Benzodiazepin - Benzodiazepine - Wikipedia

"Benzo" bu erga yo'naltiradi. Ning lotin preparati uchun benzofuran, qarang Benzofuriy.

Benzodiazepinlar
Giyohvand moddalar sinfi
Vikidatada

Benzodiazepinlar (BZD, BDZ, BZlar), ba'zan "benzos", sinflari psixoaktiv dorilar yadrosi kimyoviy tuzilishi a benzol uzuk va a diazepin uzuk. Birinchi shunday dori, xlordiazepoksid (Librium), edi tasodifan topilgan tomonidan Leo Sternbax 1955 yilda va 1960 yilda taqdim etilgan Hoffmann – La-Rosh, 1963 yildan beri benzodiazepinni ham sotmoqda diazepam (Valium).[1] 1977 yilda benzodiazepinlar dunyoda eng ko'p buyurilgan dorilar edi.[2] Ular odatda ma'lum bo'lgan giyohvand moddalar oilasida kichik trankvilizatorlar.[3]

Benzodiazepinlar ta'sirini kuchaytiradi neyrotransmitter gamma-aminobutirik kislota (GABA) da GABAA retseptorlari, ni natijasida tinchlantiruvchi, gipnoz (uyquni keltirib chiqaradigan ), anksiyolitik (tashvishga qarshi), antikonvulsant va mushak gevşetici xususiyatlari. Ko'proq qisqa ta'sir ko'rsatadigan benzodiazepinlarning yuqori dozalari ham sabab bo'lishi mumkin anterograd amneziya va ajralish.[4] Ushbu xususiyatlar benzodiazepinlarni davolashda foydali qiladi tashvish, uyqusizlik, qo'zg'alish, soqchilik, mushaklarning spazmlari, spirtli ichimliklarni olib tashlash va a premedikatsiya tibbiy yoki tish protseduralari uchun.[5] Benzodiazepinlar qisqa, vositachilik yoki uzoq muddatli ta'sirga ega. Uyqusizlikni davolash uchun qisqa va oraliq ta'sirli benzodiazepinlarga afzallik beriladi; Anksiyete davolash uchun uzoqroq ta'sir qiluvchi benzodiazepinlar tavsiya etiladi.[6]

Benzodiazepinlar odatda qisqa muddatli foydalanish uchun xavfsiz va samarali hisoblanadi, bu ikki-to'rt hafta deb hisoblanadi,[7] kognitiv buzilish va paradoksal ta'sir tajovuzkorlik yoki xulq-atvor kabi disinhibisyon vaqti-vaqti bilan yuz beradi. Odamlarning ozchilik qismi qo'zg'alish yoki vahima kuchayganligi kabi paradoksal reaktsiyalarga ega bo'lishi mumkin.[8] Benzodiazepinlar, shuningdek, xavfning oshishi bilan bog'liq o'z joniga qasd qilish.[9] Xavotirlari tufayli uzoq muddatli foydalanish munozarali hisoblanadi samaradorlikni pasaytirish, jismoniy qaramlik, benzodiazepinni olib tashlash sindromi va xavfning ortishi dementia va saraton.[10][11][12][13] Uzoq vaqt davomida benzodiazepinlarni to'xtatish ko'pincha jismoniy va ruhiy salomatlikni yaxshilaydi.[14][15] Keksalar ham qisqa, ham xavfi yuqori uzoq muddatli salbiy ta'sir,[14][16] va natijada barcha benzodiazepinlar Pivo ro'yxati kattalar uchun noo'rin dorilar.[17] Homiladorlik paytida benzodiazepinlarning xavfsizligi to'g'risida tortishuvlar mavjud. Ular katta bo'lmagan bo'lsa-da teratogenlar, ular sabab bo'ladimi-yo'qligi noaniqligicha qolmoqda tanglay yorig'i oz sonli chaqaloqlarda va tug'ruqdan oldin tug'ilish natijasida neyroxavioral ta'sirlar yuzaga keladimi;[18] ular sabab bo'lganligi ma'lum yangi tug'ilgan chaqaloqdagi tortishish belgilari.

Benzodiazepinlar haddan tashqari dozada qabul qilinishi mumkin va xavfli bo'lishi mumkin chuqur behushlik. Biroq, ular avvalgilariga qaraganda kamroq zaharli hisoblanadi barbituratlar va benzodiazepin qabul qilingan yagona dori bo'lsa, o'lim kamdan-kam hollarda bo'ladi. Boshqalar bilan birlashtirilganda markaziy asab tizimi (CNS) depressantlar kabi alkogolli ichimliklar va opioidlar, toksik va potentsial dozani oshirib yuborish ehtimoli oshadi.[19][20] Benzodiazepinlar odatda noto'g'ri ishlatiladi va qabul qilinadi kombinatsiyada boshqalari bilan giyohvandlik.[21][22][23]

Tibbiy maqsadlarda foydalanish

Midazolam deb nomlangan ikkita 10 ml lik shisha. Chapdagi shishada qizil rangda yorliq bor va 1 mg / ml; o'ngdagi yashil rangda va 5 mg / ml ni aytadi. Ikkala shisha ham juda yaxshi nashrga ega.
Midazolam 1 & 5 mg / ml in'ektsiyalar (Kanada)
Shuningdek qarang: Benzodiazepinlar ro'yxati

Benzodiazepinlarga ega psixoleptik, tinchlantiruvchi, gipnoz, anksiyolitik, antikonvulsant, mushak gevşetici va amnezik harakatlar,[4][5] kabi turli xil ko'rsatkichlarda foydali bo'lgan spirtli ichimliklarga qaramlik, soqchilik, tashvishlanish buzilishi, vahima, qo'zg'alish va uyqusizlik. Ko'pchilik og'iz orqali yuboriladi; ammo, ular ham berilishi mumkin vena ichiga, mushak ichiga, yoki to'g'ri ichak.[24]:189 Umuman olganda, benzodiazepinlar yaxshi muhosaba qilinadi va qisqa muddatlarda juda ko'p sharoitlarda xavfsiz va samarali dorilar hisoblanadi.[25][26] Bag'rikenglik ularning ta'siriga qarab rivojlanishi mumkin va xavfi ham mavjud qaramlik va to'xtatilgandan so'ng, pulni olib tashlash sindromi paydo bo'lishi mumkin. Ushbu omillar, psixomotor, kognitiv yoki xotira buzilishi kabi uzoq muddatli foydalanishdan keyin yuzaga kelishi mumkin bo'lgan boshqa ikkilamchi ta'sirlar bilan birgalikda ularning uzoq muddatli qo'llanilishini cheklaydi.[27][28] Uzoq muddatli foydalanishning ta'siri yoki noto'g'ri foydalanish sabab yoki yomonlashuv tendentsiyasini o'z ichiga oladi kognitiv nuqsonlar, depressiya va tashvish.[14][16] The Britaniya Kolumbiyasidagi shifokorlar va jarrohlar kolleji benzodiazepinlarni opioidlarda va undan uzoq vaqt foydalanganlarda qo'llashni to'xtatishni tavsiya qiladi.[29] Benzodiazepinlar sog'liq uchun jiddiy salbiy oqibatlarga olib kelishi mumkin va ushbu topilmalar, ayniqsa benzodiazepin bo'lmagan retseptorlari agonistlari bilan birgalikda foydalanishni kamaytirish bo'yicha klinik va tartibga soluvchi harakatlarni qo'llab-quvvatlaydi.[30]

Vahima buzilishi

Ularning samaradorligi, toqatliligi va tez boshlanishi tufayli anksiyolitik vahima buzilishi bilan bog'liq bo'lgan tashvishlarni davolash uchun benzodiazepinlar tez-tez ishlatiladi.[31] Shu bilan birga, benzodiazepinlarni vahima buzilishi uchun uzoq muddat foydalanish bo'yicha mutaxassislar o'rtasida kelishmovchiliklar mavjud. Benzodiazepinlarni qabul qiladiganlarning qarashlari uzoq muddatli ta'sir ko'rsatmaydi [32] va davolanishga chidamli holatlar uchun saqlanishi kerak[33] ular uzoq muddatli istiqbolda ham samarali serotoninni qaytarib olishning selektiv inhibitörleri.[34]

The Amerika psixiatriya assotsiatsiyasi (APA) ko'rsatmalari[34] Umuman olganda, benzodiazepinlar yaxshi muhosaba qilinadi va ularni vahima buzilishida dastlabki davolashda qo'llash ko'plab nazorat ostida o'tkazilgan sinovlar yordamida kuchli qo'llab-quvvatlanadi. APA vahima buzilishining davolash usullarini boshqasiga tavsiya etish uchun etarli dalillar yo'qligini ta'kidlamoqda. Benzodiazepinlar, SSRIlar o'rtasida davolashni tanlash, serotonin-norepinefrinni qaytarib olish inhibitörleri, trisiklik antidepressantlar va psixoterapiya bemorning tarixi, afzalligi va boshqa individual xususiyatlariga asoslangan bo'lishi kerak. Selektiv serotoninni qaytarib olish inhibitörleri, vahima buzilishi bo'lgan ko'plab bemorlar uchun farmakoterapiyaning eng yaxshi tanlovi bo'lishi mumkin, ammo benzodiazepinlar ham tez-tez ishlatiladi va ba'zi tadkikotlar shuni ko'rsatadiki, bu dorilar hali ham SSRIlarga qaraganda ko'proq chastotada qo'llaniladi. Benzodiazepinlarning bir afzalligi shundaki, ular antidepressantlarga qaraganda anksiyete simptomlarini tezroq engillashtiradi va shuning uchun simptomlarni tezkor nazorat qilish muhim bo'lgan bemorlarda afzal bo'lishi mumkin. Biroq, bu afzallik rivojlanish imkoniyati bilan qoplanadi benzodiazepinga qaramlik. APA depressiv simptomlari yoki yaqinda paydo bo'lgan shaxslar uchun benzodiazepinlarni tavsiya etmaydi giyohvand moddalarni suiiste'mol qilish. APA yo'riqnomasida, umuman olganda, vahima buzilishining farmakoterapiyasi kamida bir yil davom etishi va klinik tajriba qaytalanishni oldini olish uchun benzodiazepin bilan davolanishni davom ettirishni qo'llab-quvvatlaydi. Benzodiazepin toleransi va uni olib tashlash haqida katta tashvishlar tug'dirilgan bo'lsa-da, uzoq muddatli benzodiazepinlardan foydalangan bemorlarda dozani sezilarli darajada oshirish bo'yicha dalillar mavjud emas. Ko'pgina bunday bemorlar uchun benzodiazepinlarning barqaror dozalari bir necha yillar davomida samaradorligini saqlab qoladi.[34]

Buyuk Britaniyada joylashgan ko'rsatmalar Sog'liqni saqlash va klinik mukammallikni ta'minlash milliy instituti (NICE), turli metodologiyadan foydalangan holda muntazam ravishda ko'rib chiqishni amalga oshirdi va boshqacha xulosaga keldi. Ular platsebo nazorati ostida bo'lmagan tadqiqotlarning to'g'riligiga shubha qilishdi. Va, topilmalari asosida platsebo bilan boshqariladigan tadqiqotlar, ular benzodiazepinlarni bag'rikenglik va kabi ikki-to'rt haftadan keyin foydalanishni tavsiya etmaydi jismoniy qaramlik tez rivojlanish, shu bilan birga olib tashlash alomatlari bilan qayta tashvish olti hafta yoki undan ko'p foydalanishdan keyin sodir bo'ladi.[32][35] Shunga qaramay, benzodiazepinlar hali ham uzoq muddatli davolash uchun buyuriladi tashvishlanish buzilishi aniq bo'lsa-da antidepressantlar kabi psixologik terapiya tavsiya etiladi birinchi darajali davolash bilan variantlar antikonvulsant dori pregabalin ikkinchi yoki uchinchi qator davolash sifatida ko'rsatilgan va uzoq muddatli foydalanish uchun mos.[36] NICE ning ta'kidlashicha, benzodiazepinlarni vahima buzilishida uzoq vaqt davomida yoki bo'lmagan holda ishlatish agorafobiya litsenziyasiz ko'rsatma bo'lib, uzoq muddatli samaradorlikka ega emas va shuning uchun klinik ko'rsatmalar tomonidan tavsiya etilmaydi. Kabi psixologik davolash usullari kognitiv xulq-atvor terapiyasi vahima buzilishi uchun birinchi darajali terapiya sifatida tavsiya etiladi; benzodiazepindan foydalanish ushbu davolash usullaridan terapevtik yutuqlarga xalaqit berishi aniqlandi.[32]

Benzodiazepinlar odatda og'iz orqali yuboriladi; ammo davolanish uchun vaqti-vaqti bilan tomir ichiga lorazepam yoki diazepam yuborilishi mumkin vahima hujumlari.[24]

Umumiy tashvish buzilishi

Benzodiazepinlar qisqa muddatli boshqarishda kuchli samaradorlikka ega umumiy tashvish buzilishi (GAD), ammo umuman olganda uzoq muddatli yaxshilanishni ishlab chiqarishda samarali bo'lmadi.[37] Ga binoan Sog'liqni saqlash va klinik mukammallikni ta'minlash milliy instituti (NICE), agar kerak bo'lsa, benzodiazepinlar GADni zudlik bilan boshqarishda ishlatilishi mumkin. Biroq, ular odatda 2-4 xaftadan ko'proq vaqt davomida berilmasligi kerak. NICE ning GADni uzoq muddat boshqarish uchun tavsiya etadigan yagona dori-darmonlari antidepressantlardir.[38]

Xuddi shu tarzda, Kanada Psixiatriya Assotsiatsiyasi (CPA) benzodiazepinlarni tavsiya qiladi alprazolam, bromazepam, lorazepam va diazepam faqat ikkinchi qator tanlovi sifatida, agar ikki xil antidepressant bilan davolash muvaffaqiyatsiz tugagan bo'lsa. Ular ikkinchi darajali vositalar bo'lishiga qaramay, benzodiazepinlar cheklangan vaqt davomida qattiq tashvish va qo'zg'alishni bartaraf etish uchun ishlatilishi mumkin. CPA ko'rsatmalariga ko'ra, 4-6 xaftadan so'ng benzodiazepinlarning ta'siri platsebo darajasiga tushishi mumkin va benzodiazepinlar antidepressantlarga qaraganda yumshatishda samarasizdir. ruminativ tashvish, GAD ning asosiy belgisi. Ammo, ayrim hollarda, antidepressantga qo'shimcha sifatida benzodiazepinlar bilan uzoq muddatli davolanish oqlanishi mumkin.[39]

2015 yilgi tekshiruv nutq terapiyasidan ko'ra dorilar bilan katta ta'sir ko'rsatdi.[40] Foyda bilan dori-darmonlarni o'z ichiga oladi serotonin-noradrenalinni qaytarib olish inhibitörleri, benzodiazepinlar va serotoninni qaytarib olishning selektiv inhibitörleri.[40]

Uyqusizlik

Temazepam (Normison) 10 mg tabletkalar

Benzodiazepinlar uyqusizlikni qisqa muddatli davolashda foydali bo'lishi mumkin. Qarama-qarshilik xavfi tufayli ularni 2 dan 4 haftagacha foydalanish tavsiya etilmaydi. Dori vositalari xavfsizligi qo'mitasining hisobotida, uyqusizlik uchun benzodiazepinlardan uzoq muddat foydalanish ko'rsatilgan bo'lsa, davolanish imkoni boricha vaqti-vaqti bilan bo'lishi kerakligi tavsiya qilingan.[41] Benzodiazepinlarni vaqti-vaqti bilan va eng past samarali dozada qabul qilish afzaldir. Ular uxlashdan oldin yotoqda yotadigan vaqtni qisqartirish, uxlash vaqtini uzaytirish va umuman, bedorlikni kamaytirish orqali uyqu bilan bog'liq muammolarni yaxshilaydilar.[42][43] Biroq, ular engil uyquni ko'paytirish va chuqur uyquni kamaytirish orqali uyqu sifatini yomonlashtiradi. Gipnozlarning boshqa kamchiliklari, shu jumladan benzodiazepinlar, ularning ta'siriga nisbatan bardoshlik, uyqusizlikni tiklash va sekin to'lqinli uyquni qisqartirish va uyqusizlik va uzoq muddatli tashvish va qo'zg'alish davri bilan ajralib turadigan bo'shashish davri.[44][45]

Uyqusizlikni davolash uchun tasdiqlangan benzodiazepinlar ro'yxati aksariyat mamlakatlar orasida deyarli o'xshashdir, ammo qaysi benzodiazepinlar rasmiy ravishda uyqusizlikni davolash uchun buyurilgan birinchi darajali gipnoz qiluvchi vositalar sifatida belgilanadi.[43] Kabi uzoqroq ta'sir qiluvchi benzodiazepinlar nitrazepam va diazepam keyingi kungacha davom etishi mumkin bo'lgan qoldiq effektlarga ega va umuman tavsiya etilmaydi.[42]

Xavfsizlik muammosiga javoban 1992 yilda benzodiazepinlar chiqarilgandan beri, uyqusizlik va boshqa uyqu buzilishi bo'lgan shaxslarga benzododiazepinlar (1993 yilda 2,3% dan 2010 yilda amerikaliklarning 13,7% gacha) buyuriladi, kamroq benzodiazepinlar (1993 yilda 23,5%) 2010 yilda 10,8%).[46][47] Yangi yoki yo'qligi aniq emas benzodiazepin bo'lmagan gipnoz qiluvchi dorilar (Z-dorilar) qisqa muddatli benzodiazepinlarga qaraganda yaxshiroqdir. Ushbu ikki guruh dorilarining samaradorligi o'xshash.[42][45] AQSh ma'lumotlariga ko'ra Sog'liqni saqlash tadqiqotlari va sifat agentligi, bilvosita taqqoslash shuni ko'rsatadiki, benzodiazepinlarning nojo'ya ta'sirlari benzodiazepinlarga qaraganda ikki baravar tez-tez bo'lishi mumkin.[45] Ba'zi ekspertlar, birinchi navbatda, uyqusizlikni uzoq muddatli davolash sifatida benzododiazepinlardan foydalanishni taklif qilishadi.[43] Biroq, Buyuk Britaniya Sog'liqni saqlash va klinik mukammallikni ta'minlash milliy instituti Z-dorilar foydasiga ishonchli dalillarni topmadi. NICE tekshiruvi shuni ta'kidladiki, qisqa muddatli Z-dori vositalari uzoq muddatli benzodiazepinlar bilan klinik tekshiruvlarda noo'rin taqqoslangan. Qisqa ta'sirli Z-dori-darmonlarni qisqa muddatli benzodiazepinlarning tegishli dozalari bilan taqqoslash bo'yicha sinovlar bo'lmagan. Shunga asoslanib, NICE Gipnoz vositasini tannarxi va bemorning xohishiga qarab tanlashni tavsiya qildi.[42]

Keksa kattalar benzodiazepinlardan uyqusizlikni davolashda boshqa muolajalar natija bermasa foydalanmasliklari kerak.[48] Benzodiazepinlardan foydalanganda bemorlar, ularning parvarishchilari va ularning shifokori zararlanish xavfini, shu jumladan, ikki marta kasallanishni ko'rsatadigan dalillarni muhokama qilishlari kerak. transport to'qnashuvlari haydovchi bemorlar orasida, va katta yoshli bemorlar uchun yiqilish va sonning sinishi.[48][49][50]

