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

There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved.
 ...
PMID:Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. 844 13

Neuropathic cancer pain may be less responsive to opioids than other pain. Several studies suggest that N-methyl-D-aspartate (NMDA)-receptor antagonists could play a role in the treatment of neuropathic pain. Ketamine is an NMDA-receptor antagonist that is used as an anesthetic and has been suggested as a useful drug for neuropathic pain. Subanesthetic doses of ketamine can yield analgesia without hypnosis. We describe a patient who developed neuropathic cancer pain unresponsive to opioid escalation and spinal administration of a combination of bupivacaine-morphine and was subsequently treated by subcutaneous continuous ketamine infusion. A starting dose of 150 mg/day provided good pain relief and a dramatic reduction of the oral morphine dose (from 5 g to 200 mg). A slow and progressive increase of ketamine and morphine dosage (400 mg and 200 mg by the subcutaneous route, respectively) continued to provide adequate pain relief after 13 months of therapy despite signs of progressive disease.
 ...
PMID:Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain. 853 99

Pre-emptive analgesia is based on the idea that analgesia initiated before a nociceptive event will be more effective than analgesia commenced afterwards, and that its effects will outlast the pharmacological duration of action of the analgesic used. The idea of pre-emptive analgesia is based upon experimental neurophysiological work demonstrating that afferent nociceptive impulses result in alterations of central nervous system function. These changes, most easily elicited by C-fibre afferents, particularly affect the spinal dorsal horn. Termed central sensitisation, they are reflected by reduced pain thresholds (allodynia), increased responses to pain (hyperalgesia), after-discharging or spontaneous activity of dorsal horn neurons (wind-up), and extension of hypersensitivity to unaffected tissues (secondary hyperalgesia). Their biochemical basis is now being unravelled, with excitatory amino acid (e.g. NMDA) and neuropeptide (e.g. substance P) neurotransmitters playing prominent roles. Blockade of these receptors has recently been shown to depress the central sensitisation associated with nociception. Ketamine, a non-competitive NMDA receptor blocker, for example, has been shown modulate postoperative pain in a positive way. Although the existence of central sensitisation is now being clinically demonstrated, studies of pre-emptive analgesia in the surgical context have not revealed clinically significant effects. This is probably because surgical nociception is much longer-lasting, multimodal and intense than its experimental counterparts. Clinical studies have so far only used short-term analgesia. To permit extrapolation from the experimental to the clinical situation, pre-emption in the surgical context must correspond adequately to the duration and extent of the nociception involved. Studies of pre-emptive analgesia in a clinically relevant form, i.e. where nociception and analgesia are correctly matched, are called for.
 ...
PMID:[Pre-emptive analgesia]. 859 63

