The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to update the 2016 version of the Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient, outpatient and community SCI rehabilitation settings in Canada. METHODS: The guidelines were updated in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The working group identified and reviewed 46 additional relevant articles published since the last version of the guidelines. The panel agreed on 3 new screening and diagnosis recommendations and 8 new treatment recommendations. Two key changes to these treatment recommendations included the introduction of general treatment principles and a new treatment recommendation classification system. No new recommendations to model of care were made. CONCLUSIONS: The CanPainSCI recommendations for the management of neuropathic pain after SCI should be used to inform practice.

Methadone for Pain Management: A Pharmacotherapeutic Review.

Methadone is increasingly being used for its analgesic properties. Despite the increasing popularity, many healthcare providers are not familiar with methadone's complex pharmacology and best practices surrounding its use. The purpose of this narrative review article is to discuss the pharmacology of methadone, the evidence surrounding methadone's use in acute pain management and both chronic cancer and non-cancer pain settings, as well as highlight pertinent safety, monitoring, and opioid rotation considerations. Methadone has a unique mechanism of action when compared with all other opioids and for this reason methadone has come to hold a niche role in the management of opioid-induced hyperalgesia and central sensitization. Understanding of the mechanisms of variability in methadone disposition and drug interactions has evolved over the years, with the latest evidence revealing that CYP 2B6 is the major determinant of methadone elimination and plays a key role in methadone-related drug interactions. From an acute pain perspective, most studies evaluating the use of intraoperative intravenous methadone have reported lower pain scores and post-operative opioid requirements. Oral methadone is predominantly used as a second-line opioid treatment for select chronic pain conditions. As a result, several oral morphine to oral methadone conversion ratios have been proposed, as have methods in which to rotate to methadone. From an efficacy standpoint, limited literature exists regarding the effectiveness of methadone in the chronic pain setting with most of the available efficacy data pertaining to methadone's use in the treatment of cancer pain. Many of the prospective studies that exist feature low participant numbers. Few clinical trials investigating the role of methadone as an analgesic treatment are currently underway. The complicated pharmacokinetic properties of methadone and risks of harm associated with this drug highlight how critically important it is that healthcare providers understand these features before prescribing/dispensing methadone. Particular caution is required when converting patients from other opioids to methadone and for this reason only experienced healthcare providers should undertake such a task. Further randomized trials with larger sample sizes are needed to better define the effective and safe use of methadone for pain management.

Expanding Role of NMDA Receptor Antagonists in the Management of Pain.

Pain management is complex regardless of whether the pain is acute or chronic in nature or non-cancer or cancer related. In addition, relatively few pain pharmacotherapy options with adequate efficacy and safety data currently exist. Consequently, interest in the role of NMDA receptor antagonists as a pharmacological pain management strategy has surfaced. This narrative review provides an overview of the NMDA receptor and elaborates on the pharmacotherapeutic profile and pain management literature findings for the following NMDA receptor antagonists: ketamine, memantine, dextromethorphan, and magnesium. The literature on this topic is characterized by small studies, many of which exhibit methodological flaws. To date, ketamine is the most studied NMDA receptor antagonist for both acute and chronic pain management. Although further research about NMDA receptor antagonists for analgesia is needed and the optimal dosage/administration regimens for these drugs have yet to be determined, ketamine appears to hold the most promise and may be of particular value in the perioperative pain management realm.

Therapeutic drug monitoring guided raltegravir dosing for prevention of vertical transmission in a premature neonate born to a woman living with perinatally acquired HIV.

We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/ml at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.

Drug interactions between antiretrovirals and drugs used to treat benign prostatic hyperplasia/lower urinary tract symptoms.

INTRODUCTION: Significant advances in antiretroviral (ARV) therapy have transformed HIV into a chronic manageable disease. Co-morbidities associated with aging, such as benign prostatic hyperplasia (BPH), are becoming increasingly prevalent in the HIV-infected population. The pharmacological treatment of BPH involves medications mainly metabolized by CYP 450 enzymes, while many ARVs have inducing or inhibiting effects on the CYP 450 system. Consequently, there is potential for significant pharmacokinetic (PK) interactions between these two classes of medications. AREAS COVERED: This article reviews the pharmacology and metabolism of selected BPH drug therapies and ARVs, in addition to highlighting potential interactions between these two drug categories. The authors also present PK evidence of interactions from available clinical trials, product monographs and international conference abstracts. Potentially significant drug interactions are summarized and strategies for management are discussed. EXPERT OPINION: Drugs most likely to interact with BPH medications include protease inhibitors, the non-nucleoside reverse transcriptase inhibitors efavirenz, nevirapine, etravirine, and the cobicistat-boosted integrase inhibitor elvitegravir. Clinically significant PK interactions with BPH medications and dolutegravir, raltegravir, rilpivirine, or the investigational agent doravirine do not appear to exist. Clinicians working with HIV-infected individuals need to recognize the potential for interactions involving BPH and ARV treatments to ensure effective and safe drug therapy use.