آ تی یغتبيی ب آ تی عش ت ی ب آنکبن ئیذ بی اسگ ت دکتش يذسط
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1 آ تی یغتبيی ب آ تی عش ت ی ب آنکبن ئیذ بی اسگ ت دکتش يذسط
2 ات ک ئیذ ب یغتبيی يبعت عم ب ثبص فیم ب يحم يبعت عم ب س تشا غ یت س رخیش آصاد عبصی یغتبيی انف: ای ن ژیکی یبص ث Ca ا شژی حغبعیت عشیغ ة : ؽی یبیی يکب یکی يشفی ت ث ک ساسی اص دعت داد گشا ن ب
3 يکب یضو اثش H 1 H 2 H 3 H 4 H 1 Couples to G q protein to activate phospholipase C Found throughout the CNS and densely concentrated in hypothalamus stimulates wakefulness Also seen in smooth muscles and endothelium Pruritus, pain, vasodilation, vascular permeability, hypotension, flushing, headache, tachycardia, bronchoconstriction, stimulation of vagal afferent nerves and cough receptors, AV conduction time, intracellular Ca
4 H 2 Couples to G s -protein to activate adenylyl cyclase camp Found predominantly in the GI tract, Increases secretion of gastric acid from parietal cells In the stomach Also seen in cardiac muscles and brain and some immune cells vascular permeability, hypotension, flushing, headache, tachycardia
5 H 3 Couples with G i- protein to inhibit adenylyl cyclase Proposed as a neural presynaptic auto-receptor serving to modulate histamine synthesis and release in the CNS, as well as neurotransmitters (e.g. Ach, dopamine, GABA, serotonin, NE) by decreasing Ca influx It is also in Peripheral tissue, including the gastric mucosa, where it may negatively control gastric acid secretion Pruritus (no mast cell involvement), nasal congestion, prevent excessive bronchoconstriction, food intake
6 H 4 Couples with G i -protein to inhibit adenylyl cyclase The H 4 receptor is highly expressed on bone marrow, peripheral blood leukocytes and intestinal tissue, a potential target in allergic and inflammatory diseases Pruritus (no mast cell involvement), nasal congestion, differentiation of myeloblasts and promyelocytes
7 H 1 اثشات ثش اسگب بی ثبفت بی ثذ 1 -اثشات لهجی ػش لی گؾبد ؽذ ػش ق کب ؼ فؾبس عیغت نیک دیبعت نیک ا ذ تیهی و H 2 يغتمیى یب اص عشیك ضشثب لهت افضایؼ ا مجبض لهت ) 2 H) ادو ) 1 H) گش گشفت گشو ؽذ عشدسد کب ؼ ا مجبض يب یچ بی د هیض ) 1 H) آصاد ؽذ nitric oxide اص 2 -يب یچ بی صبف GI H 1 افضایؼ ا مجبض
8 يب یچ بی صبف ثش ؼ ا مجبض H يب یچ بی صبف دیگش اسگب ب سحى 5- اثشات يتبث نیكی
9 6- اػصبة تحشیک اػصبة حغی خبسػ دسد H 3 آصاد ؽذ Ach ثؼضی اص آيی ب پپتیذ ب سا دس اػصبة يشكضی يحیغی كب ؼ يی د ذ. 7- ثبفت بی تشؽحی H 2 افضایؼ تشؽح اعیذ يؼذ پپغی فبکت س راتی (افضایؼ آد هیم عیکالص camp کهغیى داخم عه نی)
10 Triple Response 1. Localized red spot Due to direct vasodilator effect of histamine 2. Brighter red flush (flare) extending around original spot Due to indirect histamine stimulation of axons that cause vasodilation 3. Wheal that occupies original localized red spot Due to direct vasoconstriction and edema formation
11 آ تبگ یغت بی یغتبيی انف: آ تب گ یغت فیضی ن ژیکی 2 ة ج آدس شژیک : ي بس ک ذ بی آصاد ؽذ یغتبيی کش ي نی nedocromil آگ یغت بی کت تیف : آ تب گ یغت بی سعپت س بی یغتبيی
12 آ تب گ یغت بی سعپت س H 1 Diphenhydramine, Dimenhydrinate, pyrilamine, chlorpheniramine, Dexchlorpheniramine, Hydroxyzine, promethazine, cyproheptadine, clemastine, Cetirizine, Terfenadine, loratodine, fexofenadine, desloratadine Longer duration of action غم ا ل گش يتجب ظ غم د و ع و اسد CNS ی ؽ ذ
