Remimazolam je novi intravenski anestetik iz skupine benzodiazepina. Molekularna struktura remimazolama omogućuje mu poseban farmakokinetički profil te ga izdvaja od drugih lijekova u istoj skupini. ...Zbog bočnoga esterskog lanca u strukturi remimazolam metaboliziraju nespecifične esteraze na inaktivne metabolite, što rezultira njegovim ultrakratkim djelovanjem i brzim oporavkom koji nije ovisan o funkciji niti jednog organskog sustava. S mehanizmom djelovanja nalik klasičnim benzodiazepinima, prvenstveno midazolamu, i jedinstvenom farmakokinetikom u ovoj skupini lijekova, remimazolam se čini kao idealan sedativ za proceduralnu sedaciju za vrijeme kratkih zahvata. Učinkovitost remimazolama za proceduralne sedacije ispitivana je u tri multicentrična klinička istraživanja. Sva tri ispitivanja pokazala su učinkovitost remimazolama u proceduralnoj sedaciji, s visokim stopama uspjeha, brzim početkom i kratkim vremenom oporavka uočenim u skupinama s remimazolamom. U našoj ustanovi ispitivali smo djelovanje remimazolama za proceduralnu sedaciju za dijagnostičke gastroskopije i kolonoskopije. Cilj istraživanja bio je ustanoviti djelotvornost i sigurnost remimazolama kao sedativa za proceduralnu sedaciju. Iako na manjem uzorku, naši rezultati su u skladu s rezultatima velikih kliničkih studija.
Benzodiazepini: za i protiv Mimica, Ninoslav; Folnegović-Šmalc, Vera; Uzun, Suzana ...
Medicus (Zagreb, Croatia : 1992),
09/2002, Volume:
11, Issue:
2_Psihofarmakologija
Journal Article
Peer reviewed
Open access
Benzodiazepini se općenito dobro podnose,
imaju relativno malo nuspojava, a učinkoviti su u liječenju
anksioznih i njima srodnih poremećaja. Učinkoviti su hipnotici,
pa se rabe u liječenju poremećaja ...spavanja. Benzodiazepini
su također djelotvorni kao miorelaksansi ili antikonvulzivi,
a uvelike se rabe za ublažavanje sindroma alkoholnog
sustezanja. Imaju primjenu i kao intravenski anestetici. Farmakokinetske
osobine pojedinog benzodiazepina određuju i
indikaciju za primjenu. Bez obzira na široku primjenu benzodiazepina,
njihova primarna indikacija i nadalje ostaju
anksiozni poremećaji, i to ponajprije opći anksiozni poremećaj
i panični poremećaj. Ovi lijekovi su relativno netoksični i
sigurniji od drugih lijekova sličnog djelovanja, a uzeti u prekomjernoj
dozi rijetko dovode do letalnog ishoda. Najčešća nuspojava
ovih lijekova je neželjena dnevna sedacija, a najproblematičnija
nuspojava je ovisnost, koja se može javiti u
mnogih bolesnika tijekom kronične upotrebe. Nelagoda zbog
posljedičnog sindroma sustezanja također predstavlja
značajnu teškoću. Stoga u primjeni benzodiazepina treba biti
vrlo racionalan, tj. treba ih propisivati samo onda kada je to
indicirano, davati što je moguće nižu dozu u što kraćem vremenu.
Terapija anksioznih stanja ne bi trebala trajati dulje od
4 tjedna u kontinuitetu, a terapija za insomniju treba biti sporadična.
