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ANTAGONISMO FARMACOLOGICO

 

L'antagonismo tra farmaci può avvenire attraverso diversi meccanismi:

  1. ANTAGONISMO DI TIPO COMPETITIVO;
  2. Vintage Frye Soft Antique VintageCognac Soft Soft Zip Terri Antique Ankle VintageGrey Black Antique Bootie qqTROp;
  3. ANTAGONISMO DI TIPO FUNZIONALE;
  4. ANTAGONISMO FARMACOCINETICO O INDIRETTO.
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Madison Stacy Adams Adams Madison BlackBrown Stacy Boot Boot 1cX8nAfvxA1) L'ANTAGONISTA DI TIPO COMPETITIVO


L'antagonismo è detto di tipo competitivo perché l'antagonista compete per lo stesso recettore con la sostanza agonista. Entrambe le sostanze si possono legare allo stesso recettore ed è proprio per questo che si crea una sorta di competizione tra le due. Se in questa competizione prevale la funzione dell'antagonista, quest'ultimo impedirà la risposta biologica della cellula perché va ad occupare il recettore all'agonista.

 

Il legame dell'antagonista al recettore è un legame reversibile, che può essere rotto aumentando la sola quantità dell'agonista. Possiamo dire che in base alla concentrazione delle due sostanze prevarrà la sostanza maggiore. Nel grafico si è in presenza di tre sigmoidi. Ciascuna delle sigmoidi descrive l'effetto di una sostanza quando si lega ad un recettore. Si prende in esempio l'effetto dell'acetilcolina (Ach) su di un muscolo. Se si analizza la prima curva la contrazione, indotta dall'acetilcolina, raggiunge in poco tempo l'effetto massimo, perché la concentrazione dell'antagonista è pari a zero.
Nella seconda curva si ha una determinata concentrazione di antagonista. Questo antagonista si lega ad un certo numero di siti recettoriali sequestrandoli all'Ach. L'effetto dell'acetilcolina naturalmente sarà più basso perché molti siti recettoriali saranno occupati dall'antagonista. Per ottenere lo stesso effetto della curva 1, basta aumentare la dose dell'agonista che va a sormontare l'antagonista; in questo modo l'Ach si trova a sua disposizione tutti i recettori. Come si può notare, la curva 2, rispetto al curva 1, è spostata verso destra, però raggiunge sempre l'effetto massimo. Inoltre si può dire che l'acetilcolina è meno potente perché alcuni recettori sono occupati dall'antagonista.
Lo stesso discorso vale per la terza curva dove è stata aumentata ulteriormente la dose di antagonista. L'effetto massimo viene sempre raggiunto aumentando la dose di somministrazione di Ach.

Cosa possiamo dedurre dalla lettura di questo grafico? Possiamo dedurre che in presenza di una concentrazione variabile dell'antagonista la curva sigmoide dell'agonista si sposta sempre di più verso destra. L'agonista in presenza dell'antagonista diventa sempre meno potente, però l'effetto massimo viene raggiunto lo stesso con l'aumento della dose di agonista. Un'altra cose che cambia in questo grafico è il valore dell'EC50, che via a via che ci spostiamo verso destra diventa sempre più alto.

 

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Nel caso di antagonismo di tipo non competitivo le sostanze antagoniste si vanno sempre a legare al recettore, però il legame è di tipo covalente, quindi irreversibile. Ciò vuol dire che una volta che la sostanza si lega covalentemente al recettore non la si può più staccare dal sito di legame, nemmeno con l'aumento della sostanza agonista. Il farmaco che va a bloccare il recettore è dotato di ottima affinità con il recettore, ma non possiede attività intrinseca. Come si può notare dal grafico la sigmoide numero 1 rappresenta l'Ach senza antagonista, che come tale raggiunge l'effetto massimo perché tutti i siti di legame con i recettori sono liberi e non occupati dall'antagonista non competitivo.

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Le curve numero 2 e numero 3 rappresentano gli effetti dell'Acetilcolina con la presenza dell'antagonista non competitivo a diverse concentrazioni. Come detto in precedenza l'antagonista blocca irreversibilmente i recettori da esso occupati; perciò, anche aumentando la dose di acetilcolina, non è possibile raggiungere l'effetto massimo. Nel caso di antagonismo non competitivo l'acetilcolina diventa sempre meno efficace a differenza dell'antagonismo competitivo, dove bastava un aumento della dose dell'agonista per raggiungere il 100% dell'effetto.

 

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APPROFONDIMENTI E CURIOSITÀ

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