Edward W. Boyer

Management of Opioid Analgesic Overdose

The rate of opioid analgesic overdose is proportional to the number of opioid prescriptions and the dose prescribed. This review considers the epidemiology, mechanisms, and management of opioid analgesic overdose.

Opioid receptors and legal highs: Salvia divinorum and Kratom

Salvia divinorum and Mitragyna speciosa (“Kratom”), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the major alkaloid identified from Kratom, has been reported as a partial opioid agonist producing similar effects to morphine. An interesting minor alkaloid of Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported to activate supraspinal mu- and delta- opioid receptors, explaining their use by chronic narcotics users to ameliorate opioid withdrawal symptoms. Despite their widespread Internet availability, use of Salvia divinorum and Kratom represents an emerging trend that escapes traditional methods of toxicologic monitoring. The purpose of this article is to familiarize toxicologists and poison control specialists with these emerging psychoactive dietary supplements.

Treatment of Calcium-Channel–Blocker Intoxication with Insulin Infusion

To the Editor: Overdose of calcium-channel blockers remains an important cause of fatal poisoning.1 Conventional therapy, consisting of intravenous fluids, calcium, dopamine, dobutamine, norepineph...

Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth)

BACKGROUND Kratom (Mitragynia speciosa korth) is recognized increasingly as a remedy for opioid withdrawal by individuals who self-treat chronic pain. CASE DESCRIPTION A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants or adulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine. CONCLUSION We report the self-treatment of chronic pain and opioid withdrawal with kratom. The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal. The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood.

Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant

Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved by the US FDA for prevention of embolic stroke in patients with nonvalvular atrial fibrillation. Dabigatran has a pharmacokinetic profile that produces predictable anticoagulation responses, does not undergo CYP 450 metabolism, has few drug–drug and drug–food interactions, and does not require frequent laboratory monitoring of clotting parameters. Clinicians are rapidly prescribing this agent as a replacement for warfarin therapy. However, no therapeutic agent has been accepted to reliably reverse the hemorrhagic complications of dabigatran. As of yet, there is no solid evidence to guide management of bleeding complications; management should start with local control of bleeding when possible and transfusion of pRBCs if needed. Transfusion of FFP would not be expected to help control bleeding. Limited and mixed data exist for transfusion of factor VIIa and prothrombin complex concentrates; these therapies should be considered as well as dialysis, which will increase elimination in patients with life-threatening or closed-space bleeding due to dabigatran. We present an article that reviews the pharmacokinetics, clinical trial literature, and consensus guidelines regarding this novel oral anticoagulant.

The Internet and psychoactive substance use among innovative drug users.

Objective. The Internet contains an extraordinary amount of information on the recreational use of psychoactive substances. We investigated the effect of the Internet on the drug-use knowledge, attitudes, and behaviors of adolescents. Methods. Cross-sectional survey of adolescents being managed for substance abuse. Results. Of 12 patients (9 male, 3 female) who had used the Internet to learn about psychoactive substances, 100% reported that Internet-based information had affected the ways in which they had used psychoactive substances. Of the 12 respondents, 8 described adopting behaviors intended to minimize the risks associated with psychoactive substance use. Respondents also reported changes in the use of a wide variety of illicit substances as well as over-the-counter and prescription pharmaceuticals. Examiners assessed whether quotations demonstrated that respondents’ knowledge, attitudes, and behaviors toward psychoactive substance use were affected by Internet information. Despite the subjective nature of the research question, there was a highly significant agreement between coders. Conclusions. Web-based data on psychoactive substances seem to influence a broad range of drug-use behaviors in adolescents. Information on the ways that the Internet is being used by this vulnerable population should be considered in the design of Web sites to prevent the initiation and use of psychoactive substances.

Mitragyna speciosa, A Psychoactive Tree from Southeast Asia with Opioid Activity

Mitragyna speciosa Korth. (Rubiaceae) is a tree that is commonly found in Southeast Asia. Leaves from this tree have been traditionally been used for both their stimulant properties as well as an opium substitute. The tree/leaves are currently illegal in four countries, but is currently legal and widely available in the United States. To date over 40 compounds have been isolated from the leaves. The major alkaloid found within the crude extract, mitragynine, has been the subject of many pharmacological studies. In addition to the pharmacological studies, two total syntheses of mitragynine have been published as well as general structure-activity relationships (SARs) with respect to opioid activity.

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study.

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkins malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenströms diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkins diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.

Diversion of Buprenorphine/Naloxone Coformulated Tablets in a Region with High Prescribing Prevalence

ABSTRACT The purpose of this article was to characterize practices of buprenorphine/naloxone (B/N) diversion in a region with a high prescribing prevalence. A cross-sectional, open-ended survey was administered to individuals entering opioid addiction treatment programs in two New England states. The authors obtained formative information about the knowledge, attitudes, beliefs, practices, and street economy of B/N diversion. The authors interviewed 51 individuals, 49 of which were aware of B/N medication. Of that number, 100% had diverted B/N to modulate opiate withdrawal symptoms arising from attempted “self-detoxification,” insufficient funds to purchase preferred illicit opioids, or inability to find a preferred source of drugs. Thirty of 49 (61%) participants obtained the illicit drug from an individual holding a legitimate prescription for B/N. A high proportion of individuals in the study locations who sought treatment for opioid addiction self-reported the purchase and use of diverted B/N. The diversion of B/N may be minimized by modifying educational, treatment, monitoring, and dispensing practices.

Monoamine Oxidase Inhibitor Poisoning Resulting from Internet Misinformation on Illicit Substances

The Internet may represent a new mechanism by which adolescents initiate the use of illicit substances. The existence of multiple partisan websites providing misinformation regarding the safety of these substances may lead to an increase in unsafe behavior among this age group. Adverse outcomes related to Internet‐based drug information are rarely identified. We report a case of an adolescent whose use of the Internet to obtain drug information led to severe poisoning from the combination of a monoamine oxidase inhibitor, harmaline, and a hallucinogenic tryptamine, 5‐methoxydimethyltryptamine (5‐MeO‐DMT).