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mapa strony: Start. arrow Wszechnica arrow 02.2010 - RECEPTARIUSZ - "Mieszanka uspokajająco-nasercowa."


 


02.2010 - RECEPTARIUSZ - "Mieszanka uspokajająco-nasercowa." Drukuj Email
luty 2010, nr 42/20 online
 
 
 
MIESZANKA USPOKAJAJĄCO-NASERCOWA

   Mieszanki uspokajająco-nasercowe to jedne z najczęściej obecnie wykonywanych leków recepturowych do użytku wewnętrznego. Ich zaletą jest możliwość połączenia kilku składników w kompozycje nie występujące w preparatach gotowych. Najczęściej ordynowane są jako remedium w nerwicach wegetatywnych.
    
NERWICA WEGETATYWNA

    W skrócie można powiedzieć, że nerwica wegetatywna polega na objawianiu się dolegliwości psychicznych w postaci nasilonych zaburzeń wegetatywnych, które dominują w obrazie choroby. Objawy fizyczne mogą być bardzo zróżnicowane – bardzo często jest to „kołatanie serca”, a także różnego rodzaju objawy ze strony układu pokarmowego i moczowo-płciowego. Choroba może również objawiać się jako zawroty i bóle głowy, duszności, drżenia, nasilona potliwość, czy wreszcie poprzez doznania związane ze skurczem mięśni gładkich lub szkieletowych typu „uczucie kuli w gardle”, drętwienie kończyn, mrowienie. Tym silnie odczuwanym, fizycznym symptomom mogą towarzyszyć objawy psychiczne, lękowe tj. „wrażenie umierania”, lub uczucie rychłej utraty świadomości. Objawy te mogą utrzymywać się długotrwałe, ale zdarza się także, że występują napadowo, jako tzw. „przełomy wegetatywne”. Mogą pojawić się w sytuacjach, w których pacjent nie jest narażony na stres, czy zdenerwowanie, co powoduje, że nie kojarzy on tych dolegliwości z problemami psychicznymi. Szybko natomiast nabiera on przekonania, że cierpi na poważną chorobę narządową, czego jednak nie potwierdzają specjalistyczne badania. Towarzyszy temu strach o własne zdrowie i obawa o to, że „prawdziwa choroba” nie została prawidłowo zdiagnozowana. Chorzy czują się zagubieni, niekiedy nie znajdują zrozumienia w otoczeniu dla swoich cierpień, co zwykle tylko pogarsza ich sytuację zdrowotną – potęguje lęk, powoduje zamknięcie się w sobie, sprzyja narastaniu fobii i drażliwości, jednocześnie potęgując objawy wegetatywne. Opisywane jest to jako „objaw błędnego koła” – czyli wzajemne nasilanie się dolegliwości z kręgu psychicznych i fizycznych. Często pojawiają się kłopoty ze snem.
   Podstawowym kierunkiem leczenia takich pacjentów powinna być psychoterapia i uświadomienie chorym, że ich cielesne dolegliwości mają źródło w różnego rodzaju nieuświadomionych problemach emocjonalnych (stres, frustracja, niepowodzenia zawodowe lub osobiste).
   Leczenie farmakologiczne zwykle polega na podawaniu leków uspokajających, niekiedy również przeciwdepresyjnych.

MIXTURA SEDATIVA, HYPNOTICA, CARDIACA

   
   Istnieje co najmniej kilka tradycyjnych przepisów na mieszanki uspokajające o ustalonym składzie i własnym nazewnictwie jak np. Mixtura Valerianae bromata R.P. czy Mixtura Pavlovi RP. Poniższy przepis to jedna z najbardziej rozbudowanych receptur na mieszankę uspokajająco-nasercową. Zawiera dodatkowo składnik przeciwbólowy (w tym przypadku metamizol, ale istnieją także przepisy, w których jest to pabialgina).
 

