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)

Clonidine, an alpha 2-adrenergic agonist, can potentiate opioid-induced analgesia. In a double-blind placebo-controlled study in human volunteers, we sought to determine whether clonidine also potentiates opioid-induced respiratory depression. Hypercapnic ventilatory responses (minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure) were measured in five healthy male volunteers on two separate occasions (with or without clonidine, approximately 3.5 micrograms.kg-1 orally) under the following conditions: baseline, 2 h after clonidine/placebo (alfentanil concentration of 0), and during computer-controlled alfentanil infusions to approximate plasma concentrations of 5, 10, 20, 40, and 80 ng.ml-1. Plasma alfentanil concentrations were measured before and after each rebreathing test, and clonidine concentrations were measured after each rebreathing test. The end-tidal CO2 (PET(CO2)) was measured continuously. Data were analyzed by repeated-measures analysis of variance. The PET(CO2) and measured concentrations of alfentanil were included as covariates, and a compound symmetry error analysis was assumed. Statistical significance was achieved when P less than 0.05. For minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure there was a statistically significant relationship to the covariates of PET(CO2) and plasma alfentanil concentration. Clonidine, when compared to placebo, caused a small but significant depression of mean inspiratory flow rate. There was similarly a small, but statistically insignificant, depression of minute ventilation by clonidine. The mouth occlusion pressure was not affected by clonidine treatment. Clonidine treatment did not potentiate alfentanil-induced respiratory depression. Although the combination of an opioid and an alpha 2-adrenergic agonist may act synergistically for the analgesic response, there is no synergistic effect by this drug combination on respiratory depression.
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PMID:Ventilatory effects of clonidine alone and in the presence of alfentanil, in human volunteers. 159 10

Benzodiazepine drugs have been shown to suppress respiratory function in patients with chronic obstructive pulmonary disease (COPD). We designed a placebo-controlled crossover study to compare the effects of a new benzodiazepine, estazolam ('ProSom'), with those of flurazepam ('Dalmane') on cardiopulmonary function in COPD patients. 29 patients completed all treatment phases (estazolam 2 mg, flurazepam 30 mg or placebo). Respiratory and cardiovascular function were assessed in awake patients on days 1 and 5 (acute and cumulative effects). Eight patients were also assessed during sleep in each period. The effects of estazolam and flurazepam on ventilatory response to CO2 and mouth occlusion pressure were no different from those of placebo. However, acute administration of flurazepam lowered tidal volume and increased inspiratory flow. Although no clinical signs of respiratory depression were observed with any long term treatment, flurazepam decreased oxygen saturation and inspiratory time and increased respiratory frequency. Neither drug altered breathing control during sleep. Our results indicate that estazolam 2 mg is equally as safe a hypnotic agent as flurazepam for patients with mild COPD.
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PMID:Effects of estazolam and flurazepam on cardiopulmonary function in patients with chronic obstructive pulmonary disease. 160

Twenty-eight elderly patients scheduled for urological surgery were randomly assigned to receive, in a double-blind study, subarachnoid hyperbaric bupivacaine 15 mg with 50 micrograms (group A, n = 7), 25 micrograms (group B, n = 7), or 12.5 micrograms (group C, n = 7) of fentanyl or 1 ml of saline (group D, n = 7) in a total volume of 4 ml. The pattern of breathing and the ventilatory response to CO2 were studied before and 90, 150 and 480 min after the subarachnoid injection. In group A, mild pruritus and sedation occurred in five patients, while nausea, vomiting and periodic breathing occurred in two. In group B, mild pruritus and sedation were observed in four patients, while nausea and vomiting occurred in two. No significant differences in minute ventilation, respiratory drive and respiratory timing were observed between the groups. Patients receiving fentanyl 50 micrograms showed a percentual change from baseline values as function of time (slope VE/PE'CO2) significantly below baseline at 90 and 150 min (p less than 0.05). However, the baseline values in this group reverted after 480 min. No side effects were observed in groups C or D. It is concluded that subarachnoid fentanyl 50 micrograms can cause an early respiratory depression and its use as a postoperative analgesic should be avoided in the elderly.
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PMID:Ventilatory effects of subarachnoid fentanyl in the elderly. 162 64

