Kobieta i jej układ oddechowy Paweł Górski Uniwersytet Medyczny w Łodzi

Osobnicze Rasowe Etniczne Kulturowe Zależne od płci

Alkohol Analgetyki Sedativa w tym leki przeciwhistamionowe Opioidy Inne Mechanizm Zależny od: 1. Bezpośredniej interakcji z hormonami steroidowymi 2. Ekspresji receptorów 3. Aktywności enzymów degradujących

Aktywność CYP 3A4 jest wyraźnie wyższa u kobiet niż u mężczyzn, w mniejszym stopniu wyższa CYP 2A6. Meibohm B i wsp. Clin Pharmakokinetics 2002, 41, 329 Al. Koudsi N i wsp. Eur J Clin Pharmacol 2006, 62, 481

Poprawa Pogorszenie Bez zmian Im cięższy przebieg astmy tym mniejsza szansa poprawy

1.Physiological changes masking/aggravating allergic symptoms 2.Factors related to adherence with therapy 3.Pregnancy and a course of allergy 4.Dosage. Is it stable? 5.What should be considered as an antiallergic treatment in pregnancy? 6.Safety 7.Recommendations

Symptoms…why? Structural changes in the airways, as well as in the thoracic cage and in the muscles, especially in the diaphragm Mucosal changes in both the upper and the lower airways Dyspnoea during pregnancy- always asthma?

Rhinitis-total 22%, smokers 69% Ellegard E et al.: Gynecol Obstet Invest 2000, 49, 98 Hypersecretion, oedema, hyperaemia Schofman MA. J Fla Med. Assoc 1961, 48, 160 Nasal obstruction, sneezing, epistaxis No studies have been performed but Coughing, sputum production are very frequent Popovich J.1998

Airways mucosa Tissue hydratation, mucous glands hypertrophy, H1R expression, eosinophil recruitment Oestrogens Progesterone Hamano N et al.: Int Arch Allergy Immunol 1998, 115, 220 Hamano N et al.; Allergy Asthma Proc 1998, 19, 263 H1R expression, eosinophil recruitment

One study suggests an improvement in asthma symptoms and airway reactivity in the first trimester (Juniper EF et al.: Am Rev Respir Dis 1989, 140, 924) Acute attacks are likely to be experienced at weeks Asthma exacerbation usually occurs between 29 and 32 week Worsening is particularly expected in women at the onset or towards the end of their reproductive time No additional treatment during delivery is needed because in the final phases of pregnancy PGE2 and cortisol levels increase Benyon HLC et al.: Lancet 1988,332,370 Stenius-Aarniala B et al.; Thorax 1988,43, 12

Education Psychotherapy Allergen avoidance Immunotherapy Pharmacotherapy

Pharmakokinetics Absorption of agents administered orally is limited because of deleyed stomach emptying and reduced intestinal motility The volume of distribution is increased The metabolic activity of the liver is increased, accelererating the metabolism of lipophylic drugs Renal filtration is increased, leading to enhanced elimination of water-soluble agents These modifications are responsible for reduced plasma concentration and reduced half-life of most drugs Take it into consideration when optimizing dosage and route of administration Tsatsaris V et al.: Clin Pharmacokinet 2004, 43, 833

It depends on the course that is usually unstable in moderate/severe allergy and asthma Progesterone produces downregulation of lymphocyte beta-2 receptors Tan KS et al.; Br J Pharmacol 1996, 41, 414 It does not seem to be clinically important

Outcomes of ICS use in pregnancy ICSStudiesOutcomes BUD Kallen 1999 Ericson 1999 Norjavaara 2003 Namazy 2004 Summarized population 7559 Neither increased congenital malformations, stillbirth, nor decreased birth weight vs general population BDP Brown 1977 Greenberger 1983 Schatz 1997 Dombrowski1996, 1999 Namazy 2004 Summarized population 1704 Neither increased congenital malformations, stillbirth, nor decreased birth weight vs general population

FDA category Anti-inflammatory mechanism Controller B ICS Budesonide Cromolyn, nedocromil Montelukast, zafirlukast Cetirizine, loratadine and azatadine, clemastine, chlorphenyramine, diphenhydramine, ciproheptadine C ICS Beclomethasone, fluticasone, flunisolide, triamcinolone Cell stabilizers Antileukotriens Antihistamines Leukotriene modifierZileuton LABA Salmeterol, formoterol Methylxanthine Theophylline Antihistamines Fexofenadine, hydroxysine

Conclusions Uncontrolled airway allergy is a risk factor for some poor pregnancy outcomes ICS are recommended for all severities of persitent asthma as like topical CS for all types of allergic rhinitis in pregnant women and in women in childbearing age. Although all modern ICS are probably safe, budesonide is currently recommended in the management of both asthma and rhinitis If asthma/rhinitis control is a target of the management of allergic pregnant women, a combination of ICS and LABA is preferably recommended Antileukotriens, antihistamines especially cetirizine and loratadine may be applied if they are needed Specific immunotherapy and vaccination against influenza may be carried on Education, allergen avoidance, psychological support are useful and should be always performed