Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics and analgesic effect of i.v. ketamine in doses of 125 microgram kg-1 and 250 microgram kg-1 were determined in five healthy volunteers. Analgesia was measured with the submaximal effort tourniquet test. Both doses of ketamine prolonged the period of pain-free ischaemic exercise while the plasma ketamine concentration was greater than 100 ng ml-1. Ketamine was distributed rapidly (T 1/2 alpha = 17 min). The elimination half-life was 186 min.
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PMID:Pharmacokinetics and analgesic effect of ketamine in man. 745 84

We report the case of a 39-year-old man with severe pain due to unresectable squamous-cell carcinoma of the maxillary sinus that had invaded cranial bone and had metastasized to the cervical spine. Tolerance to opioids had developed, and high doses of transdermal, continuous intravenous, and epidural opioids did not control his pain. An acute episode of extremely severe head pain was immediately controlled with a subanesthetic dose of ketamine after failure of a stress dose of corticosteroid and intravenous lidocaine. Because the patient was terminally ill and invasive procedures were not options, we controlled his pain using a low-dose ketamine infusion until his death 13 days later. Ketamine may be a good co-analgesic for breakthrough pain and for severe pain caused by terminal cancer when invasive techniques are inappropriate. Its mechanism of action may include reversal of opioid tolerance in addition to an inherent analgesic effect.
J Pain Symptom Manage 1995 May
PMID:Effective treatment of severe cancer pain of the head using low-dose ketamine in an opioid-tolerant patient. 754 37

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor channel blocker known to inhibit "wind-up" and hence central hyperexcitability of dorsal horn neurons. We sought to assess the effect of ketamine on single and repeated nociceptive stimuli. A placebo-controlled, human (12 volunteers) experimental study was conducted in which several psychophysical (pain detection and tolerance thresholds, magnitude ratings) and electrophysiologic (withdrawal reflex) techniques were used 1) to investigate whether a ketamine (0.5 mg/kg) bolus followed by a 20-min infusion (9 micrograms.kg-1.min-1) inhibits central temporal summation to repeated nociceptive electrical stimuli, and 2) to assess quantitatively the hypoalgesic potency using several experimental nociceptive stimuli (argon laser, pressure, electrical). Facilitation of the withdrawal reflex to and pain rating of repeated electrical stimuli (five pulses at 2 Hz) were inhibited by ketamine. Reflex and pain rating to a single stimulus did not change. The pressure pain detection and tolerance thresholds were increased significantly by ketamine, whereas the laser heat pain and tolerance thresholds remained stable compared with placebo. The stimulus response function showed that ketamine reduced the responses to the highest electrical stimulus intensities (1.4, 1.6, and 1.8 times the reflex threshold). We conclude that ketamine inhibits central temporal summation in humans and has a marked hypoalgesic effect on high intensity nociceptive stimuli.
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PMID:The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study. 759 84

The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.
Pain 1995 May
PMID:Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia. 765 32

Pain and sensory thresholds were examined before and after intravenous administration of ketamine (0.15 mg/kg), morphine (0.075 mg/kg) or saline in 8 patients with post-herpetic neuralgia. A randomized, double-blind, cross-over study design was used. Post-herpetic neuralgia was associated with impaired sensory function, as shown by reduced tactile and warm sensation in the affected compared with the contralateral non-affected skin area. Neither ketamine nor morphine changed significantly the thresholds for warm, cold, heat pain or tactile sensation. However, ketamine normalized abnormal heat pain sensations in 4 patients, probably due to a central effect. Ketamine, but not morphine, produced significant relief of pain. Pain evoked by non-noxious stimulation of the skin (allodynia) was significantly inhibited by ketamine as well as by morphine. Wind-up-like pain (i.e., pain evoked by repeatedly pricking the affected skin area) was significantly inhibited by ketamine, but significantly aggravated by morphine. Side effects were observed in all the 8 patients after injection of ketamine and in 6 patients after injection of morphine. The present results support the hypothesis that the N-methyl-D-aspartic acid (NMDA) receptors are involved in the control of post-herpetic neuralgia including allodynia and wind-up-like pain. The NMDA receptors also may play a role in the modulation of thermal perception.
Pain 1994 Sep
PMID:Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. 783 84

