Opiate Pharmacology of Intrathecal Granulomas

Allen, Jeffrey W.; Horais, Kjersti A.; Tozier, Nicolle A.; Yaksh, Tony L.

doi:10.1097/00000542-200609000-00025

Cited by 87 publications

(85 citation statements)

References 29 publications

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“…For opiates, the manifestation of this toxicity is the intrathecal granuloma [37, 116, 461-463]. Our group showed that the primary determinant for intrathecal opiate granulomas is the local concentration to which the tissue adjacent to the catheter tip is exposed [49, 51, 52]. Even baclofen, which has no strong evidence of granuloma formation in humans, may have limitations in that regard  if concentrations higher than the currently available formulation (2mg/mL) is employed ([464] but see [267]).…”

Section: Current Spinal Agentsmentioning

confidence: 99%

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Yaksh

Fisher²,

Hockman³

et al. 2017

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.

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Section: Current Spinal Agentsmentioning

confidence: 99%

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Yaksh

Fisher²,

Hockman³

et al. 2017

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“…32 Systematic studies suggested that the risk of granuloma formation is correlated with local CSF concentrations. 33 Interestingly, sampling lumbar CSF in dogs proximal to the catheter tip have shown in acute pharmacokinetic studies that at the 12 mg/ml/day dose, CSF concentrations were on the order of 42,000 ng/mL. 13 Interestingly, we emphasize that in the present case, the patient displaying the granuloma received a daily dose of 36 mg/day.…”

Section: Changes In Drug Delivery and Csf/plasma Concentrationsmentioning

confidence: 59%

Characteristics of Distribution of Morphine and Metabolites in Cerebrospinal Fluid and Plasma With Chronic Intrathecal Morphine Infusion in Humans

Wallace

Yaksh

2013

Survey of Anesthesiology

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“…Veizi et al demonstrated that doses of monotherapy opioids may increase on the order of 535 ± 180% within 12 months of initiation [7]. With dose escalation comes increased intrathecal concentrations, creating concern for granulomas, non-infectious collections of cells around the catheter site [8]. To improve patient outcomes and safety, a group of expert physicians was convened to standardize approached to intrathecal therapy.…”

Section: On Label Medicationsmentioning

confidence: 99%

“…Historically defined, intrathecal therapy has challenges, including impacts on hormonal balance, space occupying granuloma, opioid dose escalation, platform inefficiencies, and limited agents that are Food and Drug Administration (FDA) labeled for this use [2, 5-8]. Importantly, intrathecal therapy requires a platform to deliver a medicine; it does not define the medicine employed.…”

Section: Introductionmentioning

confidence: 99%

The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain

Pope¹,

Deer²,

Amirdelfan³

et al. 2017

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BackgroundIntrathecal drug delivery has undergone a revitalization following a better understanding of this delivery route and its pharmacokinetics. Driven by patient safety and outcomes, clinicians are motivated to rethink the traditional spinal infusion pump patient selection criteria and indications. We review the current understanding of the pharmacology of commonly employed intrathecal agents and the clinical relevance.MethodsSearch strategies for data acquisition included Medline database, PubMed, Google scholar, along with international and national professional meeting content, with key words including pharmacology of opioids, intrathecal therapy, ziconotide, pharmacokinetics, and intrathecal drug delivery. The search results were limited to the English language.ResultsOver 300 papers were identified. The literature was condensed and digested to evaluate the most commonly used medications in practice, sto serve as a foundation for review. We review on-label medications: ziconotide and morphine, and off label medications including fentanyl, sufentail, and hydromorphine.ConclusionIntrathecal therapy has level-one evidence for use for malignant pain and nonmalignant pain, with continued cost savings and improved safety. To most effectively serve our patients, a clear appreciation for the pharmacology of these commonly employed medication is paramount..

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Opiate Pharmacology of Intrathecal Granulomas

Cited by 87 publications

References 29 publications

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Characteristics of Distribution of Morphine and Metabolites in Cerebrospinal Fluid and Plasma With Chronic Intrathecal Morphine Infusion in Humans

The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain

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