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Antihistamines

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Antihistamines 50 CONFERENCIAS MAGISTRALES Antihistamines Jorge A. Quel* In 1910 Dale and Laidlaw fírst identifíed histamine. Histalet forte pyrilamine maléate 1937 Bobitt and Staut produced the first H 1 oldest ciass of Hl antagonists antagonist. 1942 The fírst antiHISTAMINE (phen- CNS some sedation benzamine) was released for the treatment of Gastrointestinal can cause gastroinsteestinal upset allergic conditions. Anticholinergic effects weak Recently new antihistamines have been PHENOTHIAZINE discovered with minimal sedating effects and Phenergan promethazineHCL 12.5 5,25, 50 mg antiallergic and antiinflammatory effects. USE frequent added to codeine for cough me dicine. Anühistamine FIRST GENERA TION Tacaryl methdilazine HCL 8mg Ethanolamine Benadryl diphenhydramine HCí, strength 25 CNS produces heavy sedation or 50 mg are also used as sleeping pills. PIPERAZINES Atarax hydroxyzine Rondec-TR carbinoxamine maléate, 8mg. USE motionsickness and urticaria CNS produces dull mental alertness Tavist clemastine fumarate, 2.68 mg. ALKYLAMINES Naldecon phenyltoloxamine, 15mg. Actifed triprolidine HCL 2.5mg Chlor-trimeton chlorpheniramine maléate, 4, 8, ACTION: Very potent Hl antagonist 12mg Polaramine CNS frequency of drowsiness varíes with dexchlorpheniramione maléate, 2, antihistamine compounds. 4, 6 mg Anticholinergic effects are weak. Dimetapp brompheniramine maléate, 4mg Gastrointestinal: side effects are rare. Drixora dexbrompheniramine maléate, 6mg USE are very effective with modérate drowsiness Ethylened iamines in adults; in childrens produce central nervous PBZ tripelennamine 25 to 50 mg stimulation more so than others group used in pregnancy * Inmunólogo Pediatra. Director Ejecutivo Hispanic American Allergy and Inmunology Association. Marina del Rey, Ca. U.S.A. Número Especial - Honduras Pediátrica - Vol. XXI No. 3 - Septiembre - Año 2000 51 Memorias XXI CONGRESO CENTROAMERICANO Y DEL CARIBE DE PEDIATRÍA y XII CURSO INTERNACIONAL DE PEDIATRÍA OTHERS better than those who received eiíher Trinaiíne azatadine maléate, Img placebo or diphenhydramine, but less well USE rhinitis than children without allergies. Periactin cyproheptadine HCI, 4mg USE urticarias. INCREASE RISK OF WORK-RELATED INJURIES (GILMORE, 1996). SECOND GENERATION Seldane terfenadine 1a. Síudy conducted with Group Health Coo- USE due to interaction with macrolites, can perative of Puget Sound. 2b. Patients produce cardio toxicity prescribed sedating antihistamines had elevated ri sk of i nj ury (1:1.5) Hismanal astemizole 5 0% i ncrease ri sk of traum atic work- USE due to interaction with macrolites, can related injury produce cardio toxicity and weighí gain ANT1H1STAMINE DOS1NG COMBINING Claritine loratadine lOmg (syrup Img per mi) SEDATING AT N1GHT AND NON SEDATING IN THE DAYTIME. METABOLITES Allegra fexofenadine HCI 30, 60, 180mg 1. Chlopheniramine pm dosing (in and syrup metabolite of combination with terfenadine am dosing) terfenadine (seldane) demonstrated and adverse effect on daytime sleepiness and level of alertness. 2. Zyrtec cetirizine HCI tablets 5, 10 mg and Chlorpheniramine pm dosing (in syrup Img 4ml metabolite of combination with terfenadine am dosing) atarax demonstrated an adverse effect on day time brain functioning. TOPICALS Azteline azelastine nasal spray BRONCHODIATION EFFECTS OF ANTI- HISTAMINE. Livostin levocabastine eye drops 1. Produce increase forcé expiratory volume first second in pulmonar test. POORER SCHOOL PERFORMANCE (VUURMAN, 1992) Antihistamines exert many effects that have anti=allergic or anti-inflammatory conse- 1. Study compared performance oí children quences. with SAR and matched normáis on the use of a didactic computer These effects are unrelated to their H1 receptor simulation in a classroom setting. blockade activity 2. Children who received diphenhydramine The precise mechanisums by which these effects or placebo leamed signifícantly less than are exerted have not been elucidated but appear to normal (non-allergy) controls. be related to the caíionic amphiphilic nature of 3. Children who receved loratadine performe the antihistamine molecule and the ability of the 52 Número Especial - Honduras Pediátrica - Vol. XXÍ No. 3 - Septiembre - Año 2000 Memorias XXI CONGRESO CENTROAMERICANO Y DEL CARIBE DE PEDIATRÍA y XII CURSO INTERNACIONAL DE PEDIATRÍA antihistamine molecuíe to inserí itself in cell membranes. However, it should be clearly stated that clinical The effects occur on many inflammatory cells-the effects of this anti-allergic/anti-inflammatory model best studied is mast ceill/basophil activity are unclear. histamine reléase The concentrations of antihistamines necessary to The ability of antihistamines to prevent mast cell achieve these effects in vitro are oftentimes