Surgical stress and general anesthesia can suppress immune function and thus may increase postsurgical infections and tumor metastasis. We previously reported that two narcotics commonly used in high-dose opiate anesthesia (fentanyl and sufentanil) suppress natural killer (NK) cell activity in rats. Such doses of narcotics also cause respiratory depression accompanied by hypoxia, hypercarbia, and acidosis, which might account for the observed narcotic-induced NK suppression. In the present study, we compared the effects of fentanyl on NK activity in ventilated and non-ventilated rats. Fentanyl significantly suppressed NK cell activity to the same magnitude in the two groups, although the groups significantly differed in CO2 and O2 levels. The fact that high-dose fentanyl-induced NK suppression can be demonstrated in ventilated rats accentuates the relevance of these findings to clinical studies showing NK suppression in the immediate postoperative period. Such immunosuppression could be a risk factor for patients undergoing surgery, especially in cancer-related operations.
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PMID:Narcotic-induced suppression of natural killer cell activity in ventilated and nonventilated rats. 164 47

Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has been reported to produce analgesia with limited depression of ventilation. We quantified the effects of pentamorphone (0.08, 0.24, and 0.60 micrograms/kg, IV) on ventilatory responses to hypercapnia and hypoxia in 12 healthy volunteers. Normoxic hypercapnia and isocapnic hypoxia were induced through a rebreathing method. During each test we recorded ventilation (VE), end tidal carbon dioxide tension (PETCO2), and arterial oxygen saturation (SO2) using a pulse oximeter. Using linear regression analysis of the relationships between VE and PCO2 during hypercapnia and VE and SO2 during hypoxia, we determined the slope (slope CO2) and intercept (V55), both at PCO2 55 mm Hg, and the slope (slope O2) and intercept (V80) at SO2 80%. Pentamorphone produced dose-related reductions in the ventilatory responses to both hypercapnia and hypoxia. Maximal depression occurred 15 min after injection of pentamorphone with all doses; the highest dose (0.60 micrograms/kg) produced 48% and 53% reductions in slope CO2 and V55, and 42% and 22% reductions in slope O2 and V80, respectively, relative to parallel saline controls. The respiratory depressant actions of pentamorphone were short-lived, as all parameters returned to baseline levels within 45 min. Testing was continued for 180 min after injection, but no delayed ventilatory effects were detected, and minimal side effects were reported, even at the highest dose. The findings confirm previous reports that pentamorphone has limited ventilatory depressant effects in humans in doses that (in other studies) have been associated with clinically effective analgesia.
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PMID:Depression of ventilatory responses to hypoxia and hypercapnia after pentamorphone. 169 39

To determine whether the risk of midazolam-induced ventilatory depression is related to the rate of midazolam administration, we compared the effect of rapid (over 15 s) and slow (over 5 min) administration of midazolam (0.1 mg/kg IV) on the hypercarbic ventilatory response of 10 healthy volunteers. During the first 5 min after the start of midazolam injection, the slope of the ventilatory response to CO2 was significantly lower when the subjects received midazolam rapidly (P less than 0.001). However, after completion of the infusion (between 5 and 20 min), depression of the CO2 response curve slope was independent of the rate of midazolam administration. Similarly, although minute ventilation and tidal volume measured at an end-tidal CO2 tension of approximately 46 mm Hg decreased more quickly after rapid administration of midazolam (P less than 0.001), these variables did not differ significantly between the two rates of administration once the slow infusion was complete. These results suggest that slow administration of midazolam provides no independent protection from respiratory depression.
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PMID:Slow injection does not prevent midazolam-induced ventilatory depression. 163 61

