Intrathecal drug therapy for long-term pain management

Abstract

The use of long-term intrathecal drug delivery for the treatment of intractable pain or intolerable medication adverse effects has expanded to include the treatment of patients with chronic or cancer-related pain. Important considerations for the use of intrathecal drug therapy include the appropriate selection of patients, delivery systems, and medications, as well as potential complications of therapy and quality-assurance measures necessary to ensure patient safety.

The Effect of Pulsatile Flow on Intrathecal Drug Delivery in the Spinal Canal

“…The treatment typically delivers drugs like morphine via the cerebrospinal fluid (CSF) to specific receptor sites in dorsal regions of the spinal cord. 12,28,30 Clinical studies show that the IT delivery affords perfect pain control using a small fraction of the dose and fewer side effects compared to the other methods such as intravenous or oral administration. 21,28 However, IT administration of baclofen offers a safe and effective treatment for severe spasticity because of a variety of causes such as multiple sclerosis, cerebral palsy, traumatic and hypoxic brain injury, and spinal cord injury.…”

Advancing Safety in Intrathecal Analgesia

“…Finally, compounding of medications for intrathecal pumps is by nature considered "high risk" by United States Pharmacopeia (USP) 797 guidelines, as most ingredients must be sourced from a nonsterile source to achieve therapeutic concentrations and converted into sterile preparations. 13,14 Since implementation of the ITPD, no incidents of dosing parameters have been exceeded based on its calculations.…”

“…15 The ITPD functionality then completes a series of calculations and, based on available products, converts to detailed compounding instructions including stepwise preparation of ingredients, multiple pharmacist verifications at appropriate junctures, validation testing of equipment, and all documentation according to USP 797 high-risk compounding standards. 13,14,16 In addition, the ITPD is programmed to integrate ingredient solubility, stability, conversion factors for salt formulations, isotonicity, and aliquots to correct for measurements lower than current equipment capabilities. 6,[17][18][19][20] Finally, cost of ingredients for charges is calculated based on availability of medication options and pharmacy location as appropriate.…”

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

“…Within several years the first clinical trial was conducted and published (Wang et al, 1979), which laid the groundwork for what would become an effective approach for continuous localized delivery of analgesic medication to the spinal cord, where the first synapse of the pain pathway can be inhibited. The development and ongoing optimization of intrathecal drug delivery systems have enabled a subset of chronic pain patients, who are unresponsive to systemic treatment, to receive long term chronic spinal infusion of specific medications with physicochemical characteristics amenable to these systems (Ghafoor et al, 2007). Therefore, in addition to the neurochemical and neurophysiological information obtained from decades of localized spinal delivery to the first synapse (Yaksh, 2002), the rat model of chronic intrathecal infusion directly seeded the translation of this important option for some patients with severe pain.…”

“…Intrathecally delivered ziconitide (SNX-111), an N-type calcium channel blocker, reduces thermal hypersensitivity in nerve-injured rats (Scott et al, 2002) and provides analgesic relief to cancer and herpes simplex virus (HIV) patients (many with peripheral neuropathy) (Staats et al, 2004). Additionally, the introduction of the spinal catheterization method described above (Yaksh and Rudy, 1976a), led to an important treatment option for many patients for whom systemic opioid medication is not effective (Ghafoor et al, 2007). While the correspondent rodent to human pharmacology is not intended to be a comprehensive list, it does illustrate similar pharmacological outcomes within pain models that compared to the human pain condition.…”