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27 Cards in this Set
- Front
- Back
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What cells of the bodies release histamine?
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Mast Cells
Basophils Neurons |
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What are the various types of histamine antagonists?
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H1 receptor antagonists - antiallergy drugs, anti-emetics, and vertigo treatment
H2 receptor antagonists - Anti-acid H3 receptor antagonists - tricked you! no drug H4 receptor antagonists - we still don't know what the fuck this is! |
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Besides histamine what are some other enhancers of gastric acid secretion?
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gastrin and vagal stimulation
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What is the H3 receptor for?
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Histamine can function as a neurotransmitter through the H3 receptor and cause its own inhibition by binding to the presynaptic H3 receptors
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What are the pathophysiological actions of histamine?
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Anaphylaxis
Seasonal Allergies Duodenal ulcers - larege release of histamine in the stomach Systemic Mastocytosis - mast cell infiltration of tissue with massive histamine release Gastrinoma (Zollinger-Ellison Syndrome) - tumor that secretes gastrin |
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What amino acid is used to make histamine?
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L-histidine
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How is histamine metabolzed?
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P450 system 2 pathways:
Methylation to N-methyl histamine (N-methyl transferase) then to N-methyl imidazoleacetic acid (monoamine oxidase) and elimination in the urine Undergo oxidative damination to imidazoleacetic acid (diamine oxidase) then ribosylation to imidazoleacetic acid riboside also renally eliminated in urine |
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What are the messenger systems of the various histamine receptors?
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H1 - Gq PLC to increase intracellular Ca leading to ca calmodulin MLCK and contraction (smooth muscle effect) or Ca calmodulin to activate NOS smooth muscle relaxation
H2 - Gs coupled to Adenylate Cyclase increasing cAMP. increase in cAMP activating PKA inactivating MLCK relaxation of smooth muscle or int he heart increasing PKA increasing open Ca Channel causing myocyte contraction H3 coupled to Gi/o N-type voltage gated Ca channel and reduces Ca influcs and inhibits release of presynaptic transmitter H4 coupled to Gi/o in mast cells and eosinophils and trigger calcium mobilization |
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Where are H1 receptors found?
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Smooth muscles, endothelial cells, and in CNS
Within the bronchial tree causes smooth muscle constriction through PLC Within blood vessels causes vasodialtion through NOS pathway Within endothelial cells causes contraction leading to vascular leak and edema Within peripheral nerve endings, causes pain and itching within CNS causes allergic rhinitis and motion sickness |
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Where are H2 receptors found?
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GI parietal cells, vascular smooth muscle cells, cardiac cells
Within GI Parietal cells regulates gastric acid secretion Within vascular smooth muscle vasodialtion from cAMP within the heart cAMP mediated contraction |
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Where are there both H1 and H2 receptors?
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The cardiac cells:
H2 mediate both ionotropy and chronotropy H1 receptors are in the AV node and slow conduction |
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Where are H3 receptors found?
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Mostly CNS and Some peripheral nervous system
Can act as a neurotransmitter in feedback inhibition of histamine synthesis and release May also control other neutransmitters |
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Where are H4 receptors found?
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highly expressed in bone marrow and white blood cells
Important for mast cell chemotaxis |
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What is meant by the triple response to Histamine (aka "Triple response of Lewis")
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It is a test for allergies using histamine (all through H1 receptor) which causes following subdermal injections:
Red spot - direct vasodilation effect (H1 mediated NO) Flare - indirect vasodilation (activated sensory neuron axonal reflex) Wheal - Increase in capillary permeability with accumulation and edema |
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What are two groups of substances that can cause degranulation and release of histamine?
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IgE-antibody induced releasers
Non-immune releasers |
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what is the source of redman's syndrome and what is the instigating agent?
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flush and red from vasodilation due to histamine related reactions caused by vancomycin IV administration
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What are some drugs that inhibit the release of histamine?
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Albuterol
Cromolyn Na |
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What are some causes of non-immune release of histamine?
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Aspirin or NSAIDs
Morphine or other opioids Vancomycin Polymixin B X-ray contrast media Succinylcholine, d-tubocurarine, compound 48/80 Anaphylatoxins - C3a and C5a Cold or solar exposure leading to itching and urticaria |
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What are the pharmacological effects of histamine?
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Mild allergic to anaphylaxis (both involve H1 and H2 receptors):
Dilation of small blood vessels --> flushing (H1 response) Decreased TPR and BP (H1 initial and H2 sustained) Increased Capillary permeability, edema (H1 response) |
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What are the histamine related drugs?
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Mast Cell stabilizers (Cromolyn Na, nedocromil-tilade, albuterol)
H1 Receptor Antagonists (1st and 2nd generation) H2 Recpetor Antagonists (ranitidine, Cimetidine) |
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What are the the various types of H1 receptor antagonists and how do they function?
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First Generation were sedating due to CNS penetration
Second generation drugs are nonsedating due to inability to penetrate CNS |
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What are the important first generation H1 antagonists?
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Diphenhydramine (benedryl) - prototype
Chlorpheniramine Promethazine - for motion sickness Cyclizine, Meclizine - motion sickness and vertigo |
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What are the uses of generation 1 H1 antagonists?
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Adjunctive to anaphylaxis
Motion sickness Antiemetic Antivertigo Local anesthetic Antitussive |
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What are some adverse effects of First generation H1s?
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Sedation
Tachyarrhythmias Allergic reaction with topical use Peripheral antimuscarinic effects (atropine like) - dry mouth, blurred vision, constipation, urinary retention |
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What are the uses and types of second generation drugs?
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Antiallergy uses
Cetirizine (zyrtec) Fexofenadine (allegra) Loratadine (Claritin) Desloratidine (clarinex) -metabolite of loratadine Loratidine - half dose for Hive tx Azelastin (intranasal spray) |
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What are the adverse effects of second generation H1 antagonists?
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Cardiac K channels causing prolonged QT with resultant torsades de pointes - tx with?? (Mg!)
Cetirizine appears to have CNS and sedative actions erythromycin and ketoconazole inhibit the metabolism of fexofenadine and loratadine |
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What are the pharmacokinetics of the second generation of H1 antagonists?
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excreted in mainly unmetabolized forms
Cetirizine and loratadine primarily excreted in urine Fexofenadine excreted in feces all drugs induce the cytP450 |
