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

摘要

Intrathecal therapy has undergone a relative resurgence in pain care. Improved pharmacokinetic and pharmacodynamic understanding of the intrathecal space coupled with expert guidance statements has improved patient safety and outcomes [1, 2]. Interestingly, the positioning of intrathecal therapy as salvage therapy innately reduces the treatment therapies likelihood of success, as parallels can be drawn to research in spinal cord stimulation [3]. Positioning intrathecal therapy as salvage therapy after failure of high dose systemic opioids is no longer the standard of care based on best practices.Recent data suggests an epidemic of opioid misuse in the United States, with approximately 15,000 deaths annually in a reported by the Center for Disease Control (CDC) [4]. The intrathecal delivery route for opioids has advantages over systemic medication delivery in that reduced systemic exposure is thought to improve the side effect profile, while intrathecal delivery may provide a better analgesic effect because of advantages in potency. Also this route of delivery dramatically impacts the risks of diversion and misuse.Intrathecal therapy, for both end of life pain care and chronic conditions has leveled evidence to demonstrate efficacy [5]. 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. In the United States, intrathecal agents are delivered by approved devices that are carefully monitored for safety and efficacy. In the past, only one device has been commonly used for this purpose. (Synchromed II, Medtronic Neurological, Minneapolis, Mn). In 2014, the FDA approved a second device that allowed for intrathecal delivery (Prometra I, Flowonix, Jersey City, New Jersey). Common platform choices are now more completely MRI conditional with the introduction of the Prometra 2 by Flowonix [9]. Currently, the Medtronic Synchromed II is the only therapy with the patient therapy manager (PTM), although Flowonix has a patient controlled dosing strategy awaiting FDA approval. These options allow the physician and health care team to preprogram an intermittent bolus that can be delivered by the patient.The purpose of this review is to describe the pharmacokinetic and dynamic differences of opioid therapy and ziconotide therapy currently employed for use as intrathecal agents. This review describes both on label and off-label medications. We will review each medication separately and then provide summative comments. Table(?11)Table 1