Benzodiazepini su se u povijesti dokazali kao miorelaksansi i antikonvulzivi u neurologiji, kao anksiolitici u psihijatriji, uz hipnotičko djelovanje u terapiji izbora za insomniju, a takđ er i u ...odvikavanju od alkoholne ovisnosti. Također su opravdali svoju široku primjenu u anesteziologiji i drugim kliničkim granama. Vremenom su se u psihijatrijskoj primjeni benzodiazepina pojavile kontroverze koje je pokrenula mogućnost zloporabe, štetnog djelovanja, intoksikacija, te ovisnosti. S druge strane revolucionarna pojava selektivnih inhibitora ponovne pohrane serotonina (SIPPS) benzodiazepine je pomaknula u sjenu. Uz to su se pojavile preporuke raznih znanstvenih i stručnih institucija kojima je uporaba benzodiazepina ili isključena ili reducirana ili svedena na kratkotrajnu mjeru liječenja. Klinička nam iskustva međutim pokazuju da se benzodiazepini i dalje često rabe u dugotrajnom tretmanu i to iz više razloga: zbog same tradicije propisivanja; zbog toga što ih sami pacijenti preferiraju; zbog poteškoća koje se javljaju kod prekida uzimanja čak i onda kad su uzimane niske doze; zbog brzog djelovanja i dobre učinkovitosti a s vrlo malo početnih nuspojava. Drugi lijekovi, odnosno alternativa benzodijazepinima - SIPPS, nemaju brzo očekivani odgovor, a nuspojave su im puno neugodnije. Stoga neki autori smatraju da je razlog prelaska s benzodiazepina na SIPPS u mnogim preporučenim slučajevima često nedostatno opravdan.
Analizirano je 170 slučajeva akutnih otrovanja u 60 pacijenata i 110 pacijentica (srednja dob 31 godina) koji su obrađivani u Hitnoj internoj poliklinici Kliničke bolnice "Merkur" u razdoblju od 1. ...siječnja do 1. studenoga 1999. U 168 (98%) pacijenata otrovanje je bilo namjerno izazvano. Devedeset posto otrovanja dogodilo se kod kuće. U 134 (79%) pacijenata samoubojstvo je pokušano lijekovima. Uzrok akutnog otrovanja u 81 (48%) bili su benzodiazepini, a u 19 (11%) slučajeva antidepresivi. Pretežiti uzrok otrovanja u muškaraca bio je alkohol (u 18 slučajeva, 11%) ili kombinacija alkohola i psihoaktivnog preparata (u 10 slučajeva, 6%). Narkotici su bili uzročnici akutnog otrovanja u 31 (18%) pacijenata i među njima bio je najzastupljeniji kokain. Ostali uzročnici akutnog otrovanja bile su sintetske droge kao ecstasy (3 slučaja, 2%) te udisanje ugljičnog monoksida (6 slučaja, 4%) i klorovodične kiseline (2 slučaja, 1%). U 68 (40%) pacijenata pokušaj suicida bio je posljedica depresije. Prethodnih suicidalnih namjera bilo je u 24 (14%) pacijenata. Na prijemu u Hitnu internu polikliniku bilo je ukupno 50 (29%) komatoznih pacijenata, a uzrok otrovanja kokain u 31 (18%), benzodiazepin u 11 (6%) i alkohol u 8 (5%) slučajeva. Od tih pacijenata na daljnjem tretmanu u Jedinici intenzivne njege zadržana su 24 pacijenta. Smrtni ishod zabilježen je u troje pacijenata visoke dobi (više od 70 godina) koji su se otrovali antidepresivima, a uzrok smrti bile su ventrikularna aritmija i respiratorna depresija. Rezultati ovog istraživanja daju korisne podatke kako za pružanje neposredne medicinske skrbi tako i pri planiranju zdravstvene zaštite u namjerno izazvanim akutnim otrovanjima.
