GPR: 2020 - Week 06

• GPR Quiz
• Answer
• DDx1
• DDx2
• DDx3
• Acknowledgments
• Reference(s)

Clinical history

A 61 year-old man with a history of bipolar disorder, polysubstance use disorder, seizure, and well-controlled HIV presented to the ED with AMS and multiple falls after ingesting an unknown substance. The patient's partner provided a plastic bag containing a light-colored powder, which he reported was ingested by the patient. An extensive workup for the patient's AMS was unrevealing. After five days of persistent AMS, the clinical team requested identification of the powder.

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delorazepam A slow-onset, long-acting benzodiazepine Functions via binding to the interface of the γ2 and α1 subunits of the subset of GABA_A receptors within neuronal synapses that possess a benzodiazepine binding site. Benzodiazepines act as positive allosteric modulators increasing the total chloride ion conductance across the neuronal cell membrane. The membrane becomes relatively hyperpolarized increasing the difference between the resting and threshold potentials. This decreases the likelihood of action potential initiation for a fixed stimulus. The elimination half-life of delorazepam is 60-140 hours meaning that it would be expected to take about 12-30 days to be completely eliminated. Compare this to a fast-onset, short-acting benzodiazepine such as midazolam with a half-life of 1.5-2.5 hours, which would be completely eliminated in 7-13 hours.

dexmedetomidine alpha2-adrenergic agonist Causes sedation, anxiolysis, hypnosis, analgesia, and sympatholysis Rapid-onset and half-life of 4 minutes Used for sedation in ICU patients who are mechanically ventilated Also indicated for sedation of nonintubated patients prior to and/or during surgical and other procedures

methohexital Binds to GABA_A receptors and increases the length of the timescale over which the channels are open for a given synaptic concentration of GABA Half-life is 3-8 minutes Used in induction for endotracheal intubation and ED sedation Effects include sedation and amnesia but no analgesia

(nor)ketamine Acts as a selective, uncompetitive antagonist of the NMDA receptor as well as at a large number of other sites including opioid and acetylcholine receptors but whose collective effects are less well understood Norketamine is a relatively long-acting, lower-potency metabolite of ketamine with a half-life of 12 hours (as opposed to 2.5-3 hours for ketamine). Effects include analgesia and induction of a state in which respiration and airway reflexes are maintained while patients are unaware of their surroundings Commonly used in pediatric EDs for sedation in the context of moderate to severe injuries

• Jim Flood
• Bill Young

• O'Brien (2005). "Benzodiazepine Use, Abuse, and Dependence". The Journal of Clinical Psychiatry: 66.
• https://pubchem.ncbi.nlm.nih.gov/compound/17925
• https://www.drugbank.ca/
• NMS Labs 27100 Identification of Controlled Substances, Pharmaceuticals, and Steroids ( https://www.nmslabs.com/forensic-testing/criminal-investigation/illicit-drugs , https://www.nmslabs.com/sites/default/files/2018-11/Crime_Lab_Services_Listing_2017.pdf )

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This week's Gross Pathology Roundup was presented by Cameron Ray Smith on MD, PhD.