Дигидрокодеин: Описание, применение и свойства опиоидного анальгетика.
Dihydrocodeine
Дигидрокодеин: обезболивающее опиоидное средство, используемое при боли и кашле. История, формы выпуска, противопоказания и риски внутривенного введения.
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Содержание
Введение
Опиоид
Opioid
Дигидрокодеин – это полусинтетический опиоидный анальгетик, назначаемый для облегчения боли или тяжелой одышки, или в качестве противокашлевого средства, как самостоятельно, так и в сочетании с парацетамолом (ацетаминофеном) (как в кодидрамоле) или аспирином. Он был разработан в Германии в 1908 году и впервые поступил в продажу в 1911 году. Обычно доступен в виде таблеток, растворов, эликсиров и других пероральных форм, а в некоторых странах также выпускается в виде инъекционного раствора для глубокого подкожного и внутримышечного введения. Как и в случае с кодеином, следует избегать внутривенного введения, поскольку оно может привести к анафилаксии и опасному для жизни отеку легких. В прошлом применялись суппозитории с дигидрокодеином. Дигидрокодеин доступен в форме суппозиториев по рецепту. Дигидрокодеин используется как альтернатива кодеину. Он был впервые описан в 1911 году и одобрен для медицинского применения в 1948 году. Дигидрокодеин был разработан в процессе поиска более эффективных средств от кашля, особенно для снижения распространения туберкулеза, коклюша и пневмонии в период примерно с 1895 по 1915 год. Он имеет сходную химическую структуру с кодеином. Дигидрокодеин в два раза сильнее кодеина. Хотя дигидрокодеин и имеет чрезвычайно активные метаболиты, такие как дигидроморфин и дигидроморфин-6-глюкуронид (в сто раз более мощные), эти метаболиты образуются в таких малых количествах, что не оказывают клинически значимого эффекта. Дигидрокодеин также является исходным компонентом и химической основой для ряда подобных полусинтетических опиоидов, таких как ацетилдигидрокодеин, дигидрокодеиноновый энолацетат, дигидроизокодеин, никокодеин и никодикодеин.
Dihydrocodeine is a semi synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co dydramol) or aspirin. It was developed in Germany in 1908 and first marketed in 1911. Commonly available as tablets, solutions, elixirs, and other oral forms, dihydrocodeine is also available in some countries as an injectable solution for deep subcutaneous and intra muscular administration. As with codeine, intravenous administration should be avoided, as it could result in anaphylaxis and life threatening pulmonary edema. In the past, dihydrocodeine suppositories were used. Dihydrocodeine is available in suppository form on prescription. Dihydrocodeine is used as an alternative to codeine. It was first described in 1911 and approved for medical use in 1948. Dihydrocodeine was developed during the search for more effective cough medication, especially to help reduce the spread of tuberculosis, pertussis, and pneumonia in the years from c. a. 1895 to 1915. It is similar in chemical structure to codeine. Dihydrocodeine is twice as strong as codeine. Although dihydrocodeine does have extremely active metabolites, in the form of dihydromorphine and dihydromorphine 6 glucuronide (one hundred times more potent), these metabolites are produced in such small amounts that they do not have clinically significant effects. Dihydrocodeine is also the original member and chemical base of a number of similar semi synthetic opioids such as acetyldihydrocodeine, dihydrocodeinone enol acetate, dihydroisocodeine, nicocodeine, and nicodicodeine.
