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| {{drugbox | IUPAC_name = methyl 1-(2-methoxycarbonylethyl)-4-(phenyl-propanoyl-amino) -piperidine-4-carboxylate | image = Remifentanil.png | CAS_number = 132875-61-7 | ATC_prefix = N01 | ATC_suffix = AH06 | ATC_supplemental = | PubChem = 60815 | DrugBank = APRD01216 | C=20 | H=28 | N=2 | O=5 | molecular_weight = 376.447 g/mol | smiles = | melting_point = 5 | bioavailability = Not applicable (intravenous administration)| protein_bound = 70% (bound to plasma proteins) | metabolism = cleaved by non-specific plasma and tissue esterases| elimination_half-life = 1-20 minutes | pregnancy_category = | legal_US = Schedule II legal_NL = List I| routes_of_administration = Intravenous}}
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| '''Remifentanil''' (marketed by Abbott as '''Ultiva®''') is a potent ultra short-acting synthetic [[opioid]] [[analgesic]] [[medication|drug]]. It is given to patients during surgery to relieve pain and as an adjunct to an [[anaesthetic]]. Remifentanil is used for [[sedation]] as well as combined with other medications for use in [[general anesthesia]]. The use of remifentanil has made possible the use of high dose opioid and low dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.
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| ==Dosing==
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| It is administered in the form ''remifentanil hydrochloride'' and in adults is given as an [[intravenous infusion]] in doses ranging from 0.1 microgram per kilogram per minute to 0.5 (µg/kg)/min. Children may require higher infusion rates (up to 1.0 (µg/kg)/min).<ref>Weale NK, Rogers CA, Cooper R, Nolan J, Wolf AR. Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery. Br J Anaesth. 2004 Feb;92(2):187-94.</ref> Doses listed in the package insert from its manufacturer are much higher than those used in actual clinical practice. The clinically useful infusion rates are 0.025-0.1 (µg/kg)/min for sedation (rates adjusted to age of patient, severity of their illness and invasiveness of surgical procedure). Small amounts of other sedative medications are usually co-administered with remifentanil to produce sedation. Clinically useful infusion rates in [[general anesthesia]] vary but are usually 0.1-1 µg/kg/min[http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19980206000098&DocTypeID=3&UserTypeID=0]. Remifentanil is also used in computer controlled infusion pumps in a concept called target controlled infusion or [[TCI]]. A target plasma concentration is entered in microgram/ml into the pump and it thereafter keeps the infusion at an optimal speed. Two dosing modes are therefor common when using remifentanil clinically, the µg/kg/min and microgram/ml when using target controlled infusions.
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| ==Metabolism==
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| Unlike other synthetic opioids which are hepatically metabolised, remifentanil has an [[ester]] linkage which undergoes rapid hydrolysis by non-specific tissue and [[plasma esterase]]s. This means that accumulation does not occur with remifentanil and its [[context-sensitive half-life]] remains at 4 minutes after a 4 hour infusion.
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| Remifentanil is metabolised to a compound (remifentanil acid) which has 1/4600 the potency of the parent compound.<ref>Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther. 1997 Apr;281(1):226-32</ref>
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| Due to its quick metabolism and short effects remifentanil has opened up new possibilities in anesthesia. When remifentanil is used together with a hypnotic drug (i.e. one that produces sleep) it can be used in relative high doses. This is because remifentanil will be rapidly eliminated from the blood plasma on termination of the remifentanil infusion, hence the effects of the drug will quickly dissipate even after very long infusions. Due to synergism between remifentanil and hypnotic drugs (such as [[propofol]]) the dose of the hypnotic can be substantially reduced. This leads often to more haemodynamic stablity during surgery and a quicker post-operative recovery time.
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| ==Side-effects==
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| Remifentanil is a specific [[Opioid receptor|μ-receptor]] agonist. Hence, it causes a reduction in [[sympathetic nervous system]] tone, [[respiratory depression]] and [[analgesia]]. The drug's effects include a dose-dependent decrease in [[heart rate]] and [[arterial pressure]] and [[respiratory rate]] and [[tidal volume]]. [[Muscle rigidity]] is sometimes noted.
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| The most common side effects reported by patients receiving this medication are a sense of extreme "dizziness" (often short lived, a common side effect of other fast-acting synthetic phenylpiperidine narcotics such as [[fentanyl]] and [[alfentanil]]) and intense itching ([[pruritus]]), often around the face. These side effects are often controlled by either altering the administered dose (decreasing or in some cases, increasing the dose) or by administering other [[sedative]]s that allow the patient to tolerate or lose awareness of the side effect.
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| Because pruritus is due to excessive serum histamine levels, antihistamines such as diphenhydramine (benadryl) are often co-administered. This is done with care, however, as excessive sedation may occur.
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| Nausea can occur as a side effect of remifentanil, however, it is usually transient in nature due to the drug's short half life which rapidly removes it from the patient's [[Circulatory system|circulation]] once the infusion is terminated.
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| == Potency ==
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| Remifentanil has a similar potency to fentanyl
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| ==Circumventing Naltrexone==
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| Remifentanil has been used with some success to circumvent [[naltrexone]] in patients who are in need of pain management.
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| ==Administration==
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| Remifentanil can be administered as part of a TIVA (Total Intravenous Anaesthesia technique) using TCA. Target Controlled Anaesthesia. The short context-sensitive half-life allows the plasma level or effector site level to be achieved quickly and recovery to occur quickly.
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| Induction levels of 4 pg/ml are commonly used.
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| ==Regulation==
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| In [[Hong Kong]], Remifentanil is regulated under Schedule 1 of [[Hong Kong|Hong Kong's]] Chapter 134 ''Dangerous Drugs Ordinance''. It can only be used legally by health professionals and for university research purporses. The substance can be given by pharmacists under a prescription. Anyone who supply the substance without prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 ([[Hong Kong dollar|HKD]]) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
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| ==References==
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| <references/>
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| ==External links==
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| {{General anesthetics}}
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| {{Analgesics}}
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| [[de:Remifentanil]]
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| [[fr:Rémifentanil]]
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| [[ja:レミフェンタニル]]
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| [[th:รีมิเฟนทานิล]]
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| [[es:Remifentanilo]]
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| [[Category:Opioids]]
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| [[Category:Piperidines]]
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| [[Category:Drugs]]
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