Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketamine was introduced into clinical anaesthesia in 1965. Since then it has been demonstrated to lower airway resistance and to increase lung compliance in the asthmatic patient. It has also proved useful in anesthetizing asthmatic patients with or without symptoms. In several case reports it has been used successfully in the management of status asthmaticus resistant to conventional therapy but so far no controlled clinical trial has been carried out to support this empirical use of ketamine. The limited magnitude of the side effects permits the use in status asthmaticus when all other treatment has failed. Experiments with animals and with human preparations have suggested one or more of the following mechanisms of action: a sympathomimetic effect, a direct relaxant effect, an antagonism to histamine and acetylcholine and a membrane stabilizing effect as with local analgesics. Until investigations have been published ketamine is recommended as an anaesthetic for the asthmatic patient and for the patient who has previously reacted with bronchospasm when intubated or anaesthetized. Prospective clinical trials should be planned.
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PMID:[Ketamine as a broncholytic agent in status asthmaticus and as an anesthetic for patients with bronchial asthma]. 150 92

Ketamine is a cardiovascular stimulant through its sympathomimetic effects; however, its direct inotropic effect has been reported as positive in rat and negative in rabbit ventricular myocardium. This study reexamines the effect of ketamine on the contractile properties of mammalian ventricular myocardium. In isolated, electrically stimulated ferret right ventricular papillary muscles, the authors assessed the inotropic effect of ketamine (10(-6) M to 3 x 10(-4) M in 0.5 log M increments) alone and in various pharmacologic conditions designed to delineate ketamine's site(s) of action. Ketamine exerted a positive inotropic effect that was maximal at 10(-4) M. Bupranolol (10(-7) M) abolished this positive inotropic effect, whereas phentolamine (10(-6) M) did not. Depletion of norepinephrine stores by reserpine also eliminated ketamine's positive inotropic effect, indicating that ketamine caused indirect activation of the beta-adrenoceptor. Ketamine did not exert a positive inotropic effect in the presence of simultaneous inhibition of neuronal norepinephrine uptake with desmethylimipramine (DMI) (5 x 10(-6) M) and extraneuronal uptake with corticosterone (5 x 10(-5) M). It is likely that ketamine's action is to inhibit norepinephrine uptake at the neuroeffector junction rather than to augment norepinephrine release. In the presence of corticosterone, ketamine exerted a smaller positive inotropic effect than that seen with ketamine alone. Ketamine produced a small increase in force development in the presence of DMI, but this did not reach statistical significance. Inhibition of neuronal catecholamine uptake appears to be the predominant mechanism of ketamine's positive inotropic effect.
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PMID:Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle. 202 Dec 5

Effects of ketamine on responses to sympathomimetic amines were studied using isolated aortic and pulmonary artery strips from the rabbit. Ketamine (1.1 x 10(-5) to 3.7 x 10(-4) M) potentiated adrenaline-contracted strips. Potentiation was not impaired in tissues from animals pretreated with reserpine, with 6-hydroxydopamine, or its tissues pretreated with cocaine. Pretreatment of the strips with the catechol O-methyltransferase (COMT) inhibitors tropolone or pyrogallol or the inhibitor of extraneuronal uptake 17 beta-estradiol blocked the potentiation by ketamine; in addition, potentiation by the COMT and extraneuronal uptake inhibitors was abolished or greatly reduced by ketamine. In rabbit aorta, ketamine potentiated responses to the catecholamines (adrenaline greater than nordefrine greater than noradrenaline) but not to the noncatecholamines phenylephrine, methoxamine, and synephrine; instead a slight relaxant effect was observed. Ketamine potentiated, whereas cocaine inhibited, responses to tyramine Experiments using the technique of oil immersion demonstrated that ketamine reduced the rate at which aortic strips inactivate adrenaline even when monoamine oxidase (MAO) and neuronal uptake processes were fully inhibited. Uptake studies showed that ketamine and 17 beta-estradiol reduced extraneuronal accumulation of [3H]adrenaline in aortic strips. We conclude that ketamine is an inhibitor of extraneuronal uptake in the vascular smooth muscles studied and the importance of this mechanism in producing its known cardiovascular effect is discussed.
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PMID:Ketamine potentiates catecholamine responses of vascular smooth muscle by inhibition of extraneuronal uptake. 729 68