Медицинское применение
Одобренным показанием для дигидрокодеина является лечение умеренной или умеренно выраженной боли, а также кашля и одышки. Как и в случае с другими препаратами этой группы, противокашляная доза обычно ниже, чем обезболивающая, и дигидрокодеин является эффективным средством для подавления кашля, как и все другие препараты, непосредственно полученные из кодеина (см. ниже), а также его аналоги – гидрокодон, оксикодон и этилморфин, препараты опия и сильный опиоид гидроморфон. Для облегчения боли дигидрокодеин обычно выпускается в форме таблеток или капсул, содержащих 15–16 мг или 30–32 мг, в сочетании с другими активными ингредиентами, такими как аспирин, парацетамол (ацетаминофен), ибупрофен или другие. Дигидрокодеин с контролируемым высвобождением доступен для лечения как боли, так и кашля, согласно нижеприведенной информации, в виде восковых таблеток, содержащих 60–120 мг действующего вещества. Некоторые препараты, предназначенные для лечения кашля и подобных состояний, содержат другие активные ингредиенты, такие как антигистаминные средства, деконгестанты и другие. Также доступны и другие пероральные формы, такие как пакетики с шипучим порошком, сублингвальные капли, эликсиры и т.п., в различных странах. Инъекционный дигидрокодеин чаще всего вводят в виде глубокой подкожной инъекции.
Approved indication for dihydrocodeine is the management of moderate to moderately severe pain as well as coughing and shortness of breath. As is the case with other drugs in this group, the antitussive dose tends to be less than the analgesic dose, and dihydrocodeine is a powerful cough suppressant like all other members of the immediate codeine family (see below) and their cousins hydrocodone, oxycodone and ethylmorphine, whole opium preparations, and the strong opioid hydromorphone. For use against pain, dihydrocodeine is usually formulated as tablets or capsules containing 15–16 mg or 30–32 mg with or without other active ingredients such as aspirin, paracetamol (acetaminophen), ibuprofen, or others. Controlled release dihydrocodeine is available for both pain and coughing, as indicated below, as waxy tablets containing 60 to 120 mg of the drug. Some formulations, intended for use against coughing and the like, have other active ingredients such as antihistamines, decongestants and others. Other oral formulations, such as packets of effervescent powder, sublingual drops, elixirs and the like are also available in many locations. Injectable dihydrocodeine is most often given as a deep subcutaneous injection.
Побочные эффекты
Как и при применении других опиоидов, при повторном приеме дигидрокодеина развивается толерантность и физическая и психологическая зависимость. Все опиоиды могут ухудшать умственные или физические способности, необходимые для выполнения потенциально опасных задач, таких как вождение автомобиля или управление механизмами, при применении в больших дозах. Частыми побочными эффектами являются зуд, покраснение и другие эффекты расширения кровеносных сосудов, вызванные высвобождением гистамина в ответ на лекарственный препарат, действующий через один или несколько типов рецепторов в ЦНС или другие реакции в организме. Антигистамины первого поколения, такие как трипеленнамин (Пирабензамин), клемастин (Тавист), гидроксизин (Атаракс), дифенгидрамин (Бенадрил), ципрогептадин (Периактин), бромфенирамин (Диметап), хлорфенирамин (Хлор Триметон), доксиламин (Найквил) и феноилтолоксамин (Пергогезическая оригинальная формула), не только купируют побочные эффекты, вызванные гистамином, но и в различной степени обладают анальгетикосберегающим (потенцирующим) действием. Антигистаминный препарат прометазин (Фенерган) также может положительно влиять на печеночный метаболизм дигидрокодеина, как и кодеин. Более высокие дозы прометазина могут взаимодействовать с большинством других опиоидов, за исключением семейства петидинов (Демерол и аналогичных), посредством этого или других неизвестных механизмов. Как и в случае с любыми лекарствами, побочные эффекты зависят от принимающего препарат человека и могут варьироваться по степени тяжести от легких до крайне выраженных, от головных болей до затрудненного дыхания. Запор – это почти универсальный побочный эффект дигидрокодеина и большинства опиоидов, возникающий из-за замедления перистальтики кишечника. Именно поэтому дигидрокодеин, этилморфин, кодеин, опиумные препараты и морфин используются для прекращения диареи и лечения синдрома раздраженного кишечника (СРК) в его диарейных и циклических формах, а также других состояний, вызывающих гипермоторику или кишечные спазмы. Опиумные/опиоидные препараты часто используются в качестве крайней меры при сильной боли и органической слабости кишечника. Обычно лучше лечить СРК непсихотропными опиоидами, такими как лоперамида гидрохлорид, который остается в кишечнике, не вызывая сонливости и позволяя многим людям работать с механизмами и т.д. При СРК гиосцинбутилбромид (Buscopan в Великобритании) и мебеверина гидрохлорид (Colofac) могут быть эффективны как в сочетании с опиумными соединениями, так и без них. Препараты из Списка 3, остающиеся безрецептурными, могут быть выданы только после консультации с фармацевтом. Это лекарственное средство Списка 4 (только по рецепту) при смешивании с одним или несколькими другими терапевтически активными веществами и при содержании не более 100 мг дигидрокодеина в дозе.