To improve our understanding of the respiratory pharmacology of intravenous induction agents, the authors compared the acute effects of intravenous (iv) propofol 2.5 mg.kg-1 and iv thiopental 4.0 mg.kg-1 on the ventilatory response to CO2 (VeRCO2) of eight healthy volunteers. The slope of VeRCO2 decreased from 1.75 +/- 0.23 to a minimum of 0.77 +/- 0.14 1.min-1.mmHg-1 (mean +/- standard error) 90 s after propofol; similarly, the slope of VeRCO2 decreased from 1.79 +/- 0.22 to a minimum of 0.78 +/- 0.23 l.min-1.mmHg-1 30 s after thiopental. For both drugs, the slope was less than control in the 0.5-5-min period after injection (P less than 0.05). The slope returned to baseline within 6 min after thiopental; in contrast, after propofol, the slope remained less than control for the entire 20-min follow-up period (P less than 0.05 at 6-10, 11-15, and 16-20 min after injection). Also, from 6-10, 11-15, and 16-20 min after injection, the slope was less after propofol than at corresponding times after thiopental (P less than 0.05). Recovery of consciousness was approximately 4 min slower after propofol than after thiopental; nonetheless, awareness scores returned to baseline within 14 min after both drugs. The authors conclude that propofol 2.5 mg.kg-1 iv produces longer-lasting depression of VeRCO2 than a 4.0 mg.kg-1 iv dose of thiopental; after propofol, ventilatory depression may persist despite apparently complete recovery of consciousness.
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PMID:Time course of ventilatory depression following induction doses of propofol and thiopental. 174 14

Kainic acid (KA) injections into the retrotrapezoid nucleus (RTN) of anesthetized deafferented cats profoundly decreased phrenic activity (PA) and CO2 sensitivity (J. Appl. Physiol. 68: 1157-1166, 1990). In this study small electrolytic lesions of the RTN produced the same results, indicating that the KA destroyed cells. We then asked whether anesthetic depression or the absence of peripheral chemoreceptors could explain the degree of respiratory depression observed. In decerebrate cats electrolytic lesions of the RTN resulted in a decrease in PA similar to that seen under anesthesia. CO2 sensitivity was decreased by RTN lesions that extended into the caudal RTN but less so than under anesthesia. KA injections resulted in an initial increase in PA followed by a continuous decrease, a pattern similar to that seen under anesthesia but with a slower time course. CO2 sensitivity was essentially absent. Peripheral chemodenervation produced a small further decrease in PA and a downward shift of the CO2 response without change in slope. Blood pressure was unaffected by RTN lesions but was decreased by more-caudal lesions without respiratory effects. The RTN appears to be necessary for the maintenance of eupneic phrenic activity and CO2 sensitivity even in decerebrate cats with intact peripheral chemoreceptors.
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PMID:Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats. 175 59

Conscious animals subjected to inspiratory flow-resistive loading augment respiratory drive [as measured by airway occlusion pressure (P100)] independently of changes in chemical drive. Past studies of anesthetized subjects, however, have failed to demonstrate this response, and investigators have concluded that its presence depends on a state of consciousness. We tested the hypothesis that respiratory depression due to anesthesia or endogenous opioids rather than unconsciousness per se was responsible for this observation. Miniature piglets were anesthetized with ketamine and xylazine and subjected to hyperoxic CO2 rebreathing trials with and without added inspiratory resistance, before and after treatment with the opioid antagonist naltrexone. Before naltrexone there was a parallel leftward shift in the occlusion pressure vs. PCO2 relationship without a change in slope (delta P100/delta PCO2). After naltrexone there was a 45.5 +/- 15% increase in slope with loading. Addition of incremental doses of pentobarbital markedly reduced this increase in slope. We conclude that anesthetized animals can demonstrate flow-resistive load compensation in the form of augmented neuromuscular output not due to increased chemical drive. Failure to observe this response in past studies may reflect respiratory depression due to the anesthetic agents employed.
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PMID:Occlusion pressure response to inspiratory flow-resistive loading in anesthetized swine. 176 73

Administration of propofol in paediatric anaesthesia is relatively recent. Cardiovascular effects are minimal. Respiratory depression observed is in part in relation with the decrease of CO2 response. EEG tracing does not show spikes or "burst suppression" for usual doses. Pharmacokinetics are similar to those reported for young adults with the exception of a larger central compartment volume. Dosage depends particularly on age, injection speed and premedication. Propofol is often used for induction, halogenated agents taking over with a narcotic and a myorelaxant. Main disadvantages is pain on injection which are reduced by addition of lignocaine. Spontaneous movements during induction appeared chiefly with low doses. The most important advantage of propofol is the rapidity and the quality of recovery. Propofol has its place in paediatric anaesthesia and in addition sedation in intensive care unit is an new unexplored field.
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PMID:[Propofol in pediatric anesthesia]. 177 70


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