Tutqanoq

Uzoq muddatli konvulsiv epileptik tutilishlar a shoshilinch tibbiy yordam odatda tez ta'sir qiluvchi benzodiazepinlarni yuborish orqali samarali kurashish mumkin antikonvulsanlar. Kasalxona sharoitida, vena ichiga yuborish klonazepam, lorazepam va diazepam birinchi qatorda tanlovdir. Jamiyatda tomir orqali yuborish amaliy emas va shuning uchun rektal diazepam yoki bukkal midazolam midazolamni afzal ko'rish bilan ishlatiladi, chunki uni boshqarish osonroq va ijtimoiy jihatdan maqbuldir.[51][52]

Benzodiazepinlar birinchi marta kiritilganda, ular barcha turlarini davolash uchun g'ayrat bilan qabul qilingan epilepsiya. Biroq, uyquchanlik va bag'rikenglik doimiy foydalanish bilan bog'liq muammolarga aylanadi va endi ularning hech biri ko'rib chiqilmaydi birinchi qator uzoq muddatli epilepsiya terapiyasini tanlash.[53] Clobazam butun dunyo bo'ylab epilepsiya klinikalari tomonidan keng qo'llaniladi va klonazepam Gollandiya, Belgiya va Frantsiyada mashhur.[53] Clobazam 2011 yilda Qo'shma Shtatlarda foydalanish uchun tasdiqlangan. Buyuk Britaniyada ham klobazam, ham klonazepam epilepsiyaning ko'plab shakllarini davolash uchun ikkinchi darajali tanlovdir.[54] Clobazam, shuningdek, juda qisqa muddatli tutilish uchun foydali rol o'ynaydi profilaktika va katamenial epilepsiya.[53] Epilepsiyada uzoq muddatli foydalanishdan keyin to'xtatish reabilitatsiya xurujlari xavfi tufayli qo'shimcha ehtiyotkorlikni talab qiladi. Shuning uchun, doz olti oygacha yoki undan uzoqroq vaqt davomida asta-sekin torayib boradi.[52]

Spirtli ichimliklarni olib tashlash

Xlordiazepoksid uchun eng ko'p ishlatiladigan benzodiazepin hisoblanadi spirtli ichimliklarni zararsizlantirish,[55] lekin diazepam muqobil sifatida ishlatilishi mumkin. Ikkalasi ham ichishni to'xtatish uchun turtki beradigan shaxslarni zararsizlantirishda ishlatiladi va qisqa muddat davomida benzodiazepin dori-darmonlariga nisbatan bag'rikenglik va qaramlikni rivojlanish xavfini kamaytirish uchun buyuriladi.[24]:275 Yarim umr ko'rish muddati uzoqroq bo'lgan benzodiazepinlar detoksikatsiyani toqatli qiladi va xavfli (va o'limga olib kelishi mumkin) spirtli ichimliklarni olib tashlash ta'siri kamroq bo'ladi. Boshqa tomondan, qisqa muddatli benzodiazepinlar olib kelishi mumkin yutuq xurujlari, va shuning uchun ambulatoriya sharoitida detoksikatsiya qilish tavsiya etilmaydi. Oksazepam va lorazepam ko'pincha giyohvand moddalarni to'plash xavfi bo'lgan bemorlarda, xususan, keksa yoshdagi va u bilan kasallanganlarda qo'llaniladi siroz, chunki ular boshqa benzodiazepinlardan farqli ravishda metabolizmga uchraydi konjugatsiya.[56][57]

Benzodiazepinlarni davolashda afzal qilingan tanlovdir spirtli ichimliklarni olib tashlash sindromi, xususan, soqchilikning xavfli asoratlarining oldini olish va davolash uchun deliryum.[58] Lorazepam mushak ichiga so'rilishi taxmin qilinadigan yagona benzodiazepindir va u o'tkir xurujlarning oldini olish va nazorat qilishda eng samarali hisoblanadi.[59]

Tashvish

Benzodiazepinlar ba'zida o'tkir tashvishlarni davolashda ishlatiladi, chunki ular ko'pchilik odamlarda simptomlarni tez va sezilarli yoki o'rtacha darajada engillashtiradi;[32] ammo, ularni bag'rikenglik va qaramlik xavfi va uzoq muddatli samaradorlikning etishmasligi tufayli foydalanishning 2-4 xaftaligidan keyin tavsiya etilmaydi. Uyqusizlikka kelsak, ular tartibsiz ravishda "kerak bo'lganda" ishlatilishi mumkin, masalan, xavotir eng yomon holatlarda. Boshqa farmakologik muolajalar bilan taqqoslaganda, benzodiazepinlar ikki baravar yuqori bo'lib, bekor qilinganda asosiy holat qaytalanishiga olib keladi. Umumiy bezovtalikni uzoq muddatli davolash uchun psixologik terapiya va boshqa farmakologik terapiya tavsiya etiladi. Antidepressantlar remissiya darajasi yuqori bo'lib, umuman olganda, qisqa va uzoq muddatda xavfsiz va samaralidir.[32]

Boshqa ko'rsatkichlar

Benzodiazepinlar ko'pincha turli xil sharoitlarda buyuriladi:

  • Ular qabul qilayotgan bemorlarni tinchlantirishi mumkin mexanik shamollatish yoki juda og'ir ahvolda bo'lganlar. Ushbu vaziyatda xavf tug'dirishi sababli ehtiyotkorlik bilan foydalaniladi nafas olish tushkunligi va tavsiya etiladi dozani oshirib yuboradigan benzodiazepin tozalash inshootlari mavjud bo'lishi kerak.[60] Ular, shuningdek, odamlarni ventilyatorlardan chiqargandan so'ng, keyinchalik TSSB ehtimolini oshirishi aniqlandi.[61]
  • Benzodiazepinlar rivojlangan kasalliklarda, xususan, boshqa davolash usullari simptomlarni etarlicha nazorat qila olmagan hollarda nafasni (nafas qisilishini) davolashda ko'rsatiladi.[62]
  • Benzodiazepinlar samarali bo'lib, xavotirni yumshatish uchun operatsiyadan bir necha soat oldin beriladigan dori-darmon hisoblanadi. Ular shuningdek ishlab chiqaradilar amneziya, bu foydali bo'lishi mumkin, chunki bemorlar protseduradan yoqimsizlikni eslay olmaydilar.[63] Ular, shuningdek, bemorlarda qo'llaniladi tish fobi shuningdek, refraktsion jarrohlik kabi ba'zi oftalmik protseduralar; garchi bunday foydalanish munozarali va faqat juda xavotirga tushganlarga tavsiya etiladi.[64] Midazolam ushbu preparat uchun eng ko'p buyuriladi, chunki u kuchli sedativ ta'sirga ega va tez tiklanish muddati hamda suvda eruvchanligi bilan in'ektsiya paytida og'riqni kamaytiradi. Ba'zida diazepam va lorazepam ishlatiladi. Lorazepam ayniqsa amnezik xususiyatlarga ega bo'lib, amneziya kerakli ta'sirga ega bo'lganda uni yanada samarali qilishi mumkin.[24]:693
  • Benzodiazepinlar kuchli mushaklarni bo'shashtiruvchi xususiyatlari bilan mashhur va mushaklarning spazmlarini davolashda foydali bo'lishi mumkin,[24]:577–578 toqatlilik ko'pincha ularning mushaklarning gevşetici ta'siriga rivojlanadi.[14] Baklofen[65] yoki tizanidin ba'zan benzodiazepinlarga alternativ sifatida ishlatiladi. Tizanidinning diazepam va baklofen bilan solishtirganda yuqori toqatliligi borligi aniqlandi.[66]
  • Shuningdek, benzodiazepinlar vahima qo'zg'atadigan davo uchun ishlatiladi gallyutsinogen mastlik.[67] Benzodiazepinlar, shuningdek, o'tkir qo'zg'aladigan odamni tinchlantirish uchun ishlatiladi va agar kerak bo'lsa, mushak ichiga yuborish orqali yuborilishi mumkin.[68] Ular ba'zida o'tkir kabi psixiatrik favqulodda vaziyatlarni qisqa muddatli davolashda samarali bo'lishi mumkin psixoz kabi shizofreniya yoki mani ta'siriga qadar tez tinchlanish va tinchlantirishni keltirib chiqaradi lityum yoki neyroleptiklar (antipsikotiklar) kuchga kiradi. Lorazepam eng ko'p ishlatiladi, ammo klonazepam ba'zida o'tkir psixoz yoki mani uchun buyuriladi;[69] qaramlik xavfi tufayli ulardan uzoq muddatli foydalanish tavsiya etilmaydi.[24]:204 Faqatgina benzodiazepinlardan va o'tkir psixozni davolash uchun antipsikotik dorilar bilan birgalikda foydalanishni o'rganish bo'yicha keyingi tadqiqotlar talab etiladi.[70]
  • Klonazepam, benzodiazepin ko'plab shakllarini davolash uchun ishlatiladi parazomniya.[71] Ko'z harakatining tez buzilishi klonazepamning past dozalariga yaxshi ta'sir ko'rsatadi.[72][73] Bezovta qilinadigan oyoq sindromi Klonazepamdan foydalanish uchinchi darajali davolash usuli sifatida klonazepam yordamida davolanishi mumkin, chunki klonazepamdan foydalanish hali ham o'rganilmoqda.[74][75]
  • Ba'zida benzodiazepinlar ishlatiladi obsesif-kompulsiv buzilish (OKB), garchi ular odatda ushbu ko'rsatkich uchun samarasiz deb hisoblansa. Biroq, samaradorlik bitta kichik tadqiqotda topildi.[76] Benzodiazepinlarni davolanishga chidamli holatlarda davolash usuli sifatida ko'rib chiqish mumkin.[77]
  • Antipsikotiklar odatda deliryumni davolashning birinchi usuli hisoblanadi; ammo, qachon deliryum spirtli ichimliklar yoki sedativ gipnoz yordamida kelib chiqadi chekinish, benzodiazepinlar birinchi darajali davolashdir.[78]
  • Kam miqdordagi benzodiazepinlarning salbiy ta'sirini kamaytiradigan ba'zi dalillar mavjud elektrokonvulsiv terapiya.[79]

