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)

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.
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PMID:Intravenous anesthesia for the patient with left ventricular dysfunction. 1670 33

Obstetric patients undergoing caesarean section under general anaesthesia require rapid induction due to high risk of aspiration. Rocuronium provides the shortest onset of action of nondepolarizing blocking agents. Onset time can be shortened by the priming principle. Ketamine has been shown to improve intubating conditions when used in association with rocuronium. Even if ketamine crosses the placenta rapidly, it does not produce neonatal depression unless used in doses above 1-1.5 mg x kg(-1). We present a case of elective caesarean section due to pelvic disproportion managed in general anaesthesia. Following 5 min of preoxygenation, a priming dose of 0.04 mg x kg(-1) of rocuronium was administered. The patient was maintained on spontaneous breathing with 100% oxygen by face mask for 3 min and then induced in rapid sequence with thiopental 2 mg x kg(-1), ketamine 1 mg x kg(-1) and 0.4 mg x kg(-1) or rocuronium. Intubation was performed 30 s after induction (twitch tension 17%) with an excellent clinical intubating score. No adverse events such as muscle weakness or patient discomfort were observed or reported by the patient. Time from injection of the intubating does of rocuronium to recovery of 25% of single twitch was 26 min. Recovery index (T25-75) was, instead, of 3 min and 25 s. The combination of the induction agents thiopental and ketamine, associated with low dose priming with rocuronium, have guaranteed excellent intubating conditions in this clinical context.
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PMID:Thiopental--ketamine association and low dose priming with rocuronium for rapid sequence in duction of anaesthesia for elective cesareum section. 1677 Mar 9

This study investigated the signaling pathways responsible for ketamine-induced cardiac depression in guinea pigs. The left ventricular development pressure (LVDP), velocity of the change in pressure (dP/dt), and heart rate (HR) accompanied with the total magnesium efflux ([Mg]e) were measured simultaneously in perfused hearts. The level of activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2) and p38 mitogen-activated protein (MAP) kinase. The intracellular ionized magnesium concentration ([Mg2+]i) was measured using Mag-fura 2 AM in a single cardiomyocyte. Ketamine produced reversible decreases in the LVDP, dP/dt, and HR accompanied by increases in the [Mg]e. Ketamine also produced significant activation of p38 MAP kinase and ERK 1/2, and produced a dose-dependent increase in the [Mg2+]i, which was inhibited SB203580 and PD98059. These results suggest that ketamine-induced cardiac depression can be partly responsible for the increase in [Mg2+]i and [Mg]e, accompanied by the activation of p38 MAP kinase and ERK 1/2 in guinea pigs.
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PMID:Ketamine-induced cardiac depression is associated with increase in [Mg2+]i and activation of p38 MAP kinase and ERK 1/2 in guinea pig. 1694 37

The study was conducted in 9 healthy adult goats of either sex, weighing 15-20 kg, to evaluate and compare the clinicophysiological effects of spinally administered ketamine alone and in combination with xylazine and medetomidine. Nine trials each of the three treatments were conducted randomly by injecting ketamine (2.5 mg/kg) (n = 9), ketamine and xylazine (2.5 mg/kg and 0.05 mg/kg) (n = 9) and ketamine and medetomidine (2.5 mg/kg and 10 microg/kg) (n = 9). The drugs were administered at the lumbosacral subarachnoid space under strict aseptic conditions. The treatments were evaluated on the basis of clinicophysiological, haematological, biochemical and haemodynamic observations. Ketamine produced mild to moderate analgesia of the hindquarters. Its combination with either xylazine or medetomidine produced complete analgesia of the hindquarters for 45-60 min. Ataxia was moderate in the ketamine group, whereas animals attained sternal recumbency in the combination groups. A moderate degree of sedation was recorded in the combination groups. Heart rate and respiratory rate depression in the combination groups and heart rate and respiratory rate stimulation in ketamine group were recorded. Haematological parameters decreased in all the groups. Increase in serum glucose, creatinine and urea nitrogen was recorded in all the groups. Serum electrolytes did not show any significant change. The results showed that the combination of ketamine with xylazine or medetomidine at these dose rates produced a comparable degrees of analgesia of hindquarters with transient and minimal cardiopulmonary side effects.
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PMID:Clinicophysiological effects of spinally administered ketamine and its combination with xylazine and medetomidine in healthy goats. 1729 60

Continuous i.v. infusion of propofol, or propofol plus ketamine for deep sedation and analgesia was carried out in two patients with severe epidermolysis bullosa (EB) during extensive dressing changes and deep whirlpool baths. Intermittent small doses of narcotics were given as supplement for pain relief as needed. Both patients had typical features of severe EB, including extremity contractures, severe digit deformity, difficult airways, extensive blisters and broken skin with denuded areas and severe wound infections. SpO(2) was roughly estimated by holding the probe around the earlobe periodically and no other monitors could be applied because of the skin conditions and the settings of the procedures. Retrospective anesthesia record review showed that the combined propofol and ketamine infusions provided satisfactory sedation with significantly reduced narcotic requirements compared with propofol alone. There were no noticeable side effects when ketamine was added. Ketamine appears to be a good addition to propofol and narcotics to provide sedation and analgesia when there are great concerns for respiration depression, apnea, difficult pain management and potential unstable hemodynamics during dressing changes and whirlpool baths in severe EB patients.
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PMID:Deep sedation with intravenous infusion of combined propofol and ketamine during dressing changes and whirlpool bath in patients with severe epidermolysis bullosa. 1749 25

