4th lecture - antihistaminics Flashcards
define Autacoid
“tissue hormone”
a physiologically active substance (such as a serotonin, bradykinin, or angiotensin) that is produced by the body and typically has a localized effect of brief duration.
“biological factors (molecules) which act like local hormones, have a brief duration, and act near their site of biosynthesis”
Name 5 Tissue hormones/autacoids
Anaphylatoxins
Bradykinin
Histamine
Prostaglandins
Serotonin
define Anaphylatoxins
The anaphylatoxins are complement peptides responsible for the acute inflammatory response including mediating migration and activation of a range of immunocompetent cells to the site of insult, such as a pathogen invasion site, tissue injury, etc
“Anaphylatoxins are able to trigger degranulation (release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response.”
Histamine is derived in the organism from
the decarboxylation of the amino acid histidine.
It is found in almost all animal tissues and also many plant tissues. Different in different animal species.
Histamine is most prevalent in (3)
Ehrlich’s mast cells, basophils, histaminocytes
due to which the concentration of histamine is high in organs with good blood supply: skin, mucous membranes, lungs, gastrointestinal tract.
What are Ehrlich’s mast cells?
Mast cells were described and originally named by Paul Ehrlich in 1879 based on their unique dye-staining properties.
Mast cells are found in loose (areolar) connective tissue throughout the body, in virtually every organ.
They play an important role in inducing the inflammatory cascade. Innate or adaptive immune mechanisms can induce the mast cell to degranulate, releasing inflammatory mediators into the extracellular space.
species that have higher histamine content in blood
Goats and rabbits have a higher content
species that have lower histamine content in blood
horses, dogs, cats, rats and humans have a lower content.
Histamine in the blood is linked to what leukocytes? (2)
eosinophils and basophils. The presence of a high number of eosinophils in the blood indicates allergy.
Especially high amounts of histamine occur in what type of tissue
injured, decomposing, purulent tissues.
Release of histamine typically occurs during what type of events? (4)
inflammation, allergy and anaphylactic shock.
Also - Histamine release is caused by insecticides, plant and animal based toxins, several medicinal products, anaphylatoxins and others.
It is also released due to stressors: trauma, hot, cold, UV radiation and antigen-antibody reaction (allergies).
Low levels of endogenous histamine is circulating in the blood in
free form, causing the physiological effect of histamine.
Many drugs and chemicals may produce direct degranulation of mast cells with release of histamine independently from develeopment of allergy for example (4)
morphine, codeine, vancomycin, polymyxin.
Histamine is released from tissue in what form
free form.
mechanisms of release of histamine (3)
Upon degranulation of mast cells (honey bee venom, bact. toxins, temperature and trauma)
Upon lysis of cytoplasmic granules (surfactants, radiation).
Due to specific liberators (d-Tubocurarine, morphine, foreign proteins, dextran and radiocontrast agents).
The biological roles of histamine (6)
Sleep-wake mechanism
Energy metabolism
Behavioural regulation
Involved in endocrine gland function
Regulation of autonomous functions (blood pressure, body temperature, blood glu)
Vestibular function, analgesic mechanism
Histamine is involved in the emetic response to
vestibular stimulation (motion sickness) that may be directed either through the chemoreceptors or directly to the emetic center of the brain.
Thus, Histamine-blocking drugs (H2 blockers) have been used to treat vomiting from these stimuli.
cardiovascular effects of histamine in animals (3)
causes substantial decrease in blood pressure in cats and dogs.
Blood pressure may increase in some herbivorous animals (hare, guinea pig).
The mechanism of blood pressure decrease is dilation of peripheral capillaries (H1; manifestation: redness of the skin).
but large blood vessels contract.
Effects of histamine on Smooth muscle
Histamine causes smooth muscle to contract (H1 mainly); (uterine muscle, bronchi, gastrointestinal tract).
Tissues and organs that are more often affected: skin and respiratory tract.
Histamine is stored in the respiratory tract in
mast cells and is released in the lungs in response to allergic stimulation.
Histamine effect on capillaries (2)
dilation of peripheral capillaries
permeability of capillaries is also increased
(A flow of plasma proteins and liquid occurs to the extracellular space (manifestation: edema)).
Effects of histamine on Gastric secretion
Histamine is a potent stimulant of hydrochloric acid secretion by the gastric mucosa (H2).
Histamine is the final common mediator of gastric secretion (stimulation from chemical, mechanical or nervous elements).
Anaphylaxis and allergy are Hypersensitivity phenomena associated with antigen-antibody reactions that evoke active release of
histamine from the mast cell pool.
Free histamine causes physiologic reactions.
Other autacoids also participate in tissue responses.
Histamine in large doses causes
anaphylactic shock.
features of anaphylactic shock (6)
Dilated peripheral blood vessels,
increased blood flow;
increased permeability of blood vessels, reduced blood volume.
The situation is similar to traumatic shock.
Large arteries and veins are empty of blood, peripheral ones contain excess blood.
At the same time smooth muscle is contracted.
Skin: itching, redness, mottled skin (hyperaemia), hives.
bronchospasm with tachypnoea
