Farmaci nell’ambiente. Implicazioni e prospettive

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I farmaci, e fra questi gli antibiotici in particolare, rappresentano uno strumento molto utile per curare e prevenire malattie animali e umane. Tuttavia, in seguito alla somministrazione del medicinale, una sua frazione significativa può non essere trattenuta dalla massa corporea (1). In aggiunta, recenti indagini riportano che nella routine quotidiana molte persone non recuperano correttamente i farmaci scaduti o non più utilizzati, ma tendono a svuotarne il contenuto in lavandini o sanitari (2). Tutto questo, insieme a: (i) impianti di trattamento delle acque reflue non sempre idonei allo smaltimento dei farmaci, (ii) diretta contaminazione dei suoli da parte degli animali al pascolo e (iii) comuni pratiche agricole che comportano l’applicazione sui terreni coltivati di liquami come fertilizzanti, determina l’ingresso di vari medicinali negli ecosistemi naturali (3).

La presenza di prodotti farmaceutici in acque di superficie/falda e terreni agrari è stata frequentemente osservata, causando grande preoccupazione nella comunità scientifica in merito alle possibili conseguenze sia sulla stabilità degli ecosistemi che sulla salute umana. Infatti, per le loro caratteristiche chimico-fisiche, numerose molecole sono difficilmente degradabili e possono persiste nell’ambiente fino a diversi mesi.

Per quanto riguarda lo scenario italiano, Zuccato et al. (4) hanno recentemente rilevato la presenza di alcuni fra i farmaci antibiotici più utilizzati, come penicilline e sulfamidici, in vari fiumi dell’Italia del nord, dimostrandone un’insufficiente rimozione da parte dei correnti impianti di depurazione acque. Inoltre, tali analisi hanno permesso di stimare che fino a un 10-20% di questi principi attivi sono stati scaricati nell’ambiente in seguito al loro utilizzo.

Come risultato, trattandosi di composti biologicamente attivi anche se presenti in quantità molto basse, l’azione di tali farmaci può ripercuotersi su organismi non bersaglio determinando alterazioni ingenti nella biosfera (5).

Solitamente, i danni più visibili sono stati osservati a livello di microorganismi come batteri ed enzimi. Infatti, modifiche delle comunità dei microorganismi del suolo, fondamentali per i cicli dei nutrienti e per la corretta decomposizione della sostanza organica, sono state più volte ipotizzate e collegate alla presenza di residui farmaceutici nell’ambiente (6).

Tuttavia, due articoli pubblicati recentemente su Nature hanno evidenziato ripercussioni nocive, e in qualche caso anche letali, in seguito all’esposizione indiretta a farmaci perfino in organismi vertebrati. Il primo studio ha riportato una moria di avvoltoi nel subcontinente indiano a causa della loro dieta strettamente legata al consumo di carcasse di animali in precedenza trattati con l’antinfiammatorio diclorofenac (7). In aggiunta, dal secondo studio emerge che residui di pillole contraccettive, comunemente utilizzate dalle donne, possono raggiungere le acque reflue e, in un secondo momento, fiumi, estuari e laghi, tramite le urine, originando in questo modo vari casi di femminilizzazione di pesci di sesso maschile ivi presenti (8).

Eppure, la conseguenza forse più preoccupante relativa alla presenza di farmaci come antibiotici nell’ambiente riguarda il possibile sviluppo di patogeni resistenti al principio attivo. Ad esempio, è stato visto che basse concentrazioni di antibiotici sulfamidici, dopo appena un mese dal loro ingresso in un suolo agrario, hanno causato una sostanziale alterazione della struttura di alcune comunità di importanti generi batterici, come Pseudomonas (9), lasciando così ipotizzare la formazione di qualche specie resistente. In più, considerando che queste alterazioni possono avvenire in prossimità di terreni coltivati con piante edibili, destinate quindi al consumo umano o animale, il rischio di esposizione ai patogeni aumenta. Come se non bastasse, vari esperti del settore hanno sottolineato che la presenza simultanea di più sostanze farmaceutiche negli ecosistemi è molto verosimile e quindi cocktails di farmaci potrebbero causare effetti maggiori rispetto a quelli determinati della singola sostanza (10).

Per aver un’idea dell’entità dei consumi annui di farmaci, basta pensare che nel 2007, in diverse nazioni europee, le vendite di antibiotici sono state di circa 3500 tonnellate di principio attivo nel settore veterinario e di altre 3350 per l’utilizzo umano (11). Tuttavia, considerando che farmaci a basso costo sono sempre più accessibili dalla popolazione mondiale, destinata a superare gli 8 miliardi nel 2050 con incremento di persone anziane maggiormente beneficiarie di cure terapeutiche, queste cifre potrebbero risultare addirittura sottostimate (12).

Come sta reagendo la comunità scientifica di fronte ad uno scenario di questo genere,? Un segnale di consapevolezza arriva dall’Agenzia Europea dell’Ambiente (European Environment Agency), che di recente ha suggerito alcune linee guida da adottare per limitare l’ingresso di medicinali di origine antropica nell’ambiente. Tra queste, nonostante le forti implicazioni di carattere economico, la raccomandazione favorita riguarda senz’altro l’implementazione dei sistemi di trattamento delle acque reflue con carboni attivi, reazioni di ossidazione o lampade UV (2).

