Question

Mechanism of action-

Describe the location, storage and release of histamine-

List the types of histamine receptors and the second messengers triggered by the activation of those receptors-

Explain the molecular mechanism of action of H1-receptor antagonists-

Explain the molecular mechanism of action of H2-receptor antagonists

Actions on organ systems-

Describe the pharmacological effects of H1-receptor antagonists.-

Describe the pharmacological effects of H2-receptor antagonists.

Pharmacokinetics-

Describe the metabolism and elimination of H1-receptor antagonists.-

Describe the metabolism and elimination of H2-receptor antagonists

Adverse effects, drug interactions and contraindications-

Describe the main adverse effects of H1 an H2 receptor antagonists.-

Describe the main contraindications of H1 an H2 receptor antagonists.

Answer 1

1. Histamine is a cell derived chemical mediator of inflammation. It is a vasoactive amine. Histamine along with serotonin ( 5- hydroxytryptamine) plays an important role in the early hours of inflammation.

Histamine is mostly present in the mast cells ( basophil cells).

Mechanism Of Action: The mechanism of action of histamine depends on the type of receptor to which it binds. Histamine binds to the various G protein coupled histamine receptors present on the cell surface. There are four histamine receptors :- H​​​​​1, H​​​​​​2, H​​​​​​3 and H4.

Histamine H​​​​​​1  receptors - located in the CNS( dendrites of the neurons) and in the periphery ( smooth muscles, endothelium and sensory nerves) .

Histamine after binding to the H​​​​​​1 receptors causes the majority of allergic reactions( itching,rashes and urticaria). It also causes bronchoconstriction, urinary bladder constriction, smooth muscle constriction, vasodilation of blood vessels, increased capillary permeability, release of catecholamines in adrenal medulla, enhances wakefulness and regulates appetite and body temperature.

Histamine H​​​​​​2  receptors- located in CNS ( cerebrum and cerebellum) and periphery ( parietal cells of GIT, smooth muscle cells)

Histamine after binding to H​​​​​​2  receptors enhances acid secretion from the gastric glands, dilatation of blood vessels, relaxation of uterus and urinary bladder.

Histamine H​​​​​​3 receptors - located mainly in the central nervous system. They control the release of histamine from the neurons in the brain.

Histamine H​​​​​​4 receptors- they are located in the mast cells, bone marrow,spleen ,small intestine and colon. They regulate cytokine production and secretion and play a role in hypersensitivity.

Histamine is present within the storage granules of mast cells. However, non mast cell histamine is present in brain,epidermis and gastric muscosa.

Histamine is synthesized from the amino acid histidine and is a beta imidazolylethylamine. Histamine is degraded rapidly by methylation and oxidation . Histamine cannot be taken orally becoz liver destroys all the histamine which is absorbed from the intestines.

Release of Histamine:- Histamine being positively charged is held by an acidic protein in the mast cells. During exocytosis ( cell releases its contents outside), when granules are extruded(moved outside the cell) , cationic exchange with the sodium and calcium ions present in the extracellular fluid sets histamine free. Hence it is released and binds to the receptors of the target cells.

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