The goal of therapy in patients with severe head injury is to avoid secondary brain damage. Analgesia and sedation are an essential part of the therapy, and several drugs are in current use. However, few controlled clinical trials have been performed so far, and none of these drugs has proved to be superior. Although in the past the therapy has been focused on controlling elevated intracranial pressure (ICP), many authors emphasize the role of cerebral ischaemia in the prognosis of patients. Therefore, cerebral perfusion pressure (CPP) i.e. the difference between ICP and mean arterial pressure (CPP = MAP-ICP), seems to be more important than ICP alone. Analgesics and sedatives reduce the cerebral metabolic rate (CMR), and the consequent decrease in cerebral oxygen uptake might prevent ischaemic damage in regions with low perfusion. Moreover, a decrease in CMR is often associated with a decrease of cerebral blood flow (CBF) in regions with normal perfusion and, as a result, ICP is also reduced. Basically, the cerebral effects (on ICP, CMR, and CBF) and the haemodynamic effects with respect to maintenance of a sufficient CPP are most important in the selection of drugs for analgosedation. In addition, the effects on general intensive care management must be considered (pulmonary function, immunreactivity bowel motility). The purpose of this paper is to describe drugs commonly used for analgosedation in severe head injury. Barbiturates bring about the most pronounced decrease of CMR and ICP. In the past these drugs were used routinely in high doses ("barbiturate coma"). However, no improvement in outcome was demonstrable, and vitally dangerous side effects, such as infection, pulmonary dysfunction, arterial hypotension, and renal failure often occurred. High-dose barbiturate therapy is therefore only indicated in exceptional cases, such as refractory increase in ICP with preserved CO2 response of cerebral vessels. The effect is dependent on CMR at the start of this therapy. Benzodiazepines are frequently used in patients with head injury. They cause only a moderate decrease of CMR and ICP. In general, side effects are negligible. However, a possible decrease of MAP by reduced central sympathetic drive has to be taken into account. Opioids are also frequently used in patients with head trauma. The observed cerebral effects are inconsistent. Some authors have described increases in ICP, CBF, and CMR, but in most studies no influence on these values, or a decrease, has been observed. In any case, cautious titration of these drugs and cerebral monitoring are therefore desirable. As with benzodiazepines, a decrease in MAP due to central effects is possible. In addition, opioids inhibit bowel motility. Ketamine is generally used because of its favourable circulatory effects, bronchodilatation and absence of inhibition of bowel motility. In patients with increased ICP, however, it is often considered contraindicated, since it can be associated with cerebral vasodilation and ICP increase. Other studies did not confirm an increase of ICP when controlled ventilation and additional sedation were applied. More recent studies have demonstrated the role of neuroexcitatory NMDA-receptors in ischaemic and traumatic brain damage. Since ketamine exerts an antagonistic effect on N-methyl-D-aspartate receptors (NMDA) and studies in animals have demonstrated a protective effect of ketamine against ischaemic and traumatic brain damage, controlled clinical studies in patients with head injury are desirable. Propofol results in a profound decrease of CMR and a significant decrease of ICP, but often also in haemodynamic depression. Few results obtained during long-term administration are available, but it seems to be beneficial. More clinical studies are warranted. Gamma-hydroxybutyrate (GHB) is a physiological substance, which has only sporadically been investigated for sedation in patients with head trauma. The few available studies show beneficial res
 ...
PMID:[Analgesia and sedation in patients with head-brain trauma]. 859 67

Cerebral blood flow autoregulation, CO2 reactivity and the pressure-volume relationship may be impaired or abolished in patients with intracranial mass lesions, brain trauma, cerebral vasospasm or increased cerebral elastance. Sedatives, analgetics, and anesthetics may induce major changes in cerebral blood flow, cerebral metabolism and intracranial pressure (ICP). The inadequate use of these drugs may aggravate the preexisting intracranial pathology and may worsen outcome. Thus it is important to understand the effects of sedatives, analgetics, and anaesthetics on intracranial hemodynamics and metabolism during physiological and pathological conditions. Hypnotics (barbiturates, etomidate, propofol), benzodiazepines, opioids (fentanyl, alfentanil, sufentanil) and alpha-2-adrenergic agonists (clonidine, dexmedetomidine) reduce cerebral blood flow. With ketamine, cerebral blood flow changes in a regionally specific fashion, with some territories showing increases and others showing decreases in cerebral blood flow. Cerebral metabolism is decreased during sedation and analgesia with hypnotics, benzodiazepines, and opioids, while infusion of ketamine produces stimulation as well as suppression of cerebral metabolism. This suggests that the changes in cerebral blood flow seen with these drugs occur secondary to their cerebral, metabolic effects. Alpha-2-adrenergic agonists produce no significant changes in cerebral metabolism. However, cerebral blood flow is decreased with clonidine or dexmedetomidine. This suggests uncoupling between cerebral metabolism and flow due to decreases in central catecholamine turnover. Hypnotics and benzodiazepines decrease ICP due to decreases in cerebral blood volume. However, these drugs may also decrease mean arterial blood pressure, which may result in a critical reduction in cerebral perfusion pressure. ICP remains unchanged with the use of opioids as long as mean arterial pressure is maintained constant. However, decreases in mean arterial pressure during infusion of opioids induce autoregulatory cerebral vasodilation, which in turn increases cerebral blood volume and ICP. Ketamine may increase ICP specifically in subjects with spontaneous ventilation. With mechanical hyperventilation and constant systemic hemodynamics, ketamine fails to increase ICP in most of the patients. Alpha-2-adrenergic agonists produce no significant changes in ICP, although there may be a transient decrease in ICP with lower doses.
 ...
PMID:[Effects of analgesia and sedation on cerebrovascular circulation, cerebral blood volume, cerebral metabolism and intracranial pressure]. 859 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.
 ...
PMID:[Analgesia and sedation to supplement incomplete regional anesthesia]. 859 70

