Dural Permeability to Narcotics: In Vitro Determination and Application to Extradural Administration

Abstract

The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro. Preliminary data On human postmortem material is reported. Permeability had a linear relation to the inverse of the square root of molecular weight. This is the expected relationship for a diffusion process dependent upon molecular weight. The differential mass selectivity coefficients for lumbar and cranial dura were calculated; they were similar at 0.8 and 0.9. This was greater than for diffusion in simple liquids, but much less than that for biological lipid membranes. This suggests that the low rates of diffusion are a property of the thickness of the dura rather than any inherent impermeability. A simple model for the dural transfer of drugs is described, and applied to narcotics. Its purposes were to suggest: the factors involved in the dural transfer of drugs; the physicochemical properties of drugs relevant to their dural transfer; worthwhile measurements in future studies. The model indicates that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer. Low molecular weight and slow absorption produce high dural transfers. When applied to narcotics, these factors could produce a difference of up to an order of magnitude in the amount transferred directly across the dura.

Epidural administered buprenorphine in the perioperative period

“…Compared with morphine, which tends to linger in the water phase in the cerebrospinal fluid (CSF) and spread more widely and rostrally 26 in the spinal canal due to its hydrophylicity, buprenorphine can reach the brain more quickly due to the rapid uptake into :the epidural veins, as Moore et al suggested. 27 The high lipophilicity and relatively small molecular weight of buprenorphine lead to rapid vascular removal. Late respiratory depression was not recorded in the 48 hr after surgery in any group, probably because epidural administration of morphine 80 lag.…”

“…The time from the epidural administration of the agents until the first request for pentazocine for postoperative pain relief was 10.0 _+ 5.1 hr (mean _+ SE) in Group I , 37.7 _+ 4.7 hr in Group II, 27.1 _+ 7.1 hr in Group III, and 44.4 :t: 4.1 hr in Group IV. The duration of analgesia in Groups II, HI and IV was longer than that of Group I (P < 0.05).…”

Side effects of intrathecal and epidural opioids

“…Penetration of the dura is considerably influenced by lipophilicity, but molecular weight may also play an important role. 19 Following epidural administration, cerebrospinal fluid concentrations of fentanyl peak in 10 to 20 rain 2~ while sufentanil concentrations peak in about six minutes. 21 In contrast, cerebrospinal fluid concentrations of morphine, following epidural administration, peak in one to four hours.…”

Anestesia peridural com lidocaína isolada ou associada à clonidina: efeito cardiorrespiratório e analgésico em cães

“…Todavia, apesar de o tempo anestésico não ter sido prolongado pela clonidina, a maior dispersão cranial do bloqueio foi confirmada neste estudo, de modo que, em 50% dos animais, o bloqueio atingiu até a primeira vértebra lombar, enquanto o uso isolado da lidocaína permitiu bloqueio máximo até a quarta vértebra lombar, resultados que concordam com relatos anteriores (GASPARINI et al, 2007;CASSU et al, 2010). A propagação cranial do bloqueio anestésico pode ser obtida mediante a administração de volumes elevados no espaço peridural, bem como em função das propriedades físico químicas dos fármacos empregados (MOORE et al, 1982). No atual estudo, o volume administrado no espaço peridural foi o mesmo em ambos os tratamentos, visto que, no tratamento C, o volume de lidocaína foi reduzido, visando-se a perfazer o volume final de 0,25ml kg -1 , conforme preconizado pela literatura (GASPARINI et al, 2007;CASSU et al, 2010).…”