Histamine

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  • Created by: LBCW0502
  • Created on: 29-03-19 11:17
What is histamine synthesised from?
From L-histidine by histidine decarboxylase
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What is histamine inactivated by?
Histamine N-methyl transferase, then diamine oxidase
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What is the occurrence in the body?
Most tissues, including CNS. Highest concentrations in lungs, skin and GI tract. Mast cells and basophils in complex with heparin
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What are the main actions of histamine?
Contracts smooth muscle. Dilates capillaries. Secretion of gastric acid
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Outline features of histamine research
1910 - discovered (Sir Henry Dale). 1940s - antihistamines for allergy. 1972 - H2 receptor and gastric acid secretion (Sir James Black). 1983 - H3 receptors in brain. 2000 - H4 receptors
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Outline the H1 receptor actions (1)
Local anaphylactic reactions (type I or immediate hypersensitivity) in sensitised tissues. Confirmed with antihistamines
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Outline the H1 receptor actions (2)
Histamine released from mast cells (~0.1-0.2 pmols/mast cell) during inflammatory or allergic reactions (preformed mediators e.g. histamine, De Novo synthesis e.g. PGD2, LTC4, LTD4). Important in skin, eye and nose
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What are the H1 receptor actions in allergic diseases?
Vasodilation, increased permeability (oedema) and smooth muscle contraction (lungs)
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Describe features of H1 receptor antagonists (1)
All orally active. Brain penetrating - promethazine HCl, alimemazine (sedating), chlorpheniramine, clemastine (less sedating). Peripherally acting only (non-sedating) - acrivastine (Benadryl)
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Describe features of H1 receptor antagonists (2)
Certirizine, desloratidine, fexofenadine, levocetrizine, loratadine
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What are the side effects of H1 receptor antagonists?
Atropinic actions - dries secretions, poor accommodation, confusion, short-term memory problems. Hypersensitivity reactions (skin rashes), palpitations, arrhythmias (terfenadine withdrawn). Sedation/drowsiness
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What causes drowsiness?
Histaminergic nuclei present in tuberomammilary nuclei (TM) projects to cortex and throughout brain. Histaminergic neurones fire in the awake state. H1 antagonism leads to reduced histaminergic activity resulting in drowsiness
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What are the other uses of H1 receptor antagonists? (1)
Antiemetic action - motion sickness, Meniere's disease (disorder of inner ear, episodes of vertigo, tinnitus, hearing loss)
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What are the other uses of H1 receptor antagonists? (2)
Antiemetic, dulls inner ear senses to motion. Atropinic action. Chemoreceptor trigger zone (CTZ) in medulla. Others - cyclizine, cinnarizine (slightly less sedating), promethazine HCl (sedating)
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What are the contraindications for H1 receptor antagonists? (1)
Sedating anti-histamines (anti-muscarinic side effects e.g. sweating, caution in urinary retention, angle closure glaucoma). Hepatic diseases (avoid sedating antihistamines in severe liver disease)
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What are the contraindications for H1 receptor antagonists? (2)
Epilepsy, porphyria (non-sedating are relatively safe). Avoid in pregnancy
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State features of gastric acid secretion
Depends on activation of gastrin, H2 and M3 receptors. H2 receptors on parietal cells. Stimulates cAMP system (diagram)
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Give examples of H2 receptor antagonists
Cimetidine, ranitidine, famotidine, nizatidine (similar structure to histamine)
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Describe features of H2 receptor antagonists
For peptide/duodenal ulcers and gastroesophageal reflex disease (GERD). Often with PPI e.g. omeprazole. Enhance antibiotic eradication of Helicobacter pylori
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What are the side effects of H2 receptor antagonists?
Low incidence of SE - diarrhoea, headaches, dizziness, muscle pains, rashes. Cimetidine - inhibits CYP450 - potentiation of some drugs e.g. propranolol, warfarin, androgen receptor antagonist in high doses (loss in libido, gynaecomastia)
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Describe features of the H3 receptor (1)
In CNS - autoreceptor. Histamine inhibits release of more histamine neurotransmitter (diagram)
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Describe features of the H3 receptor (2)
Affects release in CNS of - NE, 5HT, DA, ACh, NP
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What is the effect of histamine in the CNS?
Wakefulness, emesis, epilepsy, pain, schizophrenia, depression, hypothermia, food and water intake
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Describe features of H4 the receptor (1)
Discovered (2000) using biotechnology and human genome. Very similar in structure to H3 receptor. No antagonists yet. Agonist - clozapine
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Describe features of H4 the receptor (2)
Found in variety of cell types - mast cells, macrophages, neutrophils, eosinophils, resting CD4+ cells and in bone marrow. Function - unknown, possibly role in immune system/inflammation
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Summarise features of the H receptor antagonists (1)
H1 receptor antagonists (help in hypersensitivity of immune system, allergy). H2 receptor antagonists (suppression of gastric acid secretion, stomach ulcers). H3/H4 receptors (drugs still developed). Centrally penetrating modulators for H1/2 receptor
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Summarise features of the H receptor antagonists (2)
More work on basic research and clinical aspects needed. H3/4 (inflammation, cancer, neurology, obesity, psychoses, dementias, dyskinesias, pain). (Qs)
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Card 2

Front

What is histamine inactivated by?

Back

Histamine N-methyl transferase, then diamine oxidase

Card 3

Front

What is the occurrence in the body?

Back

Preview of the front of card 3

Card 4

Front

What are the main actions of histamine?

Back

Preview of the front of card 4

Card 5

Front

Outline features of histamine research

Back

Preview of the front of card 5
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