Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist used recently for analgesia in patients with chronic pain. Twenty one patients with chronic neuropathic pain were treated with oral ketamine starting at a divided dose of 100 mg/day and titrating upwards by 40 mg/day until efficacy was reached, or until side effects became limiting. A retrospective chart review was conducted to evaluate the analgesic efficacy and side effects of the treatment. Nine patients discontinued ketamine because of intolerable side effects, four patients experienced few or no side effects but had no discernible benefit, four others had equivocal responses. Four patients have continued oral ketamine for long periods. One patient has had no significant benefit or side effects but continues to use ketamine 500 mg/day and three people have used doses ranging from 100-240 mg day for over 1 year duration and have reported improvements in pain and decreased use of analgesics. The analgesic benefits of ketamine appeared to be most pronounced in, but not limited to, patients with pain histories of less than 5 years.
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PMID:Clinical experience with oral ketamine. 1068 20

Ketamine is a drug widely used for analgesia and sedation of children for diagnostic and therapeutic procedures. The authors investigated in a randomized controlled clinical trial if diazepam premedication would have a beneficial effect on side effects related to ketamine anesthesia for bone marrow punctures (BMPs) in children with acute lymphoblastic leukemia (ALL). Sixteen children 4 years or older at the time of BMP were eligible. The first 2 BMPs after complete remission was obtained were studied. BMPs were performed under ketamine anesthesia (1.0-1.5 mg/kg i.v.), as usual. Patients were randomized to receive 1 h before the first BMP blinded, either diazepam or placebo orally and before the second BMP the other way round. Blood pressure, heart rate, and oxygen saturation were monitored, and patients were observed for signs of anxiety, pain, and other side effects. The patients were interviewed after each BMP and asked for their preference 1 week after the second BMP. Ketamine anesthesia appeared as safe and effective after diazepam premedication as after placebo premedication. From the interviews and questionnaires, it was clear that half of the children preferred diazepam premedication because of less awful dreaming and more gradual falling asleep and waking up. Diazepam premedication may be useful for selected children with ALL receiving ketamine anesthesia for BMPs.
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PMID:Ketamine anesthesia with or without diazepam premedication for bone marrow punctures in children with acute lymphoblastic leukemia. 1091 48

Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.
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PMID:Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. 1102 5

Ketamine remains one of the most commonly used anaesthetic agents around the world. Despite it being the anaesthetic agent of choice in many developing nations, there is a paucity of literature describing ketamine in the developing world. In what we believe is the first randomized controlled trial to be performed in Vanuatu (formerly the New Hebrides) we compared the use of ketamine 0.9 mg/kg and diazepam 0.07 mg/kg with ketamine 0.3 mg/kg and 2% lignocaine infiltration in 50 Melanesian women undergoing post partum tubal ligation. All women received 0.5 mg/kg intramuscular pethidine. Visual analog pain scores and verbal numeric satisfaction scores were similar between the groups. However the time to obeyed command was significantly faster in the 0.3 mg/kg ketamine group (7.0+/-4.9 vs 13.0+/-9.2 min). The incidence of dreaming was similar and the content rated as pleasant by both groups. In institutions where post-anaesthesia care resources are limited, 0.3 mg/kg ketamine with local anaesthesia provides for earlier self-care of patients after tubal ligation, without compromise of analgesia, emergence or satisfaction. The implications of these findings extend to other procedures that require short general anaesthesia, which can be adequately performed with low-dose ketamine and local anaesthesia. The latter technique allows more rapid awakening.
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PMID:A randomized comparison of low-dose ketamine and lignocaine infiltration with ketamine-diazepam anaesthesia for post partum tubal ligation in Vanuatu. 1126 7

In this study, anesthesia levels obtained with tiletamine-zolazepam (TZ) and ketamine-midazolam (KM) with or without xylazine (X) were compared in rabbits. Reflexes (corneal, palpebral and withdrawal), blood parameters (PaO2, PaCO2, pH and ions HCO3-), cardiovascular function (heart rate and mean arterial blood pressure) and body temperature were evaluated before and after the injections of the anesthetic combination in the same rabbits (n = 10). With KM and TZ, no suppression of reflexes occurred. The body temperature and pH decreased and HCO3- increased similarly to KMX et TZX. Some physiological and blood parameters were less (PAM, PaCO2) and not (PaO2) affected comparatively to KMX et TZX. These protocols were of short duration of action and did not offer any anesthesia or analgesia. Therefore, their utilization should be restricted to short procedures where no painful manipulations are performed. Ketamine-midazolam-xylazine and tiletamine-zolazepam-xylazine on the other hand are indicated for interventions that require anesthesia. With these combinations, all reflexes were absent for 30-45 and 60-90 min following injections of KMX et TZX, respectively. However, these combinations induce cardiac depression, as well as a decrease of all measured blood parameters and body temperature and a reduction of PaO2. Supplementation with oxygen is recommended with the introduction of xylazine in the protocol.
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PMID:[Anesthesia of the New Zealand rabbit using the the combination of tiletamine-zolazepam and ketamine-midazolam with or without xylazine]. 1142 77

