Antidotes allow the improvement of prognosis, with both specific or non-specific mechanism of action, and they can play a critical role in the management of poisoned patients. The nature and the characteristics of these molecules are often different and their mechanisms of action are able to interact with can involve pharmacodynamics and/or pharmacokinetic of the poison. Antidotes play also a critical role in the contest of a multi-drugs treatment. Many antidotes can be considered life-saving drugs due to their capability to improve and/or strongly modify the prognosis of severe intoxications. Furthermore, antidotes can be used to counteract mass poisoning events, both conventional (eg. chemicals accidents in industry) and unconventional. Referring to unconventional events, antidotes for radio-nuclear agents should be considered with particular attention. To counteract the lack of antidotes in the health care facilities, an extraordinary antidotes stockpile is instituted by the Italian Government. Some antidotes are used in the clinical practice with different therapeutic indications and dosages, while other molecules are rarely used and poorly known by physicians. Some antidotes are manufactured only abroad and so the Italian leaflet is not provided. Beside the availability of the drug, the knowledge of information about the correct antidote’s use is crucial for the efficacy and safety of treatment, especially in case of large emergencies. The experimental work for this Thesis was performed at Pavia Poison Control Centre (PCC), IRCCS Maugeri Foundation. The aim of this study was to prepare an easily accessible manual containing the information on the antidotes used in the large emergencies. Fifteen antidotes were evaluated and six of which can be used especially during radiological emergencies. Amyl nitrite, atropine, Ca-DTPA, DMPS, DMSA, hydroxocobalamin, methylene blue, N-acetylcysteine, naloxone, PEG 400, physostigmine, potassium iodide, pralidoxime, prussian blue and sodium thiosulfate were the antidotes considered in this study. Scientific literature and commercial information were reviewed for each molecule in order to prepare complete, although synthetic antidotes files. Each file includes 20 fields containing information about the antidote (eg. pharmacology, clinical use, practical aspects such as mode of supply and conservation, approximate cost). The results of this Thesis will allow quick access to essential information about each molecule. These files could be helpful for both the pharmacist, who is responsible for antidotes supply and storage, and the healthcare professional, physician or nurse, who may be involved in the management of a large chemical or radiological emergency.
Il trattamento antidotico è un intervento specifico di cui il medico si può avvalere nella gestione in urgenza del paziente intossicato. Dal punto di vista clinico-tossicologico, gli antidoti sono molecole che, con meccanismo specifico o aspecifico, consentono il miglioramento delle prognosi quoad vitam o quoad functionem dell’intossicazione. Sono molecole di diversa natura che agiscono con meccanismi diversi intervenendo sulla cinetica o sulla dinamica del tossico. Spesso hanno un ruolo determinante, anche nel contesto di un trattamento plurifarmacologico. Numerosi antidoti sono considerati “salvavita” in quanto costituiscono l’unica terapia in grado di modificare drasticamente il decorso clinico e la prognosi di gravi intossicazioni. Alcuni antidoti vengono utilizzati anche per fronteggiare grandi eventi come intossicazione di massa dovute a incidenti di natura convenzionale (es. incidenti chimici in ambito industriale) o non convenzionale. Tra questi, sono da comprendere quelli da utilizzare in caso di eventi di natura radio-nucleare. Di fronte all’evidente insufficiente disponibilità nei servizi d’urgenza del Sistema sanitario Nazionale, per alcuni di questi antidoti, lo Stato Italiano ha istituito una dotazione straordinaria. Alcuni antidoti sono molecole utilizzate anche nella pratica clinica comune con indicazioni e posologie differenti, altri sono molecole di raro utilizzo e spesso poco note ai clinici. Alcuni sono prodotti solo all’estero e non dotati di fogli illustrativi in italiano. Oltre alla disponibilità del farmaco, la conoscenza delle informazioni necessarie per il corretto utilizzo è