Rp.
Sal. Erlenmeyeri
Tinct. Adonidis vernalis
Tinct. Convallariae maialis.
Tinct. Crataegi
Tinct. Valerianae aa 10,0
Luminali natri 0,3
Novalgini 4,0
Aqua destill. 20,0
Neospasmini ad 250,0
M.f. mixt.
D.S. 2 x dziennie łyżka stołowa
 
   Większość współcześnie wykonywanych mikstur zawiera któreś z powyższych składników w różnych kombinacjach i proporcjach. Trafiają się przepisy, ale raczej rzadko, w których dodatkowym składnikiem jest Cardiol C, Mentowal, Cardiamid czy Intractum Visci.  Podłożem (rozpuszczalnikiem) dla tych preparatów najczęściej jest woda destylowana lub - jak w powyższej recepcie - syrop. Najczęściej wykorzystywana jest Neospasmina lub Passispasmina, czasami syrop prosty, sporadycznie – Hydroksyzyna. Neospasmina zawiera wyciąg z kozłka i głogu, a Passispasmina jest bogatsza o wyciąg z męczennicy i szyszek chmielowych. Preparaty gotowe w odróżnieniu od prostych podłoży recepturowych mają tę zaletę, że wnoszą do leku własne działanie lecznicze, a także mogą szczególnie skutecznie poprawiać smak. Niekiedy jednak może okazać się, że użyte do ich produkcji substancje pomocnicze dają trudne do przewidzenia incompatibilitates, zwłaszcza przy dużej liczbie przepisanych składników, lub w przypadku użycia więcej niż jednego leku gotowego.
   Mieszanki tego typu powinny być zużyte w terminie około 7 dni, na co należy zwrócić uwagę przyjmując receptę na większą ilość leku. Szczególnie nietrwałe mogą się okazać preparaty o dużej zawartości wody, w których konserwujące właściwości etanolu (z nalewek) lub cukru (z syropów) nie są zachowane.
   Aby prawidłowo ocenić czas, w jakim mieszanka zostanie zużyta, oraz obliczyć, czy nie zostało przekroczone maksymalne dawkowanie, na recepcie powinno koniecznie widnieć dawkowanie preparatu. Pacjenci najczęściej dawkują preparat sami, wykorzystując miary „domowe”. Dla przypomnienia:
 
 
łyżeczka do herbaty – 5g
łyżeczka deserowa – 10g
łyżka stołowa – 15g
 
 
   Mieszanek tych nie sączy się, ale należy pamiętać o oznakowaniu „zmieszać przed użyciem”. Zmiana stężenia, rozcieńczenie etanolu jako rozpuszczalnika nalewek może powodować zmętnienie, co nie świadczy jednak o niekorzystnych zmianach w leku.

   W zaproponowanym we wstępie przepisie lekarz zadbał o pojawienie się niewielkiej ilości wody, co bardzo ułatwia rozpuszczenie substancji stałych. Gdyby w recepcie figurował wyłącznie syrop, najrozsądniej byłoby we własnym zakresie zamienić jego część na wodę (uważa się, że bez porozumienia z lekarzem może to być nie więcej niż 5% ogólnej masy leku). Wprawdzie również syropy zawierają przecież pewną ilość wody i rozpuszczanie w nich proszków jest możliwe. Jest to jednak proces powolny, a w przypadku syropów o ciemnej barwie uniemożliwiona jest szybka wizualna kontrola całkowitości rozpuszczenia. Ponieważ w receptach na mieszanki (szczególnie te prostsze) dosyć częsty jest – w innych typach recept rzadziej spotykany - zapis ilości substancji w stosunku wagowo-wagowym (g/g) warto przypomnieć, że zapis typu: Sal Erlenmeyeri 8,0/250,0 oznacza, iż należy użyć 8 gramów soli Erlenmeyera oraz 242 gramów wody, druga cyfra oznacza bowiem całkowitą masę gotowego roztworu.
 

   W przedstawionej recepcie, fenobarbital figuruje w łatwej do rozpuszczenia w wodzie formie soli. Niemniej zdarza się zapisanie w recepcie na lek płynny formy nierozpuszczalnej luminalu. Zasadniczo jest to błędem, który farmaceuta powinien skorygować zamieniając nierozpuszczalny fenobarbital (rozpuszczalność 1:5000) na jego formę rozpuszczalną w wodzie – sól, czyli właśnie na fenabarbital sodu (rozpuszczalność 1:1,5). Ze względu na różnice w masie cząsteczkowej obu postaci chemicznych ilość użytego surowca powinna zostać przeliczona. Przykładowe obliczenie do recepty:
 