Qo'llash mumkin bo'lmagan holatlar

Mushaklarning gevşetici ta'siri tufayli benzodiazepinler sabab bo'lishi mumkin nafas olish tushkunligi sezgir odamlarda. Shu sababli, ular odamlarda kontrendikedir myasteniya gravis, uyqu apnesi, bronxit va KOAH.[80][81] Benzodiazepinlar bilan og'rigan odamlarda ehtiyotkorlik talab etiladi shaxsiyatning buzilishi yoki intellektual nogironlik chunki tez-tez paradoksal reaktsiyalar.[80][81] Yilda katta depressiya, ular cho'kishi mumkin o'z joniga qasd qilish tendentsiyalari[82] va ba'zan o'z joniga qasd qilishning haddan tashqari dozasi uchun ishlatiladi.[81] Spirtli ichimliklar tarixi bo'lgan shaxslar, opioid va barbiturat suiiste'mol qilish benzodiazepinlardan qochish kerak, chunki bu dorilar bilan o'zaro ta'sir o'tkazish xavfi mavjud.[83]

Homiladorlik

Shuningdek qarang: Benzodiazepinlarning yangi tug'ilgan chaqaloqlarga ta'siri

Qo'shma Shtatlarda Oziq-ovqat va dori-darmonlarni boshqarish benzodiazepinlarni ikkiga ajratdi D yoki X toifasi tug'ilmagan bolaga zarar etkazish ma'nosini ko'rsatdi.[84]

Homiladorlik paytida benzodiazepinlarga ta'sir qilish xavfi biroz oshdi (0,06 dan 0,07% gacha) tanglay yorig'i yangi tug'ilgan chaqaloqlarda munozarali xulosa, chunki ba'zi tadkikotlar benzodiazepinlar va osmon yoriqlari o'rtasida hech qanday bog'liqlik yo'q. Tug'ruqdan bir oz oldin bo'lajak onalar tomonidan ulardan foydalanish floppi bolalar sindromi, azob chekayotgan yangi tug'ilgan chaqaloqlar bilan gipotoniya, gipotermiya, sustlik va nafas olish va ovqatlanish qiyinligi.[18][85] Ishlari yangi tug'ilgan chaqaloqlarni olib tashlash sindromi surunkali ravishda benzodiazepinlar ta'sirida bo'lgan chaqaloqlarda tasvirlangan bachadonda. Ushbu sindromni tanib olish qiyin bo'lishi mumkin, chunki u etkazib berilgandan bir necha kun o'tgach boshlanadi, masalan, xlordiazepoksid uchun 21 kundan keyin. Alomatlar orasida titroq, gipertoniya, giperrefleksiya, giperaktivlik va qusish va uch oydan olti oygacha davom etishi mumkin.[18][86] Homiladorlik paytida dozani pasaytirishi uning og'irligini kamaytirishi mumkin. Agar homiladorlik paytida ishlatilsa, xavfsizligi yaxshiroq va uzoqroq bo'lgan benzodiazepinlar, masalan diazepam yoki xlordiazepoksid, kabi zararli benzodiazepinlarga nisbatan tavsiya etiladi temazepam[87] yoki triazolam. Qisqa vaqt ichida eng past samarali dozani qo'llash tug'ilmagan bola uchun xavfni minimallashtiradi.[88]

Qariyalar

Keksa yoshdagi odamlarda benzodiazepinlarning foydasi eng kam va xatarlari katta.[89][90] Ular Amerika Geriatriya Jamiyati tomonidan katta yoshlilar uchun mumkin bo'lmagan nojo'ya dorilar ro'yxatiga kiritilgan.[91] Qariyalar xavfini oshiradilar qaramlik va xotira muammolari, kunduzgi sedasyon, vosita harakatini muvofiqlashtirish buzilishi va avtohalokatlar va qulash xavfining ortishi kabi salbiy ta'sirlarga nisbatan sezgirroq,[49] va xavfining ortishi son suyaklari.[92] The benzodiazepinlarning uzoq muddatli ta'siri va benzodiazepinga qaramlik qariyalarga o'xshash bo'lishi mumkin dementia, depressiya yoki tashvish sindromlari va vaqt o'tishi bilan tobora yomonlashib boradi. Kognitivga salbiy ta'sirlarni qarilik ta'sirida yanglishish mumkin. Chiqib ketishning afzalliklari orasida bilimni yaxshilash, hushyorlik, harakatchanlik, xavfni kamaytirishi va tushish va sinish xavfini kamaytirish kiradi. Asta-sekin toraygan benzodiazepinlarning muvaffaqiyati yoshi kattalar singari keksalarda ham katta. Qariyalarga benzodiazepinlarni faqat ehtiyotkorlik bilan va qisqa muddatlarda past dozalarda buyurish kerak.[93][94] Keksa odamlarda qisqa muddatli va o'rta darajadagi benzodiazepinlarga afzallik beriladi oksazepam va temazepam. Yuqori ta'sirli benzodiazepinlar alprazolam va triazolam va qariyalarga uzoq muddatli benzodiazepinlar salbiy ta'sirining kuchayishi sababli tavsiya etilmaydi. Nonbenzodiazepinlar kabi zaleplon va zolpidem va sedativ antidepressantlarning kam dozalari ba'zan benzodiazepinlarga alternativ sifatida ishlatiladi.[94][95]

Benzodiazepinlardan uzoq muddatli foydalanish kognitiv buzilish va demans xavfining ortishi bilan bog'liq bo'lib, retseptlar darajasining pasayishi demans xavfini kamaytiradi.[12] O'tmishdagi benzodiazepinni ishlatish va kognitiv pasayish tarixining birlashishi aniq emas, chunki ba'zi tadkikotlar sobiq foydalanuvchilarning kognitiv pasayish xavfi pastligi haqida xabar beradi, ba'zilari assotsiatsiyani topmaydi va ba'zilari kognitiv pasayish xavfini oshiradi.[96]

Ba'zida benzodiazepinlar demansning xulq-atvor belgilarini davolash uchun buyuriladi. Biroq, shunga o'xshash antidepressantlar, ammo ularning samaradorligi haqida ozgina dalillar mavjud antipsikotiklar bir oz foyda ko'rsatdi.[97][98] Qariyalarda tez-tez uchraydigan benzodiazepinlarning kognitiv buzilish ta'siri demansni yomonlashtirishi mumkin.[99]

Yomon ta'sir

Psixiatriya, kimyo, farmakologiya, sud ekspertizasi, epidemiologiya va politsiya va yuridik xizmatlarning narkologlari delfik tahlil 20 ta mashhur rekreatsion dorilar haqida. Ushbu grafikda benzodiazepinlar qaramlik, jismoniy zarar va ijtimoiy zarar bo'yicha 7-o'rinni egalladi.[100]
Shuningdek qarang: Benzodiazepinlarning uzoq muddatli ta'siri, Paradoksal reaktsiya § Benzodiazepinlar va benzodiazepinni olib tashlash sindromi

Benzodiazepinlarning eng keng tarqalgan yon ta'siri ularning tinchlantiruvchi va mushaklarni yumshatuvchi ta'siriga bog'liq. Ular o'z ichiga oladi uyquchanlik, bosh aylanishi, hushyorlik va konsentratsiyaning pasayishi. Tanqisligi muvofiqlashtirish yiqilish va jarohatlarga, xususan, qariyalarga olib kelishi mumkin.[80][101][102] Yana bir natija - bu haydash qobiliyatining pasayishi va yo'l-transport hodisalari ehtimolining oshishi.[103][104] Libido va erektsiya muammolarining kamayishi odatiy yon ta'sir qiladi. Depressiya va disinhibisyon paydo bo'lishi mumkin. Gipotenziya va nafasni bostirish (gipoventiliya ) vena ichiga yuborishda duch kelishi mumkin.[80][101] Kamroq uchraydigan nojo'ya ta'sirlarga ko'ngil aynish va ishtahaning o'zgarishi, loyqa ko'rish, chalkashlik, eyforiya, shaxssizlashtirish va kabuslar. Ishlari jigar toksikligi tasvirlangan, ammo juda kam uchraydi.[24]:183–189[105]

The benzodiazepinning uzoq muddatli ta'siri foydalanish o'z ichiga olishi mumkin kognitiv buzilish shuningdek, affektiv va xulq-atvor muammolari. Bezovtalik hissi, konstruktiv fikr yuritish qiyinligi, jinsiy aloqani yo'qotish, agorafobiya ijtimoiy fobiya, xavotir va ruhiy tushkunlikning kuchayishi, bo'sh vaqt o'tkazish va qiziqishlarga qiziqishning yo'qolishi, his-tuyg'ularni his qilish yoki ifoda eta olmaslik kabi holatlar ham bo'lishi mumkin. Biroq, har kim ham uzoq muddatli foydalanish bilan bog'liq muammolarga duch kelmaydi.[15][106] Bundan tashqari, o'zlikni, atrof-muhitni va munosabatlarni o'zgartirishi mumkin.[107]

Boshqa sedativ-gipnoz vositalar bilan taqqoslaganda, benzodiazepinlarni o'z ichiga olgan kasalxonaga tashrif buyurish sog'liq uchun jiddiy oqibatlarga olib kelishi ehtimoli 66% ko'proq edi. Bunga kasalxonaga yotqizish, bemorni ko'chirish yoki o'lim va benzodiazepinlar va benzodiapin bo'lmagan retseptorlari agonistlarining kombinatsiyasini o'z ichiga olgan tashriflar salomatlikning jiddiy natijalarini deyarli to'rt baravar oshirgan.[30]

2020 yil sentyabr oyida AQSh Oziq-ovqat va dori-darmonlarni boshqarish (FDA) talab qildi qutidagi ogohlantirish barcha benzodiazepin preparatlari uchun suiiste'mol qilish, suiiste'mol qilish, giyohvandlik, jismoniy qaramlik va olib tashlash reaktsiyasini sinfdagi barcha dorilar bo'yicha izchil tavsiflash uchun yangilangan bo'lishi kerak.[108]

Kognitiv effektlar

Qisqa muddatli benzodiazepinlardan foydalanish ko'plab bilim sohalariga salbiy ta'sir qiladi, eng muhimi, bu yangi materialning xotiralarini shakllantirish va mustahkamlashga xalaqit beradi va to'liq bo'lishi mumkin anterograd amneziya.[80] Biroq, tadqiqotchilar uzoq muddatli boshqaruvning ta'siri to'g'risida qarama-qarshi fikrlarga ega. Ko'rinishlardan biri shundaki, ko'plab qisqa muddatli ta'sirlar uzoq muddatli davom etadi va hatto yomonlashishi mumkin va benzodiazepinni qo'llash to'xtatilgandan keyin hal etilmaydi. Boshqa bir qarash surunkali benzodiazepinni iste'mol qiluvchilarida kognitiv nuqsonlar dozadan keyin qisqa vaqt ichida paydo bo'lishini yoki bu defitsitning sababi tashvish buzilishi ekanligini ta'kidlaydi.

