| Abstract | U ovom diplomskom radu dana su osnovna farmakološka i farmakodinamička obilježja diazepama, fokusirajući se na nove spoznaje o lijeku. Diazepam je generički naziv za lijek iz skupine benzodiazepina koji ispoljava anksiolitičko, sedativno-hipnotičko, antikonvulzivno te mišićno-relaksirajuće djelovanje. Otkrio ga je dr. Leo Henryk Sternbach 1963. godine ispitivajući djelovanja određenih boja na SŽS glodavaca. Diazepam je indiciran za liječenje anksioznosti, stanja koja su praćena s anksioznošću, kratkotrajnih nesanica, napadaja panike, sindroma alkoholnog ustezanja, nekih epileptičnih napada, spazama mišiće te kao anesteziološka premedikacija. Vrlo se dobro apsorbira kada se uzme per os, gotovo se u potpunosti veže na proteine plazme i zbog svoje velike lipofilnosti prolazi krvno moždanu barijeru. Poluvrijeme eliminacije diazepama vrlo je veliko te iznosi 24 sata do dva dana. Diazepam je pozitivni alosterički modulator GABA receptora tipa A (GABAA), ionotropnog receptora koji se aktivira vezanjem γ-aminomaslačne kiseline (GABA), najvažnije inhibitornog neurotransmitora. Biotransformacija diazepama zbiva se uz pomoć različitih varijacija enzima citokrom P450. Diazepam se općenito dobro podnosi, nuspojave su uglavnom rijetke i uključuju smanjene motoričke i kognitivne sposobnosti, umor, vrtoglavicu, zbunjenost i ataksiju. Treba biti oprezan kod uzimanja diazepama s induktorima ili ihibitorima CYP P450 enzima budući da može doći do ozbiljnih interakcija. Benzodiazepini uzrokuju navikavanje i ovisnost te uslijed naglog prekida dulje terapije može doći do simptoma ustezanja. Ne preporučuje se uzimati diazepam tijekom trudnoće i/ili laktacije. |
| Abstract (english) | This diploma thesis outlines the basic pharmacological and pharmacodynamic characteristics of diazepam, focusing on new findings about the drug. Diazepam is generic name for the drug in the group of benzodiazepines, which exhibit anxiolytic, sedative-hypnotic, anticonvulsant, and muscle-relaxing activity. It was discovered by Dr. Leo Henryk Sternbach in 1963. by examining the effects of certain dyes on the central nervous system in rodents. Diazepam is indicated for the treatment of anxiety, conditions that are accompanied by anxiety, short-term insomnia, panic attacks, alcohol withdrawal, specific epileptic seizures, muscle spasms and as anesthetic premedication. It is well absorbed when taken orally and is almost completely bound to plasma proteins. Diazepam crosses the blood brain barrier due to its high liposolubility. The half-life of diazepam is from 24 hours to two days. Diazepam is a positive allosteric modulator of the GABA receptor type A (GABAA), ionotropic receptor thet binds γ-aminobutyric acid (GABA). Biotransformation of diazepam takes place with the help of different variations of the enzyme cytochrome P450. Diazepam is well tolerated, side effects are generally rare and include reduced motor and cognitive abilities, fatigue, dizziness, confusion, and ataxia. One should be careful while taking diazepam with inducers or inhibitors of CYP P450 enzymes. Benzodiazepines cause addiction and the sudden termination of therapy may lead to withdrawal symptoms. Diazepam therapy is not recommended during pregnancy and/or breastfeeding. |