cruciale per l’efficacia e la sicurezza del trattamento, soprattutto in caso di grandi emergenze. Questo lavoro di Tesi è stato svolto presso il Centro Antiveleni (CAV) della Fondazione Salvatore Maugeri di Pavia, con lo scopo di redigere un manuale facilmente fruibile, contenente le informazioni necessarie sugli antidoti utilizzabili nelle grandi emergenze. Sono stati individuati 15 antidoti, tra cui 6 antidoti utilizzati solo o anche per eventi di natura radiologica. Le molecole oggetto della Tesi sono: amile nitrito, atropina, blu di metilene, blu di prussia, Ca-DTPA, DMSA, DMPS, fisostigmina, idrossocobalamina, ioduro di potassio, N-acetilcisteina, naloxone, PEG 400, pralidossima, sodio tiosolfato. Per ognuno di questi sono state revisionate la letteratura scientifica e le informazioni commerciali disponibili allo scopo di redigere una scheda completa, ma sintetica, su ogni singola molecola. La scheda contiene 20 campi, con informazioni relative non solo alla farmacologia e all’utilizzo clinico, ma anche agli aspetti pratici quali le modalità di approvvigionamento e di conservazione, nonché il costo indicativo. Il risultato di questa Tesi può consentire, per ogni molecola, un rapido accesso alle informazioni essenziali sia al farmacista cui compete la gestione dell’approvvigionamento e dello stoccaggio, sia all’operatore sanitario, medico o infermiere, che potrebbe trovarsi coinvolto nella gestione sanitaria di una grande emergenza chimica o radio-nucleare.
Antidoti per le emergenze chimiche e radio-nucleari
BOSSO, GIULIA
2014/2015
Abstract
Antidotes allow the improvement of prognosis, with both specific or non-specific mechanism of action, and they can play a critical role in the management of poisoned patients. The nature and the characteristics of these molecules are often different and their mechanisms of action are able to interact with can involve pharmacodynamics and/or pharmacokinetic of the poison. Antidotes play also a critical role in the contest of a multi-drugs treatment. Many antidotes can be considered life-saving drugs due to their capability to improve and/or strongly modify the prognosis of severe intoxications. Furthermore, antidotes can be used to counteract mass poisoning events, both conventional (eg. chemicals accidents in industry) and unconventional. Referring to unconventional events, antidotes for radio-nuclear agents should be considered with particular attention. To counteract the lack of antidotes in the health care facilities, an extraordinary antidotes stockpile is instituted by the Italian Government. Some antidotes are used in the clinical practice with different therapeutic indications and dosages, while other molecules are rarely used and poorly known by physicians. Some antidotes are manufactured only abroad and so the Italian leaflet is not provided. Beside the availability of the drug, the knowledge of information about the correct antidote’s use is crucial for the efficacy and safety of treatment, especially in case of large emergencies. The experimental work for this Thesis was performed at Pavia Poison Control Centre (PCC), IRCCS Maugeri Foundation. The aim of this study was to prepare an easily accessible manual containing the information on the antidotes used in the large emergencies. Fifteen antidotes were evaluated and six of which can be used especially during radiological emergencies. Amyl nitrite, atropine, Ca-DTPA, DMPS, DMSA, hydroxocobalamin, methylene blue, N-acetylcysteine, naloxone, PEG 400, physostigmine, potassium iodide, pralidoxime, prussian blue and sodium thiosulfate were the antidotes considered in this study. Scientific literature and commercial information were reviewed for each molecule in order to prepare complete, although synthetic antidotes files. Each file includes 20 fields containing information about the antidote (eg. pharmacology, clinical use, practical aspects such as mode of supply and conservation, approximate cost). The results of this Thesis will allow quick access to essential information about each molecule. These files could be helpful for both the pharmacist, who is responsible for antidotes supply and storage, and the healthcare professional, physician or nurse, who may be involved in the management of a large chemical or radiological emergency.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/25549