13 Chemical Class 1st Generation 2nd Generation Alkylamines chlorpheniramine Piperazinese hydroxyzine Cetirizine Piperidines A Ethanolamines cyproheptadine, ketotifen clemastine, dimenhydrinate, diphenhydramine fexofenadine, loratadine, terfenadine Ethylenediamines pyrilamine Phenothiazines promethazine
14 mechanism H 1 antihistamines act as inverse agonists that combine with and stabilize the inactive conformation of the H 1 receptor, shifting the equilibrium toward the inactive state
15 More effective in preventing the actions of histamine rather than reversing them Should be given early in treatment, before all the histamine binds to the receptors Human H 1 receptors have approximately 45% homology with muscarinic receptors
16 Some of properties of 2 nd and 3 rd generation decreased lipophilicity additional antiallergic properties apart from histamine antagonism interfere with mediator release from mast cells inhibit the late-phase allergic reaction by acting on leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect Desloratadine has anti-inflammatory action distinct from the second-generation antihistamines
17 - 1 خ اة آن دگی فبسيبک دی بيیک پیشیم آيی دیف یذسايی دی یذسا بت پش يتبصی یذس کغی صی کهشف یشآيی دکظ کهشف یشآيی تشف بدی fexofenadine, loratadine Cetirizine یجب آژیت تؾ ج 2 -ت ع اعتفشاؽ N/V بؽی اص حشکت: دی یذسا بت دیف یذسايی یذس کغی صی پش يتبصی
18 3- اثشات ضذ پبسكی غ ػالئى اكغتشاپیشايیذال بؽی اص داس ب تضؼیف يیؾ د 4- خ اؿ آ تی ي عکبس یک ثیؾتش ثب غم ا ل دیذ يیؾ د ثه ک کشد کهی عپت س ب: دیف یذسايی دی یذسا بت پشیم آيی
19 ثه ک کشد ادس عپت س ب ثه ک کشد α یپ تب غی پغت سال ي بس عش ت ی اثشات ثیحظ ک ذ ي ضؼی اثشات دیگش
20 ي اسد يصشف انف: اک ؾ بی حغبعیتی 2 nd generation H 1 antihistamines are drug of choice in the treatment of allergic rhinitis, allergic conjunctivitis, and chronic urticaria. Symptom relief may be incomplete H 1 antihistamines are best taken on a regular basis Responses of individuals are different Fexofenadine does not have any sedative effect
21 ي اسد يصشف ة : ت ع اعتفشاؽ بؽی اص حشکت دیف یذسايی پش يتبصی دی یذسا بت ج: ت ع بؽی اص حبيهگی
22 First-Generation H 1 Antihistamines Are Used also in: Insomnia Perioperative sedation Antiemetic effect Analgesia Akathisia Serotonin syndrome Anxiety Migraine headache Nonspecific cough
23 ػ اسض خ اة آن دگی تبسی دیذ احتجبط ادساس خؾکی د ب گه یجب تؾ ج یپ تب غی پغت سال حغبعیت خ اؿ آتش پی یک آسیت ی ع ال ی ؽذ QT The second generation medications are relatively free from adverse effects, including CNS and cardiac toxicity, when administered in standard doses and even if taken in overdose. تذاخم داس یی عبیش دپشط ک ذ بی CNS تشف بدی شا ثب کت ک بص ل یب اسیتش يبیغی تشات ژ یغیتی
24 caution intraocular pressure, cardiac or renal disease, hypertension, asthma, COPD, peptic ulcer disease, pregnancy
25 آ تبگ یغت بی H 2 عبی تذی سا یتیذی فبي تیذی Nizatidine يکب یضو اثشات س ی اسگب بی يختهف ت نیذ اعیذ يؼذ دیگش اسگب ب اثشاتی ک يشث ط ث ي اسد يصشف H 2 صخى يؼذ صخى اث ی ػؾش یغت Gastroesophageal reflex Hypersecretory conditions