To'liq tadqiqotlar etishmayotgan bo'lsa-da, avvalgi qarash 2004 yilda 13 ta kichik tadqiqotlarning meta-tahlilidan qo'llab-quvvatlandi.[107][109] Ushbu meta-tahlil benzodiazepinlarni uzoq vaqt davomida qo'llash barcha bilim sohalariga o'rtacha va katta miqdordagi salbiy ta'sirlar bilan bog'liqligini aniqladi. visuospatial xotira eng ko'p aniqlangan buzilishdir. Xabar qilingan boshqa ba'zi bir buzilishlarning IQ darajasi, visiomotorlarni muvofiqlashtirish, axborotni qayta ishlash, og'zaki o'rganish va konsentratsiyasi pasaygan. Meta-tahlil mualliflari[109] va keyinchalik sharhlovchi[107] ushbu meta-tahlilning qo'llanilishi cheklanganligini ta'kidladi, chunki mavzular asosan klinikadan olib tashlangan; birgalikda mavjud bo'lgan giyohvandlik, spirtli ichimliklarni iste'mol qilish va psixiatrik kasalliklar aniqlanmagan; va kiritilgan tadqiqotlarning bir nechtasi pulni tortib olish davrida kognitiv o'lchovlarni o'tkazdi.

Paradoksal ta'sir

Paradoksal reaktsiyalar masalan, epileptikada tutilishning ko'payishi,[110] tajovuz, zo'ravonlik, impulsivlik, asabiylashish va ba'zan o'z joniga qasd qilish harakati paydo bo'ladi.[9] Ushbu reaktsiyalar disinhibitsiyaning oqibatlari va keyinchalik ijtimoiy qabul qilinishi mumkin bo'lmagan xatti-harakatlar ustidan nazoratni yo'qotishi bilan izohlandi. Paradoksal reaktsiyalar umumiy populyatsiyada kam uchraydi, insidans darajasi 1% dan past va platseboga o'xshash.[8][111] Biroq, ular rekreatsion suiiste'molchilarda, ko'proq odamlarda ko'proq chastota bilan sodir bo'ladi chegara kishilik buzilishi, bolalar va yuqori dozali rejimlarda bemorlar.[112][113] Ushbu guruhlarda, impuls nazorati muammolar, ehtimol disinhibitsiya uchun eng muhim xavf omilidir; o'rganish qobiliyati va asab kasalliklari ham muhim xavf hisoblanadi. Disinhibitsiya haqidagi xabarlarning aksariyati yuqori dozadagi benzodiazepinlarning yuqori dozalarini o'z ichiga oladi.[111] Paradoksal ta'sir benzodiazepinlarni surunkali qo'llashdan keyin ham paydo bo'lishi mumkin.[114]

Psixiatrik simptomlarning uzoq muddatli yomonlashishi

Ba'zi bemorlarda benzodiazepinlar xavotir, uyqu va qo'zg'alish uchun qisqa muddatli foyda keltirishi mumkin bo'lsa-da, uzoq muddatli (ya'ni 2-4 xaftadan katta) foydalanish dori-darmonlarni davolash uchun mo'ljallangan alomatlarning yomonlashishiga olib kelishi mumkin. Potentsial tushuntirishlar allaqachon tashvishlanish kasalliklarida tez-tez uchraydigan, sabab bo'lgan yoki yomonlashayotgan kognitiv muammolarni kuchaytirishi mumkin depressiya va o'z joniga qasd qilish,[115][116] chuqur uyquni inhibe qilish orqali uyqu me'morchiligini buzish,[117] asosiy tashvish yoki uyqusizlikni taqlid qiladigan yoki kuchaytiradigan dozalar orasidagi tortishish alomatlari yoki tiklanish alomatlari,[115][116] xotira konsolidatsiyasini inhibe qilish va qo'rquvning yo'q bo'lib ketishini kamaytirish orqali psixoterapiyaning afzalliklarini oldini olish,[118][119][120] travma / stress bilan kurashishni kamaytirish va kelajakdagi stressga nisbatan zaiflikni oshirish.[121] Ketish paytida tashvish, uyqusizlik va asabiylashish vaqtincha kuchayishi mumkin, ammo to'xtatilgandan keyin psixiatrik alomatlar odatda benzodiazepinlarni qabul qilishdan ko'ra kamroq bo'ladi.[115][122] Ish tugatilgandan keyin 1 yil ichida sezilarli darajada yaxshilanadi.[115][123]

Jismoniy qaramlik, olib tashlash va olib qo'yishdan keyingi sindromlar

Stol ustidagi ko'k taxtada qizil va qora yorliqli oq shisha. Shuningdek, maydonchada ettita kichik tabletkalar mavjud.
Diazepam Odatda davolashda ishlatiladigan 2 mg va 5 mg diazepam tabletkalari benzodiazepinni olib tashlash.
Asosiy maqolalar: Benzodiazepinga qaramlik, Benzodiazepinni olib tashlash sindromi va o'tkir post-sindirish sindromi

Bag'rikenglik

Surunkali benzodiazepinlardan foydalanishning asosiy muammo bu bag'rikenglik va qaramlik. Tolerantlik pasaygan farmakologik ta'sir sifatida namoyon bo'ladi va benzodiazepinlarning sedativ, gipnoz, antikonvulsant va mushaklarning gevşetici ta'siriga nisbatan tez rivojlanadi. Anksiyete ta'siriga nisbatan bag'rikenglik sekinroq rivojlanib boraveradi, ammo to'rt-olti oygacha davom etadigan foydalanish samaradorligidan dalolat beradi.[14] Umuman olganda, amnezik ta'sirga nisbatan bag'rikenglik yuzaga kelmaydi.[99] Shu bilan birga, benzodiazepinlarning samaradorligini saqlab qolishining ba'zi dalillari bilan anksiyolitik ta'sirlarga nisbatan bag'rikenglik borasida tortishuvlar mavjud.[124] va bag'rikenglik tez-tez uchrab turadigan adabiyotlarni muntazam ravishda ko'rib chiqishda qarama-qarshi dalillar[25][32] va uzoq muddatli foydalanish bilan tashvish kuchayishi mumkinligi haqida ba'zi dalillar.[14] Benzodiazepinlarning amnezik ta'siriga nisbatan bag'rikenglik masalasi ham aniq emas.[125] Ba'zi dalillar shuni ko'rsatadiki, qisman bag'rikenglik rivojlanadi va "xotiraning buzilishi har dozadan keyin 90 minut ichida tor oyna bilan cheklanadi".[126]

Terapevtik ta'sirlarga nisbatan bag'rikenglik benzodiazepinlarning katta kamchiligi shundaki, ko'plab salbiy ta'sirlar saqlanib qoladi. Tolerantlik bir necha kundan haftalargacha gipnoz va mioreleksant ta'siriga, antikonvulsant va anksiyolitik ta'sirga esa bir necha oydan bir oygacha rivojlanadi.[115] Shuning uchun benzodiazepinlar uyqu va xavotirga qarshi samarali uzoq muddatli davolanishlari ehtimoldan yiroq emas. BZD terapevtik ta'siri bardoshlik bilan yo'qolganda, depressiya va impulsivlik yuqori o'z joniga qasd qilish xavfi saqlanib qoladi.[115] Bir necha tadqiqotlar uzoq muddatli benzodiazepinlarning uyqu uchun platsebodan sezilarli darajada farq qilmasligini tasdiqladi[127][128][129] yoki tashvish.[115][130][131][132] Bu nima uchun bemorlarning vaqt o'tishi bilan dozalarni ko'paytirishi va ko'pchilik birinchi samaradorligini yo'qotgandan keyin benzodiazepinning bir nechta turini olishini tushuntirishi mumkin.[117][133][134] Bundan tashqari, benzodiazepinni sedativ ta'siriga nisbatan bag'rikenglik miya sopi depressant ta'siriga nisbatan tezroq rivojlanib borganligi sababli, kerakli ta'sirga erishish uchun ko'proq benzodiazepinlarni iste'mol qiluvchilar to'satdan nafas qisilishi, gipotenziya yoki o'limga duchor bo'lishlari mumkin.[135] Anksiyete buzilishi va TSSB bo'lgan bemorlarning aksariyati kamida bir necha oy davom etadigan alomatlarga ega,[135] terapevtik ta'sirlarga nisbatan bag'rikenglikni ular uchun alohida muammoga aylantirish va yanada samarali uzoq muddatli davolanishni talab qilish (masalan, psixoterapiya, serotonerjik antidepressantlar).

