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mapa strony: Start. arrow Manuał aptekarski arrow 11.2008 - "Choroba refluksowa przełyku i objawy towarzyszące."


 


11.2008 - "Choroba refluksowa przełyku i objawy towarzyszące." Drukuj Email
11.2008, nr 27/5 online
 
 
 CHOROBA REFLUKSOWA
 
PRZEŁYKU I OBJAWY
 
TOWARZYSZĄCE
 
 –  AKTUALNE
 
STANDARDY LECZENIA

   Choroba refluksowa przełyku (gastroesophageal reflux disease, GERD) to schorzenie, którego podstawowym objawem jest wsteczne zarzucanie treści żołądkowej do przełyku.  
  Powodem wystąpienia refluksu żołądkowo-przełykowego jest dysfunkcja dolnego zwieracza przełyku polegająca na licznych, przedłużonych, samoistnych i przemijających relaksacjach. Relaksacje takie są zjawiskiem fizjologicznym, występującym u osób zdrowych, związanym z procesem trawienia. Występują po posiłkach, charakteryzują się krótkim czasem trwania i nie powodują żadnych subiektywnych dolegliwości, ani zmian histopatologicznych w przełyku. Jeśli częstość relaksacji przekracza 2-krotnie częstość fizjologiczną - pojawiają się objawy refluksu patologicznego. Refluks patologiczny może występować zarówno w ciągu dnia, jak i w nocy, niezależnie od posiłków i cechuje się wzrostem częstości i długości trwania jego epizodów, co powoduje wydłużenie czasu narażenia błony śluzowej przełyku na zarzucaną treść żołądkową. Zarzucanie treści żołądkowej do przełyku powoduje zmianę odczynu pH w dolnej części przełyku z alkalicznego na kwaśny (pH poniżej 4), co w następstwie prowadzi do powstania odczynu zapalnego śluzówki przełyku sprzyjającego rozwojowi nadżerek. U około 50% chorych z chorobą refluksową przełyku występuje refluks mieszany – dwunastniczo-żołądkowo-przełykowy. U tych pacjentów składnikami refluksu są kwasy żółciowe, które również mogą powodować znaczne uszkodzenia błony śluzowej przełyku (80% epizodów refluksu mieszanego ma odczyn kwaśny). Głównym objawem choroby jest zgaga występująca u ponad 70% pacjentów. Opisywana jest przez pacjentów jako  palenie za mostkiem, z jednoczesnym uczuciem kwaśnego smaku w jamie ustnej, nasilające się przy zginaniu się do przodu, w pozycji leżącej i po spożyciu niektórych pokarmów (czekolada, soki cytrusowe, tłuszcze, alkohol, papierosy). Choroba refluksowa przełyku występuje równie często u kobiet, jak i u mężczyzn, natomiast nadżerkowe zapalenie przełyku związane z refluksem obserwowane jest 2-3 razy częściej u mężczyzn. Zaznaczyć należy, że u ponad połowy wszystkich pacjentów z chorobą refluksową nie obserwuje się zmian zapalnych przełyku, ani powikłań  (non erosive reflux disease – NERD). W tej postaci choroby nie występuje progresja w kierunku zapalenia przełyku, a odpowiedź na leczenie jest bardzo dobra.
   Objawy choroby refluksowej przełyku podzielono na dwa zespoły: przełykowe i pozaprzełykowe. Objawy przełykowe dzieli się na: typowe zespoły objawów (typowe objawy refluksowe i refluksowy ból w klatce piersiowej) oraz zespoły objawów związane z uszkodzeniem przełyku (np. refluksowe zapalenie przełyku, refluksowe zwężenie przełyku). Objawy pozaprzełykowe podzielono na objawy o udowodnionej zależności przyczynowo-skutkowej (kaszel refluksowy, refluksowe zapalenie krtani, astma refluksowa, uszkodzenie szkliwa zębów) oraz objawy dla których związek zależności przyczynowo-skutkowej jest prawdopodobny (zapalenie zatok obocznych nosa, choroba włóknieniowa płuc, zapalenie gardła, nawracające zapalenie ucha środkowego). Czasami objawy pozaprzełykowe dominują w obrazie klinicznym, najczęściej jednak występują zarówno objawy przełykowe, jak i pozaprzełykowe.
   Jednymi z częściej występujących objawów pozaprzełykowych są objawy płucne, z których najbardziej uciążliwym dla pacjentów jest kaszel. Przyczyną kaszlu refluksowego jest mikroaspiracja cofającej się do gardła treści żołądkowej do dróg oddechowych oraz odruch przełykowo-tchawiczo-oskrzelowy regulowany przez nerw błędny. Najczęściej kaszel pojawia się wieczorem po położeniu się do łóżka, ale przed zaśnięciem oraz po wstaniu z pozycji leżącej (np. rano po wstaniu z łóżka). W ciągu dnia kaszel refluksowy pojawia się najczęściej w związku z posiłkami (obniżenie napięcia dolnego zwieracza przełyku w wyniku rozciągnięcia żołądka pokarmem). Najczęściej jest to kaszel suchy, czasami z niewielką ilością wydzieliny. Liczba napadów zależy zarówno od ogólnej liczby epizodów refluksu, jak i od czasu w jakim pH przełyku jest poniżej 4,0.