Ketamine is a new party drug, which is easy to obtain. For this reason, it is possible that physicians will be increasingly confronted with users that have medical problems. Relatively few cases of ketamine intoxication with a fatal outcome have been reported thus far. Ketamine is very hallucinogenic; people can experience unpleasant flashbacks even weeks after the drug has been eliminated from the body. Ketamine has a short half-life; the elimination half-life is about 2.5 h. A serious intoxication can lead to aspiration, acidosis, rhabdomyolysis, epileptic seizures, respiratory depression, and cardiac arrest. Ketamine is frequently used as a party drug in combination with other substances. As a result, the chance of untoward effects is increased. Anaesthetists use ketamine for short surgical procedures, sedation and analgesia. It is also used more and more often as an analgesic in patients who do not respond well to opioids.
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PMID:[Ketamine as a party drug]. 1792 12

Phencyclidine (PCP) and ketamine are dissociative anesthetics capable of inducing analgesia, psychomimetic behavior, and a catatonic state of unconsciousness. Despite broad similarities, there are notable differences between the clinical actions of ketamine and PCP. Ketamine has a lower incidence of adverse effects and generally produces greater CNS depression than PCP. Both noncompetitively inhibit NMDA receptors, yet there is little evidence that these drugs affect GABA(A) receptors, the primary target of most anesthetics. alpha6beta2/3delta receptors are subtypes of the GABA(A) receptor family and are abundantly expressed in granular neurons within the adult cerebellum. Here, using an oocyte expression system, we show that at anesthetically relevant concentrations, ketamine, but not PCP, modulates alpha6beta2delta and alpha6beta3delta receptors. Additionally, at higher concentrations, ketamine directly activates these GABA(A) receptors. Comparatively, dizocilpine (MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate]), a potent noncompetitive antagonist of NMDA receptors that is structurally unrelated to PCP, did not produce any effect on alpha6beta2delta receptors. Of the recombinant GABA(A) receptor subtypes examined (alpha1beta2, alpha1beta2gamma2, alpha1beta2delta, alpha4beta2gamma2, alpha4beta2delta, alpha6beta2gamma2, alpha6beta2delta, and alpha6beta3delta), the actions of ketamine were unique to alpha6beta2delta and alpha6beta3delta receptors. In dissociated granule neurons and cerebellar slice recordings, ketamine potentiated the GABAergic conductance arising from alpha6-containing GABA(A) receptors, whereas PCP showed no effect. Furthermore, ketamine potentiation was absent in cerebellar granule neurons from transgenic functionally null alpha6(-/-) and delta(-/-)mice. These findings suggest that the higher CNS depressant level achieved by ketamine may be the result of its selective actions on alpha6beta2/3delta receptors.
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PMID:Ketamine, but not phencyclidine, selectively modulates cerebellar GABA(A) receptors containing alpha6 and delta subunits. 1848 Feb 94

Rapid improvement of depressive symptoms occurs after the administration of the NMDA antagonist ketamine. Ketamine administration is accompanied by an increase in GLX (sum-peak of glutamate, glutamine (GLN) and GABA) and GLN in the brain, as measured by magnetic-resonance (MR) spectroscopy. In healthy subjects, we observed an increase in GLX and GLN levels after total sleep deprivation (TSD), which has a rapid antidepressant effects. We examined, if an increase in GLX or GLN is related to the therapeutic effect of TSD. We examined 13 patients with major depression by means of proton MR spectroscopy (field strength: 1.5T) before and after 24h of TSD. Two anatomical areas (dorsolateral prefrontal cortex (DLPC) and parieto-occipital cortex (POC)) were studied. In the DLPC TSD did not change GLX or its elements, whereas the total creatine and choline signal increased marginally. No change could be observed in the POC. For further exploration we took gender and the presence of vegetative characteristics of melancholic depression into account, i.e. the presence of early morning awakening, appetite and weight loss was taken into account, to define vegetative melancholia (VM). TSD led to an increase in GLX and GLN in the DLPC only of male patients. In patients with VM an increase in GLN occurred in this area. The low field strength limits the accuracy for GLX and GLN estimates. Despite the exploratory nature of the study, it nevertheless supports earlier data on the importance of glutamatergic neurotransmission and furthermore of gender and/or vegetative features in depression.
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PMID:The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression - an MR spectroscopy study. 1853 84

Recent studies with intravenous infusion of the NMDA receptor antagonist ketamine showed robust and rapid antidepressant effects within hours after treatment. Ketamine is a racemic mixture consisting of two enantiomers, R- and S-ketamine. In contrast to ketamine, S-ketamine is reported to be less prone to psychomimetic side effects, such as derealisation and hallucinations. In this report we describe the effect of ketamine and S-ketamine infusion therapy, respectively, in two patients with treatment-resistant major depression. Severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). While one patient did not respond to either treatment, in the other patient intravenous administration of ketamine as well as S-ketamine showed an antidepressant effect as assessed by a decrease in HAMD-21 and BDI at days 1 and 3 after infusion which faded until day 6. Both patients experienced psychomimetic side effects during ketamine infusion which were absent during treatment with S-ketamine. We conclude that S-ketamine might exert similar antidepressant effects as ketamine in drug-resistant depression but may be better tolerated by the patients.
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PMID:Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. 1922 12

Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 microM) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1beta release in primary cultured microglia. However, ketamine (100 and 250 microM) did not significantly inhibit the LPS-induced TNF-alpha production in microglia, except at the higher concentration (500 microM). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.
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PMID:Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation. 1934 93


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