Antihistaminique 327725 29864589 2008-05-22T20:01:04Z 90.7.42.5 /* Tricycliques */ {{ébauche|médecine}} Un '''antihistaminique''' est un [[médicament]] qui sert à réduire ou à éliminer les effets de l'[[histamine]], un médiateur chimique endogène libéré entre autre au cours des [[allergie|réactions allergiques]], par action sur les [[récepteur de l'histamine|récepteurs de l'histamine]]. Seuls les agents qui ont pour effet thérapeutique principal la modulation négative des récepteurs de l'histamine sont appelés antihistaminiques ; il existe d'autres agents à action antihistaminergique, mais on ne les désigne pas comme de vrais antihistaminiques. Dans l'usage général, le terme antihistaminique désigne uniquement les '''antagonistes des récepteurs H<sub>1</sub>''', que l'on appelle les '''antihistaminiques H<sub>1</sub>'''. <!--It has been discovered that these H<sub>1</sub>-antihistamines are actually [[inverse agonist]]s at the histamine H<sub>1</sub>-receptor, rather than [[receptor antagonist|antagonists]] ''per se''. (Leurs, Church & Taglialatela, 2002)--> <!--In allergic reactions an [[allergen]] (a type of [[antigen]]) interacts with and cross-links surface IgE [[antibody|antibodies]] on [[mast cell]]s and [[basophil]]s. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through [[histamine receptor]]s. Histamine, acting on H<sub>1</sub>-receptors, produces [[pruritis]], [[vasodilatation]], [[hypotension]], [[flushing]], [[headache]], [[tachycardia]], [[bronchoconstriction]], increases [[vascular permeability]], potentiates [[pain]], and more. (Simons, 2004) While H<sub>1</sub>-antihistamines ameliorate these effects, it is only efficacious if administered prior to the allergen-challenge. In severe allergies, such as [[anaphylaxis]] or [[angioedema]], these effects may be so severe as to be life-threatening. [[Epinephrine]], often in the form of an autoinjector ([[Epi-pen]]), is required by people with such hypersensitivities.--> ==Utilisation clinique des antihistaminiques== ===Indications=== Les antihistaminiques H<sub>1</sub> sont utilisés dans le traitement d'états allergiques où l'histamine joue un rôle médiateur. Spécifiquement, ces indications peuvent comprendre : (Rossi, 2004) * [[rhinite]] allergique * [[conjonctivite]] allergique * maladies allergiques [[peau|dermatologiques]] ([[dermatite de contact]]) * [[urticaire]] * [[prurit]] ([[dermatite atopique]], morsures d'insectes) * réactions [[anaphylaxie|anaphylactiques]] ou anaphylactoïdes - uniquement comme adjuvant * nausées et vomissements (antihistaminiques H<sub>1</sub> de première génération) * sédation (antihistaminiques H<sub>1</sub> de première génération) Selon la nature de l'état allergique, les antihistaminiques peuvent être administrés : * en administration locale (topique) (au travers de la [[peau]], du [[nez]] ou de [[œil|yeux]]) * ou par voie systémique. Voir les vidéos en 3D, dans l'encyclopédie médicale Vulgaris, consacrées à l'asthme et à l'allergie[http://video.vulgaris-medical.com/index.php/Pneumologie]. ===Effets secondaires=== <!--[[Adverse drug reaction]]s are most commonly associated with the first-generation H<sub>1</sub>-antihistamines. This is due to their relative lack of selectivity for the H<sub>1</sub>-receptor. The most common adverse effect is sedation - this "side effect" being utilised in many [[over-the-counter|OTC]] sleeping-aid preparations. Other common adverse effects in first-generation H<sub>1</sub>-antihistamines include: dizziness, [[tinnitus]], blurred vision, [[euphoria]], uncoordination, [[anxiety]], [[insomnia]], tremor, [[nausea]] and vomiting, [[constipation]], [[diarrhoea]], dry mouth, and dry cough. Infrequent adverse effects include: urinary retention, [[palpitation]]s, [[hypotension]], [[headache]], [[hallucination]], and [[psychosis]]. (Rossi, 2004) The newer second-generation H<sub>1</sub>-antihistamines are far more selective for peripheral histamine H<sub>1</sub>-receptors and, correspondingly, have a far improved tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include: drowsiness, fatigue, headache, nausea and dry mouth. (Rossi, 2004)--> ==Antihistaminiques H<sub>1</sub> de première génération== <!--These are the oldest antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic [[acetylcholine receptor]]-antagonists ([[anticholinergic]]) agents as well. These agents also commonly have action at α-[[adrenergic receptor]]s and/or [[5-HT receptor]]s. This lack of receptor-selectivity is the basis of the poor tolerability-profile of some of these agents, especially compared with the second-generation H<sub>1</sub>-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes. The first H<sub>1</sub>-antihistamine discovered was [[piperoxan]], by Forneau and [[Daniel Bovet]] (1933) in their efforts to develop a [[guinea pig]] animal-model for [[anaphylaxis]]. Bovet went on to win the 1957 [[Nobel Prize in Physiology or Medicine]] for his contribution. Following their discovery, the first-generation H<sub>1</sub>-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties.-> ===Éthylènediamines=== <!--Ethylenediamines were the first group of clinically-effective H<sub>1</sub>-antihistamines developed. *[[mepyramine]] (pyrilamine) *[[antazoline]] --> ===Éthanolamines=== <!--Diphenhydramine was the prototypical agent in this group. Significant [[anticholinergic]] adverse effects, including sedation, are observed in this group but the incidence of gastrointestnal adverse effects is relatively low. (Nelson, 2002; Rossi, 2004) *[[diphenhydramine]] *[[carbinoxamine]] *[[doxylamine]] *[[clemastine]] *[[dimenhydrinate]]--> ===Alcylamines=== <!--The [[isomer|isomerism]] is a significant factor in the activity of the agents in this group. ''E''-triprolidine, for example, is 1000-fold more potent than ''Z''-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H<sub>1</sub>-receptor binding site. (Nelson, 2002) Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical [[central nervous system|CNS]] stimulation. (Rossi, 2004) *[[pheniramine]] *[[chlorphenamine]] (chlorpheniramine) *[[dexchlorphenamine]] *[[brompheniramine]] *[[triprolidine]]--> ===Pipérazines=== *[[Fluphenazine]] *[[Perphénazine]] *[[Prochlorpérazine]] *[[Trifluopérazine]] <!--These compounds are structurally-related to the ethylenediamines and the ethanolamines; and produce significant [[anticholinergic]] adverse effects. Compounds from this group are often used for motion sickness, vertigo, nausea and vomiting. The second-generation H<sub>1</sub>-antihistamine cetirizine also belongs to this chemical group. (Nelson, 2002) *[[hydroxyzine]] *[[meclizine]]--> ===Tricycliques=== *[[Amitriptyline]] ==Antihistaminiques H<sub>1</sub> de deuxième génération== <!--These are newer drugs that are much more selective for peripheral H<sub>1</sub> receptors in preference to the [[central nervous system]] histaminergic and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions compared with first-generation agents, while still providing effective relief of allergic conditions.--> ===Systémique=== * [[acrivastine]] * [[astémizole]] * [[cétirizine]] et [[lévocétirizine]] * [[fexofénadine]] * [[loratadine]] et [[desloratadine]] * [[mizolastine]] * [[terfénadine]], non utilisée en raison d'un risque d'[[arythmie cardiaque]] (torsades de pointes) <!--(withdrawn from most markets due to risk of [[cardiac arrhythmia]]s and replaced with fexofenadine)--> ===Topiques=== * [[azélastine]] * [[lévocabastine]] * [[olopatadine]] ==Autres agents== ===Inhibiteurs de la libération de l'histamine=== Ces substances agissent en évitant la dégranulation et la libération de médiateurs par les mastocytes.<!--These agents appear to stabilise the mast cells to prevent degranulation and mediator release.--> * [[cromoglicate]] (cromolyn) * [[nédocromil]] ===Antihistaminiques H<sub>2</sub>=== ''article principal : [[Antihistaminique H2]]'' <!--Clinically-relevant histamine H<sub>2</sub>-receptors are found principally in the [[parietal cell]]s of the [[stomach|gastric]] mucosa. H<sub>2</sub>-receptor "antagonists" are also [[inverse agonist]]s, rather than true [[receptor antagonist|antagonists]]; and are used to reduce the secretion of [[gastric acid]]. Examples include [[cimetidine]], [[ranitidine]], and [[famotidine]].--> ===Antihistaminiques H<sub>3</sub> et H<sub>4</sub>=== <!--These are experimental agents and do not yet have a defined clinical use.--> ===Autres agents ayant une activite antihistaminergique=== <!--Many drugs, used for other indications, possess unwanted antihistaminergic activity. These include [[tricyclic antidepressants]], [[antipsychotic]]s, ''etc''.--> ==Voir aussi== * [[Antihistaminique H2]] ==Références== * Fourneau E, Bovet D (1933). Recherches sur l'action sympathicolytique d'un nouveau derive du dioxane. ''Arch Int Pharmacodyn'' '''46''', 178-91. * Leurs R, Church MK, Taglialatela M (2002). H<sub>1</sub>-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. ''Clin Exp Allergy'' '''32''', 489-98. * Nelson, WL (2002). In Williams DA, Lemke TL (Eds.). ''Foye's Principles of Medicinal Chemistry'' (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1 * Rossi S (Ed.) (2004). ''[[Australian Medicines Handbook]] 2004''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2 * Simons FER (2004). Advances in H<sub>1</sub>-antihistamines. ''N Engl J Med'' '''351''' (21), 2203-17. {{Portail médecine}} [[Catégorie:Antihistaminique|*]] [[bs:Antagonisti H1 receptora]] [[ca:Antihistamínic]] [[da:Antihistamin]] [[de:Antihistaminikum]] [[en:H1 antagonist]] [[es:Antihistamínico]] [[fi:Antihistamiini]] [[it:Antistaminico]] [[ja:抗ヒスタミン薬]] [[ko:H1 항히스타민제]] [[nl:Antihistaminicum]] [[pl:Antagoniści receptora H1]] [[sk:Antihistaminikum]] [[sv:Antihistamin]] [[th:สารต้านฮิสตามีน]] [[tr:Antihistaminik]] [[uk:Антигістамін]] [[zh:抗組織胺]]