HISTAMINE & ANTIHISTAMINES (Part #1):






General Overview of Histamine:

Histamine, serotonin and prostaglandin belong to a group of endogenous compound called Autakoids

What is prostaglandin?

Prostaglandin is a group of lipids made at site of tissue damage and they do control inflammation, blood flow, blood clot and labour induction

What are Autacoids?

Autacoids is actually comes from a greek word ‘autos’ it means ‘self’ and ‘akos’ means ‘medicinal agent or remedy’.

These heterogeneous substances have different structures and pharmacological activities

They are called local hormones because they all have the common feature of being formed by tissue on which they act.

They are differ from endocrine glands in a way that autacoids are produced by many tissues rather than in specific endocrine glands

What is histamine?

It is a chemical messenger mostly generated in mast cells

Histamine along with multi-receptor systems mediates cellular responses like

-       - Allergic and inflammatory reactions

-       - Gastric acid secretions

-       - Neurotransmission in brain

Histamine has no clinical therapeutic effect but antihistamine or you can say histamine receptor blockers have important therapeutic applications

Location of histamine:

Histamine is present in all tissues but significantly in lungs, skin, blood vessels, GI tract.

But in mast cells and basophils it is present in high concentration

What is mast cells?

Mast cells play important role in how immune system respond to certain bacteria and parasites and they help control other type of immune responses

What is basophil?

Basophil is a white blood cell which defend body from allergens, pathogens and parasites

As you all know that histamine is an amine and histidine when undergoes decarboxylation and in the presence of histidine decarboxylase it converts into histamine and you know well histidine is an amino acid.

Histidine decarboxylase enzyme is found in cells of neuron, gastric parietal cells, mast cells and Basophils.

There is a very important note, in mast cells histamine is stored in granules if it is not stored then it is inactivated by amine oxidase enzyme rapidly

Release of histamine:

Histamine chemical mediators release in response to certain stimuli. The stimuli include destruction of cells as a result of cold, toxins from microorganisms or you can say toxins from organisms, venoms from insects and spiders or trauma or allergies or anaphylaxis

What is anaphylaxis?

Anaphylaxisis actually causes immune system to release fluid of chemicals that can cause you to go into shock this is anaphylaxis

Mechanism of Action:

Histamine produce effects by binding to histamine receptors like h1 h2 h3 and h4

Clinically useful drugs usually act on h1 and h2 receptors

H1 receptors are important in producing smooth muscle contraction the second is increasing capillary Permeability.

Histamine promotes vasodilation of small blood vessels by causing the vascular endothelium to release nitric oxide and the second function of histamine is it enhances the secretion of pro-inflammatory cytokines in cell and local tissues

What are pro-inflammatory cytokines?

It regulate growth cell activation differentiation and homing of the immune cells to the site of infection

H1 receptors on which histamine acts mediate many pathological processes like Allergic Rhinitis, atopic dermatitis, conjunctivitis, urticarial, bronchoconstriction, asthma and anaphylaxis

What is allergic rhinitis?

Where your nose gets irritated by something you are allergic to such as pollen which causing sneezing

What is atopic dermatitis?

It is a condition that makes your skin red and itchy

What is conjunctivitis?

It is an infection or inflammation of transparent membrane conjunctiva that lines your eyelid and covers the white part of eyeball

What is urticaria?

It is a raised itchy rash that appears on skin

Histamine when acts on H1 Receptors:

Exocrine excretion:

Increases nasal and bronchial mucus production results respiratory symptoms

Bronchial smooth muscle:

It constricts bronchioles results asthma and decreased lung capacity

Intestinal smooth muscle:

Do constriction results intestinal cramps and diarrhea

Sensory nerve endings:

Causes itching and pain

Histamine when acts on H1 and H2 receptors:

Cardiovascular system:

It lowers systemic blood pressure by decreasing peripheral resistance and it causes positive ionotropism

Skin:

When acts on skin, the skin dilates capillaries, it increases permeability of capillaries results in leakage of protein and fluid into the tissues and in skin it shows triple response and

What is a triple response?

-       - wheel formation

-      -  reddening due to local vasodilation

-       - flare skin

Histamine when acts on H2 receptors:

Cardiovascular system:

It causes positive chronotropism.

Stomach:

it stimulate HCl secretion