Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether stimulus frequency affects physiological compensation to an intermittent respiratory stimulus, we studied piglets (n = 43) aged 14.8 +/- 2.4 days. A 24-min total hypercapnic hypoxia (HH) (10% O(2)-6% CO(2)-balance N(2) = HH) was delivered in 24-, 8-, 4-, or 2-min cycles alternating with air. Controls (n = 10) breathed air continuously. Minute ventilation and temperature were not different between the 2-min and 24-min groups, with neither different from controls during recovery. Piglets exposed to 8-min cycles had ventilatory stimulation, whereas those exposed to 4-min cycles had significant depression of ventilation. Despite this, piglets in these intermediate intermittent HH (IHH) groups (8- and 4-min cycles) showed more severe acidosis and attenuated temperature changes (P < 0.001 and P < 0.01 for pH and temperature vs. 24 min, respectively). Cycle time affected the ability of young piglets to tolerate IHH. More severe respiratory acidosis developed when IHH was delivered in intermediate (4 min or 8 min) cycles compared with the same total dose as a single episode or in short (2 min) cycles.
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PMID:Effect of stimulus cycle time on acute respiratory responses to intermittent hypercapnic hypoxia in unsedated piglets. 1257 6

Twin to twin transfusion syndrome (TTTS) affects 10 to 15% of monochorionic twin pregnancies. Untreated, perinatal loss exceeds 80%, of which survivors have a great risk for long-term neurological disorders as psychomotor retardation or cerebral palsy. TTTS can be treated using foetoscopy and selective ablation of the twin-to-twin blood vessels under local or regional anaesthesia. However, local or regional anaesthesia does not always result in excellent maternal comfort, nor does it provide foetal immobilisation, necessary for optimal surgical conditions. Using a continuous infusion rate of remifentanil 0.1 microg/kg/min, perfect foetal immobilisation and excellent maternal sedation was achieved. Only mild respiratory acidosis was observed as a result of mild respiratory depression. In no mother apnoe occurred. All haemodynamic parameters, both foetal and maternal, remained stable during the procedure. Maternal sedation, respiratory depression and foetal immobilisation were quickly reversible following cessation of the remifentanil infusion.
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PMID:Remifentanil for foetal immobilisation and maternal sedation during endoscopic treatment of twin-to-twin transfusion syndrome : a preliminary dose-finding study. 1551 1

Blood specimens from 146 suspected gamma-hydroxybutyrate (GHB) overdose cases, presenting to an emergency department in Washington State over a 12-month period, were analyzed for GHB and other drugs. Of these 146 patients, GHB was confirmed in approximately one-third of the patients (N = 54), sometimes in potentially toxic concentrations. These patients were aged between 17 and 59 years (median 28 years), and 83% were male. Blood GHB concentrations ranged from 29 to 490 mg/L (mean 137 mg/L; median 103 mg/L). In 36 (67%) of the 54 patients, other drugs were additionally detected. Ethanol was measured in 22 (41%) patients, with concentrations ranging from 0.01 to 0.26 g/100 mL (median 0.04 g/100 mL). Other commonly co-administered drugs included 3,4-methylenedioxymethamphetamine, marijuana, methamphetamine, cocaine, and citalopram. Frequently observed clinical symptoms on admission for the GHB overdose group included copious vomiting, ataxia, lack of gag reflex, respiratory depression, mild acute respiratory acidosis, unconsciousness, and sudden altered states of consciousness. Many patients required intubation, and several became combative and required restraints. The majority of patients were discharged within 6 h of hospital admission. However, despite presenting with similar clinical symptoms on admission, GHB was not confirmed in 92 of the 146 overdose patients, suggesting that GHB overdose cases may frequently be indistinguishable from other drug overdoses or medical conditions.
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PMID:Suspected GHB overdoses in the emergency department. 1551 99

Benzodiazepine poisoning causes coma and respiratory depression. Our objective was to determine whether, and to what extent, arterial blood gas disturbances correlated with blood or cerebral kinetics of midazolam. A 160 mgkg(-1) single dose of midazolam was infused intravenously over 20 min in catheterized male Sprague-Dawley rats. Midazolam kinetics was simultaneously determined in plasma and brain using striatal microdialysis. Midazolam concentrations were measured using a high-performance liquid chromatographic assay with ultraviolet detection. Midazolam (160 mgkg(-1)) reproducibly induced deep coma with respiratory acidosis. Plasma midazolam kinetics was well described by a bi-exponential model, with an elimination half-life of 6.4+/-1.8 h. The striatal dialysate concentration peaked at 50.0+/-8.9 min after the end of infusion, with a significant delay to peak concentration compared to plasma. Respiratory depression, assessed by the elevation in PaCO2, was more closely correlated with midazolam striatal dialysate rather than plasma kinetics. These results suggest a central mechanism for midazolam respiratory effects at toxic doses in rats. In conclusion, our study showed a delayed onset in peak PaCO2 and pH effects after the slow infusion of a toxic dose of midazolam in rats. The effects on arterial blood gases were better correlated with midazolam striatal concentrations than with plasma concentrations. This study may contribute to better understanding of benzodiazepine-induced respiratory depression in poisonings.
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PMID:Cerebral and plasma kinetics of a high dose of midazolam and correlations with its respiratory effects in rats. 1591 73

Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO2, pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A1 adenosine receptor antagonist. Isohydric hypercapnia (20% CO2, pH 7.3), but not isocapnic acidosis (5% CO2, pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5'-nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A1 receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia.
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PMID:Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats. 1677 47