   Leczenie choroby refluksowej ma na celu doprowadzenie do ustąpienia objawów, wygojenie ewentualnych nadżerek błony śluzowej przełyku, utrzymanie remisji oraz zapobieganie powikłaniom choroby oraz jej nawrotom. W początkowym etapie leczenie ogranicza się do zaleceń dotyczących zmiany stylu życia. U pacjentów u których nie występują zmiany endoskopowe zmiana stylu życia i nawyków żywieniowych są często wystarczające. Zalecana jest odpowiednia dieta prowadząca do zmniejszenia masy ciała, zaprzestanie palenia tytoniu, picia kawy i alkoholu, nie spożywanie obfitych posiłków bezpośrednio przed snem oraz unikanie pozycji leżącej po jedzeniu. Doraźnie stosuje się leki neutralizujące kwas solny. W przypadkach braku efektów postępowania niefarmakologicznego (objawy utrzymujące się przez 2 – 4 tygodnie) wprowadza się farmakoterapię. W leczeniu farmakologicznym stosuje się leki antysekrecyjne – antagonistów receptora H2 oraz inhibitory pompy protonowej (IPP). Stosowanie IPP jest postępowaniem z wyboru w leczeniu choroby refluksowej przełyku. Podstawowym czynnikiem decydującym o wyborze tych leków jest ich zdolność do utrzymywania pH w przełyku powyżej 4 przez niemal całą dobę, co ma szczególne znaczenie w przypadku leczenia kaszlu refluksowego, gdzie stosowanie tych leków jest postępowaniem z wyboru. IPP zmniejszają produkcję kwasu solnego o około 90% oraz o połowę szybciej prowadzą do wygojenia nadżerek niż antagoniści receptora H2. IPP są lekami pierwszego rzutu, nie tylko u pacjentów ze zmianami endoskopowymi, ale również u osób bez zapalenia przełyku. W większości przypadków leki te, stosowane w standardowych dawkach, podawanych dwa razy dziennie, powodują szybkie ustąpienie objawów klinicznych niezależnie od stopnia zapalenia przełyku. Leczenie trwa od 4 do 8 tygodni (leczenie fazy ostrej) i w większości przypadków powoduje ustąpienie objawów. W przypadku nieskuteczności początkowej dawki IPP zaleca się podwojenie dawki porannej, a utrzymujący się nadal brak poprawy jest wskazaniem do wprowadzenia podwójnej dawki standardowej IPP wieczorem przed posiłkiem. Pacjenci z zespołami pozaprzełykowymi choroby refluksowej powinni być leczeni przewlekle od początku podwójną dawką standardową IPP stosowaną dwukrotnie w ciągu dnia.
   W związku z tym, że choroba refluksowa przełyku charakteryzuje się wysokim procentem nawrotów (około 80% w przeciągu 6-12 miesięcy od zakończenia leczenia wstępnego), po ustąpieniu objawów istnieje konieczność kontynuowania leczenia. Leczenie podtrzymujące polega na indywidualnym doborze najmniejszej skutecznej dawki IPP. Jeżeli stosowana dawka IPP powoduje wystarczającą kontrolę objawów choroby, to w ciągu kolejnych 2 – 4 tygodni dawkę tę zmniejsza się o połowę, a w razie braku nawrotu objawów choroby po kolejnych 4 – 8 tygodniach próbuje się zaprzestać leczenia. W długotrwałym leczeniu (powyżej 3 miesięcy) IPP wykazują największy odsetek chorych pozostających w remisji w porównaniu do antagonistów receptora H2 i leków prokinetycznych.
   Istotną zaletą IPP jest to, że leki te są bezpieczne nawet stosowane w dawkach wyższych niż dawki standardowe i są dobrze tolerowane. Objawy niepożądane występują rzadko i obejmują bóle głowy, wzdęcia, biegunkę, bóle brzucha, nudności, rumień skóry. Długotrwałe stosowanie IPP może powodować umiarkowaną hipergastrynemię, jednak nie wykazano wzrostu ryzyka rozwoju rakowiaków i raków gruczołowych żołądka wynikającego z nadmiernego wydzielania gastryny. Groźne objawy uboczne, obejmujące ostre zapalenie wątroby i ostre śródmiąższowe zapalenie nerek, występują niezwykle rzadko. Leki te najsilniej działają w środowisku kwaśnym, ponieważ do ich uaktywnienia potrzebna jest jonizacja. Zaleca się więc podawanie ich 20 – 30 min. przed posiłkiem, tak aby największe stężenie leku w osoczu wystąpiło w chwili aktywacji większości pomp protonowych (aktywne wydzielania kwasu solnego).  W przypadku rzadziej występujących objawów lub łagodnego przebiegu choroby zazwyczaj wystarcza leczenie antagonistami receptorów H2 (ranitydyna, famotydyna). Leki tej grupy powodują ustąpienie objawów u około 50% chorych, natomiast nie przynoszą spodziewanych rezultatów jeśli chodzi o wygojenie zmian w błonie śluzowej i utrzymanie osiągniętej remisji. Na ogół dawki antagonisty receptora H2, łagodzące objawy choroby refluksowej przełyku i prowadzące do zagojenia, muszą być 2-3 krotnie wyższe od dawek wystarczających w leczeniu choroby wrzodowej. Ponadto szybki rozwoju tolerancji na te leki poważnie ogranicza ich przewlekłe stosowanie. W niektórych przypadkach stosuje się leki prokinetyczne, uważając zaburzenia motoryki za jeden z ważniejszych czynników patogenetycznych. Leki te zwiększają spoczynkowe napięcie dolnego zwieracza przełyku oraz poprawiają oczyszczanie przełyku z treści refluksowej. Wykazują skuteczność jedynie w łagodnych postaciach choroby refluksowej przełyku, natomiast w innych przypadkach stosowane są w połączeniu z lekami antysekrecyjnymi.
   Choroba refluksowa przełyku jest bardzo częstym schorzeniem, a jej leczenie jest przewlekłe i długotrwałe, jednak skuteczność stosowanych leków jest na tyle wysoka, aby zapewnić pacjentom całkowite wyleczenie i zdecydowanie poprawić jakość życia chorego.
   Trwają prace nad wprowadzeniem na rynek nowych preparatów mogących mieć zastosowanie w leczeniu choroby refluksowej przełyku, w tym m.in. antagonistów receptora cholecystokininy typu 2 oraz leków antysekrecyjnych obniżających wydzielanie kwasu żołądkowego na drodze hamowania kanału potasowego przez wiązanie kompetycyjne ATP-azy.
dr n. farm. Ewa Poleszak
Zakład Farmakodynamiki
Uniwersytetu Medycznego w Lublinie
 