higher and basophil degranulation extends to numerous than those achied during the admilnistration of stimuli of the degranulation process including these drugs for therapy. allergen-induced degranulation Anti-leukotrienes in the treatment of asthma Jorge A. Quel the 5 Lipoxygenase, which gives origin to LTA4. In 1938, Feldberg and Kellaway used the term slow-reacting substance of anaphylaxis (SRS-A) From LTA4 to describe a smooth muscie-contracting factor that appeared in the exúdate of the guinea-pig LT4 under the influence of LTA4 hydrolased lung when treated with cobra venom. Two years becomes LTB4 later, Kellaway and Trethewie suggested that Also, LT4 under the influence of the LTC4 SRS-A may play a role in the treatment of asthma. synthase becomes However their role in asthma was not clarified LTC4\----------LTD4- .....................------- LTE4 until much íater in 1983 by Samuelsson who called them leukotrienes due to the possiblity of In normal individuáis, inhaled LTC4 and LTD4 their leukocyte origin. are about lOOOx as active as histamine in causing bronchodilation. Bisguard has demonstrated that Of the three esential fatty acids (arachidonic, the airways of asthmatic subjects are 100 times to linolenic and alpha íinolenic), arachidonic acid is 1000 times more responsive to LTD 4 than those the one that synthesis leukotrienes. of nonasthmatic controls. The onset of action of inhaled LTD4 and LTE4 is four to six minutes When arachidonic acid coming from the compared with the ten to twenty minutes required perinuclear membranes is activated by phos- for LTC4. pholipase A2, the liberated substance follows two pathways: The fírst pathway is cyclolooxygenase There is a receptor for LTD4 and this receptor which give origin to prostaglan-dines and could be inhibited by antagonists. thromboxanes. The focus of our interest is the second pathway, 2aflrlukast(accolate) is a selective and Número Especial - Honduras Pediátrica - Vol. XXI No. 3 - Septiembre - Año 2000 53 Memorias XXI CONGRESO CENTROAMERICANO Y DEL CARIBE DE PEDIATRÍA y XII CURSO INTERNACIONAL DE PEDIATRÍA competitive antagonist of leukotriens LD4 and LTE4. Inhalational challenge studies in sensitized sheep Montelukast(singulair)is also a selecíive and showed that zafírlukast suppressed the airway competitive antagonist of leukotriens LD4 and responses to antigens, this includes the early and LTE4. late response. In humans, zafirlukast also Zileuton (zyflo)is an inhibitor of the 5 lipoxynase attenuated inhalation of various antigens such as as grass, caí dander, and ragweed including the EXERCÍSE INDUCED ASTHMA When 20 mg of early and late response. zafirlukast was given orally prior to exercise it Singulair inhibited 75% of bronchoconstriction to caused a mean máximum percentage fall in FEV1 antigens in the early phase and 57% in the late of 21.6% compared with 36.0% following phase. placebo. When 400mg zafirlukast was inhaled 30 minutes before exercise, the percentage fall DRUG 1NTERACTIONS in FE VI was 14.5% after medication compared with 30.2% after placebo. It is imporíant to Zafíriukast (accolate) metabolizes by CYP2C9 realise that patients using inhaled beta agonists (tolbutamide, phenytoin,carbamazepine) or as their regualr preventative therapy experience a CYP3A4 (dihydropyridine calcium channel loss of the bronchoprotective effect. However, blockers, cyclosporine, astemizole, cisapride). recent studies revea! that the bronchoproíective Zarfirlukast plasma ievels are reduced by effects of Zafirlukast and montelukast remain erythromycin and theophylline and Zafirlukast through many weeks of treatment. plasma levéis are increased by aspirin. COLD AIR ÍNDUCED ASTHMA Montelukast (Singulair) is metabolized in the A study of zarfirlukast in cold-induced asthma CYP450 3A4 and 2C9. After a single injection of showed a signifícant attenuation of bronco- theophilline, singulair did not cause changes in constriction 30 minutes after a single dose of the the blood level of theophilline. receptor antagonist. Phenobarbital decreased the AUC of montelukast Another study shows the effect of zileuton after a by 40 % single 800mg dose produced signifícant Clinical monitoring should be done with attenuation of the asthmatic patient's response to concominant administraron of phenobarbital and cold dry air. rifampin Zileuton (Zyfio) metabolizes by the P450 3A. ASPIRÍN INDUCE ASTMA Hepatic elevation of one or more Üver test may I. In Patients with aspirin-induced asthma occur during ziflo treatment, contraindication Zileuton reduced the main máxima! urinary LTE4 liver disease. levéis after aspirin challenge by 68%; Zileuton also blocked nasal, gastroinstesinal and dermal ANTI-LEUKOTRINES ANTAGONISTS AND responses to aspirin. INHIBITOR IN ASTMA Montelukast has demonstrated signifícant clinical improvement
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