HISTAMINE

Structure/Class	Biological amine
Pharmacodynamics	Its mechanism of action is to exert its influence by binding to histamine receptors, which are all GPCR. They may increase intracellular cAMP or intracellular Ca2+. Appears to play a role in Immediate allergic reactions and anaphylaxis Gastric acid secretion Functions as a neurotransmitter/neuromodulator Has a role in immune modulation/chemotaxis of WBCs Tissue and organ effects as follows: Immune system Causes vasodilation and increased permeability of vessels. Chemoattractant for WBCs and neutrophils. Histamine inhibits the release of lysosome contents, and inhibits some T- and B-cell function. CVS effects Vasodilation (leading to warmth/flushing/headache) Oedema (due to increased capillary permeability) Hypotension, and reflex increase in chronotropy Histamine has direct inotropic effects on the heart too. Respiratory Increased bronchial reactivity – bronchoconstriction, especially in asthmatics. Neurological system Increased nociception Increased itch. May be related to satiety and weight gain (explains the weight gain when patients are given long term anti-psychotics) GIT Increased smooth muscle contraction (abdominal pain, diarrhea) Increased secretion of gastric acid Skin Initiates the triple response.
Pharmacokinetics	Location of histamine Most histamine is sequestered and bound in granules in mast cells and basophils. Non mast cell histamine may be found in the brain, where it acts as a neurotransmitter. It is also found in the enterochromaffin-like cell (ECL cells) in gastric mucosa. Release of histamine Mast cells and basophils release histamine of IgE binds to their surface. Complement may also bind to mast cells, releasing histamine. It is possible for drugs (e.g. morphine) to release histamine. Direct mechanical injury also releases histamine.