Un secondo approccio si orienta verso il settore della farmacia “verde”, dove finora sono stati fatti molti progressi, come ad esempio l’uso di solventi meno nocivi, nuove vie di sintesi e farmaci più degradabili dopo l’uso. A tal proposito, un recente studio ha suggerito l’applicazione di tasse e incentivi per rendere questi rimedi “verdi” più appetibili alle aziende farmaceutiche rispetto a quelli convenzionali (10).

Inoltre, partendo dal presupposto che la consapevolezza dei rischi ecologici connessi ai farmaci potrebbe limitarne l’immissione nell’ambiente, la stessa Agenzia Europea dell’Ambiente incoraggia vivamente la formazione delle varie categorie legate al settore sanitario, come dottori, farmacisti, produttori di farmaci, ma anche pazienti, per favorire una gestione del farmaco più rispettosa dell’ambiente partendo in primo luogo dalle abitudini quotidiane.

Al riguardo, un buon esempio arriva dalla Svezia, dov’è tuttora in vigore un sistema volontario che ha lo scopo di informare il pubblico sul potenziale impatto ambientale legato ai farmaci, attraverso campagne informative su siti web e opuscoli informativi (10). In seguito a questa iniziativa la maggior parte dei medici sta prendendo provvedimenti per evitare il rilascio di prodotti farmaceutici in eccesso, ad esempio prescrivendo quantità di farmaci realmente legate alle necessità del paziente. Inoltre, nel corso degli ultimi vent’anni, sono stati istituiti vari programmi di smaltimento di residui farmaceutici su scala globale. Ad esempio, in Portogallo quasi tutte le farmacie del paese fanno parte di una rete di smaltimento dei medicinali, chiamata Valormed (http://www.valormed.pt/), creata nel 2001 da farmacisti, aziende farmaceutiche e associazioni di fornitori (13).

Infine, considerando le attuali prassi agronomiche come altra importante fonte d’ingresso negli ecosistemi naturali di antibiotici, e in alcuni paesi, anche di ormoni della crescita, numerosi ricercatori di rilevanza internazionale sostengono che tempi di applicazione dei reflui zootecnici più ragionevoli, uno sviluppo di adeguate raccomandazioni su quando e come non applicare i biosolidi (per esempio in caso di terreni troppo pendenti), nonché l’introduzione di zone alberate ai margini dei campi in grado di proteggere i corpi idrici, potrebbe aiutare a contenere una tale contaminazione (14).

Per concludere, è opportuno ricordare che allo stato attuale la comunità scientifica continua a sottolineare l’importanza della ricerca scientifica nello studio delle conseguenze indotte dai farmaci sia sulla biodiversità degli ecosistemi naturali che sulle possibili implicazioni a livello di salute umana.

Bibliografia

1) Sarmah AK, Meyer MT, Boxall ABA (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65:725-759

2) EEA (2010) Pharmaceuticals in the environment. Results of an EEA workshop. EEA Technical report No 1/2010

3) Jorgensen SE, Halling-Sorensen B (2000) Drugs in the environment. Chemosphere 40:691-699

4) Zuccato E, Castiglioni S, Bagnati R, Melis M, Fanelli R (2010) Source, occurrence and fate of antibiotics in the Italian aquatic environment. J Hazard Mater 179:1042-1048

5) Henschel KP, Wenzel A, Diedrich M, Fliedner A (1997) Environmental hazard assessment of pharmaceuticals. Regul Toxicol Pharm 25:220-225

6) Thiele-Bruhn S, Bloem J, de Vries FT, Kalbitz K, Wagg C (2012) Linking soil biodiversity and agricultural soil management. Curr Opin Env Sust 4:1-6

Westergaard K, Müller A, Christensen S, Bloem J, Sørensen S (2001) Effects of tylosin as a disturbance on the soil microbial community. Soil Biol Biochem 33:2061-2071

7) Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU (2004) Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 427, 630-633

8) Owen R, Jobling S (2012) The hidden costs of flexible fertility. Nature 485, 441

9) Michelini L, Reichel R, Ghisi R, Thiele-Bruhn S (2012) Willow and maize root associated soil microbial community composition and enzyme activities in the presence of the antibiotic sulfadiazine. AECT- under review

10) Boxall ABA (2012) New and emerging water pollutants arising from agriculture, OECD Publishing 1-48

11) ECDC – European Centre for Disease Prevention and Control; European Food Safety Authority (EFSA), European Medicines Agency (EMEA); European Commission’s Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) (2009) Joint Opinion on antimicrobial resistance (AMR) focused on zoonotic infections. EFSA J 7:1372

12) Depledge M (2011) Pharmaceuticals: Reduce drug waste in the environment. Nature 478, 36

13) Kümmerer K (2008) Pharmaceuticals in the environment. Sources, fate, effects and risks. Third edition. Springer ed., Berlin 1-521

14) Pope L, Boxall A, Corsing C, Halling-Sorensen B, Tait A, Topp E (2009) Exposure assessment of veterinary medicines in terrestrial systems. In Crane M, Boxall ABA, Barrett K (Eds) Veterinary medicines in the environment. CRC Press, Boca Raton129-153

Lucia Michelini è laureata in Scienze e Tecnologie per l’Ambiente e il Territorio. Attualmente sta completando i suoi studi nella scuola di dottorato in Territorio, Ambiente, Risorse e Salute dell’Università di Padova.

Immagine tratta da: Depledge M., Nature, 2011

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