Patogenetski mehanizmi u podlozi rabdomiolize uzrokovane lijekovima

master's thesis

• Title (english): Pathogenetic mechanisms in drug-induced rhabdomyolysis
• Author: Ana-Maria Uranija
• Mentor: Natalija Dedić Plavetić (mentor)
• Committee member: Stjepko Pleština (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Natalija Dedić Plavetić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathophysiology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathophysiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology

Abstract

Rabdomioliza je po život opasno stanje karakterizirano bolovima u mišićima, slabošću, tamnim obojenjem urina i porastom kreatin kinaze u serumu. Nastaje kao posljedica ozljede mišića koja može biti direktna i indirektna. Među neke od brojnih uzroka
rabdomiolize spadaju traume, opekline, strujne ozljede, ishemijski i metabolički poremećaji, primjena ilegalnih supstanci te nekih lijekova. Tema ovog diplomskog rada je literaturni pregled lijekova uključenih u etiologiju rabdomiolize, te pridruženih patogenetskih mehanizama. Lijekovi koji su obrađeni u ovom radu su antiepileptici, antipsihotici, antihistaminici, statini, izonijazid, interferon i trabektedin. Budući da se rabdomioliza najčešće javlja kao posljedica primjene statina, patogenetski mehanizmi nastanka ovog stanja pri njihovoj primjeni su detaljnije ispitani. Statini dovode do smanjenja mitohondrijskog stvaranja
ATP-a, smanjuju sintezu molekula koje su bitne za stanični metabolizam, te uzrokuju nekrotizirajuću miopatiju posredovanu imunološkim sustavom. U skupini antiepileptika su lijekovi koji svoje učinke, ali i nuspojave, ostvaruju na različite načine. Valproična kiselina inhibira β-oksidaciju masnih kiselina, smanjuje razine karnitina u plazmi i mišićima, te vjerojatno djeluje na karnitin-palmitoil transferazu. Mehanizam nastanka rabdomiolize kao posljedica primjene levetiracetama, gabapentina, i fenitoina nije u potpunosti razjašnjen. Mehanizam nastanka rabdomiolize uzrokovane primjenom antipsihotika, antihistaminika i izonijazida nije razjašnjen ali postoje različite teorije kojima se opisuju mogući mehanizmi. Patogenetski mehanizmi kojima interferoni i trabektedin uzrokuju rabdomiolizu potpuno su nepoznati.

Abstract (english)

Rhabdomyolysis is a life-threatening condition characterized by muscular pain, weakness, dark colored urine, and increased creatine kinase serum levels. It occurs as a result of direct or indirect muscle injury. Rhabdomyolysis can be caused by traumas, burns, electric injuries, ischemic and metabolic disorders, the use of illegal substances and some drugs. This thesis describes drugs which are the most common causes of drug-induced rhabdomyolysis: antiepileptics, antipsychotics, antihistamines, statins, isoniazid, interferon, and trabectedin. Rhabdomyolysis is most often reported as a result of the statin use. That is why the pathogenetic mechanisms of rhabdomyolysis development are more in-depth investigated. Statin use can lead to a decrease in the mitochondrial formation of ATP, reduce the synthesis of molecules that are essential for cellular metabolism and lead to the immune-mediated necrotic myopathy. Various antiepileptics cause
rhabdomyolysis through different cellular pathways due to their different mechanisms of action. Valproic acid inhibits the β-oxidation of fatty acids, reduces the level of carnitine in plasma and muscle, and probably inhibits carnitine-palmitoyl transferase. Rhabdomyolysis induced by levetiracetam, gabapentin, and phenytoin occurs by poorly understood mechanisms. Pathogenesis of rhabdomyolysis caused by antipsychotics, antihistamines, and isoniazid is explained by various theories in literature. Mechanisms by which usage of interferons and trabectedin lead to this condition are completely unknown.

• Keywords: rabdomioliza; lijekovi; patogenetski mehanizmi
• Keywords (english): rhabdomyolysis; drugs; pathogenetic mechanisms
• Language: croatian
• URN:NBN: urn:nbn:hr:105:377725
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-12-20 13:10:52