Pulni olib tashlash alomatlari va boshqarish

Stol ustidagi ko'k yostiqdagi oq shisha. Shishaning qopqog'i yopiq va shisha oldidagi yostiqda teskari. Kepkada o'nlab qora va sariq kapsulalar mavjud.
Xlordiazepoksid Ba'zida alternativ sifatida ishlatiladigan 5 mg kapsulalar diazepam uchun benzodiazepinni olib tashlash. Diazepam singari u uzoq vaqtga ega yarim umrni yo'q qilish va uzoq muddatli faol metabolitlar.

Benzodiazepinlarni to'xtatish yoki dozani keskin kamaytirish, nisbatan qisqa muddatli davolanish kursidan keyin ham (ikki-to'rt hafta), simptomlarning ikki guruhiga olib kelishi mumkin.tiklanish va chekinish. Rebound simptomlari - bu bemorga davolangan, ammo avvalgidan ham yomonroq bo'lgan alomatlarning qaytishi. Chiqib ketish alomatlari - bu benzodiazepin to'xtatilganda paydo bo'ladigan yangi alomatlar. Ular asosiy belgidir jismoniy qaramlik.[126]

Benzodiazepinlardan tez-tez chiqib ketish alomatlari uyqusizlik, oshqozon muammolari, titroq, qo'zg'alish, qo'rquv va mushaklarning spazmlari.[126] Kamroq tez-tez uchraydigan ta'sirlar asabiylashish, terlash, shaxssizlashtirish, derealizatsiya, ogohlantirishlarga yuqori sezuvchanlik, depressiya, o'z joniga qasd qilish xulq-atvor, psixoz, soqchilik va deliryum tremens.[136] Jiddiy alomatlar odatda keskin yoki haddan tashqari tez tortib olish natijasida yuzaga keladi. To'satdan olib tashlash xavfli bo'lishi mumkin, shuning uchun asta-sekin kamaytirish rejimi tavsiya etiladi.[11]

Semptomlar dozani asta-sekin kamaytirish paytida ham paydo bo'lishi mumkin, ammo odatda unchalik og'ir emas va uzoq davom etadigan qism sifatida saqlanib qolishi mumkin olib tashlash sindromi benzodiazepinlar to'xtaganidan keyin bir necha oy davomida.[137] Bemorlarning taxminan 10 foizi uzoq davom etadigan sindromni boshdan kechirmoqda, bu ko'p oylar yoki ba'zi hollarda bir yil yoki undan uzoq davom etishi mumkin. Uzaygan semptomlar pulni olib tashlashning dastlabki ikki oyida ko'rilganlarga o'xshaydi, lekin odatda og'irlik darajasida. Bunday alomatlar vaqt o'tishi bilan asta-sekin kamayib boradi va oxir-oqibat butunlay yo'q bo'lib ketadi.[138]

Benzodiazepinlar bemorlar va shifokorlar orasida og'ir va shikast etkazuvchi sabab bo'lganligi uchun obro'ga ega; ammo, bu pulni qaytarib olish jarayoni yomon boshqarilganligi sababli ko'p jihatdan. Benzodiazepinlardan haddan tashqari tez chiqib ketish, olib tashlash sindromining og'irligini oshiradi va muvaffaqiyatsizlik darajasini oshiradi. Sekin va asta-sekin chekinish shaxsga moslashtirilgan va agar ko'rsatilgan bo'lsa, psixologik yordam pulni olib tashlashni boshqarishning eng samarali usuli hisoblanadi. Chekishni yakunlash uchun zarur bo'lgan vaqt haqidagi fikr to'rt haftadan bir necha yilgacha. Olti oydan kam maqsad taklif qilindi,[11] ammo benzodiazepinning dozasi va turi, retsept uchun sabablar, turmush tarzi, shaxsiyat, ekologik stresslar va mavjud qo'llab-quvvatlash miqdori, chekinish uchun bir yil yoki undan ko'proq vaqt talab qilinishi mumkin.[14][24]:183–184

Chiqib ketish jismoniy jihatdan qaram bo'lgan bemorni diazepamning ekvivalent dozasiga o'tkazish yo'li bilan boshqariladi, chunki u barcha benzodiazepinlarning yarim umr ko'rish muddatiga ega, uzoq muddatli faol metabolitlarga metabolizmga uchragan va kam quvvatli tabletkalarda mavjud. kichik dozalar uchun to'rtdan biri.[139] Yana bir foydali tomoni shundaki, u suyuq shaklda mavjud bo'lib, bu hatto kichikroq pasayishlarga imkon beradi.[11] Xlordiazepoksid, which also has a long half-life and long-acting faol metabolitlar, can be used as an alternative.[139][140]

Nonbenzodiazepinlar are contraindicated during benzodiazepine withdrawal as they are xochga chidamli with benzodiazepines and can induce dependence.[14] Alcohol is also cross tolerant with benzodiazepines and more toxic and thus caution is needed to avoid replacing one dependence with another.[139] During withdrawal, ftorxinolon -based antibiotics are best avoided if possible; they displace benzodiazepines from their binding site and reduce GABA function and, thus, may aggravate withdrawal symptoms.[141] Antipsychotics are not recommended for benzodiazepine withdrawal (or other CNS depressant withdrawal states) especially klozapin, olanzapin yoki past kuch fenotiyazinlar masalan. xlorpromazin ular tutilish chegarasini pasaytiradi va olib tashlash oqibatlarini yomonlashtirishi mumkin; agar ishlatilgan bo'lsa, juda ehtiyot bo'lish kerak.[142]

Withdrawal from long term benzodiazepines is beneficial for most individuals.[114] Withdrawal of benzodiazepines from long-term users, in general, leads to improved physical and ruhiy salomatlik particularly in the elderly; although some long term users report continued benefit from taking benzodiazepines, this may be the result of suppression of withdrawal effects.[14][15]

Controversial associations

Beyond the well established link between benzodiazepines and psychomotor impairment resulting in motor vehicle accidents and falls leading to fracture; research in the 2000s and 2010s has raised the association between benzodiazepines (and Z-dorilar ) and other, as of yet unproven, adverse effects including dementia, cancer, infections, pancreatitis and respiratory disease exacerbations.[143]

Dementia

A number of studies have drawn an association between long-term benzodiazepine use and neuro-degenerative disease, particularly Alzheimer's disease.[144] It has been determined that long-term use of benzodiazepines is associated with increased dementia risk, even after controlling for protopathic bias.[12]

Yuqumli kasalliklar

Some observational studies have detected significant associations between benzodiazepines and respiratory infections such as pneumonia[145][146] where others have not.[147] A large meta-analysis of pre-marketing randomized controlled trials on the pharmacologically related Z-Drugs suggest a small increase in infection risk as well.[148] An immunodeficiency effect from the action of benzodiazepines on GABA-A receptors has been postulated from animal studies.[149][150]

Saraton

A Meta-analysis of observational studies has determined an association between benzodiazepine use and cancer, though the risk across different agents and different cancers varied significantly.[151] In terms of experimental basic science evidence, an analysis of carcinogenetic and genotoxicity data for various benzodiazepines has suggested a small possibility of carcinogenesis for a small number of benzodiazepines.[152]

Pankreatit

The evidence suggesting a link between benzodiazepines (and Z-Drugs) and pancreatic inflammation is very sparse and limited to a few observational studies from Taiwan.[153][154] A criticism of confounding can be applied to these findings as with the other controversial associations above. Further well-designed research from other populations as well as a biologically plausible mechanism is required to confirm this association.

Dozani oshirib yuborish

Asosiy maqola: Benzodiazepin dozasini oshirib yuborishi

Although benzodiazepines are much safer in overdose than their predecessors, the barbituratlar, they can still cause problems in overdose.[19] Taken alone, they rarely cause severe complications in dozani oshirib yuborish;[155] statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning from a single drug.[21] However, combining these drugs with spirtli ichimliklar, afyun yoki trisiklik antidepressantlar markedly raises the toxicity.[22][156][157] The elderly are more sensitive to the side effects of benzodiazepines, and poisoning may even occur from their long-term use.[158] The various benzodiazepines differ in their toxicity; temazepam appears most toxic in overdose and when used with other drugs.[159][160] The symptoms of a benzodiazepine overdose may include; uyquchanlik, noaniq nutq, nistagmus, gipotenziya, ataksiya koma, nafas olish tushkunligi va kardiorespiratuar hibsga olish.[157]

A reversal agent for benzodiazepines exists, flumazenil (Anexate). Its use as an antidot is not routinely recommended because of the high risk of resedation and seizures.[161] In a double-blind, placebo-controlled trial of 326 people, 4 people had serious adverse events and 61% became resedated following the use of flumazenil.[162] Numerous contraindications to its use exist. It is contraindicated in people with a history of long-term use of benzodiazepines, those having ingested a substance that lowers the seizure threshold or may cause an aritmiya, and in those with abnormal vital signs.[163] One study found that only 10% of the people presenting with a dozani oshirib yuboradigan benzodiazepin are suitable candidates for treatment with flumazenil.[164]

2
2
3
Left: US yearly overdose deaths involving benzodiazepines.[165] Center: The top line represents the number of benzodiazepine deaths that also involved opioids in the US. The bottom line represents benzodiazepine deaths that did not involve opioids.[165] Right: Chemical structure of the benzodiazepine flumazenil, whose use is controversial following benzodiazepine overdose.

