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)

1. Tryptophan increases 5HT synthesis, but the extent to which it increases 5HT release and therefore 5HT function is unclear. 2. The possibility that increased 5HT levels will lead to increased 5HT release is enhanced when 5HT neurons are firing at a higher rate. The rate of firing of 5HT neurons is increased as the level of behavioral arousal increases. Thus, altered tryptophan levels will be more likely to influence brain function at higher levels of arousal. 3. In the rat, tryptophan administration increased CSF 5HT appreciably when the animals were aroused by being put in the dark, but not when they were left in a lighted room. 4. In monkeys, the level of behavioral arousal does seem to influence the effect of altered tryptophan levels on aggression. This is consistent with the fact that altered tryptophan levels had no effect on aggression in normal subjects, but that tryptophan had a therapeutic effect in pathologically aggressive patients. 5. The confusing literature on the antidepressant effect of tryptophan can, to some extent, be explained by considering the circumstances in which tryptophan administration will lead to increases in 5HT release as well as increases in 5HT synthesis. 6. Although in some circumstances tryptophan can decrease pain perception by activation of spinal 5HT pathways, when it was given to postoperative patients it attenuated morphine analgesia by activation of a 5HT pathway in the brain. 7. The effect of altered tryptophan levels depend critically on the circumstances in which it is given.
 ...
PMID:Tryptophan availability, 5HT synthesis and 5HT function. 266 90

Analgesia can be obtained during ophthalmic surgery by regional anesthesia using local anesthetic agents. As in other indications, neurological complications may occur, especially because the site of injection is close to the central nervous system. In order to evaluate the risk of retrobulbar and facial block obtained after 40 mg lidocaine and 20 mg bupivacaine injection, pharmacokinetics of both drugs was evaluated in plasma obtained from 11 patients. In addition, 3 cerebrospinal fluid samples were analyzed. Maximal plasma concentration was 0.73 +/- 0.33 micrograms.ml-1 for lidocaine and 0.19 +/- 0.06 micrograms.ml-1 for bupivacaine, obtained 24.7 +/- 23.0 min and 12.0 +/- 3.7 min after the end of injection, respectively. CSF/plasma ratio was in the range 0.05-0.26 for lidocaine and 0.56-1.33 for bupivacaine. In all patients, regional anesthesia was sufficient to perform surgery without any other analgesic drug. No sign of cardiovascular or respiratory toxicity was observed during the study.
 ...
PMID:Pharmacokinetics of lidocaine and bupivacaine in retrobulbar and facial block. 272 18

The spinal administration of opioids may provide analgesia of long duration to patients with bilateral or midline lower abdominal or pelvic cancer pain. However, cross-tolerance to orally and parenterally administered narcotics and the rapid development of tolerance to spinal narcotics have limited their usefulness. Opioids have extensive distribution in the CSF and plasma when administered into the epidural or intrathecal space, and delivery of drug to brain stem sites may account for many of the toxic and therapeutic effects of spinal opioids. Further clinical and pharmacokinetic studies are required to provide the information regarding: the optimal opioids for use as spinal analgesics; equieffective dose ratios of spinal opioids in comparison to parenteral or oral opioids; strategies useful to forestall the development of tolerance of spinally administered opioids; the analgesic efficacy of this therapy in opioid-tolerant patients; and the role of spinally administered nonopioid analgesics in the management of cancer pain in the tolerant patient. These questions will need resolution before this therapy can be recommended for routine use in the management of cancer pain.
 ...
PMID:Role of epidural and intrathecal narcotics and peptides in the management of cancer pain. 288 Oct 34

