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  • 1
    ISSN: 1432-1041
    Keywords: Key words Hypoxaemia ; Pharmacokinetics ; Pharmacodynamics; frusemide ; paracetamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The influence of hypoxaemia on the disposition of two common drugs has been examined in ten adults with stable chronic respiratory failure. Methods: There were two experimental periods in this cross-over study: during these periods supplemental oxygen was either withheld or administered to impose clinical hypoxaemia or maintain normoxaemia, respectively. Each participant received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods. Results: The total (bound plus unbound) plasma clearance of frusemide during hypoxaemia (arterial oxygen tension, PaO2 ≤ 50 Torr) was not significantly different from the value during normoxaemia (PaO2 ≥ 60 Torr) [76.9 and 62.4 ml ⋅ min−1]. The volume of distribution was not affected by acute hypoxaemia (121 ml ⋅ kg−1 without and 109 ml ⋅ kg−1 with oxygen; P 〉 0.05). Renal and non-renal clearances of frusemide were similar during the period of hypoxaemia (31 and 38 ml ⋅ min−1, respectively) compared to respective values during supplemental oxygen delivery (29 and 32 ml ⋅ min−1). The absolute bioavailability of frusemide during hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56). The combined sodium and potassium excretion rate (expressed as a function of the frusemide excretion rate) was not altered by changing the oxygen tension. The pharmacokinetics of paracetamol were unaffected by hypoxaemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Locus coeruleus ; Mesencephalic nucleus of the trigeminal nerve ; In vitro brain slice ; Electrophysiology ; Lucifer yellow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recordings were made from neurones contained in the locus coeruleus and mesencephalic nucleus of the trigeminal nerve (MNV), in tissue slices cut from guinea-pig pons and maintained in vitro. Locus coeruleus neurones were of -52.7 ± 2.7 mV resting membrane potential; had an input resistance of 58.0 ± 7.6 MΩ and a membrane time constant of 7.3 ± 1.0 ms. These neurones fired action potentials in response to depolarizing current pulses. Depolarizing synaptic potentials (DSPs) were recorded in locus coeruleus neurones in response to focal stimulation of the surface of the slice. MNV neurones were of-51.9 ± 3.6 mV resting membrane potential; had an input resistance of 15.0 ± 1.8 MΩ and a membrane time constant of 1.35 ± 0.16 ms. These neurones were also excitable but differed from locus coeruleus neurones in that they showed accommodation to depolarizing current pulses and time-dependent anomalous rectification with hyper-polarizing current pulses. In MNV neurones focal stimulation did not give rise to DSPs. Intracellular injection of Lucifer yellow revealed that the cell bodies of locus coeruleus neurones were small and multipolar whereas MNV neurones had larger, monopolar cell bodies.
    Type of Medium: Electronic Resource
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