O'zaro aloqalar

Individual benzodiazepines may have different o'zaro ta'sirlar with certain drugs. Depending on their metabolizm pathway, benzodiazepines can be divided roughly into two groups. The largest group consists of those that are metabolized by sitoxrom P450 (CYP450) enzymes and possess significant potential for interactions with other drugs. The other group comprises those that are metabolized through glyukuronidatsiya, kabi lorazepam, oksazepam va temazepam, and, in general, have few drug interactions.[81]

Many drugs, including og'iz kontratseptivlari, biroz antibiotiklar, antidepressantlar va qo'ziqorinlarga qarshi agents, inhibit cytochrome enzymes in the liver. They reduce the rate of elimination of the benzodiazepines that are metabolized by CYP450, leading to possibly excessive drug accumulation and increased side-effects. In contrast, drugs that induce cytochrome P450 enzymes, such as Sent-Jonning ziravorlari, antibiotik rifampitsin, va antikonvulsanlar karbamazepin va fenitoin, accelerate elimination of many benzodiazepines and decrease their action.[83][166] Taking benzodiazepines with alcohol, opioidlar va boshqalar markaziy asab tizimining depressantlari potentiates their action. This often results in increased sedation, impaired motor coordination, suppressed breathing, and other adverse effects that have potential to be lethal.[83][166] Antatsidlar can slow down absorption of some benzodiazepines; however, this effect is marginal and inconsistent.[83]

Farmakologiya

Farmakodinamika

Besh subbirlik (ikkita alfa, ikkita beta va bitta gamma) markaziy ion o'tkazuvchi gözenek atrofida beshburchak shaklida nosimmetrik tarzda joylashtirilgan GABAA retseptorlari majmuasining shakli. Ikki GABA bog'lash joyining joylashishi alfa va beta subbirligi o'rtasida, bitta benzodiazepin bog'lanish joyi alfa va gamma bo'linmalari o'rtasida joylashgan.
Schematic diagram of the (α1)2(-2)2(γ2) GABAA receptor complex that depicts the five-protein subunits that form the receptor, the chloride (Cl−) ion channel pore at the center, the two GABA active binding sites at the α1 and β2 interfaces and the benzodiazepine (BZD) allosteric binding site at the α1 and γ2 interface.

Benzodiazepines work by increasing the effectiveness of the endogenous chemical, GABA, to decrease the excitability of neyronlar.[167] This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain.

GABA controls the excitability of neurons by binding to the GABAA retseptorlari.[167] GABAA retseptorlari a oqsil kompleksi joylashgan sinapslar between neurons. All GABAA receptors contain an ion kanali o'tkazadi xlorid ions across neuronal hujayra membranalari and two binding sites for the neyrotransmitter gamma-aminobutyric acid (GABA), while a subset of GABAA receptor complexes also contain a single binding site for benzodiazepines. Binding of benzodiazepines to this receptor complex does not alter binding of GABA. Unlike other positive allosteric modulators that increase ligand binding, benzodiazepine binding acts as a positive allosteric modulator by increasing the total conduction of chloride ions across the neuronal cell membrane when GABA is already bound to its receptor. This increased chloride ion influx hyperpolarizes the neuron's membrana potentsiali. As a result, the difference between resting potential and threshold potential is increased and otish is less likely.Different GABAA receptor subtypes have varying distributions within different regions of the brain and, therefore, control distinct neyron zanjirlar. Hence, activation of different GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions.[168] In terms of the mechanism of action of benzodiazepines, their similarities are too great to separate them into individual categories such as anxiolytic or hypnotic. For example, a hypnotic administered in low doses produces anxiety-relieving effects, whereas a benzodiazepine marketed as an anti-anxiety drug at higher doses induces sleep.[169]

The subset of GABAA receptors that also bind benzodiazepines are referred to as benzodiazepine receptors (BzR). GABAA retseptorlari a heteromer composed of five subunits, the most common ones being two as, two βs, and one γ (a2β2γ1). For each subunit, many subtypes exist (α1–6, β1–3va γ1–3). GABAA receptors that are made up of different combinations of subunit subtypes have different properties, different distributions in the brain and different activities relative to pharmacological and clinical effects.[170] Benzodiazepines bind at the interface of the α and γ subunits on the GABAA retseptorlari. Binding also requires that alpha subunits contain a histidin amino acid residue, (ya'ni, a1, a2, a3 va a5 containing GABAA retseptorlari). For this reason, benzodiazepines show no affinity for GABAA o'z ichiga olgan retseptorlari a4 va a6 subunits with an arginin instead of a histidine residue.[171] Once bound to the benzodiazepine receptor, the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA neyrotransmitter. This increases the frequency of the opening of the associated chloride ion kanali va hyperpolarizes the membrane of the associated neuron. The inhibitory effect of the available GABA is potentiated, leading to sedative and anxiolytic effects. For instance, those ligands with high activity at the α1 are associated with stronger gipnoz effects, whereas those with higher affinity for GABAA receptors containing α2 and/or α3 subunits have good anti-anxiety activity.[172]

The benzodiazepine class of drugs also interact with peripheral benzodiazepine receptors. Peripheral benzodiazepine receptors are present in periferik asab tizimi to'qimalar, glial hujayralar, and to a lesser extent the central nervous system.[173] These peripheral receptors are not structurally related or coupled to GABAA retseptorlari. They modulate the immunitet tizimi and are involved in the body response to injury.[174][175] Benzodiazepines also function as weak adenosine reuptake inhibitors. It has been suggested that some of their anticonvulsant, anxiolytic, and muscle relaxant effects may be in part mediated by this action.[176] Benzodiazepines have binding sites in the periphery, however their effects on muscle tone is not mediated through these peripheral receptors. The peripheral binding sites for benzodiazepines are present in immune cells and gastrointestinal tract.[8]

Farmakokinetikasi

BenzodiazepinYarim hayot
(oralig'i, hours)		Speed of Onset
Alprazolam6–15[177][178]O'rta[177]
Flunitrazepam18-26Tez
Xlordiazepoksid10–30[177]O'rta[177]
Klonazepam19–60[177]Sekin[177]
Diazepam20–80[177]Tez[177]
Lorazepam10–20[177]O'rta[177]
Midazolam1.5-2.5[179]Tez
Oksazepam5–10[177]Sekin[177]
Prazepam50–200[177]Sekin[177]

A benzodiazepine can be placed into one of three groups by its yarim umrni yo'q qilish, or time it takes for the body to eliminate half of the dose.[180] Some benzodiazepines have long-acting faol metabolitlar, such as diazepam and chlordiazepoxide, which are metabolised into desmethyldiazepam. Desmethyldiazepam has a half-life of 36–200 hours, and flurazepam, with the main active metabolite of desalkylflurazepam, with a half-life of 40–250 hours. These long-acting metabolites are qisman agonistlar.[6][139]

Kimyo

Chap tomonda ota-benzodiazepin halqa tizimining kimyoviy tuzilishi joylashgan bo'lib, u olti a'zoli halqaga birlashtirilgan ikkita azot atomini o'z ichiga olgan etti a'zoli halqadan iborat. Ikki azot atomlari bitta va to'rtta deb etiketlanadi. O'ng tomonda farmakologik faol benzodiazepinning kimyoviy tuzilishi joylashgan bo'lib, unda alkil, fenil va halogen guruhlari navbati bilan bitta, beshta va ettita pozitsiyalarga birikadi va uglerod atomi ikkinchi holatda ekzosiklik kislorod atomi bilan ikki marta bog'lanadi. . Fenil o'rnini bosuvchi vositaning orto va para pozitsiyalari navbati bilan ikki va 4 darajali yorliqlarga ega.
Chapda: The 1,4-benzodiazepine ring system. To'g'ri: 5-phenyl-1H-benzo [e] [1,4]diazepin-2(3H)-one forms the skeleton of many of the most common benzodiazepine pharmaceuticals, such as diazepam (7-chloro-1-methyl substituted).
Benzodiazepin va benzododiazepin ligandining kimyoviy tuzilishlarining superpozitsiyasi va ularning retseptor ichidagi bog'lanish joylari bilan o'zaro ta'siri.
A farmakofor model of the benzodiazepine binding site on the GABAA retseptorlari.[181] White sticks represent the carbon atoms of the benzodiazepine diazepam, while green represents carbon atoms of the nonbenzodiazepine CGS-9896. Red and blue sticks are oxygen and nitrogen atoms that are present in both structures. The red spheres labeled H1 and H2/A3 are, respectively, vodorod aloqasi donating and accepting sites in the receptor, while L1, L2, and L3 denote lipofil majburiy saytlar.

Benzodiazepines share a similar chemical structure, and their effects in humans are mainly produced by the allosterik modification of a specific kind of neurotransmitter receptor, GABAA retseptorlari, which increases the overall conductance of these inhibitory channels; this results in the various therapeutic effects as well as adverse effects of benzodiazepines.[167] Other less important harakat usullari ham ma'lum.[174][176]

Atama benzodiazepin bo'ladi kimyoviy nomi uchun heterosiklik ring system (see figure to the right), which is a fusion between the benzol va diazepin halqa tizimlari.[182] Ostida Xantsz-Vidman nomenklaturasi, a diazepin is a heterocycle with two azot atoms, five uglerod atom and the maximum possible number of cumulative er-xotin obligatsiyalar. The "benzo" prefix indicates the benzol ring fused onto the diazepine ring.[182]

Benzodiazepine drugs are substituted 1,4-benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. Different benzodiazepine drugs have different side groups attached to this central structure. The different side groups affect the binding of the molecule to the GABAA receptor and so modulate the pharmacological properties.[167] Many of the pharmacologically active "classical" benzodiazepine drugs contain the 5-phenyl-1H-benzo [e] [1,4]diazepin-2(3H)-one substructure (see figure to the right).[183] Benzodiazepines have been found to mimic protein reverse turns structurally, which enable them with their biological activity in many cases.[184][185]

Nonbenzodiazepinlar also bind to the benzodiazepine binding site on the GABAA receptor and possess similar pharmacological properties. While the nonbenzodiazepines are by definition structurally unrelated to the benzodiazepines, both classes of drugs possess a common farmakofor (see figure to the lower-right), which explains their binding to a common receptor site.[181]

Turlari

  • 2-keto compounds:
klorazepat, diazepam, flurazepam, halazepam, prazepam va boshqalar[186][187]
  • 3-hydroxy compounds:
lorazepam, lormetazepam, oksazepam, temazepam[186][187]
  • 7-nitro compounds:
klonazepam, flunitrazepam, nimetazepam, nitrazepam[186][187]
  • Triazolo compounds:
adinazolam, alprazolam, estazolam, triazolam[186][187]
  • Imidazo compounds:
climazolam, loprazolam, midazolam[186][187]
  • 1,5-benzodiazepines:
clobazam

Tarix

Diazepin halqasiga birlashtirilgan benzol halqasining kimyoviy tuzilishi diagrammasi. Cl benzolga biriktirilgan; N, H, CH3 va O diazepinga biriktirilgan.
The molecular structure of xlordiazepoksid, the first benzodiazepine. Bu tomonidan sotilgan Hoffmann – La-Rosh from 1960 branded as Librium.