Retrospektivno su analizirani telefonski pozivi vezani uz ingestije lijekova primljeni u nacionalnom Centru za kontrolu otrovanja u Zagrebu u posljednjih 15 godina. Tri skupine psihoaktivnih lijekova ...(benzodiazepini, neuroleptici, antidepresivi) bile su od posebnog značenja u ovom radu. Svi slučajevi ingestije lijekova analizirani su u dva vremenska intervala: period I (1985.–1991.) i period II (1992.–1999.) te u dvije skupine s obzirom na dob otrovanih: djeca (<16 godina) i odrasli (316 godina). Svaki telefonski poziv brojen je kao jedan slučaj trovanja, uključujući i višestruke ingestije lijekova (ingestije više od jedne vrste lijeka u isto vrijeme) koje su uključivale barem jedan psihoaktivni lijek. Kod djece, učestalost akutnih otrovanja neurolepticima bila je značajno veća u periodu II nego u periodu I (7.4%:4.4%; P<0.05). Učestalost otrovanja benzodiazepinima, antidepresivima i amitriptilinom kod djece nije se značajno razlikovala u periodu I i II (benzodiazepini – 13.5%:9.9%; antidepresivi – 1.8%:1.8%; amitriptilin – 0.3%:0.6%), kao ni učestalost višestrukih ingestija lijekova (19.4%:20.5%). Kod odraslih, učestalost otrovanja antidepresivima i amitriptilinom bila je značajno veća u periodu II nego u periodu I (antidepresivi – 13.0%:5.9%; P<0.01; amitriptilin – 7.3%:2.9%; P<0.05), kao i učestalost višestrukih ingestija lijekova (45.3%: 29.1%; P<0.01). Učestalost otrovanja benzodiazepinima i neurolepticima kod odraslih nije se značajno razlikovala u periodu I i II (benzodiazepini – 27.5%: 28.4%; neuroleptici – 20.6%: 19.7%). U oba perioda učestalost otrovanja psihoaktivnim lijekovima bila je značajno veća u odraslih nego u djece (period I – 53.9%: 19.4%; P<0.01; period II – 61.3%:19.1%; P<0.01). Od 1992. u Hrvatskoj se bilježi značajan porast broja akutnih otrovanja antidepresivima, osobito tricikličkim, u odraslih osoba, što je vezano vjerojatno uz učestalije propisivanje tih lijekova. Ovaj fenomen nije zabilježen u djece. Povećanje učestalosti akutnih otrovanja psihoaktivnim lijekovima, kao jedna od mnogih posljedica rata i posttraumatskoga stresnog poremećaja, upućuje na potrebu pažljive psihijatrijske procjene oboljelih, osobito pažljiviju uporabu antidepresiva. Rezultati ovog rada govore u prilog potrebe daljnjeg istraživanja učestalosti propisivanja psihoaktivnih lijekova u Hrvatskoj.
La substitution propose de remplacer une substance dont le patient est dépendant par un analogue pharmacologique moins nocif afin de faciliter l’arrêt ou la réduction des prises, et réduire les ...dommages induits du produit initialement consommé. Devenue classique pour les opioïdes ou le tabac, il n’existe à ce jour aucun traitement de substitution validé pour l’addiction à l’alcool. Les consommations d’alcool ou de benzodiazépines, deux agonistes des récepteurs GABAA, sont parmi les plus élevées en France, souvent associées. Alors que l’éthanol est un toxique majeur pour l’organisme, les benzodiazépines ont un meilleur profil de sécurité, malgré divers risques ou effets secondaires. Certains arguments suggèrent que les benzodiazépines pourraient être une substitution à l’alcool. Pour explorer cette hypothèse, une revue narrative de la littérature a été conduite, ne retrouvant que de rares publications, envisageant la possibilité de substitution partielle ou approchée de l’alcool par des benzodiazépines. Afin de conforter cela, des études complémentaires sont nécessaires, de validation pharmacologique ainsi que d’élaboration des abords psychosociaux d’accompagnement de cette médiation.
Substitution therapy proposes to replace a substance on which the patient is dependent by another less harmful. Substitution substances are pharmacological analogues to addictive substances, used to facilitate the cessation or reduction of their use, and to reduce their deleterious consequences. Conventionally used for opioids or tobacco, there is to date no validated substitution treatment for alcohol addiction. The use rates of both alcohol and benzodiazepines are among the highest in France, and are frequently associated. France is a country in which alcohol is the second most frequent toxic used, and the most damaging determinant of health for mortality and morbidity after smoking. Meanwhile, alcohol and benzodiazepines are the two most common GABAA receptor agonists, with multiple similarities, despite some distinct chemical properties and actions. However, ethanol has a major toxicity for the body whereas benzodiazepines have a better safety profile, despite various risks and possible side effects. Benzodiazepines are the recommended treatment for alcohol withdrawal, but the guidelines are limited in time on the first two weeks, while only few studies have addressed the pros and cons of maintaining benzodiazepines beyond the detox period.Some arguments suggest that benzodiazepines could be a substitute for alcohol. Both are GABAA receptor agonists. In practice, it is frequent to observe crossed dependences, and, in particular, situations in which subjects with alcohol dependence change for benzodiazepine dependence. However, the medical practice of durably switching alcohol for benzodiazepines has been poorly explored.
To review the pharmacological and clinical arguments for and against considering benzodiazepines as a potential substitution treatment for alcohol dependence.
