Remifentanil Anew Unique Opioid Analgesic For The 21st Century:

Ehab Abd El-mageed Tabl

Remifentanil is a fentanyl derivative with an ester linkage(3-[4-methoxycarbony1-4-{(l-oxopropy l)phenylamino}-1-piperidine]propanoic acid, methylester). It is a pure Jl agonistand the rapid breakdown of the ester linkage by non-specifictissue and plasma esterases is responsible for its uniquecharacteristics.The speed of onset of action of Remifentanil is similar tothat of Alfentanil.Remifentanil is extremely fat soluble with a steady-statevolume of distribution of 25-40 L, total clearance 4.2-5 Llmin.and terminal half-life (TY2) 10-21 min. Clearance was notaffected significantly by body weight, sex or age, and it is likelyto be independent of renal or hepatic function. Furthermore,Remifentanil is a poor substance for butyrylcholinesterases(Pseudocholinesterases) in vitro and clearance should beunaffected by cholinesterase deficiency or administration ofanticholinesterases,The mam metabolic product of ester hydrolysis is acarboxylic acid derivative (GI90291) which is mainly excretedunchanged by the kidney with a terminal half-life of 1.5-2 hs.Although elimination of GI90291 is delayed in renal failure,significant pharmacological effects are unlikely as its potencyrelative to Remifentanil is only 0.1-Rapid biotransformation to minimally active metabolitesshould be associated with a short predictable duration of actionwith no accumulation of effect on repeated dosing or withcontinuous infusion. Because of its pharmacokinetics, similarproperties were expected of Alfentanil. However, clinicalexperience has shown that prolonged infusion of Alfentanil maybe associated with prolonged recovery time. It is nowappreciated that the offset of the clinical effect is not simply afunction of the half-life, particularly in the multicompartmentalsystems. It may be affected by rate of equilibration betweenplasma and effector site, method of administration (e.g.continuous infusion, intermittent boluses, ... etc.) and durationof infusion.Pharmacodynamically, Remifentanil possesses all thefeatures of a Mu-receptor agonist. It produces analgesia andsedation. Also it shows all the complications associated withopioids such as respiratory depression, nausea and vomiting,bradycardia, hypotension, muscle rigidity and pruritus. It has anonset time of 1.1 min. ~,,--~