Pharmacological praemedication. In patients receiving regional anaesthetics induction of deep sedation prior to the performance of the block should be avoided because during the installation of the nerve block it is an advantage to have a cooperative patient. Adequate anxiolytic effects are achieved by oral administration of chloracepate (0.3-0.5 mg/kg body weight). Intraoperative sedation. Once regional anaesthesia is established deep sedation or even a light sleep might be appropriate to improve the patient's comfort. Short acting i.v. substances are the agents of choice. Propofol (1.5-5 mg/kg per h) and midazolam (0.03-0.09 mg/kg per h) are recommended. Both substances should be titrated as needed. Since respiratory depression or loss of airway patency may occur, close observation and pulse oxymetric monitoring are mandatory. Intraoperative analgesia. Restlessness due to pain is not an indication for sedatives and/or hypnotics. Pain can be caused not only by incomplete regional anaesthesia, but also by a tourniquet or uncomfortable body positions, for example, and it should be treated in different ways according to its cause. In the case of an incomplete block, a catheter technique makes a top-up dose for augmentation possible; additional peripheral nerve blocks can also be used to complete the analgesia. If these attempts are unsuccessful, systemic analgesics (preferable narcotics) or even anaesthetics must be given. Opioids are recommended only in mild to moderate pain or discomfort. The risk of respiratory depression should be considered. The administration of oxygen by mask and pulse oxymetric monitoring are useful. Ketamine is a common drug with a potent analgesic effect, which possesses the advantages of good support for the cardiovascular system, because of its sympathomimetic action, and minimal depression of the ventilatory drive. However, with the exception of a few specific indications, Ketamine is not a drug that is initially an integral part of planned regional anaesthetic procedures. In case of incomplete regional blocks administration of ketamine is more frequently the "ultima ratio" following a number of previous, unsuccessful attempts-primarily with sedatives and/or opioids-to achieve a condition that will permit surgical procedures; as a result, the hypnotic and respiratory depressant effects of subsequently administered drugs are enhanced and potentiated. An important consequence of this complex pharmacodynamic interaction scenario is a potential loss of the advantages that would otherwise be gained by using "subanaesthetic" ketamine doses (< 0.5 mg/kg), namely: a cooperative patient who is breathing spontaneously and has an intact laryngopharyngeal reflex response and, therefore, an uncompromised airway competence. Pulse oxymetric monitoring of the potentially endangered respiratory function is obligatory. The individual transition to general anaesthesia is not easy to determine. Therefore, it is essential that, whenever the need arises, intubation and mechanical ventilation intervention procedures be carried out immediately.
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PMID:[Analgesia and sedation to supplement incomplete regional anesthesia]. 859 70

Ketamine is known to increase arterial pressure and heart rate with its sympathomimetic action. However, it also relaxes vascular smooth muscle and causes hypotension. We studied such a bipartite effect in terms of ketamine induced changes of dopamine (DA) release from rat pheochromocytoma (PC-12) cells as a model of sympathetic nervous system. Without KCl stimulation, ketamine increased the DA release from PC-12 cells in a dose-related fashion (10(-4)M: 2.6 +/- 0.4, 10(-3)M : 7.5 +/- 0.3, 10(-2)M: 27.1 +/- 3.2%). The similar increase of DA release was observed with absence of extracellular Ca2+. Exposure of KCl (50 mM) to PC-12 cells increased the DA efflux from 1.7 +/- 0.4 to 14.2 +/- 0.8% (P < 0.001). The release of DA stimulated by KCl (50 mM) was reduced to 9.0 +/- 1.0% and 11.4 +/- 0.3% in the presence of ketamine 5 x 10(-4)M and 10(-3)M respectively, and increased with the ketamine concentration of 10(-3)M. These findings indicate that ketamine depresses DA efflux related to membrane depolarization (K+) but it promotes a number of spontaneous DA efflux.
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PMID:[The dual effect of ketamine on dopamine release from rat pheochromocytoma (PC-12) cells]. 899 33

Ketamine is still a relatively seldom-used anaesthetic because of its psychotomimetic and sympathomimetic side-effects and because ketamine anaesthesia is poorly controllable. At present, the enantiomer S-(+)-ketamine (Ketanest S) is clinically used. During its application, a twofold higher pharmacologic potency and a faster elimination can be expected than with the racemic-ketamine mixture. Particularly in paediatric anaesthesia, no practical experience could be gained with this new drug. Form the current standpoint, an overview is given of the possible applications of ketamine in children regarding premedication and early induction of ketamine anaesthesia in combination with midazolam because ketamine can be inserted through the nose or rectum and it can also be applied orally or intramuscularly. Ketamine widens the anaesthetist's possibilities of premedication considerably and thus a calm induction of anaesthesia with stabilized spontaneous ventilation becomes possible in children with difficult conditions for venous puncturing, in very anxious children and in those who are not able to accept the necessity of treatment. The use of ketamine for the performance of small operations, for analgosedation during diagnostic procedures, for induction of anaesthesia in children with unstable haemodynamic conditions and with cardiac defects connected with reduced lung perfusion and for analgosedation in intensive care, in particular in patients with obstructive ventilation disturbances and diseases which need a therapy with catecholamines, is discussed. To avoid complications, the children should be supervised constantly during the application of ketamine. It should be used only in low doses and any combination with centrally depressive-acting drugs--with the exception of midazolam--should be avoided. During analgosedation with ketamine and midazolam in intensive care, the anaesthetist must be aware of a cumulative effect in particular in those children with liver and kidney insufficiencies. Analgosedation with ketamine and propofol can be better controlled horizontally and therefore, this combination should be taken more into consideration in children with the exception of those with diseases of inflammatory and septic genesis.
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PMID:[Current aspects of using ketamine in childhood]. 970 51