 
Rp.
Luminali 0,3
Aqua ad 100,0
M.f. Solutio


232,24 - masa cząsteczkowa luminalu
254,22 - masa cząsteczkowa luminalu sodowego

0,3 – 232,24
x – 254,22
zatem x = 0,33
 
 
   Oznacza to, że zamiast 0,3 luminalu farmaceuta wykonujący receptę powinien odważyć 0,33 soli sodowej. Ilość wody powinna być – lege artis - adekwatnie pomniejszona o 0,03 grama w stosunku do recepty wyjściowej.
   Istnieje także możliwość ominięcia tego problemu poprzez wykorzystanie formy kwasowej, rozpuszczenie jej w etanolu i połączenie z przepisanymi w recepcie nalewkami. Jest to jednak metoda polecana głównie w sytuacjach, w których fenobarbital w postaci soli mógłby dać niezgodności z innymi współobecnymi w recepcie składnikami (np. z inną solą powodując wytrącenie osadu). Czasami ilość etanolu zawarta w samych nalewkach okazuje się wystarczająca do rozpuszczenia formy kwasowej fenobarbitalu i nie ma potrzeby sięgania po dodatkową porcję spirytusu. Obliczeń można dokonać zakładając, że fenobarbital rozpuszcza się w etanolu 95o w stosunku 1:10, a nalewki sporządzone są na spirytusie, którego stężenie można przyjąć za 70o.
   W mieszankach zawierających luminal sodowy mogą wystąpić niezgodności związane z odczynem środowiska. Roztwór fenobarbitalu sodu ma odczyn zasadowy. Niezgodności (w postaci wytrącenia osadu) mogą pojawić się po zmieszaniu go z roztworem o odczynie kwaśnym – przy czym rodzaj osadu zależeć będzie od finalnego pH roztworu. W codziennej praktyce aptecznej najbardziej warte zapamiętania są fakty na temat niezgodności fenobarbitalu sodu z nalewkami (nie daje) oraz z chlorowodorkiem papaweryny (zawsze daje niezgodność). W mieszankach zawierających sól Erlenmeyera niezgodność może dawać bromek amonu, jednakże nie zawsze, a w zależności od stężenia (szczegółowe tabele można bez trudu znaleźć w większości podręczników do receptury). Uwaga – fenobarbital sodowy szybciej rozpuszcza się w czystej wodzie niż w roztworze bromków, dlatego powinien być rozpuszczany jako pierwszy (jest to również zgodne z zasadą odważania składników od ilości najmniejszej, do największej). Nie wydaje się również błędem - nawet w receptach zgodnych - rozpuszczenie barbituranu i bromku po prostu osobno i dodanie jednego z roztworów na końcu, do reszty gotowej mieszanki. Ten tryb postępowania jest także jak najbardziej wskazany w celu uniknięcia niezgodności fenobarbitalu sodu z fosforanem kodeiny, czy chlorowodorkiem hydroksyzyny.

WŁAŚCIWOŚCI UŻYTYCH SKŁADNIKÓW

    Tinctura Adonidis i Tinctura Convallariae – głównym składnikiem nalewki z miłka wiosennego i konwalii majowej są glikozydy kardenolidowe. Ich głównym efektem działania jest zwiększenie siły skurczu serca (działanie inotropowe dodatnie) z jednoczesnym spowolnieniem jego pracy (efekt chronotropowo ujemny). Serce działa wówczas bardziej „ekonomicznie” i efektywniej wypycha krew do naczyń krwionośnych, reguluje się ciśnienie krwi, ustępują obrzęki. Nalewki te są szczególnie pomocne są w pierwszym okresie niewydolności serca.
   Należy jednak przypomnieć, że glikozydy nasercowe mają wąski zakres działań terapeutycznych.  Przedawkowanie ich może powodować wystąpienie stanów oszołomienia, splątania, zaburzenia widzenia (głównie barw), oraz nudności i wymioty pochodzenia ośrodkowego.
   Tinctura Crataegi – nalewka głogowa zawiera głównie związki flawonoidowe. Wywiera działanie spazmolityczne, również na mięśniówkę naczyń krwionośnych, łagodnie obniżając ciśnienie krwi.
   Tinctura Valerianae (Tinctura Polemoni) – nalewka kozłkowa zawiera seskwiterpeny, głównie kwas walerenowy. Działa łagodnie uspokajająco i nasennie.