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses. Itching and flushing and other effects of blood vessel dilation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine driven side effects, but are analgesic sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms. As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing. Constipation is the one side effect of dihydrocodeine and almost all opioids which is near universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound. Schedule 3 drugs, while still OTC, can only be dispensed after consultation with a pharmacist. It is a Schedule 4 (prescription only) drug when compounded with one or more other therapeutically active substances and not exceeding 100 mg dihydrocodeine per dose. Hong Kong In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine or 7 years imprisonment. Japan In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. United Kingdom In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over the counter in small amounts (less than 8 mg), when combined with paracetamol (see co dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. United States In the US, pure dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine can also be classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos. International treaties and the controlled substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient. Controlled release dihydrocodeine is a non prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine and codeine products.
Гонконг: В Гонконге дигидрокодеин регулируется в соответствии с Приложением 1 к главе 134 Указа о наркотических средствах Гонконга. Его могут использовать только медицинские работники и в целях университетских исследований. Фармацевт может выдать дигидрокодеин при наличии рецепта врача. Любое лицо, поставляющее вещество без рецепта, может быть оштрафовано на 10 000 гонконгских долларов (HKD). За незаконный оборот или производство наркотиков предусмотрен штраф в размере 5 000 000 гонконгских долларов (HKD) и пожизненное заключение. Владение веществом для потребления без лицензии Министерства здравоохранения является незаконным и влечет за собой штраф в размере 1 000 000 гонконгских долларов (HKD) или 7 лет лишения свободы.
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses. Itching and flushing and other effects of blood vessel dilation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine driven side effects, but are analgesic sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms. As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing. Constipation is the one side effect of dihydrocodeine and almost all opioids which is near universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound. Schedule 3 drugs, while still OTC, can only be dispensed after consultation with a pharmacist. It is a Schedule 4 (prescription only) drug when compounded with one or more other therapeutically active substances and not exceeding 100 mg dihydrocodeine per dose. Hong Kong In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine or 7 years imprisonment. Japan In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. United Kingdom In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over the counter in small amounts (less than 8 mg), when combined with paracetamol (see co dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. United States In the US, pure dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine can also be classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos. International treaties and the controlled substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient. Controlled release dihydrocodeine is a non prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine and codeine products.
Япония: В Японии дигидрокодеин доступен без рецепта и используется в лекарствах от кашля, таких как New Bron Solution ACE. Дигидрокодеин используется в качестве противокашляного средства во многих препаратах в качестве альтернативы декстрометорфану. Лекарства, содержащие дигидрокодеин в Японии, сочетаются с кофеином для смягчения седативного эффекта и предотвращения рекреационного использования. Лекарства от кашля, содержащие дигидрокодеин, контролируются аналогично декстрометорфану в Соединенных Штатах, поскольку их продажа строго ограничена количеством покупки и разрешена только лицам старше 20 лет.
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses. Itching and flushing and other effects of blood vessel dilation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine driven side effects, but are analgesic sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms. As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing. Constipation is the one side effect of dihydrocodeine and almost all opioids which is near universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound. Schedule 3 drugs, while still OTC, can only be dispensed after consultation with a pharmacist. It is a Schedule 4 (prescription only) drug when compounded with one or more other therapeutically active substances and not exceeding 100 mg dihydrocodeine per dose. Hong Kong In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine or 7 years imprisonment. Japan In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. United Kingdom In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over the counter in small amounts (less than 8 mg), when combined with paracetamol (see co dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. United States In the US, pure dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine can also be classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos. International treaties and the controlled substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient. Controlled release dihydrocodeine is a non prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine and codeine products.
