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83 Cards in this Set
- Front
- Back
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Where is most histamine stored?
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Most tissue histamine is bound in granules in mast cells or basophils; the histamine content of many tissues is directly related to their mast cell content
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what is the precursor to histamine?
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Histamine is formed by decarboxylation of the amino acid L-hisitidine, and is catalyzed by histidine decarboxylase
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What is the role of histamine in the stomach?
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Histamine is stored and released by the enterochromaffin-like cells of the fundus of the stomach. ECL cells release histamine to activate the parietal cells of the mucosa
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What is the role of histamine in acute inflammation?
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Upon injury to a atissue, released histamine causes local vasodilation and leakage of plasma- containing mediators of complement, and C- reactive protein and antibodies. It also has an active chemoattractive attraction for inflammatory cells.
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What medications can displace histamine in its bound form from tissues WITHOUT the help of mast cells?
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Morphine and tubocurarine
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where are mast cells especially rich
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sites of potential injury like mouth, nose, feet, internal body surfaces, and blood vessels (P points and bifurcations)
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histamine release negative feedback occurs where (H2 receptors)
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skin and blood vessels; NOT lungs
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What are the histamine receptors
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H1 to 4; all coupled to G proteins
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What are the brain histamine receptors
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H1 and 2 mostly postsynaptic and H3 presynaptic
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How do H2 receptors in gastic mucosa, cardiac muscle cells, and some immune cells have their intracellular effect?
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increase cAMP via Gs
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Where are H4 receptor are mostly found?
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leukocytes in bone marrow and circulating blood; important chemotaxic effects on eosinophils and mast cells
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What is the effect of H3 receptor activation?
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It decreases transmitter release from histaminergic and other neurons
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Histamine causes a _____ in systolic and diastolic blood pressure and an ____ in heart rate.
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decrease; increase
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What is the site of action of histamine for the vasodilator effects of histamine?
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Arterioles and precapillary sphincters
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What are the direct cardiac effects of histamine?
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Direct cardiac effects of H2 include both increased contractility and increased pacemaker rate. H1 receptors in atrial muscle decrease contractility
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What is the methacholine provaction test?
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It uses inhaled histamine in small doses to diagnose bronchial hyperreactivity in patients with suspected asthma or cystic fibrosis. Asthma patients are 100 to 1000 times more sensitive than normal patients
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What are the physiologic anatagonists to histamine?
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Epinephrine- It has smooth muscle actions opposite to those of histamine but acts at different receptors
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What is the role on histamine antagonists in treating motion sickness?
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They can significantly prevent motion sickness but not very effective against an episode of motion sickness already present.
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What is the relationship between histamine and nervous system?
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powerful stimulant of sensory nerve endings, especially pain and itching
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H3 agonists reduce the release of what in brain and peripheral nerves
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acetylcholine, amine, and peptide transmitters
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H1 distribution
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smooth muscle, endothelium, brain; Gq, increases IP3 and DAG
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H2 distribution
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gastric mucosa, cardiac muscle, mast cells, brain; Gs, increases cAMP
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H3 distribution
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presynaptic brain, myenteric plexus, other neurons; Gi, decreases cAMP
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H4 distribution
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eosinophils, neutrophils, CD4 T cells; Gi, decrease cAMP
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what can cardiovascular effects of histamine (small amounts) be blocked by
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H1-receptor antagonists alone
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what causes histamine-induced edema
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action on H1 receptor in vessels of microcirculation
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histamine in stomach
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gastric acid stimulant along with gastric pepsin and intrinsic factor; via increased adenylyl cyclase and cAMP and Ca2+
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3 separate cell types causing red spot, edema, and flare response of intradermal histamine
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smooth muscle in microcirculation, capillary/venular endothelium, and sensory nerve endings
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What are release inhibitors of histamine?
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reduce degranulation of mast cells that results from immunologic triggering by anti-IgE interaction; eg cromolyn and nedocromil
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first gen H1-receptor antagonists
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strong sedative effects; more likely to block autonomic receptors; enter CNS readily
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antiparkinsonism effects and histamine
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H1 antagonists (like diphenhydramine) have significant acute suppressant effects on extrapyramidal symptoms associated with some antipsychotic drugs
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potent H1-blocking agent that also strongly blocks serotonin receptors
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cyproheptadine
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H1 antagonists that block sodium channels in excitable membranes aka give local anesthesia?
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diphenhydramine and promethazine
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antihistaminic drugs most effective in motion sickness
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diphenhydramine and promethazine; piperazines (cyclizine and meclizine)=less sedating
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OD of antihistamines
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resemble atropine OD and treated same way
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what blocks CYP3A4 and causes significant increases in blood concentration of antihistamines
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ketoconazole, itraconazole, macrolide antibiotics (erythromycin)
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H3 receptor blockers potential uses
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sleep disorders, obesity, cognitive and psychiatric disorders
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H4 receptor blocker potential uses
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chronic inflammatory conditions like asthma; pruritus
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What is carcinoid syndrome?
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An unusual manifestation of carcinoid tumor, a neoplasn of enterochromaffin cells that secrete serotonin
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what is blocked by reserpine
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vesicle-associated transporter (VAT) = depletes serotonin, and catecholamines from vesicles
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What is precursor to serotonin?
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The amino acid L-tryptophan
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How is serotonin metabolized?
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Serotonin is metabolized by MAO to 5-HIAA
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Where is the majority of serotonin found?
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90% is in the enterochromaffin cells of the GI tract
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measure of serotonin synthesis
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urine 5-HIAA
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How are platelets able to store serotonin?
