|Trade names||Ultiva, others|
|Other names||methyl 1-(2-methoxycarbonylethyl)-4-(phenyl-propanoyl-amino)-piperidine-4-carboxylate|
|Side effects||Respiratory depression (decreased breathing), slow heart rate, low blood pressure, stiff muscles, nausea, itchiness|
|Onset of action||Within 90 sec|
|Duration of action||Up to 15 minutes|
|Bioavailability||Not applicable (intravenous administration)|
|Protein binding||70% (bound to plasma proteins)|
|Metabolism||cleaved by non-specific plasma and tissue esterases|
|Elimination half-life||1-20 minutes|
|Chemical and physical data|
|Molar mass||376.453 g·mol−1|
|3D model (JSmol)|
|Melting point||5 °C (41 °F)|
Remifentanil, sold under the brand name Ultiva among others, is an opioid medication used to treat during anesthesia to manage pain. It is given by injection into a vein. Effects begin within 90 seconds and last up to 15 minutes.
Common side effects include respiratory depression (decreased breathing), slow heart rate, low blood pressure, stiff muscles, nausea, and itchiness. Breastfeeding is not recommended for 24 hours after use. It works by activating the mu opioid receptor.
Remifentanil was approved for medical use in the United States in 1996. It is available as a generic medication. In the United Kingdom 1 mg costs the NHS about £5 as of 2021. In the United States this amount costs about 55 USD. In the United States it is classified as a Schedule II controlled substance.
Remifentanil is used as an opioid analgesic that has a rapid onset and rapid recovery time. It has been used effectively during craniotomies, spinal surgery, cardiac surgery, and gastric bypass surgery. While opiates function similarly, with respect to analgesia, the pharmacokinetics of remifentanil allows for quicker post-operative recovery.
In adults it is given as an intravenous infusion in doses ranging from 0.1 µg/kg/min to 0.5 µg/kg/min. Children may require higher infusion rates (up to 1.0 (µg/kg)/min). 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.
Remifentanil can be administered as part of an anesthesia technique called TIVA (Total Intravenous Anesthesia) using computer controlled infusion pumps in a process called target controlled infusion (TCI). A target plasma concentration is entered as ng/ml into the pump, which calculates its infusion rate according to patient factors like age and weight. Induction levels of 40 ng/ml are commonly used, but it generally varies between 3-8 ng/ml. For certain surgical procedures that produce particularly strong stimuli a level of up to 15 ng/ml might be needed. The relatively short context-sensitive half-life of Remifentanil allows the desired blood plasma level to be achieved quickly and also for the same reason, recovery occurs quickly. This allows remifentanil to be used in unique circumstances such as cesarean section.
Remifentanil's short context-sensitive half-life makes it ideal for intense pain of short duration. As such, it has been used for analgesia in labor successfully; however, it is not as effective as epidural analgesia.
Remifentanil is a specific 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.
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 sedatives that allow the patient to tolerate or lose awareness of the side effect.
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.
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 circulation once the infusion is terminated.
Remifentanil, being a μ-receptor agonist, functions like other μ-receptor agonists, such as morphine and codeine, and can cause euphoria and has the potential for abuse. However, due to its rapid metabolism and short-acting half-life the likelihood of becoming abused is quite low. Nevertheless, there have been some documentations of remifentanil abuse.
Remifentanil is considered a metabolic soft drug, one that is rapidly metabolized to an inactive form. Unlike other synthetic opioids which are hepatically metabolized, remifentanil has an ester linkage which undergoes rapid hydrolysis by non-specific tissue and plasma esterases. This means that accumulation does not occur with remifentanil and its context-sensitive half-life remains at 4 minutes after a 4-hour infusion.
Remifentanil is metabolized to a compound (remifentanil acid) which has 1/4600th the potency of the parent compound.
Due to its quick metabolism and short effects, remifentanil has opened up new possibilities in anesthesia. When remifentanil is used together with a hypnotic (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. Owing to synergism between remifentanil and hypnotic drugs (such as propofol) the dose of the hypnotic can be substantially reduced. This leads often to more hemodynamic stability during surgery and a quicker post-operative recovery time.
Prior to the development of remifentanil, most short-acting hypnotics and amnestics faced issues with prolonged use, where accumulation would result in unfavorable lingering effects during post-operative recovery. Remifentanil was designed to serve as a strong anesthetic with an ultra-short and predictable duration that would not have accumulation issues.
Society and culture
- 1 mg vial - US$30.19
- 3 mg vial - US$57.20
- 5 mg vial - US$118.15
In Hong Kong, remifentanil 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. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without 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 license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
Remifentanil is a Schedule II narcotic controlled substance in the United States with a DEA ACSCN of 9739 and a 2013 annual aggregate manufacturing quota of 3750 grams, unchanged from the prior year.
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