fot. dreamstime.com
 
Piśmiennictwo:

1.    Andersson K., Carlsson E.: Potassium-competitive acid blockade: A new therapeutic strategy in acid-related diseases. Pharmacol. Ther., 2005, 27, 365-370.
2.    Małecka-Panas E.: Nietypowe objawy choroby refluksowej - rozpoznanie i leczenie. Medical Adviser. 2002, 4, 1-6.
3.    Marlicz K.: Leczenie choroby refluksowej przełyku. Gastroenterologia w codziennej praktyce lekarskiej 2002, 6, 2-5.
4.    Muszyński J.: Postępowanie w chorobie refluksowej przełyku. Terapia, 2003, 6, 25-30.
5.    Nowak A., Marek T.: Choroba refluksowa przełyku. Medical Science Review. Gastrologia 2002, 1, 24-32.
6.    Reguła J., Kulich K.R., Stasiewicz J. i wsp.: Poczucie choroby u chorych z chorobą refluksową w Polsce. Przegl. Epidemiol. 2005, 59, 75-85.
7.    Starzyńska T., Wasilewicz M.P.:  Choroba refluksowa przełyku – terapia na żądanie. Terapia, 2008, 6, 17-20.
8.    Wocial T.: Patofizjologia, rozpoznawanie i leczenie choroby refluksowej przełyku. Terapia, 2007, 6, 13-18.




 
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