To establish reliable methods of chemical restraint and anaesthesia for mildly painful procedures in guineapigs, we compared the effects of the following anaesthetics and combinations of anaesthetics: tiletamine-zolazepam (two dosages), pentobarbital, methoxyflurane, ketamine-xylazine (three dosages), and ketamine-xylazine with methoxyflurane. Tiletamine-zolazepam induced a short period of chemical restraint but lacked analgesic effects at the doses tested. Although pentobarbital induced prolonged chemical restraint, the loss of responsiveness to painful stimuli was brief. Methoxyflurane alone induced transient anaesthesia and analgesia. Ketamine-xylazine combinations induced analgesia and chemical restraint of comparable durations, and some dosages were suitable for mildly painful procedures. The addition of methoxyflurane significantly potentiated the anaesthetic and analgesic properties of the high dosage ketamine-xylazine combination.
 ...
PMID:Evaluation of anaesthetic regimens in guineapigs. 884 46

We report the effect of a single daily dose of ketamine in a 54 year old woman with fibromyalgia and severe post-traumatic neuropathic pain. A number of different approaches for pain relief had been tried with little effect. An intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam lead to analgesia which lasted for almost two days. Long-term analgesia was also obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules every night at bedtime. The patient has now used this dose for nine months. Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of ketamine causes a long-term depression of pain intensity in some, but not in all, patients suffering chronic pain. This effect is distinctly different from the short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain. The long-term depression of the intensity of chronic pain states may be due to a reversal of NMDA receptor-dependent long-term potentiation of synapses in central pain pathways. By giving ketamine as a single dose at night the mental side-effects are reduced or avoided.
 ...
PMID:[Analgesic effect of ketamine in a patient with neuropathic pain]. 899 75

Increased postoperative pain may be caused by central nervous system plasticity, which may be related to actions of N-methyl-D-aspartic acid (NMDA) receptors on neurons in the dorsal horn of the spinal cord. Opioids act mainly on presynaptic receptors and reduce neurotransmitter release, while ketamine antagonizes NMDA receptors and prevents wind-up and long-term potentiation. Thus, we postulated that central nervous system sensitization would be prevented more effectively by the preoperative use of these two drugs simultaneously, and the effect of preemptive analgesia would be demonstrated. Ketamine, 60 mg, and morphine, 2 mg, were injected epidurally through an indwelling catheter that was inserted at the T7-8 interspace in 60 ASA physical status class 1-2 patients. The drugs were injected before induction of anesthesia (Group 1; n = 30) or immediately after removal of a surgical specimen (Group 2; n = 30). An additional 2 mg of morphine was injected when the patients complained of resting pain. The analgesic effect was assessed by the time from first analgesic injection to second dose and the number of patients who needed supplemental injections. Complications were also noted. The duration of analgesia was longer (P < 0.01) in Group 1 (31.1 +/- 16.0 h) than in Group 2 (21.1 +/- 12.0 h), and the proportion of patients who needed supplemental injections was decreased (P < 0.05) in Group 1 (56.7%) compared with Group 2 (90.0%). The incidence of adverse effects was not different between the two groups. In conclusion, preoperative administration of morphine and ketamine is more effective in reducing postoperative pain than it is when given during the operation.
 ...
PMID:Epidural morphine plus ketamine for upper abdominal surgery: improved analgesia from preincisional versus postincisional administration. 905 1

The management of pain and anxiety in pediatric patients with burns includes the challenge of striking a balance between inadequate versus excessive medication. Ketamine provides effective sedative, analgesic, and amnestic properties for children and has been used intravenously with good results. With its recent availability as an elixir, we speculated that ketamine given orally may provide effective analgesia and sedation during wound care procedures with a wide safety margin. To test this hypothesis, 19 pediatric patients with burns undergoing a wound care procedure were randomized to receive either ketamine oral suspension or 300 mg acetaminophen with codeine phosphate and diphenhydramine, our prior standard for analgesia and sedation. Intensity of pain was determined with use of a color slide algometer and demonstrated more than 400% reduction in pain with the use of ketamine (p < 0.05). The Ramsey scale was used to quantitate sedation and demonstrated that ketamine improved sedation by 360% (p < 0.05). These results substantiate improved analgesia and sedation with oral ketamine as compared to a commonly used narcotic and sedative in facilitating wound care procedures in pediatric patients with burns. These findings suggest that expanded use of ketamine oral suspension may be.
 ...
PMID:Superiority of oral ketamine as an analgesic and sedative for wound care procedures in the pediatric patient with burns. 906 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>