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master's thesis
Izoniazid - metabolizam, toksičnost i interakcije
diplomski rad
2016. urn:nbn:hr:167:196695
Međeši, Damir
University of Split
Faculty of Chemistry and Technology
Division of Chemistry
University of Split
School of Medicine

Cite this document

Međeši, D. (2016). Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad (Master's thesis). Split: University of Split, Faculty of Chemistry and Technology; Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:167:196695

Međeši, Damir. "Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad." Master's thesis, University of Split, Faculty of Chemistry and Technology; University of Split, School of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:167:196695

Međeši, Damir. "Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad." Master's thesis, University of Split, Faculty of Chemistry and Technology; University of Split, School of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:167:196695

Međeši, D. (2016). 'Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad', Master's thesis, University of Split, Faculty of Chemistry and Technology; University of Split, School of Medicine, accessed 17 November 2024, https://urn.nsk.hr/urn:nbn:hr:167:196695

Međeši D. Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad [Master's thesis]. Split: University of Split, Faculty of Chemistry and Technology; Split: University of Split, School of Medicine; 2016 [cited 2024 November 17] Available at: https://urn.nsk.hr/urn:nbn:hr:167:196695

D. Međeši, "Izoniazid - metabolizam, toksičnost i interakcije : diplomski rad", Master's thesis, University of Split, Faculty of Chemistry and Technology, Split; University of Split, School of Medicine, Split, 2016. Available at: https://urn.nsk.hr/urn:nbn:hr:167:196695

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Metadata
TitleIzoniazid - metabolizam, toksičnost i interakcije : diplomski rad
Title (english)Isoniazid – metabolism, toxicity and interactions : master's thesis
AuthorDamir Međeši
MentorMarica Medić-Šarić (mentor)
Committee memberDavorka Sutlović (predsjednik povjerenstva)
Committee memberIvana Mudnić (član povjerenstva)
Committee memberMarica Medić-Šarić (član povjerenstva)
GranterUniversity of Split
Faculty of Chemistry and Technology
(Division of Chemistry)
Split
GranterUniversity of Split
School of Medicine
Split
Defense date and country2016-10-17, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Abstract
Cilj istraživanja je najvažniji tuberkulostatik prvog reda, izoniazd (INH). Kao lijek koji je neophodan u liječenju tuberkuloze vrlo je važno proučiti putove njegovog metabolizma i toksičnosti te moguće interakcije u koje stupa s drugim lijekovima. S obzirom na strukturu INH, biotransformacija se odvija reakcijama I. i II. faze metabolizma pod utjecajem karakterističnih enzima. Međutim, prema dokazanim metabolitima veću važnost imaju reakcije II. faze. Biotransformacija se odvija reakcijama acetilacije, a nastali metaboliti podliježu reakcijama hidrolize te konjugacije s glicinom što predstavlja reakciju detoksikacije. Za toksičnost INH odgovorne su reakcije oksidacije nastalih metabolita. Metabolizam INH započinje reakcijom acetilacije pod utjecajem enzima NAT pri čemu nastaje N-acetilizoniazid koji se djelovanjem enzima CES hidrolizira u acetilhidrazin i izonikotinsku kiselinu. Oksidacijom acetilhidrazina nastaju reaktivni intermedijeri koji povećavaju rizik hepatotoksičnosti. Acetilhidrazin se acetilacijom može prevesti u diacetilhidrazin što predstavlja reakciju detoksikacije. Izonikotinska kiselina ulazi u reakcije konjugacije s glicinom te se izlučuje u obliku netoksične izonikotinurne kiseline. Toksični učinci INH povezuju se s genetskim polimorfizmom enzima NAT2. I brzi i spori acetilatori imaju povećani rizik od toksičnosti. INH ima antivitaminsko B 6 djelovanje čime onemogućava iskorištenje piridoksina pa može doći do perifernog neuritisa. U liječenju tuberkuloze (TBC) nužna je politerapija što povećava mogućnost nastanka neželjenih interakcija. TBC je bila i ostala jedna od najzaraznijih bolesti čovječanstva, bez obzira na znanstveni i tehnološki napredak u prevenciji i liječenju. Očekuju se otkrića učinkovitijih antituberkulotika s kraćim režimom terapije, novim mehanizmom djelovanja i boljom farmakokinetikom.
Abstract (english)
Diploma Thesis objective is one of the most important first line tuberculostatic drug, isoniazid. As a drug which is necessary in the treatment of tuberculosis, it is very important to study the pathways of its metabolism, toxicity and drug interactions. Considering the structure of INH, biotransformation occurs phase I and II metabolism reactions, under the influence of characteristic enzymes. However, according to proven metabolites more important are the phase II metabolism reactions. Biotransformation occurs reactions of acetylation, hydrolysis and conjugation with glycine that is a reaction of detoxification. Oxidation reactions are responsible for INH toxicity. INH metabolism begins with the reaction of acetylation by enzyme NAT to provide a N-acetylisoniazid which is hydrolyzed by enzymes CES and appears acetylhydrazine and isonicotinic acid. Oxidation of acetyhydrazine produces reactive intermediates that increase the risk of hepatotoxicity. Acetylation of acetylhydrazine produces diacetylhydrazine which is a detoxification reaction. Glycine conjugate of nicotinic acid is nicotinuric acid which is not toxic. Toxic effects of INH are associated with genetic polymorphism of enzyme NAT2. Both fast and slow acetylators, are at increased risk of toxicity. INH has the effect of anti-B 6 which prevents the utilization of pyridoxine and may cause peripheral neuritis. In the treatment of TBC, polytherapy is necessary which increases the possibility of adverse drug interactions. TBC was and still is one of the most spreaded diseases of mankind, regardless of the scientific and technological advances in prevention and treatment. It is expected that the future will bring more effective anti-tuberculosis drugs which will decrease treatment length, with new mechanism of action and improved pharmacokinetics.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:167:196695
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2016-11-22 10:44:47