Načini djelovanja anestetika

master's thesis

• Title (english): Mechanisms of action of anesthetics
• Author: Marcela Kovačević
• Mentor: Mladen Perić (mentor)
• Committee member: Ante Sekulić (predsjednik povjerenstva)
• Committee member: DINKO TONKOVIĆ (član povjerenstva)
• Committee member: Mladen Perić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Anaesthesiology, Resuscitation and Intensive Care in Surgical Specialities); Zagreb
• Defense date and country: 2015-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Anesthesiology and Reanimatology

Abstract

Cilj ovog rada je da opiše načine djelovanja anestetika, lokalnih i općih, sa naglaskom na molekularne mehanizme, ali osvrćući se i na farmakokinetiku kao bitan čimbenik koji utječe na njihov učinak. Pri pisanju rada pregledani su razni članci novijeg datuma i knjige kao pomoćna literatura s ciljem objedinjenja spoznaja sa različitih gledišta o djelovanju anestetika. Pokazano je da lokalni anestetici privremeno blokiraju provodljivost perifernog živca djelujući prvenstveno na Na+-kanale ovisne o naponu. Međutim učinak lokalnih anestetika je ovisan o brojnim farmakokinetskim i fizikalnim čimbenicima poput liposolubilnosti, pH otopine anestetika, ali i okolnog tkiva, pKa lijeka, protoku krvi, te svojstvima živca na kojeg se djeluje kao i sposobnosti anestetika da penetrira kroz membrane. Mehanizam općih anestetika je dugo bio temeljen na pretpostavci nespecifičnog djelovanja na lipidne membrane, međutim novija istraživanja potvrđuju da opći anestetici zapravo djeluju specifično na membranske proteine. Kao glavni cilj njihova djelovanja je GABAA-receptor kloridni kanal, ali ostvaruju učinak i djelovanjem na brojne druge kanale, kako inhibicijske tako i ekscitacijske. Stavljen je i naglasak na razliku u distribuciji učinka na različite regije središnjeg živčanog sustava što se ogleda u specifičnim značajkama opće anestezije koje mogu biti izražene u većoj ili manjoj mjeri. Dok su mehanizmi lokalnih anestetika prilično razjašnjeni, mehanizmi općih anestetika i dalje ostaju nejasni i predmet su brojnih istraživanja rezultati kojih će doprinijeti ne samo svrsi anesteziologije nego i općenito boljem razumijevanju aktivnosti moždanih regija.

Abstract (english)

The aim of this thesis is to explain the mechanisms of action of anesthetics, local and general, focusing on molecular mechanisms, but also describing pharmacokinetics, as an important factor which influences their effect. Many recent articles and books as complementary literature, were assessed with the goal of uniting knowledge from different points of view. It has been shown that anesthetics temporarily block conduction of peripheral nerve, acting predominantly on a sodium voltage-gated channels. However, the effect of local anesthetics is dependent on numerous pharmacokinetic and physical factors like liposolubility, pH of the solution and the surrounding tissue as well, pKa of the drug, blood flow, characteristics of the nerve and the ability of the anesthetic to penetrate the membranes. The mechanism of general anesthetics has been based for a long time on the assumption of nonspecific mechanism of action on lipid membranes, however newer researches have shown that general anesthetics are in fact acting specifically on membrane proteins. Their prime molecular target is GABAA-receptor chloride channel, but they are affecting other channels as well, inhibitory and excitatory likewise. The difference in the distribution of the effect on different regions of the central nervous system has been also highlighted since it reflects specific elements of general anesthesia more or less expressed during the procedure. While the mechanisms of local anesthetics have been well understood, mechanisms of general anesthetics are remaining unclear and are a subject of numerous studies which will contribute not only to the purpose of anesthesiology but also to better understanding of activity of brain regions.

• Keywords: anestetik; mehanizam; Na+-kanal; GABAA; živčani impuls
• Keywords (english): anesthetic; mechanism; Na+-channel; GABAA; nerve impulse
• Language: croatian
• URN:NBN: urn:nbn:hr:105:369077
• 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: 2016-04-12 12:34:55