26 عش ت ی (5- یذس کغی تشیپتبيی ( L-tryptophan GI يحم غذ ص ثشی پالکت ب - يغض( 4. پیؼ عبص يالت ی اػصبة تشیپتبيی شژیک): خهك خ ی خ اة ت ظیى ديبی ثذ دسد ک تشل فؾبس خ دپشعی اضغشاة يیگش تشؽح ACTH سي سؽذ پش الکتی TSH يتبث نیغى فبسيبک دی بيی 7 ع سعپت س
27 اثشات ثش اسگب ب ثبفت بی يختهف 1 -لهت ػش ق ا مجبض يب یچ بی ػش ق ) 1 5-HT ( ثجض دس لهت يب یچ بی اعکهتی ثشادیکبسدی ت عظ تحشیک Chemoreceptors (5-HT 3 ) ع فبص فؾبس خ HR, CO, BP کب ؼ BP افضایؼ BP کب ؼ پالکت ب اص عشیك سعپت س 5-HT 2 تج غ
28 2- عیغتى اػصبة س تشا غ یت س پیؼ عبص يالت ی - ث ػ ا ک ک ک ذ ث خ اة :Ramelteon يحشک -MT 1, MT 2 اثش يت عظ غیش اػتیبد آ س ت ع اعتفشاؽ- 5HT 3 يحشک ل ی ا ت بی اػصبة حغی دسد خبسػ يحشک ل ی ا ت بی اػصبة حغبط ث ي اد ؽی یبیی دس ػش ق کش ش ) 3 BP, HR (5-HT
29 -3 دعتگب گ اسػ ا مجبض يب یچ ب تغ یم حشکبت د دی ) 2 (5-HT افضایؼ حشکبت يؼذ ) 4 (5-HT ت ع ) 3 (5-HT ت فظ 4- کى - 2A 5-HT اعپبعى ثش ؼ ب یپش ی تالعی ػضالت اعكهتی ا مجبض ) 2 (5-HT -5
30 Serotonin Syndrome Excess synaptic serotonin associated with skeletal muscle contractions Precipitated by administration of MAO with serotonin agonists such as: SSRIs, second generation antidepressants, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, ginseng
31 Clinical Presentation HA, HTN, hyperreflexia, tremor, agitation, hyperthermia, hyperactive, bowel sounds, N/D, mydriasis, coma, agitation, mental confusion, shivering, sweating, N/D, tachycardia, myoclonus (muscle twitching) onset within hours Therapy Sedation (benzodiazepines), intubation and ventilation; consider 5-HT 2 block with cyproheptadine or chlorpromazine
32 فبسيبک ن ژی ثبنی ی عش ت ی آگ یغت بی عش ت ی -5-HT 1A - Buspirone ضذ اضغشاة -5-HT 1B, 5-HT 1D - Sumatriptan يیگش ا مجبض ػش ق يغض جه گیشی اص آصاد ؽذ ي اد انت بة صا ػ اسض: گشد دسد عی خ اة آن دگی ضؼف يب یچ ب دسد
33 فه کغتی عبیش SSRI جه گیشی اص د ثبس ثشداؽت عش ت ی 5-HT 4 -Cisapride
34 آ تب گ یغت بی عش ت ی ي بس 5-HT 2 عیپش پتبدی خ اؿ آ تی ي عکبس یک آ تی یغتبيی Ondansetron, Granisetron (5-HT 3 ) very effective for prevention of nausea and vomiting caused by chemotherapy or surgery
35 Ketanserin: blocks 5-HT 2, 5-HT 1c effective antihypertensive drug (probably acting through α 1 adrenergic receptors) antagonizes platelet aggregation Ritanserin Blocks 5-HT 2 receptors (no alpha blocking properties) May alter platelet function
36 انکبن ئیذ بی اسگ ت Claviceps purpura فبسيبک ک تیک جزة يتغیش کبفئی فبسيبک دی بيیک يکب یغى اثش سعپت س بی عش ت ی - آ تب گ یغت سعپت س بی د پبيی آگ یغت آگ یغت آگ یغت غجی یب
37 انکبن ئیذ اسگ ت د پبيی عش ت ی يب یچ بی صبف سحى ثشي کشیپتی (PA) + + اسگ ی +++ +(PA) 0 اسگ تبيی --(PA)
38 اثش س ی اسگب بی يختهف CNS -1 ت ى صایی عش ت ی آگ یغت 5-HT 2 -LSD كب ؼ پش الكتی - د پبيی ثشي کشیپتی کبثشگ نی پشگ الیذ کب ؼ تشؽح پش الکتی اص یپ فیض يیؾ ذ
39 2- يب یچ بی صبف ػش ق اسگ تبيی داس بی ؽجی آ - اعپبعى ػش ق غجی α آ تبگ یغت (5HT 2 اثش ع ال ی دسيب يیگش (آگ یغت
40 3 -يب یچ بی صبف سحى يحشک α عش ت ی افضایؼ حغبعیت سحى دس ع ل حبيهگی اسگ ی اثش Selective ث ؾی تش N/V/D GI 4 -اثشات دیگش -
41 يصبسف ثبنی ی (Vasoconstriction) يیگش انف: specific Prodrome اسگ تبيی اثش ع ال ی ج غ ؽذ ی ة پ : یپشپش الکتی ی Bromocriptine mesylate, Cabergoline, pergolide ت بیم صیبد ث سعپت س د پبيی داس ذ D 2 : خ شیضی ثؼذ اص صای ب ergonovine maleate
42 يغ يیت ػ اسض N/V/D اعپبعى ع ال ی ػش ق خ اة آن دگی تحشیک CNS ت ى
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