The first benzodiazepine, xlordiazepoksid (Librium), was synthesized in 1955 by Leo Sternbax ishlayotganda Hoffmann – La-Rosh on the development of tranquilizers. The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project. Two years later, in April 1957, co-worker Earl Reeder noticed a "nicely crystalline" compound left over from the discontinued project while spring-cleaning in the lab. This compound, later named chlordiazepoxide, had not been tested in 1955 because of Sternbach's focus on other issues. Expecting pharmacology results to be negative, and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests. The compound showed very strong tinchlantiruvchi, antikonvulsant va mushak gevşetici effektlar. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name Librium.[188][189] Following chlordiazepoxide, diazepam marketed by Hoffmann–La Roche under the brand name Valium in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of barbituratlar, and by the 1970s they had largely replaced the older drugs for sedative and gipnoz foydalanadi.[1]

The new group of drugs was initially greeted with optimism by the medical profession, but gradually concerns arose; in particular, the risk of dependence became evident in the 1980s. Benzodiazepines have a unique history in that they were responsible for the largest-ever sud jarayoni qarshi dori ishlab chiqaruvchilar in the United Kingdom, involving 14,000 patients and 1,800 yuridik firmalar that alleged the manufacturers knew of the dependence potential but intentionally withheld this information from doctors. At the same time, 117 general practitioners and 50 health authorities were sued by patients to recover damages for the harmful effects of qaramlik va chekinish. This led some doctors to require a signed consent form from their patients and to recommend that all patients be adequately warned of the risks of dependence and withdrawal before starting treatment with benzodiazepines.[190] The court case against the drug manufacturers never reached a verdict; yuridik yordam had been withdrawn and there were allegations that the consultant psychiatrists, the expert witnesses, had a conflict of interest.[191][192] The court case fell through, at a cost of £30 million, and led to more cautious funding through legal aid for future cases.[193] This made future class action lawsuits less likely to succeed, due to the high cost from financing a smaller number of cases, and increasing charges for losing the case for each person involved.[192]

Although antidepressants with anxiolytic properties have been introduced, and there is increasing awareness of the adverse effects of benzodiazepines, prescriptions for short-term anxiety relief have not significantly dropped.[10] For treatment of insomnia, benzodiazepines are now less popular than benzodiazepinlar o'z ichiga oladi zolpidem, zaleplon va eszopiklon.[194] Nonbenzodiazepines are molecularly distinct, but nonetheless, they work on the same benzodiazepine receptors and produce similar sedative effects.[195]

Benzodiazepines have been detected in plant specimens and brain samples of animals not exposed to synthetic sources, including a human brain from the 1940s. However, it is unclear whether these compounds are biosynthesized by microbes or by plants and animals themselves. A microbial biosynthetic pathway has been proposed.[196]

Jamiyat va madaniyat

Huquqiy holat

In the United States, benzodiazepines are Schedule IV drugs under the Federal Boshqariladigan moddalar to'g'risidagi qonun, even when not on the market (for example, nitrazepam va bromazepam ). Flunitrazepam is subject to more stringent regulations in certain states and temazepam prescriptions require specially coded pads in certain states.

In Canada, possession of benzodiazepines is legal for personal use. All benzodiazepines are categorized as IV jadval substances under the Nazorat ostidagi giyohvand moddalar va moddalar to'g'risidagi qonun.[197] Since 2000, benzodiazepines have been classed as targeted substances, meaning that additional regulations exist especially affecting pharmacists' records.[198] Since approximately 2014, Sog'liqni saqlash Kanada, Kanada tibbiyot birlashmasi and provincial Colleges of Physicians and Surgeons have been issuing progressively stricter guidelines for the prescription of benzodiazepines, especially for the elderly (e.g. College of Physicians and Surgeons of British Columbia).[199] Many of these guidelines are not readily available to the public.[200]

In the United Kingdom, the benzodiazepines are Class C controlled drugs, carrying the maximum penalty of 7 years imprisonment, an unlimited fine or both for possession and a maximum penalty of 14 years imprisonment an unlimited fine or both for supplying benzodiazepines to others.[201][202]

In the Netherlands, since October 1993, benzodiazepines, including formulations containing less than 20 mg of temazepam, are all placed on List 2 of the Afyun qonuni. A prescription is needed for possession of all benzodiazepines. Temazepam formulations containing 20 mg or greater of the drug are placed on List 1, thus requiring doctors to write prescriptions in the List 1 format.[203]

In East Asia and Southeast Asia, temazepam va nimetazepam are often heavily controlled and restricted. Ba'zi mamlakatlarda, triazolam, flunitrazepam, flutoprazepam va midazolam are also restricted or controlled to certain degrees. In Hong Kong, all benzodiazepines are regulated under Schedule 1 of Gonkongniki 134-bob Dangerous Drugs Ordinance.[204] Ilgari brotizolam, flunitrazepam va triazolam were classed as dangerous drugs.[205]

Internationally, benzodiazepines are categorized as IV jadval controlled drugs, apart from flunitrazepam, which is a III-jadval drug under the Psixotrop moddalar to'g'risidagi konventsiya.[206]

Dam olish uchun foydalanish

Xanax (alprazolam ) 2 mg tri-score tablets
Asosiy maqolalar: Benzodiazepin preparatini suiiste'mol qilish va Giyohvand moddalar bilan bog'liq jinoyatlar

Benzodiazepines are considered major drugs of abuse.[23] Benzodiazepine abuse is mostly limited to individuals who abuse other drugs, i.e., poly-drug abusers. On the international scene, benzodiazepines are categorized kabi IV jadval controlled drugs by the INCB, dan tashqari flunitrazepam, bu a III-jadval drug under the Psixotrop moddalar to'g'risidagi konventsiya.[207] Some variation in drug scheduling exists in individual countries; for example, in the United Kingdom, midazolam va temazepam bor Schedule III controlled drugs.[208]

British law requires that temazepam (but emas midazolam) be stored in safe custody. Safe custody requirements ensures that pharmacists and doctors holding stock of temazepam must store it in securely fixed double-locked steel safety cabinets and maintain a written register, which must be bound and contain separate entries for temazepam and must be written in ink with no use of correction fluid (although a written register is not required for temazepam in the United Kingdom). Disposal of expired stock must be witnessed by a designated inspector (either a local drug-enforcement police officer or official from health authority).[209][210] Benzodiazepine abuse ranges from occasional binges on large doses, to chronic and compulsive drug abuse of high doses.[211]

Benzodiazepines are commonly used recreationally by poly-drug users. O'lim is higher among poly-drug users that also use benzodiazepines. Heavy alcohol use also increases o'lim among poly-drug users.[21] Dependence and tolerance, often coupled with dosage escalation, to benzodiazepines can develop rapidly among drug misusers; withdrawal syndrome may appear after as little as three weeks of continuous use. Long-term use has the potential to cause both physical and psychological dependence and severe withdrawal symptoms such as depression, anxiety (often to the point of vahima hujumlari ) va agorafobiya.[16] Benzodiazepines and, in particular, temazepam are sometimes used intravenously, which, if done incorrectly or in an unsterile manner, can lead to medical complications including xo'ppozlar, selülit, tromboflebit, arterial puncture, chuqur tomir trombozi va gangrena. Sharing syringes and needles for this purpose also brings up the possibility of transmission of gepatit, HIV, and other diseases. Benzodiazepines are also misused intranazal ravishda, which may have additional health consequences. Once benzodiazepine dependence has been established, a clinician usually converts the patient to an equivalent dose of diazepam before beginning a gradual reduction program.[212]

A 1999–2005 Australian police survey of detainees reported preliminary findings that self-reported users of benzodiazepines were less likely than non-user detainees to work full-time and more likely to receive government benefits, use methamphetamine or heroin, and be arrested or imprisoned.[213] Benzodiazepines are sometimes used for criminal purposes; they serve to incapacitate a victim in cases of drug assisted rape yoki talonchilik.[214]

Umuman olganda, latifaviy dalillar buni taklif qiladi temazepam may be the most psychologically habit-forming (addictive) benzodiazepine. Temazepam abuse reached epidemic proportions in some parts of the world, in particular, in Europe and Australia, and is a major drug of abuse in many Southeast Asian countries. This led authorities of various countries to place temazepam under a more restrictive legal status. Some countries, such as Sweden, banned the drug outright.[215] Temazepam also has certain pharmacokinetic properties of absorption, distribution, elimination, and clearance that make it more apt to abuse compared to many other benzodiazepines.[216][217]

Veterinariyadan foydalanish

Benzodiazepines are used in veterinariya practice in the treatment of various disorders and conditions. As in humans, they are used in the first-line management of soqchilik, epileptikus holati va qoqshol, and as maintenance therapy in epilepsy (in particular, in cats).[218][219][220] They are widely used in small and large animals (including horses, swine, cattle and exotic and wild animals) for their anxiolytic and sedative effects, as pre-medication before surgery, for induction of behushlik and as adjuncts to anesthesia.[218][221]

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