A Case of Severe Fioricet Withdrawal Presenting During Admission to an Inpatient Psychiatric Unit.

BACKGROUND: Butalbital-containing combination (BCC) analgesics have the potential for the development of tolerance and dependence. Misuse and withdrawal of these agents should be considered in patients presenting with new-onset psychosis. This case highlights how butalbital withdrawal may be missed in the emergency department setting and underscores how early identification may affect management and prognosis. Case Presentation. A 40-year-old female with a history of migraine, depression, and anxiety presented to the emergency department (ED) with new-onset psychosis following a recent seizure-like episode. At home, the patient was prescribed butalbital-acetaminophen-caffeine (Fioricet), duloxetine, alprazolam, and zolpidem for these conditions. On arrival to the ED, the patient was disoriented and appeared to be responding to internal stimuli. Following initial medical evaluation, the patient was cleared for further psychiatric assessment, during which she developed acute-onset autonomic instability while waiting for a bed on the inpatient psychiatric unit. She then became agitated, requiring multiple emergency medications, and eventually required emergent intubation and was admitted to the intensive care unit (ICU). Following extubation, a psychiatric consultation was performed. On assessment, the patient was alert and oriented and no longer exhibited psychotic symptoms. She admitted to using butalbital-acetaminophen-caffeine (Fioricet) daily for the past 10 years and had recently run out of her prescribed medication. She acknowledged that she was taking more than prescribed and requested substance use treatment resources, for which she was subsequently discharged to an inpatient drug rehabilitation facility. CONCLUSIONS: Given the time constraints inherent to the ED setting, a complete substance use history (both illicit and prescribed) may be challenging to obtain. However, it remains critical for providers to identify patients at risk for life-threatening withdrawal from sedative, hypnotics, and anxiolytic agents.

Correlation times and adiabatic barriers for methyl rotation in SNase.

The relation of rotational correlation times to adiabatic rotational barriers for alanine methyl groups in staphylococcal nuclease (SNase) is investigated. The hypothesis that methyl rotational barriers may be useful probes of local packing in proteins is supported by an analysis of ten X-ray crystal structures of SNase mutants. The barrier heights are consistent across a set of ten structures of a native SNase and mutants containing single-point mutations or single or double insertions, most in a ternary SNase complex. The barriers for different methyls have a range of 7.5 kcal/mol, which at 300 K would correspond to a five-order-of-magnitude range in correlation time. It is demonstrated that adiabatic rotational barriers can fluctuate significantly during an MD simulation of hydrated SNase, but that a Boltzmann weighted average is predictive of rotational correlation times determined from correlation functions. Even if a given methyl is on average quite sterically hindered, infrequently sampled low-barrier conformations may dominate the Boltzmann distribution. This result is consistent with the observed uniformity of NMR correlation times for (13)C-labeled methyls. The methyl barriers in simulation fluctuate on multiple time scales, which can make the precise relationship between methyl rotational correlation time and methyl rotation barriers complicated. The implications of these issues for the interpretation of correlation times determined from NMR and simulation are discussed.

Methyl dynamics in crystalline amino acids: MD and NMR.

Correlation times for rotation of deuterated methyls in crystalline leucine, valine, and cyclo-L-alanyl-L-alanine are calculated with molecular dynamics and compared with NMR data. The simulations distinguish between methyls having different steric environments in the crystal, yielding correlation times differing by a factor of up to 30 for methyls within a given crystal. MD and NMR correlation times agree to within a factor of 2. However, averaging over nonequivalent methyls can yield correlation functions that, although actually multiexponential, are well fit by single exponentials. This may have significance for interpreting NMR data; previous NMR data did not distinguish between the methyls in these crystals. Adiabatic rotational barriers calculated with the X-ray structure differ from effective barriers during simulation by up to +/-1 kcal/mol; the difference indicates that dynamical effects have a significant role in determining rotational correlation times.