Соединенное Королевство: В Соединенном Королевстве дигидрокодеин является препаратом класса B, но доступен без рецепта в небольших количествах (менее 8 мг) в сочетании с парацетамолом (см. co-dydramol). Дигидрокодеин внесен в Список 5 Положения о контроле за наркотическими средствами 2001 года, в соответствии с которым он освобожден от запрета на владение, если он представлен в виде одной лекарственной формы, не предназначенной для инъекций и содержащей не более 100 мг (в пересчете на свободное основание) или имеющей общую концентрацию менее 2,5% (в пересчете на свободное основание). Незаконное владение дигидрокодеином может повлечь за собой лишение свободы на срок до 5 лет или неограниченный штраф.
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses. Itching and flushing and other effects of blood vessel dilation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine driven side effects, but are analgesic sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms. As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing. Constipation is the one side effect of dihydrocodeine and almost all opioids which is near universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound. Schedule 3 drugs, while still OTC, can only be dispensed after consultation with a pharmacist. It is a Schedule 4 (prescription only) drug when compounded with one or more other therapeutically active substances and not exceeding 100 mg dihydrocodeine per dose. Hong Kong In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine or 7 years imprisonment. Japan In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. United Kingdom In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over the counter in small amounts (less than 8 mg), when combined with paracetamol (see co dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. United States In the US, pure dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine can also be classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos. International treaties and the controlled substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient. Controlled release dihydrocodeine is a non prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine and codeine products.
Соединенные Штаты: В США чистый дигидрокодеин является веществом Списка II DEA, хотя препараты, содержащие небольшие количества дигидрокодеина, также могут быть классифицированы как Списки III или V в зависимости от концентрации дигидрокодеина по отношению к другим активным компонентам, таким как парацетамол (ацетаминофен). Эта классификация аналогична классификации в Великобритании. ACSCN DEA для дигидрокодеина свободного основания и всех солей – 9120. Годовой совокупный квота производства на 2013 год – 250 кг. Международные договоры и законы о контролируемых веществах большинства стран, такие как немецкий Betäubungsmittelgesetz, регулируют дигидрокодеин на том же уровне, что и кодеин. Фармацевтические препараты на основе дигидрокодеина особенно используются в случаях, когда пациенты с хронической болью могут иметь практически безрецептурный доступ к ним при условии регистрации в качестве таких пациентов в провинциальном или национальном правительстве. Дигидрокодеин с контролируемым высвобождением является безрецептурным препаратом в некоторых местах, особенно в дозировке 60 мг. В отчете организации Ivo Šandor от 2004 года указано, что Андорра, Испания, Гибралтар и Австрия имеют различную степень доступа к этим и другим продуктам, содержащим дигидрокодеин, никокодеин и кодеин.
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses. Itching and flushing and other effects of blood vessel dilation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine driven side effects, but are analgesic sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms. As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing. Constipation is the one side effect of dihydrocodeine and almost all opioids which is near universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound. Schedule 3 drugs, while still OTC, can only be dispensed after consultation with a pharmacist. It is a Schedule 4 (prescription only) drug when compounded with one or more other therapeutically active substances and not exceeding 100 mg dihydrocodeine per dose. Hong Kong In Hong Kong, dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. A pharmacist can dispense Dihydrocodeine when furnished with a doctors prescription. Anyone who supplies the substance without a prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption, without a licence from the Department of Health, is illegal and carries a $1,000,000 (HKD) fine or 7 years imprisonment. Japan In Japan, dihydrocodeine is available without a prescription; used in cough medicines such as New Bron Solution ACE. Dihydrocodeine is used as an antitussive in many products as a Dextromethorphan alternative. Medicines in Japan which contain dihydrocodeine are coupled with caffeine to offset the sedative effects and discourage recreational use. Cough medicines containing dihydrocodeine are controlled similarly to dextromethorphan in the United States, in that its sale is strictly limited by purchase quantity and is restricted to persons 20 and older for purchase. United Kingdom In the United Kingdom, dihydrocodeine is a Class B drug; but, it is available over the counter in small amounts (less than 8 mg), when combined with paracetamol (see co dydramol). Dihydrocodeine is listed in Schedule 5 of the Misuse of Drugs Regulations 2001 whereby it is exempt from prohibition on possession provided that it is in the form of a single preparation not being designed for injection and less than 100 mg (calculated as free base) or with a total concentration less than 2.5% (calculated as free base). Illegal possession of dihydrocodeine can result in up to 5 years in prison or an unlimited fine. United States In the US, pure dihydrocodeine is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine can also be classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to the UK's. The DEA's ACSCN for dihydrocodeine free base and all salts is 9120. The 2013 annual aggregate manufacturing quota is 250 kilos. International treaties and the controlled substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient. Controlled release dihydrocodeine is a non prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine and codeine products.