The epidural and intrathecal administration of opioids has gained wide acceptance among anaesthesiologists during recent years. Ketamine, an anaesthetic agent with an unusual pharmacological profile, has also attracted some interest in this context, as in subanaesthetic doses it provides marked analgesia without inducing respiratory depression. Since the first publication on the epidural administration of ketamine in humans in 1982, various studies on the pharmacology, toxicology and clinical use of ketamine by the epidural and intrathecal routes have been published. PHARMACOLOGY. There is a large body of evidence to show that systemically administered ketamine interacts with different neurotransmitter systems and may even produce local anaesthetic effects when used for intravenous regional anaesthesia. The results of animal studies suggest that ketamine may cause complete sensory and motor blockade after intrathecal administration, which leads to high concentrations in the cerebrospinal fluid. One study investigating the effects after epidural administration showed motor blockade only after high doses of ketamine. Binding to local opiate receptors seems to play only a minor role, whereas significant analgesia after even low doses of ketamine is the result of antagonism to NMDA receptors. In vitro and animal data also suggest an involvement of the descending inhibitory pathways, mainly through inhibition of re-uptake of neurotransmitters. NEUROTOXICITY. Data relating to the neurotoxicity of ketamine after intrathecal administration are confusing. While no neurotoxic effects have been observed in studies in primates and rabbits, experimental rats and monkeys have sustained lesions: they may have been caused by a faulty puncture technique or by inherent neurotoxicity of the drug. CLINICAL RESULTS. The only study of intrathecal administration of ketamine in humans revealed local anaesthetic effects after doses of 50 mg. For epidural use, doses up to 30 mg did not give adequate pain relief after surgery in controlled studies, but had some analgesic effect in patients with chronic pain syndromes. When doses of 30 mg and over were used, postoperative analgesia was generally assessed as good. CONCLUSIONS. When administered intrathecally, ketamine shows local anaesthetic effects in both animals and humans. Unfortunately, all commercially available ketamine preparations contain disinfectant agents whose intrathecal administration is prohibited. Epidurally administered ketamine doses of 30 mg and more seem to provide adequate postoperative analgesia, while smaller doses might be effective in chronic pain syndromes. More studies investigating the neurotoxicity and clinical effects of ketamine on the spinal cord are needed before wider use of the substance by this route of administration can be recommended.
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PMID:[Pharmacology and clinical results with peridural and intrathecal administration of ketamine]. 784 Apr 12

The intravenous anaesthetic ketamine is widely used in subanaesthetic doses as a potent analgesic in emergency and disaster medicine. At present, ketamine is commercially available only in its racemic form, although the S(+)-isomer has proved to be approximately three times as potent than the R(-)-isomer. In first clinical trials in Germany, S(+)-ketamine was reported to be markedly advantageous with regard to analgesia in anaesthetized patients. We therefore evaluated ketamine's analgesic and psychotropic effects in subanaesthetic doses given to healthy volunteers. MATERIALS AND METHODS. After institutional approval of the study by the university's Ethics Committee, 16 volunteers received ketamine racemate (1 mg/kg) and S(+)-ketamine (0.5 mg/kg) i.m. with 1-week intervals between injections in a randomized, double-blind fashion. Analgesia (electric pain stimulation of the median nerve), long-term memory, anterograde amnesia (recognition of simple pictures), motor coordination (Trieger test), immediate recall (short test of general intelligence) and concentration capacity (CI test: recognition of a preselected symbol among several symbols) were measured over a 60-min period and mean arterial pressure, heart rate, and ketamine plasma levels in venous blood samples were determined. Values were calculated as means and data were analysed by Wilcoxon's paired test for group comparison. RESULTS. Within 15 min, both agents induced a measurable degree of analgesia. After ketamine racemate, the level of pain tolerated increased from 38.8 +/- 14.0 to 57.0 +/- 13.7 mA and after S(+)-ketamine, from 36.9 +/- 10.5 to 53.3 +/- 15.2 mA. Ketamine racemate did not exert measurable effects on long-term memory, whereas anterograde amnesia was observed in 46% and 54% of the study subjects after 15 and 30 min, respectively. However, after S(+)-ketamine, only 8% of the volunteers demonstrated anterograde amnesia (P < 0.05). Immediate recall also declined in both groups (baseline: 5 points, after 15 min: 3.5 points for ketamine racemate, 4 points for S(+)-ketamine), whereas concentration capacity worsened from 14.5 +/- 3.8 s to 35.9 +/- 18.6 s after ketamine racemate and significantly less, from 14.8 +/- 2.5 s to 22.9 +/- 7.6 s, after S(+)-ketamine (P < 0.01). Furthermore, after 15 min, ketamine racemate induced an increase in heart rates from 73 +/- 15 b/min to 97 +/- 11 b/min, while S(+)-ketamine raised heart rates from 74 +/- 13 b/min to 89 +/- 11 b/min only (P < 0.05). Mean arterial pressure increased from 97 +/- 11 mmHg to 111 +/- 9 mmHg after ketamine racemate and from 92 +/- 11 mmHg to 110 +/- 13 mmHg after S(+)-ketamine (not significantly different). CONCLUSION. S(+)-Ketamine at half-dose of ketamine-racemate is as potent as ketamine-racemate in subanaesthetic doses with powerful analgesic properties. The (+)-isomer exerts less adverse effects on measurable cerebral functions and induces a significantly smaller increase in heart rate. Since states of impaired consciousness and disorientation are especially disturbing under emergency conditions, further investigations should be carried out to define S(+)-ketamine's position as a potent analgesic for therapeutic use in emergency and disaster medicine.
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PMID:[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. 784 Apr 17

