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41 Cards in this Set
- Front
- Back
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What are autocoids? |
Autocoids: These are biological factors which act like local hormones, have a brief duration, act near the site of synthesis and are not blood borne. |
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Functions of autocoids ?? 6 |
Autocoids take part in 1. Inflammation 2. Allergic reactions 3. Anaphylactic reactions 4. Neurotransmission 5. Gastric acid secretion 6. Neuroendocrine regulation. |
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Functions of autocoids in CNS?? 7 |
In the CNS they are responsible for 1. wakefulness 2. decreased appetite 3. regulation of drinking 4. regulation of temperature 5. regulation of blood pressure 6. secretion of adrenal hormones(ADH). 7. perception of pain. |
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What are the classifications of autocoids? |
Classification of Autacoids :1. Amine derived : histamine, serotonin 2. peptide derived : angiotensin, bradykinin, vasopressin, substance P 3. Lipid derived (eicosanoids) : leukotrienes, thromboxanes, prostaglandins, interleukins, platelet activating factor. |
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Where are mast cells found? |
Mast cells are distributed in : Skin Bronchial mucosa Gut mucosa Other mucosal surfaces. Mast cells synthesize histamine very slowly and store it in specific granules for a very long time (until needed). |
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In the ___________ histamine is not stored in granules. |
In the brain, stomach, healing tissues and some cells in the skin, histamine is not stored in granules. |
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Characteristics of Histamine |
Histamine levels in the plasma are normally very low. Histamine levels in the CSF are high. It is produced de novo. It has a high turnover(made quickly, destroyed quickly) Low steady state level. |
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What is autoinhibition? |
The histamine released can act on the mast cell it came from and inhibit the further release of histamine(autoinhibition). |
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What triggers the release of histamines? |
Antigen specific, IgE mediated. Anaphylactoid triggers; Organic bases Morphine Tubocurarine Succinylcholine chloride Contrast media used in radiography. Dextran Some neuropeptides Venom from insects (e.g mastoparan from wasps). |
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Which Diseases are associated with increased histamine? |
Urticaria pigmentosa(mastocytosis) Systemic mastocytosis Myelogenous leukemia (increased basophil number) Gastrinoma ; Zollinger-Ellison syndrome. Increase in gastrin release resulting in excessive release of histamine from ECL(enterochromaffin like) cells in the gut. Get ulcers and diarrhea. |
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Symptoms of histamine release/increase |
Urticaria. Dermographism Pruritis. Headaches. Weakness. Hypotention. Flushing of the skin. GIT disturbances. Ulcers. |
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Burning, itching, warmth are due to? |
Sensory nerve stimulation. |
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Warmth,skin flush ,hypotension are due to ? |
Vasodilation. |
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Mech. Of action of the following; Headache ------ Skin oedema/hives --- Colic/nausea ---- Acid hypersecretion ---- Bronchospasm |
Headache ------ vasodilation/stimulation of afferent nerve fibres.Skin oedema/hives --- microvascular leakage. Colic/nausea ---- GI irritation. Acid hypersecretion ---- action of histamine on H2 receptors on parietal cells. Brochospasm ---- effects of histamine on smooth muscle contraction in bronchi. |
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What is the triple response? |
Red spot ---- vasodilation Wheal ----- leakage of vessels. Flare ----- axon reflex. Stimulation of sensory afferents signals itchy pain. |
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Histamine receptors. Location, prototype and signalling molecule in order. |
H1- found in smooth muscles, microvessels, endothelium, sensory nerves. Blocker- diphenhydramine. Molecule- DAG,PLC, IP3 H2- stomach, heart, mast cell(autoinhibition), endothelium. Blocker-cimetidine. Molecule- increase in cAMP. H3- nerves, brain, gut, heart. Blocker- Impromidine. Molecule - G couple Ca entry. |
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General characteristic of histamine receptors. |
All are 7 transmembrane spanning G protein coupled receptors. When histamine binds, it causes a conformational change which exposes a region on the intracellular tail of the receptor which allows G proteins to bind. |
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H1 vs H2 vs H3 in mechanism of action? |
H1- Activates phospholipase C which causes release of IP3 . IP3 stimulates release of intracellular Ca2+ stores. H2- Activates adenylate cyclase Increase in cAMP. H3- G protein mediated Ca2+ entry from the extracellular compartment into the cell(note the difference to H1 receptors where the increase in cytosolic Ca2+ is from intracellular stores.) |
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2 functions of free intracellular calcium |
Free intracellular Ca2+may also activate Ca2+ dependent protein kinases. e.g. myosin light chain kinase in smooth muscle(causing contraction). May also activate phospholipase A2 which causes production of eicosanoids. |