A narrative review of international literature has been conducted using the following keyword algorithm: (“substitution” OR “replacement” OR “maintenance”) AND “alcohol” AND “benzodiazepine*”, without any limitation in time.
Among a few hundred articles found on PubMed, only 3 were finally retained, with only 1 controlled study, no review of literature, supplemented by references found during the readings. The possibility of alcohol substitution by benzodiazepines is addressed, with a partial or approximate terminology reserve for qualifying this substitution. Diazepam appears as the molecule of choice. Such a substitution method, out of its usual field and in a design partly innovative in care, could decrease alcohol damages and perhaps consumption levels.
Given the impossibility of conducting the synthesis of a non-existent literature, only an exploratory approach is possible, no recommendation or indication of the use of benzodiazepine as an alcoholic substitution can be formulated, without development validation studies of a such hypothesis (including researches about safety, choice of molecule, ways of psychosocial support…). In order to rethink the place of benzodiazepines in alcohol treatment strategies, owing to their frequent consumption with alcohol, the possibility of an approached alcoholic substitution using these drugs should be considered further. The prolonged used of benzodiazepines after alcohol withdrawal could consist of a harm reduction approach which could help support a psychosocial recovery. Long half-life molecules could be safer and easier to use, and should warrant future clinical trials.
Le rôle des molécules GABAergiques dans la toxicologie médico-légale en France dépend de ses différents domaines d’investigations. Si la prevalence du GHB/GBL, du baclofène et de la prégabaline est ...très faible dans les décès directement liés aux toxiques, il faut rester vigilant et les rechercher systématiquement dans le cadre de « l'expertise toxicologique de référence » car de nouveaux usages peuvent être individuellement dramatiques, comme le montrent les quelques cas annuels mortels. La prévalence des GABAergiques classiques que sont l’alcool et les benzodiazépines et apparentées reste en revanche élevée dans les décès toxiques mais le plus souvent associés à d’autres substances psychoactives. Toutes les molécules GABAergiques sont susceptibles de modifier le comportement. Dans la conduite automobile, l’alcool est systématiquement recherché, à raison, puisqu’il reste impliqué dans 30 % des accidents mortels. En revanche, l’implication des benzodiazepines et apparentés est mal décrite malgré une consommation importante, par absence d’analyse systématique. Dans d’autres situations médico-légales telles que les accidents du travail ou les faits de violence, l’expert toxicologue est également sollicité puisque l’éthanol et les médicaments psychoactifs font souvent partie des toxiques à rechercher. Enfin, dans le domaine de la soumission chimique, les molécules GABAergiques sont prioritairement impliquées puisque ce sont les benzodiazépines ou apparentés qui se disputent toujours le trio de tête depuis de nombreuses années dans les molécules répertoriées par les enquêtes nationales annuelles.
The role of GABA agonists in forensic toxicology in France depends on its different areas of investigation. If the prevalence of GHB / GBL, baclofen and pregabalin is very low in toxic deaths, it is necessary to remain vigilant and to screen it systematically within the context of toxicological expertise because new uses can be individually dramatic as shown by the few annual fatal cases. However, the prevalence of conventional GABA agonists like alcohol and benzodiazepines remains high in toxic deaths, but is most often associated with other psychoactive substances. All GABA agonists can modify behavior. In driving, alcohol is always analyzed since it remains involved in 30 % of fatal accidents. In contrast, the involvement of benzodiazepines and Z-drugs is not well described, despite significant consumption, due to a lack of systematic analysis. In other forensic situations such as workplace accidents or acts of violence, toxicologists are also solicited to analyze ethanol and psychoactive drugs. Finally, in the field of Drug-facilitated crime GABA agonists are mainly involved because benzodiazepines or Z-drugs have for many years been in the top trio of substances listed in the annual national surveys.
L’agitazione è uno degli stati patologici che più perturbano l’atto medico. La ricerca dell’eziologia è essenziale di fronte a un’agitazione, perché potrebbe essere in gioco la prognosi vitale. La ...gestione deve, quindi, essere immediata, per evitare violenza e aggressività, che possono mettere in pericolo il paziente e il personale. Le eziologie sono varie e possono essere organiche, tossiche, psichiatriche e, talvolta, intrecciate. La gestione dell’agitazione deve privilegiare gli approcci non farmacologici, come la de-escalation verbale. La contenzione fisica deve essere usata solo se gli altri mezzi di controllo sono inefficaci o inappropriati. Si tratta di una decisione medica di ultima istanza, inquadrata da rigide regole di monitoraggio. Deve esservi associata una gestione farmacologica. I trattamenti sintomatici si basano su benzodiazepine e antipsicotici e dipendono dall’eziologia. Richiedono un monitoraggio ravvicinato.