In a randomized study, 20 patients received temazepam 20 mg orally the night before and 20 mg in the morning of an operation performed under spinal analgesia (Group I); 20 patients received flunitrazepam I mg similarly (Group 2). Different aspects of the premedication were evaluated verbally, with the aid of a visual analogue scale, Maddox wing apparatus, the critical flicker fusion threshold test, blood pressure and heart rate measurements, serum and CSF cortisol and plasma ADH measurements, as well as CSF drug level determinations. Clinically, temazepam 20 mg proved to be comparable with flunitrazepam I mg, although the latter more effectively prevented cardiovascular changes and pre-operative hormonal stress reaction. No correlation was found between the CSF drug level (bioassayed by radioreceptor assay) and the clinical response of the two benzodiazepines, nor was there any correlation between the cortisol or ADH levels versus the CSF drug levels. On the whole, flunitrazepam proved to be marginally better than temazepam as an oral premedicant.
 ...
PMID:Temazepam versus flunitrazepam as an oral premedication in adult surgical patients. 289 5

The use of intraspinal narcotics has been widely accepted as pain relief treatment for intractable cancer pain. Intraspinal low doses of morphine induce a potent selective long lasting analgesia. To avoid repetitive lumbar puncture, a drug delivery device was surgically implanted in 41 patients. The surgical procedure is described. The mean amount of morphine needed was 1.48 +/- 0.25 mg per day at time of surgery, rising to 6.86 +/- 1.47 mg per day after a mean survival time of 65 days. Tolerance became a major problem in 18 patients, which nearly all were selected at a late disease stage and previously received narcotics for pain relief. However, no clear-cut prognostic factor had a predictive value for the appearance of tolerance. In some cases, it could be successfully treated by intraspinal injection of local anaesthetics or clonidine. CSF leakage was noted in 11 patients; this was a challenge for us, as no other authors reported such a high rate for this complication. Aseptic meningitis was noted three times. In all cases but one, the symptoms resolved with appropriate treatment.
 ...
PMID:[Analgesia with an implanted device for repetitive intrathecal injections of morphine]. 300 65

In this Phase I study of rh GM-CSF three patients have been entered at each of the following dose levels--0.3, 1, 3, 10 and 30 micrograms/kg/day. The mean total white cell count (x 10(9)/l) over the first ten days of rh GM-CSF rose from 11 to 14 at 3 micrograms/kg, 8 to 23 at 10 micrograms/kg and 7 to 27 at 30 micrograms/kg. Side effects included transient pyrexias after the first two infusions of rh GM-CSF and bone pains which were severe and required analgesia in two patients receiving 30 micrograms/kg and one receiving 10 micrograms/kg. No neutralizing antibodies to rh GM-CSF have been detected in the six patients tested to date. Patients are now being studied at 60 micrograms/kg/day.
 ...
PMID:Phase I study of recombinant DNA granulocyte macrophage colony stimulating factor. 307 48

Both placental and blood-lumbar CSF transfer of diazepam (5 mg orally) and its two metabolites, N-desmethyldiazepam and unconjugated oxazepam, was measured (by GLC) in 15 patients undergoing Caesarean section under spinal analgesia. Differing from our earlier studies with atropine (Virtanen et al. 1982; Kanto et al. 1981 & 1987), a reasonably fast penetration of diazepam and its two metabolites through the two biological membranes was found. Diazepam, N-desmethyldiazepam and to a lesser extent unconjugated oxazepam accumulated on the foetal side of the placenta, apparently due to a higher degree of plasma protein binding in the foetus. No accumulation was found in CSF, probably due to the lack of binding proteins in this tissue compartment. Concerning atropine, lumbar CSF with an incomplete drug penetration was found to be a "deeper" compartment than amniotic fluid, but in the present study with diazepam there was no clear difference between these two tissue compartments.
 ...
PMID:Placental and blood-CSF transfer of orally administered diazepam in the same person. 311 32

