Antiallergic drugs are pharmacological agents used to treat immediate-type hypersensitivity reactions. Their mechanism of action aims to interrupt the pathological cascade where immunoglobulin E (IgE) and inflammatory mediators play a key role, causing symptoms ranging from mild pruritus to anaphylactic shock.
Main markerImmunoglobulin E (IgE), which triggers the cascade of allergic reactions.
Nature of allergensMost are haptens that acquire immunogenicity only upon binding to proteins.
Etiotropic approachIdentifying the allergen and completely avoiding contact with it is the most effective strategy.
Intracellular signalActivation of cGMP synthesis and an increase in calcium ion concentration during mast cell degranulation.
Pathogenesis of the Allergic Reaction
Allergy represents a state of altered organism reactivity. A type 1 hypersensitivity reaction proceeds through three consecutive stages:
Immunological stage (Sensitization). Upon initial entry into the body, allergens (house dust, pollen, mold, drugs) are recognized by antigen-presenting cells (APCs). APCs interact with T lymphocytes via the major histocompatibility complex (MHC). This leads to the activation of B lymphocytes and the synthesis of specific antibodies—immunoglobulin E (IgE). Released interleukin-4 (IL-4) further stimulates B lymphocytes, creating a "vicious cycle." Finally, IgE binds to FcεR1 receptors on mast cell membranes.
Pathochemical stage (Degranulation). Upon re-exposure, the allergen binds to the fixed IgE. This triggers an intracellular cascade: cGMP synthesis is activated and intracellular calcium levels rise. Inflammatory mediators are released: histamine is immediately released from granules, while leukotrienes (LTC4, LTD4), prostaglandin D2 (PgD2), and platelet-activating factor (PAF) are synthesized de novo.
Pathophysiological stage. Mediators act on tissues. Histamine binds to the H1 receptor, which is coupled to a Gq protein. Phospholipase C (PLC) is activated, hydrolyzing phosphatidylinositol into diacylglycerol (DAG) and inositol trisphosphate (IP3). This causes a sharp increase in intracellular calcium and leads to smooth muscle contraction (e.g., development of bronchospasm). Clinically, this can manifest as mild forms (urticaria, eye redness, itching) or severe, life-threatening conditions (asthma attack, anaphylactic shock).
Sites of Action and Mechanisms
Pharmacotherapy is indicated when allergen elimination is impossible. Drugs are classified based on the localization of their effect within the allergic cascade:
Free IgE binding (Anti-IgE therapy): drugs disrupt the bond between the immunoglobulin and the mast cell receptor, preventing sensitization.
Mast cell membrane stabilizers: block the degranulation process, preventing the release of allergic mediators outward.
Leukotriene pathway blockers: inhibit the effects of already released leukotrienes (inflammatory mediators) or block the enzymes responsible for their synthesis.
H1-histamine receptor blockers: competitively bind to histamine receptors, preventing the calcium cascade trigger and muscle contraction.
Mixed-action drugs: uniquely combine the properties of a membrane stabilizer (inhibiting degranulation) and an H1-receptor blocker.
Classification of Antiallergic Drugs
According to their mechanisms of action, the main groups of drugs include:
Other groups: glucocorticoids (GCs) and symptomatic agents (used in severe forms).
Mnemonic
Allergy pathogenesis can be remembered by the rule of three "P"s (in Russian, Pervichny, Povtorny, Posledstviya): Primary contact (immunological stage and IgE synthesis), Primary/repeat contact (pathochemical stage and degranulation), Pathological tissue consequences (pathophysiological stage and bronchospasm).
Frequently asked questions
How do first- and second-generation H1-antihistamines differ?
Feature
First-Generation Drugs
Second-Generation Drugs
Sedative effect
Pronounced sedative action
Do not cause sedation
Selectivity
Low selectivity (also block M-cholinergic and $\alpha$-adrenergic receptors)
High selectivity for $H_1$ receptors
BBB passage
Cross the blood-brain barrier
Practically do not cross the blood-brain barrier
Duration
Shorter duration of action
Longer duration of action
What side effects are characteristic of first-generation H1-antihistamines?
Anticholinergic action — prominent in first-generation drugs.
Sedative effect (sedatio) — pronounced central nervous system depression.
Receptor blockade (blockade) — non-selective blocking of M-cholinergic and $\alpha$-adrenergic receptors.
Why do most allergens not cause an immune response by themselves?
Most of them are haptens—low molecular weight substances. They acquire immunogenicity only after binding to endogenous carrier proteins.
How does the "vicious cycle" work in allergies?
During the reaction, interleukin-4 (IL-4) is released, which further stimulates B lymphocytes to synthesize new portions of IgE, thereby amplifying the immune response.
What is the difference between histamine and leukotrienes during the degranulation stage?
Histamine is already pre-formed and stored in mast cell granules, being released immediately. Leukotrienes, on the other hand, are synthesized de novo during cell activation.
What is the role of phospholipase C in the pathophysiological stage of an allergy?
When histamine binds to the H1 receptor, phospholipase C is activated. It hydrolyzes phosphatidylinositol into diacylglycerol and inositol trisphosphate, leading to increased intracellular calcium and smooth muscle spasm.
Go deeper
The role of antigen-presenting cells (APCs) and the major histocompatibility complex (MHC) in sensitization.
Intracellular signaling pathways during mast cell degranulation (role of cGMP and calcium ions).
Mechanism of phospholipase C activation and phosphatidylinositol hydrolysis upon H1-receptor stimulation.
Differences between first- and second-generation antihistamines.
Use of glucocorticoids in the treatment of severe allergic reactions (anaphylactic shock, asthma).