Izazovi i mogućnosti u primjeni amfetamina

master's thesis

• Title (english): Challenges and opportunities in amphetamine use
• Author: Nera Cetina
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2022-11-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

U ovom diplomskom radu prikazan je povijesni pregled upotrebe amfetamina od njihovog otkrića pa sve do danas. Nakon njihovog otkrića, širu primjenu su našli za vrijeme 2. Svjetskog rata kada su davani primjenjivani vojnicima kao psihostimulansi. Zbog potencijala zlouporabe i rizika za razvoj ovisnosti, danas je njihova primjena strogo regulirana.Krajem četrdesetih godina prošlog stoljeća došlo je do spoznaja o potencijalu amfetamina za razvijanje ovisnosti. Iz tog razloga uvedena je stroga regulativa propisivanja i njihove upotrebe.
Bez obzira na sve to,rizike, oni su našli svoju primjenu u liječenju ADHD-a, narkolepsije i pretilosti. Amfetamin je po kemijskom sastavu α-metilfenetilamini, a dolazi kao racemična smjesa. Dokazano je da d-amfetamin ima veću farmakološku aktivnost od l-amfetamina. Općenito amfetamini pokazuju brzu apsorpciju i dosežu maksimalnu koncentraciju lijeka u krvi nakon 1-3 sata pri oralnoj primjeni, a poluvrijeme eliminacije iznosi 9-11 sati. Da bi se smanjila učestalnost doziranja lijeka i povećavala adherencija na terapiju, posebno kod djece, razvijeni su novi terapijski sustavi s produljenim oslobađanjem lijeka te prolijek lisdeksamfetamin, kompleks d-amfetamina i l-lizina koji se razgrađuje u eritrocitima i oslobađa aktivnu komponentu d-amfetamina. Novi terapijski sustavi s produljenim oslobađanjem također su razvijeni da bi smanjili mogućnost zloupotrebe koja je bila više izražena kod oblika s trenutnim oslobađanjem.
Iako amfetamini imaju svoje pozitivne učinke, njihova zloupotreba može dovesti do razvoja ovisnosti te ozbiljnih kardiovaskularnih, cerebrovaskularnih i psihičkih nuspojava.
Dosadašnja istraživanja rađena su na manjem broju ispitanika, uglavnom zdravih odraslih osoba, u kraćem vremenskom periodu, te se nameće potreba za daljnjim istraživanjima koja bi uključila kroničnu primjenu lijeka s amfetaminima te procjenjivala akutnu i odgođenu korist i rizike primjene, posebice one od razvoja ovisnosti i kardiovaskularnih te psihičkih komplikacija, s naglaskom na dječju i adolescentsku populaciju.

Abstract (english)

This Bachelor's Thesis presents a historic review of amphetamine use from discovery until today. After their discovery, they found wider usage during World War II when they were given to soldiers as psychostimulants. The knowledge about amphetamine abuse potential has been recognized in the late 1940s. Therefore, a more strict regulatory control has been implented in prescription and use. Nevertheless, amphetamines have been used in treatment of ADHD, narcolepsy and obesity. Amphetamine is an α-methylphenethylamine and comes in the form of racemic mixture. It was confirmed that d-amphetamine shows higher pharmacological activity than l-amphetamine. Pharmacokinetic studies show their fast absorption with maximal blood concentration after 1-3 hours in oral application, with half-life of 9-11 hours. In order to decrease frequency of drug application and increase adherency, especially in child population, new therapeutic systems have been developed with prolonged release and a prodrug lisdexamphetamine, complex of d-amphetamine and l-lysine, which converts to the active d-amphetamine component in red blood cells. New therapeutic systems with prolonged release have also been developed to decrease abuse potential which occured at immediate release dosage forms.
Although aphetamines show positive therapeutic effects, their recreational abuse can cause addiction and lead to serious cardiovascular, cerebrovascular and psychiatric side effects.
Clinical studies have been performed on limited number of subjects so far, mainly on heatlhy volunteers and in shorter period of time. Therefore, there is a need for larger studies that would include populations with chronic amphetamine therapy and that would enable conclusions of acute and delayed usage and risks of application like development of addiction, cardiovascular and psychiatric complications, especially in children and adolescent population.

• Keywords: amfetamini; ovisnost; ADHD; narkolepsija; pretilost; stimulansi; farmakokinetika; farmakodinamika; farmaceutski oblici
• Keywords (english): amphetamine; metamphetamine; addiction; ADHD; narcolepsy; obesity; stimulants; drug abuse; pharmacokinetics; pharmacodinamics; pharmaceutical dosage forms; mechanism of action
• Language: croatian
• URN:NBN: urn:nbn:hr:163:545805
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-11-28 14:47:22