Opioid therapy

This chapter on opioids is in two parts: basic science and clinical. It includes the current evidence on where and how opioids work to mediate analgesia, non-analgesic effects, and unwanted side effects. In addition, the activity and impact of opioids in brain networks is discussed. These complex dynamic concepts are explained through functional magnetic resonance imaging findings and enables a greater understanding of opioid mechanisms. Mechanism and evidence of less studied side effects such as opioid-induced hyperalgesia along with immune and endocrine side effects are examined. Current genomic evidence and clinical application of this is discussed. The clinical part of the chapter gives complete information on the pharmacology of all opioids which are in clinical use, along with detailed information on when to prescribe and how to prescribe effectively and safely. Finally, the challenges of opioid prescribing in the twenty-first century are addressed. Identification of patient risk factors and appropriate prescribing and monitoring are presented in an agreed and practical way.

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.

Hypoxic-ischemic encephalopathy in a young man due to tramadol overdose

Objective: Tramadol is a synthetic analgesic with two mechanisms. The opioid and non-opioid mechanisms are responsible for tramadol side effects. Non-opioid side effects of tramadol are due to the reuptake inhibitions of serotonin and norepinephrine. Some of the side effects include anaphylactoid reactions, CNS depression, hypoglycemia, hypotension, respiratory depression, seizures, and serotonin syndrome. Seizure may happen in therapeutic doses. If the frequency of tramadol seizures increases, ischemic brain injury and hypoxic-ischemic encephalopathy can be induced. Case Report: We report a young man with a history of tramadol abuse that was admitted with status epilepticus in Imam Reza hospital in Mashhad, Iran. Due to his altered mental status, he was intubated and antiepileptic agents were prescribed. He was transferred to ICU. After regaining consciousness, he was extubated and with the prescription of rehabilitation support he was discharged. Conclusion: Tramadol is a synthetic analgesic agent with less potential for dependence. It is important to mention that the overdose of this drug is common. This drug has two mechanisms. This paper reports a case that developed generalized tonic clonic seizures due to tramadol and hypoxic ischemic encephalopathy. With adequate treatment and supportive care, patient’s mental status improves and he/she can be discharged.