Pain and its treatment are known to have adverse effects on the organism, including deterioration in myocardial, diaphragmatic, and small bowel function. The provision of adequate intravenous analgesia, and the choice of agent, can ameliorate or exacerbate these manifestations of the stress response. The choice of agent, opioid or non-opioid, has in some respects become more difficult as more information has become available regarding the merits and adverse effects of each. Increased awareness of the frequency of hypoxemia secondary to the opioids' ability to cause an obstructive sleep apnea picture, and the cost efficiency of ketorolac through a reduction in opioid toxicity, contrast with recent studies which suggest that the gastrotoxic and nephrotoxic effects of ketorolac may occur earlier than previously suspected. The suitability of using the dissociative anesthetic agent ketamine in critically ill patients remains to be proven. Ketamine provides intense analgesia at subanesthetic doses. Its centrally mediated sympathomimetic action encourages hemodynamic stability, and it is relatively devoid of respiratory depressant activity. Increasing experience with ketamine outside the operating room has resulted in its successful use in cases of severe bronchospasm and status epilepticus.
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PMID:Intravenous analgesia. 992 88

To characterise ketamine-induced sympathomimetic action, we examined the effects of ketamine on in vivo cardiac sympathetic nerve endings function. Using adult cats given anaesthesia with pentobarbital, dialysis probes were implanted in the left ventricular myocardium and dialysate noradrenaline (NA) concentrations were measured as an indicator of NA output at the cardiac sympathetic nerve endings. Ketamine was locally administered through the dialysis probe, and dialysate NA responses were obtained in the following conditions. (1) In the resting state, ketamine (10 mM) increased dialysate NA concentration. This increase in dialysate NA was not altered by addition of omega-conotoxin GVIA (N-type Ca(2+) channel blocker) or desipramine (membrane NA uptake blocker). (2) Sympathetic activation by electrical stimulation of the stellate ganglia (ES-SG; exocytotic NA release): ES-SG caused an increase in dialysate NA, which was further augmented by addition of desipramine. During co-administration of desipramine and ketamine, dialysate NA response to ES-SG was smaller than with desipramine alone. Further, there was no significant difference in the dialysate NA response to ES-SG between ketamine and ketamine + desipramine. These data suggested that both exocytosis and NA uptake function were impaired by ketamine. (3) Non-exocytotic NA release by ouabain: ouabain caused increases in dialysate NA. These increases in dialysate NA were suppressed by ketamine, which impaired the membrane outward NA transport evoked by ouabain. We conclude that ketamine impaired exocytotic and non-exocytotic NA release. However, ketamine spontaneously evoked NA efflux that was independent of exocytosis and insensitive to NA transporter.
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PMID:Effects of ketamine on exocytotic and non-exocytotic noradrenaline release. 1242 80

Ketamine is a dissociative anaesthetic that is being used in non-medical contexts. The effects of ketamine are very similar to those of phencyclidine, another dissociative anaesthetic that has enjoyed considerable popularity as a recreational drug. The effects of ketamine include analgesia, cardiovascular and respiratory stimulation, dissociation, hallucinations and anaesthesia. The potential dangers of uncontrolled ketamine use include psychosis and violence, accidents and marked psychomotor and cognitive impairment. Although studies have shown potential for tolerance to and physical dependence on ketamine, further investigation of these phenomena is needed. Ketamine is thought to produce most of its effects through antagonist activity at the PCP site of the NMDA receptor complex. Ketamine has sympathomimetic properties resulting from enhancement of catecholamine, and particularly dopamine, activity. While opioid receptor activity has been identified, this is relatively weak and the contribution to the effects of ketamine is not clear. Although much is known of the clinical uses and effects of ketamine, as yet little is understood of ketamine as a recreational drug and potential drug of dependence.
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PMID:Pharmacological properties of ketamine. 1620 65

Ketamine is believed to have sympathomimetic effects, although the central mechanism remains unclear. Using an in vitro splanchnic nerve-spinal cord preparation from neonatal rats, our previous investigations have demonstrated that tonic sympathetic activity is spontaneously generated from the thoracic spinal cord. We designed this study to investigate whether applications of ketamine to the cord would augment sympathetic activity and whether this action was dependent on N-methyl-d-aspartate receptors. Bath application of ketamine significantly reduced sympathetic activity in a concentration-dependent manner. Ketamine in 10, 20, 40, 80, and 120 microM reduced the sympathetic activity to 82.6% +/- 4.4% (P < 0.05), 61.7% +/- 5.1%, 42.8% +/- 4.2%, 24.9% +/- 4.4%, and 9.2% +/- 2.7% of the control value, respectively (P < 0.01, n = 8 for each test). The 50% inhibitory concentration of ketamine on sympathetic activity was 32 muM. Pretreatment with DL-2-amino-5-phosphonovaleric acid, a selective competitive N-methyl-d-aspartate receptor antagonist, did not alter ketamine-induced depression of sympathetic activity. These results suggest that ketamine reduces sympathetic activity by mechanisms that are independent of N-methyl-d-aspartate receptor activity.
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PMID:Ketamine attenuates sympathetic activity through mechanisms not mediated by N-methyl-D-aspartate receptors in the isolated spinal cord of neonatal rats. 1649 32


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