Reakcije preosjetljivosti na lijekove te mehanizmi nastanka, klinička slika i dijagnostički pristup

master's thesis

• Title (english): Drug hypersensitivity reactions : underlying mechanisms, clinical presentation and diagnostic approach
• Author: Robert Marčec
• Mentor: Robert Likić (mentor)
• Committee member: Iveta Merčep (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Robert Likić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Nuspojave lijekova predstavljaju značajan javnozdravstveni problem u modernoj medicini, a reakcije preosjetljivosti na lijekove relativno su česta nuspojava koju kategoriziramo kao nuspojava tipa B. Nastanak većine reakcija preosjetljivosti objašnjavao pomoću koncepta alergijsko imunološke stimulacije haptenom koja se temelji na općenitoj klasifikaciji reakcija preosjetljivosti koju su 1963. objavili autori Gell i Coombs. Tom klasifikacijom reakcije preosjetljivosti dijelimo na četiri tipa ovisno o imunološkom mehanizmu nastanka. Tip 1 reakcije posredovane su imunoglobulinima E te dovode do nastanka klasične kliničke slike alergijske reakcije. Tip 2 reakcije posredovane su imunoglobulinima M ili G usmjerenim protiv sastavnica vlastitih stanica ili izvanstanične matrice. Tip 3 reakcije su posredovane imunokompleksima koji svojim odlaganjem u tkiva dovode do upalne reakcije. Tip 4 reakcije posredovane su staničnom imunošću. Iako je nastanak većine reakcija preosjetljivosti na lijekove objašnjiv konceptom preosjetljivosti po Gell i Coombsu, u novije doba predložen je i koncept farmakoloških interakcija lijekova s imunoreceptorima (p-i koncept) koji dalje nadopunjuje naše znanje o nastanku reakcija preosjetljivosti i njihovog farmakogenetskoj podlozi. Prema p-i konceptu lijekovi se mogu izravno vezati na imunosne receptore i izravno dovesti do aktivacije staničnog imunosnog odgovora i nastanka reakcije preosjetljivosti na lijek. Klinička slika reakcija preosjetljivosti je raznolika, od benignih kožnih osipa pa sve do životno ugrožavajućih stanja poput anafilakse ili toksične epidermalne nekrolize. Dijagnostički postupak pri sumnji na reakciju preosjetljivosti na lijekove se temelji na opsežnoj anamnezi, kožnim i laboratorijskim testiranjima te provokacijskim testovima. Ključne riječi: nuspojave lijekova, reakcije preosjetljivosti na lijekove.

Abstract (english)

Drug side effects are a significant public health problem in modern medicine. Drug hypersensitivity reactions are a relativly common side effect that is categorized as a type B side effect. The mechanisms underlying drug hypersensitivity reactions are most often explaind using the concept of allergic-immune stimulation by haptens, which is based on the general classification of hypersensitivity reactions published in 1963 by the authors Gell and Coombs. This classification of hypersensitivity reactions is divided into four types depending on the underlying immune mechanism. Type 1 reactions are mediated by immunoglobulin E and leed to the development of a classical clinical picture of an allergic reaction. Type 2 reactions are mediated by immunoglobulins M or G directed against cell components or the extracellular matrix. Type 3 reactions are mediated by immunocomplexes which by precipitating into tissues result in an inflammatory reaction. Type 4 reactions are mediated by cellular immunity. Although the occurrence of most drug hypersensitivity reactions can be explained by the concept of hypersensitivity according to Gell and Coombs, the concept of pharmacological drug interactions with immunoreceptors (p-i concept) has recently been proposed to supplement our knowledge of hypersensitivity reactions and their pharmacogenetic basis. According to the p-i concept, drugs can bind directly to immune receptors and directly activate the cellular immune response whicih results in the occurence of drug hypersensitivity reactions. The clinical picture of drug hypersensitivity reactions is diverse, ranging from benign skin rashes to life-threatening conditions such as anaphylaxis or toxic epidermal necrolysis. The diagnostic procedure in case of suspicion of a drug hypersensitivity reaction is based on an extensive history, skin and laboratory testing, and provocation testing.

• Keywords: alergijske reakcije; nuspojave lijekova; reakcije preosjetljivosti na lijekove
• Keywords (english): allergic reactions; drug hypersensitivity reactions; drug side effects
• Language: croatian
• URN:NBN: urn:nbn:hr:105:242968
• 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: 2023-01-19 08:05:32