An Asian multiparous woman weighing 47 kg, who suffered from a rare myopathy, congenital fibre type disproportion, was given morphine 10 mg intramuscularly for labour analgesia. After delivery, she had diastolic hypertension and proteinuria and was prescribed magnesium sulphate. Some hours later she became unresponsive with little respiratory effort. Blood gas analysis revealed a respiratory acidosis. Naloxone administration reversed the symptoms. Further doses were required as the respiratory depression recurred. Opioid-related narcosis is the most likely diagnosis in this case. Other possible differential diagnoses were magnesium overdose or a post-ictal state. The presence of a myopathy could render this patient susceptible to the respiratory effects of opioids. Other explanations for an exaggerated and delayed response to opioids include co-administration of other respiratory depressant drugs such as magnesium sulphate, co-morbidity such as renal impairment and genetic variability in the metabolism of morphine. Robust guidelines and highlighting patients with risk factors are required to prevent this complication from recurring.
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PMID:Opioid-related narcosis in a woman with myopathy receiving magnesium. 1764 82

In experiments reported here, we tested the ability of CGP-48506 to reverse the depressed cardiac contractility associated with hypercapnic acidosis in isolated rat cardiac myocytes. CGP-48506 is a cardiotonic agent that directly and specifically promotes the actin-cross-bridge reaction. Myocytes superfused at pH 6.8 demonstrated a significantly reduced extent of cell shortening, but an increase in the peak amplitude of the Ca2+ transient. Moreover, cells in acidosis showed small, but significant, decreases in time to peak shortening to 50 percent relaxation. Superfusion of the cells with 3, 7, and 10 micro-molar CGP-48506 restored the inhibited contractility as a function of concentration with no significant effects on the Ca2+-transient. Moreover, 10 micro-molar CGP-48506 completely reversed the depressed myocyte contraction associated with an increase in time to peak shortening and time to 50 percent and 75 percent relaxation. Our results indicate that the depression of contractility associated with acidosis is due to a reduced myofilament response to Ca2+, which can be overcome by agents working downstream from troponin C through a direct effect on the actin-myosin interaction.
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PMID:Reversal of effects of acidosis on contraction of rat heart myocytes by CGP-48506. 1850 12

Fatalities have been attributed to combinations of high-dose buprenorphine with benzodiazepines. In rats, high-dose buprenorphine combined with midazolam was shown to induce sustained respiratory acidosis, while buprenorphine alone did not. However, the effects of buprenorphine combined with pharmacological doses of benzodiazepines remain unknown. Our objective was to compare the acute effects of four selected benzodiazepines used intravenously at equi-efficacious doses in rats, alone and in combination with buprenorphine on sedation, respiratory rate and arterial blood gases. Buprenorphine (30 mg/kg) did not significantly modify sedation level or respiratory rate, but induced mild and transient effects on pH and PaCO(2) (P < 0.05). Similarly, despite having no effects on respiratory rate, nordiazepam (10 mg/kg), bromazepam (1 mg/kg) and oxazepam (12 mg/kg) mildly and transiently altered pH and PaCO(2) (P < 0.05), whereas clonazepam (5 mg/kg) did not. Buprenorphine combined with each benzodiazepine induced no significant effects on respiratory rate or blood gases, in comparison with buprenorphine alone. However, combinations of oxazepam or nordiazepam with buprenorphine significantly deepened sedation. While both combinations reduced respiratory rate, buprenorphine + 30 mg/kg clonazepam significantly increased PaCO(2) and buprenorphine + 30 mg/kg nordiazepam decreased PaO(2). In conclusion, not all benzodiazepines induce significant respiratory depression at therapeutic doses. We were unable to demonstrate significant effects on rat ventilatory parameters of buprenorphine combined with equi-efficacious pharmacological doses of benzodiazepines in comparison with buprenorphine alone. Our results may suggest that effects of these combinations are rather mild. Respiratory failure may, however, result from the association of buprenorphine with elevated doses of benzodiazepines.
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PMID:Effects of various combinations of benzodiazepines with buprenorphine on arterial blood gases in rats. 1868 26

Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (micro1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (T(I)) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (T(E)) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO(2) (P < 0.01) and T(E) (P < 0.001) but only partially on T(I) (P < 0.001). Naltrindole reduced methadone-related effects on T(E) (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO(2) (P < 0.05) Respiratory effects as a function of plasma R-methadone concentrations showed a decrease in PaO(2) (EC(50): 1.14 microg/ml) at lower concentrations than those necessary for PaCO(2) increase (EC(50): 3.35 microg/ml). Similarly, increased T(I) (EC(50): 0.501 microg/ml) was obtained at lower concentrations than those for T(E) (EC(50): 4.83 microg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in T(E) is caused by mu1- and delta-opioid receptors while increase in T(I) is caused by mu-ORs.
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PMID:Mechanisms of respiratory insufficiency induced by methadone overdose in rats. 2000 23

All infants have some degree of hypoxia and respiratory acidosis at birth, but these conditions are more profound in the asphyxiated newborn. The newborn infant is very susceptible to cooling and may require warming. Skin temperature should be maintained between 36-36.5 degrees .(2) Resuscitation of the asphyxiated newborn must include both ventilatory and metabolic correction.Newborn infants may have cardiorespiratory problems due to asphyxia, drugs given to the mother, intrathoracic disease, anemia, hypovolemia (due to antepartum hemorrhage), hypotension, etc. There is no substitute for oxygen which is the drug of choice in respiratory depression of the newborn. The use of stimulating drugs like Coramine, picrotoxin, alphalobectine, and Megamide has no place in the resuscitation of the asphyxiated newborn.
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PMID:Resuscitation of the newborn. 2046 96


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