Drugs online research references
Pediatr Res. 1996 Oct;40(4):564-70.
Influence of sedation on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs.
Jakubowska AE, McCrabb GJ, Harding R.
Department of Physiology, Monash University, Melbourne, Victoria, Australia.
Our aim was to determine the effects of two commonly used sedatives, promethazine and diazepam, on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs. In eight lambs fitted with obstructable rubber face masks, we recorded electrocortical, electroocular, and electromyographic activities to identify sleep-wake states; intrapleural pressure, heart rate, and percentage O2 saturation (Sao2) were also recorded. In each lamb, arousal and respiratory responses were measured after tidal airflow was obstructed during rapid eye movement (REM) and nonREM sleep. Each lamb was studied, on different days, when unsedated and after being mildly sedated with either promethazine or diazepam. Seven of the lambs were studied while sleeping after being sedated with promethazine (1.6 +/- 0.07 mg/kg, orally with milk) and six were studied after sedation with diazepam (0.31 +/- 0.03 mg/kg, intramuscularly). In unsedated lambs, airflow obstruction led to augmentation of respiratory efforts, bradycardia, hypoxemia, and arousal; in REM sleep, arousal was delayed and occurred at lower Sao2 (16 +/- 3 s; 75.3 +/- 3%) compared with nonREM sleep (8 +/- 1 s; 90 +/- 1%). Sedation increased the arousal latency in both REM and nonREM sleep and caused arousal to occur at lower Sao2; in some sedated lambs Sao2 fell to less than 30% before arousal. The augmentation of inspiratory and expiratory efforts immediately before arousal was increased after sedation. We conclude that promethazine and diazepam depress arousal responses in sleeping lambs leading to profound hypoxia, and that this may be due to impaired sensitivity to augmented respiratory efforts and other physiologic changes during airflow obstruction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8888284&dopt=Abstract
J Physiol. 1996 Oct 15;496 ( Pt 2):379-94.
Oscillatory bursting of phasically firing rat supraoptic neurones in low-Ca2+ medium: Na+ influx, cytosolic Ca2+ and gap junctions.
Li Z, Hatton GI.
Department of Neuroscience, University of California, Riverside 92521, USA.
1. Whole-cell patch recordings were obtained from supraoptic nucleus (SON) neurones in horizontal brain slices of adult male rats. Low-Ca2+ or Ca(2+)-free perifusion medium induced oscillatory bursting activity in all sixty-nine cells displaying both phasic firing and depolarizing after-potentials (DAPs). In fifteen non-phasic cells without DAPs, Ca(2+)-free medium produced little or no oscillatory bursting. 2. Typical bursts started with rapid membrane depolarization, resulting in a plateau with superimposed action potentials, and ended several hundred milliseconds later in swift repolarization. Prominent bursting was observed at membrane potentials from -50 to -70 mV, with maximum amplitudes of 12.2 +/- 0.7 mV (mean +/- S.E.M.) around -70 mV. Development of oscillatory bursting was dependent on reduction of [Ca2+]o, with a threshold for the bursting < or = 1.2 mM Ca2+. 3. Bursting was abolished by addition of TTX, Co2+, Ni2+ or Mg2+ into the Ca(2+)-free medium, or by replacement of external Na+ with choline or Li+. Low concentrations of TEA or increased [K+]o prolonged burst durations and enlarged oscillation amplitudes. 4. Voltage-clamp techniques were used to examine the persistent Na+ current (INaP), and revealed that low [Ca2+]o shifted the threshold for INaP activation in a negative direction and enhanced the amplitude of this current. These changes in INaP were abolished by adding Co2+ or Mg2+ to Ca(2+)-free medium. 5. Direct diffusion of BAPTA or heparin into neurones or bath application of ryanodine suppressed bursting. Oscillations were also eliminated by the uncoupling agents heptanol, halothane or acidification. 6. CNQX, APV, bicuculline, CGP35348 (GABAB receptor antagonist), promethazine, atropine, d-tubocurarine and suramin had no obvious effects on oscillatory bursting. Blockers of transient Ca2+, or hyperpolarization-activating cation currents also did not alter bursting activity. 7. These results suggest that intrinsic burst activity in SON neurons perifused with low-Ca2+ or Ca(2+)-free medium involves enhanced Na+ influx through persistent Na+ channels, and requires the presence of rapid intracellular Ca2+ mobilization that might also explain the selective existence of oscillatory bursting in phasically firing cells. Intercellular communication through gap junctions appears to be important in determining neuronal activity of the neuroendocrine cells in low-Ca2+ medium.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8910223&dopt=Abstract
Anesth Prog. 1995;42(3-4):139-43.
Augmenting sedation with hypnosis in drug-dependent patients.
Lu DP, Lu GP, Hersh EV.
Department of Oral Medicine, University of Pennsylvania, Allentown, USA.
The successful use of conscious sedation in patients physically dependent on centrally acting drugs is problematic for the dental anesthesiologist because of the concomitant development of tolerance to standard sedative agents. Dosage requirements necessary to adequately sedate these patients are often higher than recommended and carry an increased risk of drug overdose. The following report summarizes our experience with 18 drug-dependent patients in whom hypnosis was employed in conjunction with a standard sedation regimen. Attempts to complete various dental procedures while employing sedation alone on these patients had previously failed. All patients exhibited highly fearful or phobic behavior toward dental treatment as assessed by the Corah Dental Anxiety Scale. If an intravenous sedative regimen (midazolam or diazepam plus methohexital) was employed, hypnotic induction preceded the administration of the sedative drugs. If an intramuscular sedative regimen was employed (meperidine plus promethazine), the hypnotic induction took place after drug administration. With the combined hypno-sedative approach, treatment outcomes were judged to be good or excellent in 11 of 18 patients. Interestingly, in five of seven patients for whom the treatment outcome was rated poor or fair, the possibility of tolerance or cross-tolerance existed between a drug being abused and the sedative regimen. In contrast, this possibility existed in only 1 of 11 patients with good or excellent treatment outcomes. We conclude that hypnosis can augment the effects of sedation in this patient population. However, it is also important to choose a sedative regimen where tolerance is unlikely to exist.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8934982&dopt=Abstract
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