Химия
Он доступен в виде следующих солей, в приблизительном порядке убывания частоты использования: битартрат, фосфат, гидрохлорид, тартрат, гидроиодид, метилиодид, гидробромид, сульфат и тиоцианат. Коэффициенты пересчета солей в свободное основание составляют 0,67 для битартрата, 0,73 для фосфата и 0,89 для гидрохлорида. Дигидрокодеин является исходным веществом для ряда умеренно сильных наркотических средств, включая, в частности, гидрокодон, никокодеин, никодикодеин, тебаин и ацетилдигидрокодеин. В то время как превращение кодеина в морфин – сложная и малоэффективная задача, дигидрокодеин можно превратить в дигидроморфин с очень высоким выходом (более 95%). Дигидроморфин широко используется в Японии. Дигидроморфин можно количественно превратить в гидроморфон с использованием трет-бутоксида калия. Дигидрокодеин можно предварительно обнаружить с помощью реактива Фрёде.
It is available as the following salts, in approximate descending order of frequency of use: bitartrate, phosphate, hydrochloride, tartrate, hydroiodide, methyliodide, hydrobromide, sulfate, and thiocyanate. The salt to free base conversion factors are 0.67 for the bitartrate, 0.73 for the phosphate, and 0.89 for the hydrochloride. Dihydrocodeine is the parent drug of a series of moderately strong narcotics including, among others, hydrocodone, nicocodeine, nicodicodeine, thebaine and acetyldihydrocodeine. Whereas converting codeine to morphine is a difficult and unrewarding task, dihydrocodeine can be converted to dihydromorphine with very high yields (over 95%). Dihydromorphine is widely used in Japan. The dihydromorphine can be quantitatively converted to hydromorphone using potassium tert butoxide. Dihydrocodeine can be presumptively detected by the Froehde reagent.
Рекреационное использование
Поскольку дигидрокодеин может вызывать эйфорию при приеме в дозах, превышающих терапевтические, его довольно часто используют в рекреационных целях. Обычно рекреационная доза варьируется от 70 до 500 мг, а у людей с развившейся толерантностью – и больше. При употреблении дигидрокодеина без медицинского контроля часто добавляют потенцирующие вещества и адъюванты, особенно каризопродол, глутетимид, гидроксизин и антигистаминные препараты первого поколения, чтобы усилить эффект и уменьшить побочные эффекты, такие как зуд.
As dihydrocodeine can provide a euphoric high when taken in higher than therapeutic doses, it is quite commonly used recreationally. The typical recreational dose can be anything from 70 mg to 500 mg, or, in users with tolerance, even more. Potentiators and adjuvants are often included when dihydrocodeine is used in an unsupervised fashion, especially carisoprodol, glutethimide, hydroxyzine and first generation antihistamines, both to intensify the effect and lessen side effects such as itching.
