antihistamines Flashcards
describe the histamine receptors
H1-4, all GPCRs
H1: Gq type, cause acute allergic reaction, activation causes increase in intracellular calcium
H2: Gs type, causes gastric acid secretion, activation stimulates adenyl cyclase
H3: Gi/o type, involved in neurotransmitter modulation, activation of receptor inhibits adenyl cyclase
H4: Gi/o type (suspected), involved in immunomodulation, activation causes increase in intracellular calcium
what are actions of histamine of smooth muscle
causes relaxation in arteriolar and arterial smooth muscle via H1
causes contraction of smooth muscle in veins, bronchial and gastrointestinal smooth muscle and uterus via H1
causes relaxation in rat uterus via H2
what are actions of histamine on gastric acid secretions
causes gastric acid secretion via H2 receptors
what are clinical uses of histamine antagonists
H1 antagonists: e.g diphenhydramine (crosses blood brain barrier); sedation, treatment of motion sickness, allergies (not preffered because of drowsiness)
H1 antagonists not entering CNS: e.g cetirizine; allergies (only partially effective)
H2 antagonists: e.g ranitidine; suppression of gastric secretion for healing of duodenal ulcers
what causes peptic ulcer formation
formed by imbalance between tissue damaging chemicals such as gastric acid and peptic enzymes and tissue protective agents such as;
mucus secretion, bicarbonate secretion
what factors may contribute to peptic ulcers
NSAIDs, alcohol, gastric hyperactivity, gastric reflux, ischaemia, shock
what are stimulators of gastric acid secretion
acetylcholine, gastrin (peptide hormone), histamine
where is gastric acid secreted from
parietal cells in the oxyntic glands
what drugs are used to treat peptic ulcers
H2 receptor antagonists, proton pump inhibitors, antacids, coating agents, prostaglandins, anticholinergic agents
what is mechanism for proton pump inhibitors
e.g omeprazole
decrease acid secretion by blocking the H+/K+ ATPase of parietal cells
they are weak bases, stronger inhibitors of gastric acid secretion than H2 antagonists and are long lasting (days)
how are antacids used to treat peptic ulcers
neutralise gastric acid, however do not raise pH sufficiently to acheive ulcer healing, used to relieve pain from erosion and ulceration
e.g aluminium hydroxide
how are coating agents used in treatment of peptic ulcers
agents act as protective barrier for mucosa
e.g sucralfate (aluminium hydroxide and sulphated sucrose): forms complex matrix with mucus which limits proton diffusion and actions of pepsin
how do anticholinergic agents treat peptic ulcers
decrease acid secreation by blocking muscarinic receptors on parietal cells
name some 1st and 2nd generation H1 antagonists and some H2 antagonists, what is difference between 1st and 2nd gen H1 antagonists
H1 1st gen: diphenhydramine
H1 2nd gen: cetrizine, astemizole
H2: cimetidine, ranitidine
1st gen; cross CNS barrier, have atropine like actions (muscarinic antagonists)
2nd gen; do not cross SNS
what are effects of histamine on neurotransmitter release
histaminergic neurones involved in vasopressin release from posterior pituitary
involved in emesis, consciousness and temperature regulation
presynaptic H3 autoreceptors act in neuromodulation
