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      Baclofen therapeutics, toxicity, and withdrawal: A narrative review

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          Abstract

          Baclofen is an effective therapeutic for the treatment of spasticity related to multiple sclerosis, spinal cord injuries, and other spinal cord pathologies. It has been increasingly used off-label for the management of several disorders, including musculoskeletal pain, gastroesophageal reflux disease, and alcohol use disorder. Baclofen therapy is associated with potential complications, including life-threatening toxicity and withdrawal syndrome. These disorders require prompt recognition and a high index of suspicion. While these complications can develop following administration of either oral or intrathecal baclofen, the risk is greater with the intrathecal route. The management of baclofen toxicity is largely supportive while baclofen withdrawal syndrome is most effectively treated with re-initiation or supplementation of baclofen dosing. Administration of other pharmacologic adjuncts may be required to effectively treat associated withdrawal symptoms. This narrative review provides an overview of the historical and emerging uses of baclofen, offers practical dosing recommendations for both oral and intrathecal routes of administration, and reviews the diagnosis and management of both baclofen toxicity and withdrawal.

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          Diagnosis and Pharmacotherapy of Alcohol Use Disorder

          Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder (AUD) and has been recommended, only 1 in 6 US adults report ever having been asked by a health professional about their drinking behavior. Alcohol use disorder, a problematic pattern of alcohol use accompanied by clinically significant impairment or distress, is present in up to 14% of US adults during a 1-year period, although only about 8% of affected individuals are treated in an alcohol treatment facility.
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            Clinical Pharmacokinetics and Pharmacodynamics of Propofol

            Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.
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              European Academy of Neurology guideline on trigeminal neuralgia

              Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN.
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                Author and article information

                Journal
                SAGE Open Med
                SAGE Open Med
                SMO
                spsmo
                SAGE Open Medicine
                SAGE Publications (Sage UK: London, England )
                2050-3121
                3 June 2021
                2021
                : 9
                : 20503121211022197
                Affiliations
                [1 ]Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center, Dallas, TX, USA
                [2 ]Department of Neurological Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
                [3 ]Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
                Author notes
                [*]Bryan T Romito, Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9068, USA. Email: Bryan.Romito@ 123456UTSouthwestern.edu
                Author information
                https://orcid.org/0000-0002-5011-9179
                https://orcid.org/0000-0001-7178-4613
                Article
                10.1177_20503121211022197
                10.1177/20503121211022197
                8182184
                34158937
                3e902aec-4648-4503-a74b-60e341509a2b
                © The Author(s) 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 10 January 2021
                : 13 May 2021
                Categories
                Review
                Custom metadata
                January-December 2021
                ts1

                baclofen,spasticity,toxicity,withdrawal
                baclofen, spasticity, toxicity, withdrawal

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