История
Два известных потребителя дигидрокодеина — Уильям С. Берроуз, который описывал его как "вдвое сильнее кодеина и почти такой же хороший, как героин", и Герман Геринг, известный морфинозависимый (Гитлер называл его "морфинистом"), потреблявший до 100 таблеток (3 грамма) дигидрокодеина в день. Он был захвачен союзниками с большим количеством препарата в чемодане, предположительно более 20 000 таблеток. По другим данным, Герман Геринг принимал 20 таблеток утром и 20 вечером, чтобы избежать синдрома отмены морфина. В Германии наблюдался серьезный дефицит морфина, поэтому Геринг использовал огромные количества дигидрокодеина. Он также употреблял морфин и оксикодон, начав с терапевтического применения морфина после ранения в пах во время Ноябрьского пивного путча 1923 года в Мюнхене, а затем использовал дигидрокодеин в начале 1930-х годов от зубной боли.
Two famous users of dihydrocodeine were William S. Burroughs, who described it as "twice as strong as codeine and almost as good as heroin" and Hermann Göring, who was a known morphine addict (Hitler referred to him as the "morphinist"), consumed up to 100 tablets (3 grams) of dihydrocodeine per day and was captured by the Allies with a large quantity of the drug in a suitcase, reportedly more than 20,000 tablets. Another account suggest Hermann Göring was taking 20 tablets in the morning and 20 at night to ward off morphine withdrawals. Germany was experiencing a massive shortage of morphine, and as a result Göring used massive amounts of dihydrocodeine. He also used morphine and oxycodone, beginning with therapeutic use of morphine after being wounded in the groin during the November 1923 Beer Hall Putsch in Munich and then used dihydrocodeine in the early 1930s for toothache.
Brand names for dihydrocodeine products include Drocode, Paracodeine, Parzone, Rikodeine, Trezix, Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution ACE, Huscode, Drocode, Paracodin, Paramol (UK), Codidol, Dehace, DHC Continus, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Remedeine, Dico, Synalgos DC (US), and DF 118.
Подготовка и доступность
Дигидрокодеиновые препараты, которые можно приобрести без рецепта во многих странах Европы и тихоокеанского региона, обычно содержат от 2 до 20 мг дигидрокодеина в одной дозе в сочетании с одним или несколькими другими активными ингредиентами, такими как парацетамол (ацетаминофен), аспирин, ибупрофен, антигистаминные препараты, сосудосуживающие средства, витамины, лекарственные травяные препараты и другие подобные ингредиенты. В некоторых из этих стран и заморских территориях таблетки дозировкой 30 мг и 60 мг с контролируемым высвобождением доступны без рецепта, и фармацевты вполне могут отпускать препараты дозировкой 90 и 120 мг по своему усмотрению. В Соединенных Штатах наиболее распространенными обезболивающими брендами, содержащими дигидрокодеин, являются: DHC Plus (16 и 32 мг), Panlor SS (32 мг), ZerLor (32 мг), Panlor DC (16 мг) и Synalgos DC (16 мг). Эти комбинированные препараты также включают парацетамол (ацетаминофен) и кофеин. Аспирин используется в препарате Synalgos DC. Дигидрокодеин иногда выпускается в комбинации с парацетамолом под названием ко-дидрамол (BAN) для обеспечения более выраженного обезболивающего эффекта, чем при использовании каждого из компонентов по отдельности (см. Synergy § Drug synergy). В Великобритании и других странах доступны таблетки 30 мг, содержащие только дигидрокодеин в качестве активного ингредиента, а также таблетки 40 мг дигидрокодеина, доступные в Великобритании под названием DF 118 Forte. Оригинальный продукт, содержащий дигидрокодеин, – Паракодин, – это эликсир дигидрокодеина гидроиодида, также доступный в виде суспензии, подобной Tussionex, во многих европейских странах. Во многих европейских странах и в других регионах мира наиболее распространенными препаратами дигидрокодеина являются таблетки пролонгированного действия, изготовленные из гранул смеси ингредиентов, почти всегда с использованием битартрата дигидрокодеина, четырех разных размеров, в связующем на основе воска. Наиболее распространенные торговые названия таблеток пролонгированного действия: Didor Continus, Codidol, Codi Contin, Dicodin (производится во Франции и является основным продуктом, содержащим тартратную соль), Contugesic, DHC и DHC Continus. В Японии дигидрокодеин доступен в виде таблеток, содержащих 2,5 мг дигидрокодеина фосфата и кофеина, сосудосуживающее средство d,l-метилэфедрина HCl и антигистамин хлорфенирамин, а также в виде пакетов с гранулами, которые шипят, как Alka Seltzer, содержащих 10 мг дигидрокодеина с лизоцимом и хлорфенирамином, и продаются без рецепта под названием New Bron Solution ACE. Эти две формы могут содержать цитрат фенилтолоксамина в качестве антигистаминного компонента. В других странах тихоокеанского региона Дикогезик аналогичен DF 118 от Glaxo/Smith Kline. Производитель New Bron Solution ACE, SS Pharmaceutical Co., Ltd, также выпускает препарат, содержащий ибупрофен и дигидрокодеин, под названием S. Tac EVE, который также включает d,l-метилэфедрина HCl, хлорфенирамин, безводный кофеин и витамины B1 и C. Серия Panlor производится компанией Pan American Laboratories в Ковингтоне, штат Луизиана, и они также выпускают несколько рецептурных сиропов от кашля на основе дигидрокодеина в Соединенных Штатах.
