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Aina Meducci 2012


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Pharmocology revision- Histamine and antihistamine

My friend of mine was having a severe gastric that puts her on bed for a week. When she seek the doctor, he gave her antihistamine shot to reduce the formation of gastric juice that was already corroded her stomach wall- Ranitide. Let's do revision on pharmacology!



Histamine is a biogenic amine chemical involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter.

Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues.

Mast cell produce histamin when activated

The release of histamine (hist = because it's made up of histidine residues, amine = because it's a vasoactive amine) causes several allergic symptoms.
1) It contributes to an inflammatory response.
2) It causes constriction of smooth muscle) or even saved by preventing or shortening asthma attacks.

Histamine can cause inflammation directly as well as indirectly. Upon release of histamine by an antigen activated mast cell, permeability of vessels near the site is increased. Thus, blood fluids (including leukocytes, which participate in immune responses) enter the area causing swelling. This is accomplished due to histamine’s ability to induce phosphorylation of an intercellular adhesion protein found on vascular endothelial cells . That is why histamine is known as being vasoactive.

Gaps between the cells in vascular tissue are created by this phosphorylation, allowing blood fluids to seep out into extracellular space. Indirectly, histamine contributes to inflammation by affecting the functions of other leukocytes in the area. It has been suggested that histamine release triggers the release of cytokines and inflammatory mediator by some neighboring leukocytes. These chemicals in turn increases the inflammatory response.

Histamine's second type of allergic response is one of the major causes for asthma. In response to an allergen (a substance that triggers an allergic reaction), histamine, along with other chemicals, causes the contraction of smooth muscle. Consequently, the muscles surrounding the airways constrict causing shortness of breath and possibly complete trachial-closure, an obviously life-threatening condition. If the effects of histamine during an allergic reaction are inhibited, the life of an allergic person can be eased (in the case of inflammation) or even saved by preventing or shortening asthma attacks.


An allergic dog


A histamine antagonist, commonly referred to as antihistamine, is a pharmaceutical drug that inhibits action of histamine by blocking it from attaching to histamine receptors.

H1 antihistamines are used to treat symptoms of allergy, such as runny nose and watery eyes. Allergies are caused by a body's excessive type I hypersensitivity response to allergens, such as pollen. An allergic reaction, which if severe can lead to anaphylaxis, results in excessive release of histamines and other mediators by the body. Other uses of H1 antihistamines alleviate symptoms of local inflammation that result from various conditions, such as insect stings, even if there is no allergic reaction.

Other common antihistamines include the H2 antagonists (cimetidine), which are widely used for the treatment of acid reflux and stomach ulcers, because they decrease gastric acid production.

Antihistamines suppress the histamine-induced wheal (swelling) and vasodilation (flare) response by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.

They effectively exert competitive antagonism of histamine for H1-receptors. Itching and sneezing are suppressed by antihistamine blockade of H1-receptors on nasal sensory nerves. Antihistamines are commonly used for relief of allergies caused by intolerances of proteins.

Example of antihistamine drug

1st generation antihistamine (non selective, classical)

These are the oldest H1-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well.

These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially compared with the second-generation H1-antihistamines. Animals response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes. It also has high lipid solubility and there can pass trough blood brain barrier and cause sedation.


  • Promethazine
  • Hydroxyzine
  • Chlorphenamine
  • Meclozine
  • Dimenhydrinate and More

2nd generation of antihistamine

Second generation H1-antihistamines are newer drugs that are much more selective for peripheral H1 receptors in preference to the central nervous system histaminergic and cholinergic receptors.

This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions. The reason for their peripheral selectivity is that most of these compounds are zwitterionic at physiological pH (around pH 7.4). As such, they are very polar, (lower lipid solubility) meaning that they do not cross the blood brain barrier and act mainly outside the central nervous system.


  • Loratidine
  • Acrivastine
  • Ebastine and more

Histamine synthesis and metabolism

Histamine is derived from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic vasoactive amine.

Storage: Most tissues bound histamine in (mast cells and basophils) and lungs, skin and intestinal mucosa (for allergic reaction) and free histamin in the hypothalamus that acts as a neurotransmitter in the nedocrine system.

Synthesis of histamine

Mast cells store histamine (bound histamine)

Free antihistamine act as neurotransmitter

Histamine receptors

There are 4 known histamine receptor

  • H1 receptor
  • H2 receptor
  • H3 receptor
  • H4 receptor

H1 Receptor

Location: Smooth muscle, endothelial cells

Major effects: Acute allergic effects

Response: Increase GI and bronchial smooth muscle, increase large arteries, increase coronary blood flow, sedation, increased vascular permeability, positive inotropic effect on heart, DECREASE small arteries

Agonist: 2-Methylhistamine, histamine

Antagonist (antihistamine) : Pyrilamine, Tripelennamine, chlorpheniramine, dimenhydrinate (antimetic) , diphenhydramine, promethazine, terfenadine, astemizole, and more

H2 receptor

Location: Gastric parietal cells

Major effects: Secretion of gastric juice

Response : Increase gastric acid secretion, reduce small arteries, positive inotropic effect on heart, increase heart rate, increase coronary blood flow, reduce sympathetic nervous system transmission.

Agonist: Histamine, 4-methylhistamine, impromidine

Antagonist (antihistamine): Cimetidine, Ranitidine, roxatidine, famotidine, lafutidine, nizatidine (all of these drugs are used to reduce gastric juice secretion)

Histamine (H2) involved in the formation of gastric acid in stomach and
antihistamine inhibits/reduce it

H3 receptor

Location: Central nervous system

Major effect: **Modulating neurotransmission (but they are experimental and do not yet have a define clinical use)

Response: Reduce the release of histamine, NE, serotonin and Ach**

Agonist: Histamin, other's not yet discover (NVMS pharmacology)

Antagonist: Thioperamide here

H4 receptors

Location: Mast cells, eosinophils, T cells, dendritic cells

Major effect: (** still investigating) regulating immune responses

Response: Mediate mast cell chemotaxis (wikipedia sources)

Agonist: Histamine, others not yet discover (NVMS pharmacolocy)

Antagonist: Thioperamide here

Sources: Wikipedia sources (Histamine,anti-histamine, histamine receptor), Histamine and antihistamine receptors (www.vivo.colostate.edu), Histamine (www.bio.davidson.edu)

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