| Abstract | Ovisnost o opioidima problem je koji postoji dugi niz godina širom svijeta, a nastaje zlouporabom opioidnih analgetika koji se koriste za liječenje boli. Bol smatramo jednim od važnijih osjeta koji tijelu omogućuju brzu reakciju na bolne podražaje i zaštitu od opasnosti. Osjet boli prenosi se pomoću Aδ i C vlakana od izvora boli koje registriraju nociceptori na slobodnim aksonima neurona te kroz leđnu moždinu prenose signale do područja mozga bogatih opioidnih receptorima. Najefektivniji lijekovi za liječenje boli su opioidni analgetici poput morfina, kodeina i fentanila. U tijelu djeluju kao ligandi za opioidne receptore. To su vrsta G proteinom spregnutih receptora, široko rasprostranjenih po tijelu, građenih od 7 transmembranskih uzvojnica koji prilikom vezanja endogenih liganda ili opioidnih lijekova potiču nastajanje analgezije i ugode u organizmu. Za razvoj ovisnosti najznačajnije su tri skupine opioidnih receptora: μ-receptori, ĸ-receptori i δ-receptori koji se razlikuju po endogenim ligandima koji na njih djeluju te po ulogama koje imaju prilikom razvoja ovisnosti ili otežavanja liječenja iste. Pa se tako μ-receptori povezuju sa sustavom nagrađivanja, ĸ-receptori s motivacijom i δ-receptori s promjenama raspoloženja. Aktivacijom opioidnih receptora pokreću se signalne kaskade preko podjedinica G proteina, ali i signalni put povezan s β-arestinom, te se putevi razlikuju u posljedicama koje uzrokuju. Dugotrajna izloženost opioidnih lijekovima ima negativan utjecaj na sustav nagrađivanja te puteve neurotransmitera dopamina, što posljedično dovodi do razvoja ovisnosti, tolerancije te sindroma ustezanja prilikom naglog prestanka uzimanja opioidnih lijekova. |
| Abstract (english) | Opioid addiction has been a problem for many years worldwide, arising from the misuse of opioid analgesics used for pain treatment. Pain is considered one of the essential sensations that allow the body to quickly react to painful stimuli and protect itself from danger. The sensation of pain is transmitted through Aδ and C fibers from the pain source registered by nociceptors on the free axons of neurons and transmitted through the spinal cord to areas of the brain rich in opioid receptors. The most effective drugs for pain treatment are opioid analgesics such as morphine, codeine, and fentanyl. In the body, they act as ligands for opioid receptors. These receptors are a type of G-protein-coupled receptor, widely distributed throughout the body, composed of 7 transmembrane helices, which, upon binding with endogenous ligands or opioid drugs, facilitate developtment of analgesia and the sensation of pleasure in the body. The most significant receptors for addiction development are three groups of opioid receptors: μ-receptors, ĸ-receptors, and δ-receptors, which differ in the endogenous ligands that act on them and their roles in addiction development or complicating its treatment. For example, μ-receptors are associated with the reward system, ĸ-receptors with motivation, and δ-receptors with mood changes. Activation of opioid receptors triggers signaling cascades through G-protein subunits and a signaling pathway associated with β-arrestin, with pathways differing in their consequences. Prolonged exposure to opioid drugs negatively impacts the reward system and dopamine neurotransmitter pathways, which subsequently leads to the development of addiction, tolerance, and withdrawal syndrome upon sudden cessation in usage of opioid drugs. |