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. Histamine in the brain. Histamine is synthesised and degraded by enzymes in _________. |
. Histamine in the brain. Histamine is synthesised and degraded by enzymes in synaptosomes. |
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H1 receptors in the brain. Location and functions. |
Found in hypothalamus . Affect wakefulness(many antihistamines cause drowsiness) Appetite suppression. |
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H1/H2 receptors involved in : |
Drinking Thermoregulation Secretion of ADH Blood pressure regulation P.s: H3 receptors are Poorly understood, might Modulate H1 effects. |
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Functions of histamine H2 receptors in the heart. |
Increase in atrial and ventricular force via H2 receptors(increase in Ca2+).Increase in heart rate by reducing the diastolic depolarisation time at the SA node (H2 receptors). |
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Functions of histamine H1 receptors in the heart. |
Decrease in the AV conduction time (H1 receptors) Arrhythmia in high doses (both H2 and H1?) |
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Mechanism of action of histamines in smooth muscles (bronchial and gut) |
H1: contraction H2: relaxation (via increase in cAMP ) is a weak minor compensation (modulates H1effects of constriction) |
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Mechanism of action of histamine in the vessels. |
H1 activates endothelial relaxation via NO(+PG12) . H2 activates a slower onset of direct relaxation.(some microcirculations are very sensitive to histamine,so that a H1 spasm may dominate.) |
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Uses of histamine agonists. |
No therapeutic use Only used in specialties such as in bronchial hypereactivity testing for asthmatics Used by dermatologists as a positive control to test for allergen reactivity. |
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H1 antagonists uses |
Hay fever Allergic conjunctivitis Rhinitis Some skin disorders |
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What are Other potential uses of H1 antagonists |
Colds (useless,may even be harmful due to their sedative effect) Asthma (never used any more even though the air ways of the asthmatic are filled with mast cells.) Useful in histamine overproduction diseases Motion sickness(not as effective as scopolamine) Vomiting(not as good as ondansetron) |
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H2 antagonists are often used to treat? |
Peptic ulcers Dyspepsia/heart burn. Gastric reflux. |
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What are the characteristics of classic H1 antagonists? |
Are sedative Often short acting(3 – 6 hours) May have significant anti-cholinergic action. |
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Characteristics of Non sedating(new generation) H1 antagonists. |
Low or zero CNS penetration. Long acting Little anticholinergic effects |
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Polymorphic Ventricular Tachycardia (PVT) may occur with ____ and _____ if these drugs are taken in high doses or in conjunction with certain macrolide antibiotics (___) and/or certain anti-fungals (____). |
Polymorphic Ventricular Tachycardia (PVT) may occur with astemizole and Terfenadine if these drugs are taken in high doses or in conjunction with certain macrolide antibiotics (erythromycin and clarithromycin) and/or certain anti-fungals (ketaconazole and itraconazole). These other drugs inhibit a hepatic cytochrome p450 enzyme which is required for the metabolism of these 2 H1 antagonists. |
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Examples of H2 antagonists; |
Cimetidine Ranitidine Famotidine Nizatidine |
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What are mast cells ? |
Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. |
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Types of mast cells |
Two types of mast cells exist ………….(1) connective tissue type found in connective tissue and skin (2) mucosal type found in gastrointestinal mucosa and peripheral pathways |
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What are the end effects of mast cell degranulation? |
The end effects of mast cell degranulation include (1) vasodilation with tissue edema (2) leakage of serum proteins(3) extravasation of leukocytes leading to local inflammatory response,[4] smooth muscle contraction(bronchoconstiction) and [5] pruritus. |
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What are the G protein coupled receptors? |
G- protein coupled receptors ( GPCRs) or 7-transmembrane domain receptors ( 7TMRs) or heptahelical receptors or serpentine receptors, are a large protein family of receptors that sense molecules outside the cell and activate the inside signal transduction pathways and ultimately cellular response, coupling with G proteins |
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They are called 7 transmembrane receptors because _________. |
They are called 7 transmembrane receptors because they pass through the cell membrane 7 times. |
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Gastric acid secretion is regulated by an intricate interplay of __________ |
Gastric acid secretion is regulated by an intricate interplay of Neural acetylcholine hormonal gastrin paracrine (histamine, somatostatin) mechanisms. |
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Gastric acid secretion is regulated by an intricate interplay of __________ |
Gastric acid secretion is regulated by an intricate interplay of Neural acetylcholine hormonal gastrin paracrine (histamine, somatostatin) mechanisms. |