BROMKI

   Bromki wykazują słabe działanie uspokajające, a w większych dawkach – nasenne. Sole bromu wchłaniają się z przewodu pokarmowego, ale większość komórek jest nieprzenikliwa dla jonów bromkowych. Wchłonięte bromki gromadzą się więc w płynach międzykomórkowych i wypierają jony chloru. Ten antagonizm, na który szczególnie podatne są neurony uważany jest za główny mechanizm ich działania na układ nerwowy.
    Bromki już w dawkach terapeutycznych mogą wywołać działania niepożądane w postaci podrażnień przewodu pokarmowego, przy czym efekt ten nasila się w kolejności:
bromek sodu < bromek potasu < bromek amonu
    Bromek sodu zawiera 77% bromu, bromek potasu – 67%, a bromek amonu – 82% bromu. Najsilniej działa bromek amonu, ale – tak jak pokazuje powyższa nierówność - równocześnie najsilniej drażni przewód pokarmowy. Dodatkowo jest nietrwały i łatwo się rozkłada uwalniając wolny brom.
    Duże dawki soli bromu mogą wywołać groźny zespół toksyczny – bromizm (bromismus). Efekt ten może wystąpić także przy długotrwałym zażywaniu soli bromu na skutek tendencji tych związków do kumulowania się w organizmie. Powolność wydalania bromków z ustroju tłumaczy się tym, że nerki jednakowo reagują zarówno na bromki, jak i na chlorki, bromki nie są więc wydalane szybciej, choć są związkami obcymi dla organizmu. Na zatrzymanie się bromków w organizmie wpływać może także ubogie w sól pożywienie – organizm pokrywa wówczas zapotrzebowanie na jony chlorkowe – jonami bromkowymi. Roztwory chlorku sodowego są więc jednym z antidotów w zatruciu bromkami. Najbardziej charakterystyczne objawy bromizmu to zaburzenia neurologiczne i psychiczne (w ciężkich przypadkach nawet śpiączka) oraz wysypka skórna przypominająca trądzik (tzw. acne bromata). Zmiany skórne wywołane są przez fakt, iż związki bromu wydalane są z potem, powodując przy tym podrażnienie i stany zapalne powłok ciała. Oprócz zatruć przewlekłych zdarzają się także zatrucia ostre, choć znacznie rzadziej. Mogą się one zakończyć zgonem  - zwykle wśród objawów narkozy i zapalenia płuc. Zapalenie płuc jest efektem hamowania odruchów wykrztuśnych pochodzących ze śluzówki gardła i nagromadzenia śluzu oraz - tak jak w przypadku zmian skórnych - silnie drażniącym wpływem na komórki powlekające; w tym przypadku - śluzówkę dróg oddechowych.
    Sole bromu mają niezbyt przyjemny smak, który zazwyczaj maskuje w leku recepturowym dodatek syropu. Można zatem uznać, że dodatek np. Neospasminy działa zarówno jako adiuvans, jak i jako corrigens.
 
 
Bromek sodu (natrium sedativum) –  słony
Bromek potasu (kalium sedativum) –  gorzki
Bromek amonu  (ammonium sedativum) – cierpki
 
 
   W praktyce aptecznej często spotyka się na receptach nazwy gotowych mieszanek soli bromu o określonym składzie:
 
 
Sal Erlenmeyeri:
bromek sodowy : bromek potasowy : bromek amonowy w proporcjach  2:2:1
Mixtura Nervinae:
bromek sodowy : bromek potasowy : bromek amonowy w proporcjach 1:2:1
 
 
   Istnieją doniesienie o obniżeniu poziomu libido przy długotrwałym stosowaniu bromków. Efekt ten miałby być skutkiem zmniejszenia wytwarzania testosteronu. Niektóre publikacje podważają wiarygodność takiego działania soli bromu.
    Ze związków nieorganicznych bromu warto wymienić także bromek wapniowy, obecnie spotykany rzadko. Obecny może być np. w recepcie pediatrycznej skomponowanej z myślą o podawaniu m.in. w spazmofilii (tężyczce) dziecięcej, w przebiegu której występuje niski poziom wapnia zjonizowanego we krwi, z równoczesnym nasileniem pobudliwości nerwowo-mięśniowej.
    Farmakopea Polska VI nie określa maksymalnych dawek jednorazowych dla bromków. Ustala jedynie maksymalne dawki dobowe – wynoszące odpowiednio 1,0 g dla bromku sodu i potasu oraz 0,5 g dla bromku amonu.

