Personalizirano liječenje kardiovaskularnih bolesti uz pomoć analize farmakogena

master's thesis

• Title (english): Personalized treatment of cardiovascular diseases with the help of pharmacogene analysis
• Author: Josip Kujundžić
• Mentor: Tamara Božina (mentor)
• Committee member: Mila Lovrić (predsjednik povjerenstva)
• Committee member: Slavica Potočki (član povjerenstva)
• Committee member: Tamara Božina (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Chemistry, Biochemistry and Clinical Chemistry); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Kardiovaskularne bolesti su globalno vodeći uzrok smrti. One se liječe primjenom brojnih lijekova iz raznih skupina. S obzirom na postojanje razlika među pojedincima u odgovorima na lijekove, u terapiji ovih bolesti je potreban precizan i učinkovit pristup. Farmakogenomika, koja proučava utjecaj genskih varijacija na odgovore bolesnika na lijek, donosi značajan napredak u personalizaciji terapije. U ovom preglednom radu analiziraju se važni farmakogeni koji utječu na farmakodinamiku i farmakokinetiku lijekova s djelovanjem na kardiovaskularni sustav. To uključuje pregled polimorfizama membranskih prijenosnika i enzima zaduženih za biotransformaciju lijekova. Primjeri enzima čiji se geni analiziraju su CYP2C9, CYP2C19 i CYP2D6. Njihovi aleli se mogu fenotipski razlikovati s obzirom na razinu enzimske aktivnosti, prema čemu se osobe konačno svrstavaju između sporog i vrlo brzog metabolizatora. Membranski prijenosnici također mogu imati promijenjenu transportnu funkciju zbog varijacija u genima, od kojih su SLCO1B1 i ABCG2 važni kod primjene statina. Zbog ovih razlika pacijenti mogu biti izloženi višim ili manjim količinama lijekova nego što je potrebno i posljedično imati neželjene nuspojave ili smanjen terapijski učinak. Društva kao što su CPIC i DPWG stoga daju kliničarima preporuke o odabiru terapije i doziranju ovisno o genotipu/fenotipu pacijenta.

Abstract (english)

Cardiovascular diseases are the leading cause of death globally. They are treated with numerous drugs from various classes. Given the differences among individuals in drug responses, a precise and effective approach is needed in the therapy of these diseases. Pharmacogenomics studies genetic variations that influence drug responses, advancing personalized therapy. This review paper analyzes important pharmacogenes that affect the pharmacodynamics and pharmacokinetics of drugs acting on the cardiovascular system. It includes a review of polymorphisms of membrane transporters and enzymes responsible for drug biotransformation. Examples of enzymes whose genes are analyzed include CYP2C9, CYP2C19, and CYP2D6. Their alleles can differ phenotypically regarding the level of enzymatic activity, categorizing individuals as slow to ultra-rapid metabolizers. Membrane transporters can also have altered transport functions due to gene variations, with SLCO1B1 and ABCG2 being important in the use of statins. Due to these differences, patients may be exposed to higher or lower amounts of drugs than necessary, resulting in unwanted side effects or reduced therapeutic efficacy. Groups such as CPIC and DPWG provide clinicians with recommendations on therapy selection and dosing based on the patient's genotype/phenotype.

• Keywords: kardiovaskularne bolesti; farmakogenomika; personalizirana medicina
• Keywords (english): cardiovascular diseases; pharmacogenomics; personalized medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:046860
• 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: 2024-07-02 15:24:36