Ketamine may prevent postoperative hyperalgesia. In patients undergoing arthroscopic meniscectomy using general anesthesia, we tested whether a single intraoperative dose of ketamine enhanced postoperative analgesia and improved functional outcome compared with a typical multimodal analgesic regimen. After the induction of anesthesia, 50 patients were randomly assigned to ketamine (0.15 mg/kg IV just after the induction of anesthesia) or a vehicle placebo. Standardized general anesthesia included propofol, alfentanil, and nitrous oxide. Bupivacaine (0.5%) and morphine (5 mg) were given intraarticularly at the end of surgery. Postoperative analgesia was initially provided with morphine and subsequently with naproxen sodium (550 mg orally twice daily) and Di-Antalvic (400 mg acetaminophen and 30 mg dextropropoxyphene) as needed. Pain scores, analgesic requirements, side effects, and ability to walk were assessed in the ambulatory unit and at home for three postoperative days. Times to awakening and to discharge were similar in the two groups. However, the Ketamine group had significantly less postoperative pain at rest and during mobilization on Days 0, 1, and 2. Furthermore, they consumed significantly fewer Di-Antalvic tablets than the control group (13 [7-17] vs 27 [16-32], median [25%-75% interquartile range]). Patients given ketamine were also able to walk for longer periods of time on the first postoperative day. In conclusion, adding small-dose ketamine to a multimodal analgesic regimen improved postoperative analgesia and functional outcome after outpatient knee arthroscopy.
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PMID:Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. 1152 27

1. Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit or alpha4 and beta2 subunits expressed in Xenopus laevis oocytes. 2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values of 20 and 50 microM respectively. Inhibition of the alpha7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the alpha4beta2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more effectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both alpha7 (IC(50) value of 122 nM) and alpha4beta2 (IC(50) value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3. Ketamine is a noncompetitive inhibitor at both the alpha7 and alpha4beta2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the alpha7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the alpha4beta2 nAChR. 4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic.
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PMID:Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes. 1160 28

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.
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PMID:Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. 1176 65

To evaluate the role of oral ketamine as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain, 9 cancer patients (5 men, 4 women) taking maximally tolerated doses of either morphine, amitriptyline, sodium valproate, or a combination of these drugs for intractable neuropathic pain, and reporting a pain score of >6 on a 0-10 scale, were studied prospectively to evaluate analgesia and adverse effects. Ketamine in the dose of 0.5 mg/kg body weight three times daily was added to the existing drug regimen. Patients were taught to maintain a pain diary wherein they daily recorded their pain, sedation, and vomiting scores, and other side effects. A decrease of more than 3 from the baseline in the average pain score, or a score of < or =3 was taken as a successful response. Seven patients exhibited a decrease of more than 3. Four patients experienced nausea, of which one had vomiting. Two developed loss of appetite. Eight patients reported drowsiness during the first two weeks of therapy (P = 0.001), and this gradually improved over the next two weeks in 5 of these 8 patients. Three patients withdrew from the study, two owing to excessive sedation and another due to a "feeling of unreality." None of the patients reported visual or auditory hallucinations. This experience suggests that low dose oral ketamine is beneficial and effective in the management of intractable neuropathic pain in patients with advanced cancer. However, its utility is limited in some patients by the adverse effects that accompany its use.
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PMID:Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients. 1177 70

NMDA receptors are assumed to play an important role for neuronal plasticity. In vitro and animal experiments confirmed that NMDA antagonistic drugs can prevent hyperexitability of dorsal root neurons after strong pain stimuli. Clinical data, however, are more or less controversial in this respect. It was the aim of the present prospective, randomised, double-blind study to verify if low-dose preoperative ketamine, an NMDA antagonist, provides relevant postoperative analgesia in surgical patients and to re-examine positive results published by other investigators. 80 ASA I-II patients undergoing elective laparoscopic or proctologic surgery received at induction of general anaesthesia a single i.v. bolus dose of either ketamine 0.15 mg/kg or placebo (0.9% NaCl). Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using the opioid piritramide. Cardiovascular parameters, respiration, sedation, cumulative piritramide consumption and pain scores (visual analogue scale 1-10, verbal rating scale 0-4) were monitored at 1, 2, 3, 4, 5, 6, 12 and 24 hours after surgery. Additionally, a retrospective pain score was documented after the 24 hours observation period. There was no statistically significant difference in any study parameter. Cumulative PCA piritramide consumption after 24 hours was 25.0+/-16.2 mg in the ketamine group and 29.5+/-20.4 mg in the placebo group. Ketamine-specific side effects such as hallucinations or bad dreams were not observed. It is concluded that under the study conditions used, low dose ketamine, contrary to previously reported results [30], does not provide a clinically relevant pre-emptive analgesic effect in postoperative patients.
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PMID:[Lack of pre-emptive analgesic effect of low-dose ketamine in postoperative patients. A prospective, randomised double-blind study]. 1181 Mar 63


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