Ambroksolio poveikis gydant kosulį

Ambroksolio poveikis gydant kosulį

Įvadas

 

Kosulys yra svarbus organizmo apsauginis mechanizmas (1). Jis skirstomas į ūminį, kuris trunka trumpiau nei 3 savaites, poūmį, trunkantį nuo 3 iki 8 savaičių, ir lėtinį, kuris užsitęsia ilgiau nei 8 savaites (2). Ūminį kosulį dažniausiai sukelia ūminės viršutinių kvėpavimo takų infekcijos (2). Poūmis kosulys stebimas po persirgtos viršutinių kvėpavimo takų infekcijos. Lėtinis kosulys, kuris yra susijęs su blogesne gyvenimo kokybe, dažniausiai yra įvairių lėtinių ligų simptomas – lėtinės obstrukcinės plaučių ligos (LOPL), astmos, rinito, gastroezofaginio refliukso (2, 3). Lėtinį kosulį gali sukelti rūkymas ir kai kurių vaistų vartojimas (2). Lėtinis kosulys pasireiškia 9,6 proc. asmenų visame pasaulyje (3). Europoje šis simptomas vargina 12,7 proc. asmenų (3).

Kosulys gali būti neproduktyvus (vadinamasis sausas) ir produktyvus (vadinamasis šlapias). Pavyzdžiui, sergant gastroezofaginio refliukso liga, būdingas lėtinis neproduktyvus kosulys (4). Lėtinis produktyvus kosulys būdingas sergant bronchektaze, LOPL, astma (4). Sergant ūmine viršutinių kvėpavimo takų infekcija, ūmins kosulys pradžioje būna neproduktyvus, o vėliau tampa produktyvus (5). Ūmins produktyvus kosulys būdingas sergant pneumonija ir kokliušu (5).

Vieni produktyviam kosuliui palengvinti skirtų medikamentų yra mukolitikai. Šios grupės vaistai suskystina gleives suardydami mukopolisacharidines grandines, todėl sekretas lengviau pašalinamas iš kvėpavimo takų (6). Ankstyvas mukolitikų paskyrimas gali sustabdyti poūmio kosulio vystymąsi (7). Vienas šios grupės vaistų atstovų yra ambroksolis. Jis skiriamas produktyvaus kosulio metu susidarančioms gleivinėms skystinti, sergant ūminėmis arba lėtinėmis bronchų ir plaučių ligomis (8). Ambroksolis yra bromheksino metabolitas. Išgėrus šio vaisto, poveikis pasireiškia vidutiniškai po 30 min. ir trunka 6–12 val. priklausomai nuo vienkartinės dozės dydžio (8). Šiame straipsnyje apžvelgiamas ambroksolio poveikis.

 

Antiuždegiminis ambroksolio poveikis

 

Uždegimas yra imuninės sistemos atsakas į žalingą dirgiklį. Uždegimo vietoje aktyvinamos uždegiminės ląstelės, kurios skatina proteolizinių fermentų, citokinų, natrio oksido ir superoksido anijono išsiskyrimą (9). Uždegimo pažeistuose audiniuose uždegiminės ląstelės sulaikomos veikiant leukotrienams, granuliocitų ir makrofagų kolonijas stimuliuojančiam faktoriui. Fiziologinis uždegiminio atsako vaidmuo yra žalingų veiksnių sunaikinimas, tačiau ne visada pavyksta išvengti veiksnių, sukeliančių uždegimą, poveikio (pvz., alergeno, tabako dūmų), todėl šis procesas gali užsitęsti (9). Tada vystosi lėtinės uždegiminės ligos. Sergant ūmine liga, pavyzdžiui, ūmine viršutinių kvėpavimo takų infekcija, uždegiminis atsakas į virusą sukelia audinių pažeidimą ir simptomų pasireiškimą (9). Atlikta daug tyrimų, analizuojančių ambroksolio antiuždegiminį poveikį.

Sergant ūminiu uždegimu, chemoatraktantai ir / ar citokinai, turintys šių savybių, pirmieji pradeda uždegiminio atsako procesą. Vienas svarbiausių chemoatraktantų ūminio uždegiminio atsako metu (pvz., virusinės infekcijos) yra leukotrienas B4 (LTB4). Jis skatina monocitų, makrofagų ir neutrofilų funkcijas (9). Tyrimai rodo, kad leukotrienas B4 dalyvauja ir LOPL patogenezėje. Tyrimuose, kuriuose naudotas ūminio uždegimo modelis, ambroksolis efektyviai sumažino LTB4 išskyrimą iš monocitų ir neutrofilų (9). Yra duomenų, kad ambroksolis slopina neutrofilų atsaką į įvairius chemoatraktantus (9).