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They concentrate it using an active serotonin transporter mechanism(SERT), then they concentrate it in vesicles by a vesicle- associated transporter (VAT)
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What type of receptor are the serotonin receptors?
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7 families of 5-HT-receptor subtypes; 6 involve G protein coupled and one is ligand-gated channel (5-HT3)
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What type of receptor is 5-HT3
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member of nicotinic/GABAa family of Na+, K+ channel proteins; area postrema, sensory, and enteric nerves
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serotonin is a precursor to
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melatonin in pineal gland
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Which serotonin receptors are involved for the vomiting reflex and where are they located?
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5-HT3 receptors in the GI tract and in the vomiting center of the medulla
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Serotonin is a potent _____ of pain and itch sensory nerve endings
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stimulant
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What serotonin receptor is involved in bronchiolar smooth muscle and what are its effects?
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5-HT2A receptor; it has a direct small stimulant effect but it also facilitates AcH release from bronchial vagal nerve endings. This results in bronchoconstriction and hyperventilation ( like in carcinoid syndrome)
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Serotonin causes_______ of vascular smooth muscle and _____ in skeletal muscle and heart
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contraction; dilation
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Damaged Coronary vessels react to serotonin by ______.
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constricting
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What causes the flushing seen in serotonin release ( like from a carcinoid tumor).
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Venoconstriction with increased capillary filling
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What are the cardiac effects of prolonged exposure to elevated serotonin?
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Subendocardial fibroplasia, which can lead to valvular or electrical malfunction
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what is the difference between common and classic migraines?
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Classic migraines have an aura ( could involve nausea and vomiting, visual scotomas, hemianopsia, speech abnormalities) then a severe throbbing unilateral headache. Common migraines lack an aura
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What is the mechanism for pain in migraine headaches?
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It involves the trigeminal nerve distribution to intracranial arteries that releases neurotransmitters (like calcitonin gene related peptide) that causes extravasation of plasma and plasma proteins into the perivascular space. The perivascular edema causes activation of pain nerve endings inthe dura
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What is the effects of triptans on blood vessels?
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They mediate vasoconstriction on cerebral and meningeal vessels
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chemoreceptor reflex (Bezold-Jarisch reflex)
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activation of 5-HT3 receptors on afferent vagal nerve endings; marked bradycardia and hypotension
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What are the effects of activating melatonin receptor MT1
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activation results in sleepiness
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What are the effect of activating melatonin receptor MT2
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light-dark synchronization
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What is ramelteon
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selective MT1 and 2 agonist approved for insomnia; no addiction liability
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What is relationships between cardiovascular system and serotonin
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direct contraction of vascular smooth muscle via 5-HT2; dilates vessels in skeletal muscle and heart; reflex bradycardia via 5-HT3
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triphasic BP response to serotonin
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1) decrease HR, CO, and BP via chemoreceptor 2) increase due to vasoconstriction 3) decrease due to vasodilation to vessels supplying skeletal muscle
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How does serotonin cause platelet aggregation?
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5-HT2 receptor activation
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What are the serotonin receptors with activity in the GI tract and what is their function?
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stimulant of smooth muscle (tone and facilitating peristalsis) via 5-HT2; 5-HT4 in enteric nervous system motility-enhancing (increase acetylcholine)
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What is serotonin syndrome
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skeletal muscle contractions precipitated when MOA inhibitors given with serotonin agonists (especially SSRIs)=hyperthemia
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What is buspirone
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5-HT1a agonist; anti-anxiety agent
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What serotonin receptor acts in appetite suppression?
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5-HT2c in CNS agonists
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What are triptans?
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5-HT1d/1b agonists; migraine headaches; eg sumatriptan
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What patients are triptans are contraindicated in?
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coronary artery disease (can cause vasospasm) and angina
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What is ondansetron?
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prototypical 5-HT3 antagonist; prevention of nausea and vomiting associated with surgery and cancer chemotherapy
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What sertonin agonist is used in GERD?
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Cisapride, a 5- HT4 agonist
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What serotonin agonist is used in IBS?
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Tegaserod, a partial 5- HT4 partial agonist
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What are the symptoms ergotism (ergot poisoning) aka St. Athony's fire
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dementia with florid hallucinations, prolonged vasospasm-may result in gangrene; stimulation of uterine smooth muscle
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What are the different ways to accidently ergot OD?
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By eating bread made with contaminated flour (contaminated with Claviceps purpurea fungus); taking too much ergot medication for migraine headache- tell patients no more than 6mg for a migraine attack and no more than 10mg a week- effects are cummulative
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ergot derivatives bromocriptine, cabergoline, and pergolide on pituitary dopamine receptos
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directly suppress prolactin secretion by activating regulatory dopamine receptors; it acts as agonists or partial agonists at dopamine receptors
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What are the effects of ergotamine and alpha receptors
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partial agonist; dissociates slowly-long-lasting and atagonist effects; little/no B adrenoceptor effect
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ergots and uterine smooth muscle
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stimulant due to combined alpha agonist, serotonin, and other effects; ergonovine used in obstetrical applications (post-delivery bleeding)
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ergots used in migraine
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ergotamine traditional; also dihydroergotamine IV for intractable migraine
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what can treat ergot prolonged vasospasm
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refractory to most; large doses of nitroprusside or nitroglycerin can be successful
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contraindications for ergots
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obstructive vascular diseases and collagen diseases
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chronic use of methysergide caused
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CT proliferation in retroperitoneal space, pleural cavity, and endocardial tissue causing hydronephrosis or cardiac murmur
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