Farmakokinetičke interakcije u podlozi nuspojava lijekova

professional thesis

• Title (english): Pharmacokinetic interactions behind the adverse drug reactions
• Author: Katarina Vučić
• Mentor: Viola Macolić-Šarinić (mentor)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2015-02-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Farmakokinetičke interakcije očituju se neželjeno smanjenim ili pojačanim učinkom lijeka od njegovog očekivanog djelovanja, zbog promjene njegove koncentracije u krvi uslijed istodobne primjene s jednim ili više drugih lijekova. Posljedično tome, nuspojave nastale zbog farmakokinetičkih interakcija karakterizirane su pojačanim ili smanjenim farmakološkim učinkom lijeka. U procjeni mogućeg uzroka nuspojave pri kliničkoj primjeni nekog lijeka kod pacijenta uvijek je potrebno uzeti u obzir komedikaciju, komorbiditet, te individualnu genetsku različitost u aktivnosti enzima i transportera, koji sudjeluju u eliminaciji i izlučivanju „aktivnog“ oblika lijeka i njegovih metabolita iz organizma. Stoga je procjena uzroka nuspojave pri kliničkoj primjeni nekog lijeka vrlo kompleksna. Zbog starenja populacije i polipragmazije interakcije lijekova su česte, a mogu dovesti i do teških ili ozbiljnih nuspojava, te biti i uzrok hospitalizacija. Većina se farmakokinetičkih (FK) interakcija može predvidjeti i spriječiti, najčešće prilagodbom doziranja, odnosno smanjenjem ili povećanjem doze određenog lijeka u kliničkoj primjeni, zatim izbjegavanjem ili čak kontraindiciranošću istodobne primjene dva specifična lijeka koji mogu stupiti u značajnu interakciju, te mjerama opreza pri primjeni lijekova s uskom terapijskom širinom/“kritičnom dozom“. Cilj ovog preglednog rada je prikazati podatke o prijavama nuspojava na lijekove u 2013.g. u Republici Hrvatskoj, s osvrtom na lijekove s uskom terapijskom širinom, te prikazati pregled mehanizama nastanka FK interakcija lijekova i naglasiti predvidivost i mogućnost izbjegavanja pojedinih FK interakcija i nastanka posljedičnih nuspojava, što povećava sigurnost primjene lijeka.

Abstract (english)

Pharmacokinetic interactions are manifested by undesirably reduced, or increased action of the drug from the expected effects, occurring due to changes in its blood concentration when co-administered with one or more other drugs. Consequently, adverse reactions due to pharmacokinetic interactions are characterized by increased or reduced pharmacological effect of the drug. In assessing the probable cause of side effects in clinical use of a drug, the patient's comedication, comorbidity, and individual genetic diversity in the activities of enzymes and transporters involved in the elimination and excretion of "active" form of the drug and its metabolites from the body have to be taken into account. Therefore, the assessment of causes of adverse reactions in clinical use of a drug is very complex. Due to the population aging and polypharmacy, drug interactions are common and can lead to severe or serious adverse events, and be the cause of hospitalization. Most of the pharmacokinetic (PK) interactions can be predicted and prevented, usually by adjusting the dosage or by reducing or increasing the dose of a particular drug in clinical use, and avoiding or even contraindicating co-administration of two specific drugs that can enter into a significant interaction. Additionally, special precaution is needed when administering the narrow therapeutic/critical dose drugs. The aim of this paper is to present reported adverse effects in year 2013. in Croatia and to provide an overview of the mechanisms of PK drug interactions and emphasize the predictability and the possibility of avoiding certain PK interaction and consequent occurrence of side effects in order to increases the safety of clinical drug administration, highlighting the narrow therapeutic index drugs.

• Keywords: farmakokinetičke interakcije; lijekovi; nuspojave; CYP enzimi; transportni proteini; izlučivanje; lijekovi s uskom terspijskom širinom; lijekovi kritične doze; politerapija
• Keywords (english): pharmacokinetic interactions; comedication; adverse drug reactions; CYP enzymes; transport proteins; secretion; narrow therapeutic index drugs; critical dose; polytherapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:816988
• Study programme: Title: Clinical pharmacology and toxicology; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni/a magistar/magistra kliničke farmakologije s toksikologijom (sveučilišni/a magistar/magistra kliničke farmakologije s toksikologijom)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-08-13 08:51:26