Author/Editor		Ferjan, Ilonka; Kržan, Mojca; Lipnik-Štangelj, Metoda; Žiberna, Lovro; Stanovnik, Lovro; Černe, Katarina
Title		Farmakologija kanabinoidov
Translated title		Pharmacology of cannabinoids
Type		članek
Vol. and No.		Letnik 84, št. 6
Publication year		2015
Volume		str. 456-471
ISSN		1581-0224 - Zdravniški vestnik
Language		slv
Abstract		Odkritje receptorjev za derivate iz konoplje in endokanabinoidnega sistema je privedlo do številnih možnosti za terapevtsko uporabo kanabinoidov. V osrednjem živčevju kanabinoidi učinkujejo predvsem modulatorno, uravnavajo sproščanje drugih nevrotransmitorjev prek aktivacije receptorjev CB1. Aktivacija receptorjev CB2 zunaj osrednjega živčevja povzroča zmanjšanje vnetnega odgovora in povečanje apoptoze nekaterih tumorskih celic. S kanabinoidi lahko zdravimo slabost in bruhanje, izzvano s citostatiki; stimuliramo apetit; blažimo nevropatsko bolečino in spastičnost pri multipli sklerozi ter bolečino pri bolnikih z rakom. Učinkovitost pri drugih boleznih in stanjih se še preverja. Izolacija in identifikacija posameznih kanabinoidov iz konoplje in sinteza bolj selektivnih derivatov povečuje terapevtske možnosti. Ob tem se pojavljajo številni problemi z neželenimi učinki, zlasti, kadar gre za uporabo pripravkov iz konoplje z neznano količinsko in kakovostno sestavo. Med toksičnimi učinki kanabinoidov so najbolj zaskrbljujoči kronični učinki, kot so odvisnost, toleranca z odtegnitvenimi simptomi, povečano tveganje za ponovni akutni miokardni infarkt in povečano tveganje za razvoj psihoz oziroma poslabšanje simptomov pri že obstoječi psihozi. Akutni učinki so bolj izraženi pri otrocih, pri katerih je bila pri naključnem zaužitju opažena huda depresija osrednjega živčevja. Za potencialna zdravila iz konoplje in sintetične kanabinoide morajo veljati enaka pravila kot za druga potencialna zdravila. Tudi če je snov naravnega (rastlinskega) izvora in ima biološke učinke, moramo uporabnost za zdravljenje in sprejemljivo varnost za bolnika dokazati v nekliničnih preizkušanjih in kliničnih študijah, dovoljenje za promet pa mora izdati ustrezen organ. Bolniki pa si zaslužijo tudi kakovostno izdelana zdravila, ki vedno vsebujejo predpisano količino t. i. remedii cardinalis.Background: In this article, a facial reconstruction with implant-supported craniofacial epitheses and our clinical experience with the substitution of auricular and orbital region are described. Materials and methods: In this case series, 9 patients with 28 endosseous implants performed in the period between 2006 and 2013 were included. Two-stage and one-stage procedures were opted for; the former in six patients, and the latter in three patients. There were four patients with congenital defects of facial structures, and five patients who had undergone ablative oncological surgery; three among them received postoperative radiotherapy. In two patients adjuvant therapy with hyperbaric oxygen was used before and after implantation. We analysed the success of combined surgical-prosthodontic treatment. Results: We placed 28 titanium implants in 9 patients. A successful osseointegration was observed in 27 implants; only one endosseous implant failed to integrate and fell out of the bone (in an irradiated patient). The final implantsupported epithesis was achieved in six patients. Among them there were five ear-substituting epitheses and one epithesis substituting the eye and periorbital region. The final epithesis could not be made in three patients; in one patient too much keloid formed to fix a prosthodontic bar to the implants, the other two patients died because of the progression of malignancy. Conclusion: The surgical technique for rehabilitation using implant-supported facial epitheses is simple and reliable. In certain indications, it is the only proper option for aesthetic and socially acceptable rehabilitation. The major problem remains soft tissues surrounding the implants. Due to their stability and appearance, the implantsupported epitheses are superior to the adhesiveretained epitheses.The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in the central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cell populations. The cannabinoids have been authorized to treat chemotherapy-induced nausea and vomiting; to stimulate appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. The isolation and identification of different cannabinoids from Cannabis, and synthesis of novel, more selective derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoid formulations with an unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and an increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects, e.g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subjected to the same regulations as other potential drugs. The safety and efficacy of any potential drug candidate regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, and the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of remedium cardinale.
Keywords		cannabis endocannabinoids receptors function preparations toxicity legal status konoplja endokanabinoidi receptorji funkcija zdravila toksičnost legalni status