Uždegiminiame atsake svarbus vaidmuo tenka ir interleukinams (IL). Vienas jų, IL-8, pasižymi neutrofilus ir makrofagus pritraukiančiu poveikiu. Tyrimai rodo, kad skiriant ambroksolį IL-8 išskyrimas iš bronchų epitelio ląstelių sumažėja (9). Pacientus, sergančius LOPL, gydant ambroksoliu, po 10 dienų užfiksuotas sumažėjęs IL-8 kiekis kraujyje ir seilėse (9). Be to, remiantis moksline literatūra, ambroksolis sumažina lėtinio bronchito ir / ar LOPL paūmėjimų dažnį (9).

Uždegiminiame procese dalyvauja ne tik neutrofilai ir monocitai, bet ir kitos ląstelės – bazofilai, eozinofilai. Jie veikia sergant alerginėmis ligomis. Šios ląstelės reaguoja į 2 tipo T limfocitų pagalbininkų (Th2) ir putliųjų ląstelių gaminamus citokinus – IL-4, IL-13, IL-5, taip pat mediatorių cisteinilo leukotrieną, vazoaktyviuosius peptidus (pvz., histaminą) (9). Tyrimai parodė, kad ambroksolis sumažino cisteinilo leukotrieno, IL-4, IL-13 ir histamino kiekį, taip pat histamino išsiskyrimą iš putliųjų ląstelių (9, 10). Astma sergantiems pacientams ambroksolis sumažino kvėpavimo takų jautrumą metacholinui, skyrus jį 14 dienų po 90 mg (9).

In vitro tyrimas atskleidė reikšmingą IL-1 išskyrimo iš makrofagų ir IL-2 išskyrimo iš mononuklearinių ląstelių periferiniame kraujyje ir bronchų alveoliniame lavaže sumažėjimą skyrus ambroksolį (9). Šis vaistas sumažino interferono gama išskyrimą. Tyrime su gyvūnais, sergantiems  ūminiu plaučių uždegimu, ambroksolis sumažino IL-6 ir navikų nekrozės faktoriaus alfa kiekį (9, 10). Gibbs su bendraautoriais tyrimu įrodė, kad ambroksolis slopina imunoglobulino (Ig) E nulemtą histamino išskyrimą iš odoje esančių putliųjų ląstelių (11).

 

Antioksidacinis ambroksolio poveikis

 

Tyrimai atskleidė, kad ambroksolis pasižymi laisvuosius radikalus neutralizuojančiu poveikiu (9, 10, 12). Manoma, kad jis gali apsaugoti nuo oksidacinio streso, kurį sukelia tabako dūmai ir kitos įkvepiamos toksinės medžiagos (10). Tyrimas su laboratoriniais gyvūnais parodė, kad ambroksolis gali apsaugoti širdį nuo citotoksinių medžiagų (pvz., doksorubicino) sukeltos riebalų peroksidacijos (10). Ambroksolis slopina hialurono rūgšties skilimą bei peroksinitrito ir hipochloro rūgšties sukeltą alfa-1 antiproteinazės pažeidimą, superoksido anijono, vandenilio peroksido ir azoto oksido gamybą (9).

Dauguma tyrimų, vertinančių ambroksolio antioksidacines savybes, yra atlikti su laboratoriniais gyvūnais arba in vitro. Mokslinėje literatūroje randama nedaug tyrimų, atliktų su pacientais. Ambroksolis turi didelį afinitetą plaučių audiniui, todėl apie 20 kartų didesnė jo koncentracija nustatoma plaučiuose nei kraujo serume. Ambroksolis kvėpavimo takuose skatina surfaktanto gamybą (12). Surfaktanto sudėtyje randama antioksidantų. Taigi, didindamas surfaktanto kiekį, ambroksolis netiesiogiai sumažina oksidacinį stresą plaučiuose (12). …

Daugiau skaitykite žurnale „Internistas“ Nr.1, 2018 m.

Parengė gyd. Laura Tamašauskienė


145 mintys apie “Ambroksolio poveikis gydant kosulį

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