Ketamine-induced changes in the spontaneous and evoked electroencephalogram have been well documented in animals and humans. In contrast to the action of hypnotics, ketamine does not result in a dose-dependent suppression of neural activity. Many studies have revealed excitatory activity with induction of synchronized high-voltage slow waves in the electroencephalogram (EEG). Somatosensory evoked responses (SEP) have been found to be enhanced following induction of anaesthesia with ketamine. However, increases in amplitude were small compared with the SEP-enhancing effects of etomidate. The increase in somatosensory evoked responses may reflect dose-dependent disinhibition and/or increased excitation of cerebral neuronal activity induced by ketamine. Attenuation of late cortical somatosensory evoked responses following stimulation of thin C- and A delta-nerve fibres has been reported in volunteers given low-dose ketamine. Changes in SEP amplitude correlated to changes in subjective pain sensation. From this it was concluded that the analgesic effect of ketamine can be assessed by electrophysiological measurement methods. Recent studies suggest that the analgesic effect of the racematic ketamine mixture can probably be related to the effects of S-(+)-ketamine isomer, which has been shown to be involved in the activation of an opioidergic mechanism. Auditory evoked responses (AEP) of short latencies with origins in the brain stem have been shown to be slightly altered by ketamine. From this it was concluded that these components may not be used for assessment of the depth of anaesthesia. In contrast to the effects of hypnotics, mid-latency AEP components may be recorded during ketamine anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ketamine and evoked potentials]. 784 Apr 19

Several situations arise in the PICU patient that require the administration of drugs for sedation and analgesia. A "cookbook" approach is impossible because of the diversity of patient and clinical scenarios. When amnesia is required, these authors prefer a continuous infusion of a benzodiazepine such as midazolam or lorazepam. Although the majority of clinical experience has been with midazolam, lorazepam either by bolus dose or continuous infusion offers a cost-effective alternative. When analgesia is required, the addition of a continuous infusion of narcotic or the use of a PCA device in the older patient should prove effective. Although fentanyl is frequently chosen, morphine is an effective and cost-effective alternative for patients with stable cardiovascular function. The synthetic narcotics are recommended for neonates, especially following cardiac surgical procedures and those at risk for pulmonary vasospasm. Narcotics may also be used for the treatment of agitation in those situations that do not necessarily require analgesia. Our clinical experience suggests that narcotics may be more effective for sedation than benzodiazepines in children less than 1 year of age. When the above agents fail to be effective or are associated with cardiovascular depression, alternatives may include ketamine or pentobarbital. Ketamine may be useful for the unstable patient or those with a bronchospastic component to their disease process. We have found pentobarbital to be effective when the combination of benzodiazepines and narcotics fails to provide the desired level of sedation. Aside from these techniques, regional anesthesia may offer a more effective means of controlling pain in the PICU patient. These techniques may be effective when parenteral narcotics are inadequate or lead to undesired effects. Although most commonly used for postoperative analgesia, their use in patients with pain from other causes (e.g., multiple trauma) may be indicated, especially when parenteral narcotics may interfere with respiratory function or the ongoing assessment of the patient's mental status.
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PMID:Pain management and sedation in the pediatric intensive care unit. 798 86

Hyperactivity of N-methyl-D-aspartate (NMDA) receptors may be one of the factors in the genesis of neuropathic pain. Ketamine is an NMDA-blocking agent widely used in human medicine. Ketamine (at 250 mcg/kg i.v. slow push) was administered to 6 patients for control of chronic neuropathic pain syndromes in double-blind placebo-controlled fashion. All 3 patients with peripheral nervous system (PNS) disease-related pain, and 2 of 3 patients with central pain and dysesthesia syndromes responded with a temporary decrease in the rating of ongoing pain. The allodynia, hyperalgesia and after-sensation present in 5 patients improved after the administration of ketamine. Dose-response estimation in 2 patients with PNS-related neuropathic pain revealed that ketamine was effective in dose-related fashion. Continuous subcutaneous infusion of ketamine administered to 1 patient with PNS-related neuropathic pain caused no additional improvement in pain control but caused intolerable cognitive and memory side effects. In contrast, side effects during single-dose injections were mild and well tolerated. Ketamine affected the evoked pain and associated after-sensation in chronic neuropathic pain syndromes more than the ongoing constant pain.
Pain 1994 Jan
PMID:Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. 815 41


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