Histamine

What is histamine?

Histamine is an endogenous substance that exerts its effects on many tissues & organs.It is also called an autacoid i.e. a molecule which is secreted locally to increase or decrease the activity of nearby cellsFound in most mammalian tissue. conc in plasma & other body fluids.Significant amount in CSF.Involved in local immune responses.Regulate physiological functions in gut.Acts as a neurotransmitter.Because of its many physiological effects, drug that inhibit its release or actions have therapeutic value

Synthesis & Storage

Produced locally by mast cells & basophils found in nearby connective tissue.Synthesized by decarboxylation of the amino acid histadine by the enzyme histidine decarboxylaseAfter synthesis it is stored in secretory granules as an inactive complex or is rapidly inactivated.High conc in tissue containing large no. of mast cells. Eg. Skin, bronchial tree mucosa, intestinal mucosa.Also present in neurons as neurotransmitter.

Physiological Effects

Plays central role in hypersensitivity & allergic reactions.Has important physiological roles.Mediates diverse group of processes ranging from vaso- dilation to gastric secretion.Direct positive inotropic & chronotropic effects on heart.Contraction of bronchiolar smooth muscle.Responsible for regulation of BP, body temperature, fluid homeostasis & pain sensation.Modulates neurotransmitter release.

Major Physiologic Actions of Histamine

Mechanism of Action

Histamine acts by combining with cellular histamine receptors.4 types of receptors have been discovered.H1, H2, H3, H4 receptorsThe pharmacologic actions of histamine depend on the tissue & type of receptors present at the area of release

Histamine Release From Mast CellsA.Antigen- mediated histamine release.Specific antigen-antibody interaction degranulation of mast cells & basophilsrelease of histamineAllergens are the most frequent cause.Certain drugs esp. high molecular- wt molecules also caused sensitization & degranulation of mast cells on subsequent drug exposure.Non antigen- mediated histamine release.Do not require prior sensitization.Drugs, high molecular wt proteins, venoms & others.damage or disrupt cell membranesrelease of histamine.Eg. Morphine, codeine, radiocontrast media.Cytotoxics cause disruption of cell membranerelease of histamine

Antigen Mediated Histamine Release

Pathophysiology of Allergic ReactionIn a localised allergic reaction , an allergen (antigen) first penetrates the epithelial surface (e.g. skin, nasal mucosa). The allergen can also be delivered systemically, as in the case of allergic response to penicillin.The allergen will stimulates the production of IgE antibodies that are specific for that allergenThe IgE then binds to receptors on mast cells & basophils, in a process known as sensitization.Once immune cells are sensitized, they can detect & respond rapidly to a subsequent exposure to the same allergen.Upon such a exposure, the allergen binds to & cross-links the IgE/receptor complexs, triggering cell degranulationHistamine released by mast cells & basophils binds to H1 receptors on vascular smooth muscle cells & vascular endothelial cells.Stimulation of H1 receptors causes blood vessel dilation & increase vascular permeability

Symptoms Associated With Histamine Release From Mast CellsMild cutaneous release : erythema, urticaria and/or itching

Moderate Release : skin reactions, tachycardia, moderate hypotension, respiratory distress

Severe Release (anaphylaxis) : severe hypotension, ventricular fibrillation, cardiac arrest, respiratory arrest due to severe bronchoconstriction & epiglotal swelling

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