The objectives of this study were to compare the pharmacokinetic properties and the duration of analgesia following intrathecal administration (L5-S1) of 2 mg morphine in 2 forms: (1) an isobaric (NaCl 0.9%) and (2) a hyperbaric solution (7% dextrose). The study was carried out on 5 cancer patients with severe, intractable pain in the lower half of the body. Samples of CSF were collected at the level of the 10th thoracic vertebra at regular intervals for 15 h after administration. Morphine concentrations were determined by HPLC. The pharmacokinetic properties of the solutions (I and II) were quite different. Peak levels (I) were reached in 5-15 min (30 and 60 micrograms/ml); they then fell rapidly during the 1st hour (7 and 11 micrograms/ml) with an elimination half-life of 10 and 15 min, followed by a change in slope (elimination half-life of 108 and 140 min). Peak levels (II) were reached in 4-5 h (0.8-3.3 micrograms/ml); they then fell progressively according to a single exponential function (elimination half-life: 144-246 min). The duration of analgesia for a dose of 2 mg was 30 h for solution 2 and 24 h for solution 1. The hyperbaric solution, which produced the same degree of analgesia as the isobaric solution, limited the cephalad diffusion of morphine and reduced or abolished the central depressant effects of the drug.
 ...
PMID:CSF morphine levels after lumbar intrathecal administration of isobaric and hyperbaric solutions for cancer pain. 336 53

Since its introduction to North America in 1942, the use of epidural catheter analgesia has increased dramatically. Improved equipment, methods and medications have broadened its application to include among others, surgical anesthesia, chronic pain relief and the management of postoperative pain. Numerous techniques for epidural puncture and insertion of the catheter have been described. Although complications have been associated with placement of an epidural catheter, these are rare when performed by an experienced anesthesiologist. Epidural analgesia was first accomplished by blockade with local anesthetics. Bupivacaine has been called the local anesthetic of choice for epidural infusion. Bolus administration of epidural local anesthetics gives effective analgesia; however, its use is limited by brief duration and occasionally severe hypotension. Epidural local anesthetics have been administered by continuous infusion in an attempt to minimize side effects. Nevertheless, hypotension, as well as motor block, numbness, nausea and urinary retention have occurred. Epidural analgesia with local anesthetics is effective in relieving postoperative pain, but its safety and feasibility have been questioned because of the frequent, potentially serious side effects. These problems led to trials of epidural narcotics for postoperative pain management. The exact site of action of epidural narcotic analgesics is debatable; however, the bulk of evidence supports a direct spinal action. Epidural narcotics appear to specifically inhibit nociceptive stimuli. The prolonged and profound analgesia that occurs with epidural narcotics relative to parenteral administration is due to a higher concentration of drug reaching the CSF through the epidural route. Since nervous transmission is not completely blocked this technique cannot provide anesthesia during operation. Morphine has been the most frequently used narcotic for epidural analgesia. Results of several recent, randomized double-blind studies have shown that epidural narcotics give adequate analgesia comparable with that observed with epidural bupivacaine. Epidural morphine provides a greater duration of analgesia and may cause fewer side effects. Improved analgesia has been reported when epidural narcotics are used in combination with local anesthetics. Continuous administration of low dosage epidural narcotics has been shown to have less frequent side effects than bolus administration. Nevertheless, pruritus, urinary retention, hypotension and severe respiratory depression have been reported with both methods.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Epidural catheter analgesia for the management of postoperative pain. 351 98

Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious and definite advantages over conventional pain therapy; however, the field is still at an early stage of development. More research is clearly needed to provide methods for coping with some of the drawbacks of this method of pain relief. Important areas for future research include (1) the CSF kinetics of opiates; (2) the physiological mechanisms underlying the rostral spread of drugs within the CSF compartment; (3) a search for safer and more selective drugs; and (4) an evaluation of the extent to which pain-modulating systems at different levels in the CNS can be regulated by opiates and drugs interfering with other neurotransmitters. In this context it is essential to emphasize the importance of simultaneous study of the pharmacokinetics and the pharmacodynamic/clinical effects in providing a rational basis for a better understanding of the mechanisms of actions underlying spinal opiate analgesia.
 ...
PMID:Pharmacokinetics and pharmacodynamics of epidural and intrathecal morphine. 351 70


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