Dihydrocodeine products which can be purchased over the counter in many European and Pacific Rim countries generally contain from 2 to 20 mg of dihydrocodeine per dosing unit combined with one or more other active ingredients such as paracetamol (acetaminophen), aspirin, ibuprofen, antihistamines, decongestants, vitamins, medicinal herb preparations, and other such ingredients. In a subset of these countries and foreign possessions, 30 mg tablets and 60 mg controlled release tablets are available over the counter and chemists may very well be able to dispense the 90 and 120 mg strengths at their discretion. In the United States, the most common analgesic brands with dihydrocodeine are: DHC Plus (16 and 32 mg), Panlor SS (32 mg), ZerLor (32 mg), Panlor DC (16 mg) and Synalgos DC (16 mg). These combination products also include paracetamol (acetaminophen) and caffeine. Aspirin is used in the case of Synalgos DC. Dihydrocodeine is sometimes marketed in combination preparations with paracetamol as co dydramol (BAN) to provide greater pain relief than either agent used singly (see Synergy § Drug synergy). In the UK and other countries, 30 mg tablets containing only dihydrocodeine as the active ingredient are available, also a 40 mg Dihydrocodeine tablet is available in the UK as DF 118 Forte. The original dihydrocodeine product, Paracodin, is an elixir of dihydrocodeine hydroiodide also available as a Tussionex style suspension in many European countries. In many European countries and elsewhere in the world, the most commonly found dihydrocodeine preparations are extended release tablets made by encasing granules of the ingredient mixture, almost always using the bitartrate salt of dihydrocodeine, of four different sizes in a wax based binder. The usual strengths are 60, 90, and 120 mg. Common trade names for the extended release tablets are Didor Continus, Codidol, Codi Contin, Dicodin (made in France and the major product containing the tartrate salt), Contugesic, DHC, and DHC Continus. Dihydrocodeine is available in Japan as tablets which contain 2.5 mg of dihydrocodeine phosphate and caffeine, the decongestant d,l methylephedrine HCl, and the antihistamine chlorpheniramine, and packets of granules which effervesce like Alka Seltzer with 10 mg of dihydrocodeine with lysozyme and chlorpheniramine, marketed for OTC sale as New Bron Solution ACE. These two formulations may have once contained phenyltoloxamine citrate as the antihistamine component. Elsewhere in the Pacific Rim, Dicogesic in analogous to Glaxo/Smith Kline's DF 118. The manufacturer of New Bron Solution ACE; SS Pharmaceutical Co., Ltd, also markets an ibuprofen with dihydrocodeine product called S. Tac EVE, which also includes d,l methylephedrine HCl, chlorpheniramine, anhydrous caffeine, and vitamins B1 and C.
The Panlor series is manufactured by Pan American Laboratories of Covington, Louisiana, and they also market several dihydrocodeine based prescription cough syrups in the United States.