New Synthetic Opioids: Clinical Considerations and Dangers.

Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For point of reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids. During much of this period, fentanyl has been the most commonly used synthetic opioid. This time when fentanyl was the most popular opioid has been called the "third wave" of the opioid crisis, partly because it led to a sharp rise in deaths from overdoses. Other synthetic opioids, such as carfentanil, protonitazene, and isotonitazene, have also become more widely diverted for nonmedical used. Carfentanil is an even more potent fentanyl derivative that was initially used in the mid-1980s as a general anesthetic for large animals such as elephants. Related to its strong affinity for mu opioid receptors, carfentanil is still utilized in medicine and science today as a radiotracer for positron emission tomography imaging. Protonitazene and isotonitazene belong to a novel class of synthetic opioids called benzimidazoles that were manufactured in the 1950s as novel analgesics. These agents have come under recent scrutiny as designer synthetic opioids becoming more prevalent. However, to date, there is incomplete data regarding the prevalence of synthetic opioids, as traditional toxicology screenings may not be sensitive to detect these compounds at such low doses post-mortem, particularly when blood is drawn from the periphery instead of central tissues such as the brain, lung, or heart. This narrative review aims to highlight the clinical challenges presented by these new synthetic opioids.

Vasectomy Regret or Lack Thereof.

Background: Vasectomy is a procedure that results in permanent yet reversible sterility and remains a great contraceptive option for many. Previous research studies have highlighted frequency of vasectomy utilization, defining characteristics of individuals who opt for this method, various surgical techniques, and the risks and benefits associated with the procedure. What remains to be defined is why or why not individuals may experience post-vasectomy regret and whether the previous characteristics correlate. Objective: The objective of this review is to synthesize information regarding reasons individuals may regret their vasectomy and seek reversal, what options exist for accomplishing the reversal, and patients' fertility prognosis post-vasovasostomy. Methods: This review utilized a combination of secondary and tertiary data analysis across a wide scope of academic databases pertaining to the topic of interest. Results: Typically, most males who have sought a vasectomy are satisfied with their decision, however, approximately 6% of this population seeks reversal. Key factors influencing vasectomy regret include age at the time of vasectomy, parental status, pre- and post-operative relationship status, unresolved physical and psychosexual problems, and development of chronic scrotal pain following the procedure. Few options exist for vasectomy reversal including microsurgical reconstructive vasectomy reversal (VR) and sperm extraction for in vitro fertilization. There is no guarantee that fertility will be restored in any case but a major predictive factor for success is the time interval prior to reversal. Conclusion: Vasectomy is intended to be a permanent form of contraception; however, a minor chance remains that individuals may experience post-operative regret due to various factors. This warrants proper comprehensive counseling by the patient's provider regarding benefits and risks, procedural outcomes, opportunities for reversal, and fertility prognosis.

Historical Pathways for Opioid Addiction, Withdrawal with Traditional and Alternative Treatment Options with Ketamine, Cannabinoids, and Noribogaine: A Narrative Review.

Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson's disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal.