in managing systemic mast cell diseases such as mastocytosis and mast cell activation syndrome (MCAS), which involve abnormal accumulation or activation of mast cells throughout the body. Ketotifen is also used for other allergic-type conditions like atopic dermatitis (eczema) and food allergies.

<span class="mw-page-title-main">Azelastine</span> Chemical compound

Azelastine, sold under the brand name Optivar among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.

<span class="mw-page-title-main">Mometasone</span> Steroid medication

Mometasone, also known as mometasone y 3 s, is a steroid medication used to treat certain skin conditions, hay fever, and asthma. Specifically it is used to prevent rather than treat asthma attacks. It can be applied to the skin, inhaled, or used in the nose. Mometasone furoate, not mometasone, is used in medical products.

A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.

<span class="mw-page-title-main">Antihistamine</span> Drug that blocks histamine or histamine agonists

Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.

<span class="mw-page-title-main">Fluticasone furoate</span> History, Structure, Drug Mechanisms of Fluticasone Furoate.

Fluticasone furoate, sold under the brand name Flonase Sensimist among others, is a corticosteroid for the treatment of non-allergic and allergic rhinitis administered by a nasal spray. It is also available as an inhaled corticosteroid to help prevent and control symptoms of asthma. It is derived from cortisol. Unlike fluticasone propionate, which is only approved for children four years and older, fluticasone furoate is approved in children as young as two years of age when used for allergies.

References

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