BARBITURANY

   W większości mieszanek uspokajających głównym składnikiem sedatywnym jest fenobarbital (syn. Luminal, Gardenal). Fenobarbital należy do grupy barbituranów. Ta grupa leków przeciwlękowych i nasennych uważana jest obecnie za niszową, a wypierają bezpieczniejsze benzodiazepiny.
   Największe zastosowanie znajduje w tej chwili luminal, z którym zapewne większość farmaceutów ma do czynienia nie tylko pod postacią surowca do receptury, ale także pod postacią tabletek w dawce 15 i 100 mg, czopków – 15 mg oraz preparatów złożonych – tabletek Bellergot i kropli Milocardin.

   Na niekorzystny profil działania barbituranów działają:
   - niski indeks terapeutyczny
   Podane w dużych dawkach powodują śmierć wskutek zahamowania oddychania i krążenia. Barbiturany, podobnie jak beznodiazepiny nasilają działanie GABA (neuroprzekaźnika hamującego), ale wiążą się z innym miejscem w kompleksie receptora, a ich działanie jest mniej specyficzne.
   - wywoływanie tolerancji i uzależnienia
   Już kilkutygodniowe stosowanie może być przyczyną wystąpienia objawów abstynencji po zaprzestaniu kuracji. Jednocześnie nagłe odstawienie barbituranów nie jest wskazane.
   - często powodują interakcje z innymi lekami  z powodu wpływu na enzymy mikrosomalne
   Są silnymi induktorami enzymatycznymi, zmniejszającymi efekt działania niektórych leków. Po odstawieniu barbituranu enzymy wątrobowe działają zatem jakby wolniej, pozbawione indukcyjnego wpływu barbituranu, co sprawia, że metabolizowane przez nie leki mogą wywierać silniejszy efekt.

   Barbiturany wywierają także inne, niekiedy specyficzne działania niepożądane. Osłabiają one wchłanianie wapnia i skracają biologiczny okres półtrwania witaminy D3, co pogarsza uwapnienie kości. U predestynowanych do tego osób mogą także wywołać napad porfirii. Barbiturany przechodzą przez łożysko i przenikają do mleka matki. Fenobarbital działa nasennie długo (8-10 godzin), utrzymując się w organizmie, co po przebudzeniu może być przyczyną bólów głowy, senności i złego samopoczucia.
   Pomimo szeregu wad, barbiturany, a właściwie głównie jeden - fenobarbital ciągle znajdują zastosowanie w medycynie - w anestezjologii (przede wszystkim w premedykacji) i w leczeniu padaczki. Ale nie tylko. Rzadko wspominane, ale ciekawe właściwości barbituranów (przede wszystkim właśnie fenobarbitalu) to:
 - Obwodowe zmniejszenie napięcia mięśni gładkich i łagodzenie skurczów w obrębie przewodu pokarmowego. Działanie przeciwskurczowe ujawnia się już przy 1/10 dawki nasennej. Działanie to wykorzystuje się pomocniczo w napadach kolek, także w pediatrii.
- Zmniejszenie zużycia tlenu przez mózg, co może przyczynić się do zmniejszenia obrzęku mózgu po zabiegach chirurgicznych i chronić przed zawałem mózgu w wyniku niedokrwienia.
- Pobudzenie estryfikacji bilirubiny, co wykorzystuje się w hiperbilirubinemii Gilberta i w leczeniu żółtaczki jąder podstawy mózgu (kernicterus) u noworodków.
- Łagodne obniżenie ciśnienia tętniczego i zmniejszenie częstości rytmu serca na skutek upośledzenia przewodnictwa nerwowego w zwojach. Efekt ten jest wyraźniejszy u osób z nadciśnieniem.
- Hamowanie wytwarzania hormonu tyreotropowego - dzisiaj uważane raczej za efekt niepożądany - znajdowało zastosowanie w leczeniu tyreotoksykoz.

PODSUMOWANIE

   Nawiązując do przepisu recepturowego podanego we wstępie, w szczególności po analizie właściwości użytych składników dobrze byłoby przemyśleć, jakie informacje powinni od farmaceuty uzyskać pacjenci stosujący tego typu mieszanki. Przede wszystkim chorzy nie powinni traktować tych mikstur jako „trochę mocniejszych kropli nasercowych”, czy jako „ziółek”. Zdarza się „rodzinne” zażywanie tych preparatów, czy też udostępnianie leku osobom całkiem postronnym. W obliczu różnorakich interakcji, jakie mogą powodować ich składniki jest to potencjalnie niebezpieczne. Z pewnością należy także wspomnieć o tym, że ich łączenie z innymi preparatami o podobnym działaniu jest niewłaściwe.  

mgr farm. Olga Sierpniowska

 

 
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