Les niveaux de consommation de benzodiazépines en France sont préoccupants, entraînant, au-delà du risque iatrogène, un coût non négligeable.
Ce travail a pour objectif de définir l’impact de ...l’évaluation systématique des accès anxieux par la passation d’une échelle visuelle analogique (EVA) sur la consommation de benzodiazépines, en proposant une stratégie thérapeutique adaptée au niveau d’angoisse.
Nous avons mené une étude prospective monocentrique séquentielle. Nous avons mis en place, durant une période de trois mois, comme condition à la délivrance de benzodiazépines en « si besoin », l’évaluation des accès anxieux par une EVA ainsi qu’une alternative aux psychotropes sous la forme d’une réassurance. Nous avons ensuite comparé les consommations de benzodiazépines avant et après introduction de l’EVA. Enfin, nous avons comparé les consommations du service durant la période d’inclusion aux consommations des années précédentes à la même période de l’année.
Notre étude n’a pas permis de mettre en évidence un impact de l’introduction d’une EVA sur la consommation de benzodiazépines (p=0,44). Cependant nous avons observé une diminution de la consommation moyenne globale lors de la même période au cours de l’année précédente.
L’EVA immédiatement couplée à une stratégie de réassurance ne semble pas être une solution efficace pour réduire la consommation hospitalière de benzodiazépines.
The optimal management of psychiatric symptoms requires constant adaptation of therapeutic strategy to clinic evolution. If benzodiazepines are a treatment of choice for acute anxiety states in hospitals, their excessive consumption is a concern, revealing a preference of chemical anxiolysis to non-drug alternatives, yet effective for episodes of low or moderate intensities. Faced with an acute anxiety, choice of various therapeutic options requires evaluating its intensity in order to establish an appropriate therapeutic response. To enable systematic and accurate evaluation of an anxious state, Visual Analogue Scale (VAS) seems to be the most suitable tool. The application of VAS to measure anxiety is widely validated by previous research on the subject. We assume that the self-assessment of anxiety is likely to lead to a reduction in benzodiazepine use.
This study aims to determine the impact of systematic evaluation of acute anxious state by VAS, on consumption of benzodiazepines, by proposing a therapeutic strategy adapted to the anxiety level.
This is a comparative, prospective, multicentric study. Both studied samples came from a population of patients hospitalized in psychiatric crisis service, and recruited sequentially over a period of three months each. For the first group, our practices did not change; for the second group, we introduced VAS as a systematic tool for evaluating each acute episode. Have been included all patients over a period of six months, for which was provided a conditional anxiolytic treatment by benzodiazepine, regardless of their pathology. Then we have compared individual and overall consumption of benzodiazepines (inmg diazepam-equivalent per day of hospitalization) of the two samples. Finally, we compared the consumption of the service during the inclusion period with the consumption of the previous years at the same time of the year.
Our study did not reveal the impact of the introduction of EVA on the consumption of benzodiazepines (P=0.44). However, we observed a decrease in overall average consumption during the same period in the previous year.
The evaluation of a symptom, subjective by nature, by an outside observer, is undeniably biased. The benefit of self-evaluation has been proven in the treatment of other acute symptoms such as pain. With VAS, the objective is to better know the intensity of a symptom, to offer the patient a matched care. Its use as an investigative tool of acute anxious states in hospitals appeared to be a promising lead, especially concerning the implementation of non-pharmacological anxiolytic strategies, as an alternative to over-consumption of benzodiazepines. Unfortunately, its use to evaluate acute anxious states didn’t permit to reduce benzodiazepines’ consumption. Our results are compared with data from the actual scientific literature.
The adaptation of the therapeutic anxiolytic strategy by self-assessment of the intensity of an anxiety state appears unfortunately inappropriate, both on an individual level, and as a public health point of view. We have to try to find other ways, which would allow preferring non-drug strategies and reducing the consumption of benzodiazepines.
