Morphine and Alfentanil Permeability Through the Spinal Dura, Arachnoid, and Pia Mater of Dogs and Monkeys

Bernards, Christopher M.; Hill, Harlan F.

doi:10.1097/00000542-199012000-00020

Cited by 100 publications

(35 citation statements)

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“…21,26 Bernard et al showed that lipophilic drugs were easily absorbed into the spinal cord capillaries, and that these drugs were also lost from the spinal CSF by crossing the arachnoid-dural membranes into the epidural space, with greater permeability than hydrophillic drugs. 27 In the present study, there would have been an additional loss of some of the drug due to leakage through the dural Figure 8 Amplitude of EPs in the injured groups. Both the SSEP and CEP showed a signi®cant decrease in amplitude after injury without any subsequent recovery.…”

Section: Discussionmentioning

confidence: 65%

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

Imamura

Tator

1998

Spinal Cord

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A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The eects of intrathecal administration of nimodipine on spinal cord blood¯ow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n=5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n=5), or 0.2 mg/kg (n=5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n=5); and intrathecal nimodipine 0.05 mg/kg (n=5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased signi®cantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were signi®cant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic bene®t from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no bene®cial eect on SCBF or EPs after acute spinal cord injury.

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Section: Discussionmentioning

confidence: 65%

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

Imamura

Tator

1998

Spinal Cord

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“…A recent publication has suggested that the principal barrier to diffusion following epidural administration in dogs and monkeys is the pia-arachnoid mater. 17 To gain access to the CSI~ epidural compounds must diffuse through the dura and arachnoid mater. The cranial arachnoid is a delicate nonvascular membrane between the dura mater and CSF and is made up of leptomeningeal cells.…”

Section: Discussionmentioning

confidence: 99%

In vitro determination of human dura mater permeability to opioids and local anaesthetics

1993

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In vitro determination of human dura mater permeability to opioids and local anaesthetics Identification of specific opiate receptors in the brain and spinal cord and the subsequent demonstration that spinal (epidural and intrathecal) administration of opiates may lead to segmental spinal analgesia is the basis for epidural narcotic injection, i-3 Studies in animals and humans have demonstrated recently that pre-and postsynaptic receptors in the substantia gelatinosa of the dorsal horn of the spinal cord may be a major site of action of spinal opioids? The epidural route of administration offers several advantages over direct intrathecal (cerebrospinal fluid) administration, such as accessibility to all spinal segments and the possibility of repeated doses through an indwelling catheter. However, following epidural injection, there are at least three competing processes: transfer across the meninges, vascular uptake, and distribution into extradural adipose tissue. In order to gain access to the cerebrospinal fluid epidural opioids must first penetrate the dura mater. Clinical studies have demonstrated CAN J ANAESTH 1993 / 40: 2 / pp 165-9

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“…Caudal epidural administration of 0.02mg kg -1 alfentanil and 0.08mg kg -1 butorphanol in horses did not produce analgesic effects, behavioral or cardiovascular changes (NATALINI & ROBINSON, 2000). Epidurally administered opioids may spread within the epidural space, may be taken up into the epidural vasculature, may transfer to the subarachnoid space, and may be taken up into the epidural fat (COUSIN & MATHER, 1984;WEDDEL & RITTER, 1981;BERNARDS & HILL, 1990). Epidural opioid analgesia requires diffusion from the site of injection to the opioid receptors of the spinal cord dorsal horn.…”

Section: Introductionmentioning

confidence: 99%

“…Epidural opioid analgesia requires diffusion from the site of injection to the opioid receptors of the spinal cord dorsal horn. In order to reach the receptors, opioids must diffuse through the spinal meninges; the dura mater, arachnoid mater, and pia mater (BERNARDS & HILL, 1990). Spinal meningeal permeability to opioids has been shown to occur in dogs after the epidural administration of morphine.…”

Section: Introductionmentioning

confidence: 99%

“…Spinal meningeal permeability to opioids has been shown to occur in dogs after the epidural administration of morphine. Lipid solubility and molecular weight quantitatively affect the spread of an epidurally administered opioid from the epidural space to the spinal cord receptors, although studies have demonstrated that hydrophobicity correlates better than molecular weight with permeability coefficients (COUSIN & MATHER, 1984;BERNARDS & HILL, 1990). In dogs and monkeys alfentanil is 3.7 times more permeable through the spinal meninges than morphine, and the authors suggested that the arachnoid mater was the major diffusion barrier between the epidural space and the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

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Plasma and cerebrospinal fluid alfentanil, butorphanol, and morphine concentrations following caudal epidural administration in horses

Natalini

2006

Cienc. Rural

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Morphine and Alfentanil Permeability Through the Spinal Dura, Arachnoid, and Pia Mater of Dogs and Monkeys

Cited by 100 publications

References 0 publications

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

In vitro determination of human dura mater permeability to opioids and local anaesthetics

Plasma and cerebrospinal fluid alfentanil, butorphanol, and morphine concentrations following caudal epidural administration in horses

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