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)

A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in man was designed and the possibility of clinical application in assessing analgesics was investigated. Ultrasonic stimulus was given to Japanese subjects on the palmer distal part of the 2nd, 3rd and 4th fingers of both hands. The latent time between start of the stimulation and withdrawal of the hand when perceiving pain was considered the pain threshold. The ultrasonic evoked pain was a sharp pin-prick type, without sensations such as thermal and mechanical. The pain threshold lowered with increasing either stimulus intensity or water bath temperature when the hand of the subject was immersed during measurement. Normal threshold to ultrasonic stimulation measured in both 50 men and 50 women gave nearly normal distribution curves; women being more sensitive to ultrasonics than men. Analgesia with codeine phosphate (20 mg p.o.), aspirin (1.5, 1.0, 0.5 g p.o.), aminopyrine (100 mg p.o.) and mefenamic acid (500 mg p.o.) in volunteers of both sexes was demonstrated significantly using this method under double blind circumstances. Pentobarbital, diazepam, butylscopolamine, bromelain and placebo each in the usual dose used clinically failed to alter the pain threshold. Humans were at least 25 fold more sensitive than mice to the analgesics used herein.
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PMID:Clinical assessment of analgesics using ultrasonic stimulation. A new method. 33 41

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.
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PMID:Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy. 42 99

Anti-writhing assays to detect analgesia or specific activity against selected agonists were performed on albino mice. Acetylcholine Cl, bradykinin triacetate, phenylquinone, and serotonin creatinine sulfate were used as agonists. 10 compounds, including 5 standard analgetics, were tested against each agonist. Attempts to study histamine phosphate as an agonist were not successful. Results of these investigations showed satisfactory analgetic acitivity for codeine phosphate and acteyl salicylic acid (ASA) in all assays. weaker analgetics displayed varying degrees of activity depending on the agonist tested. Acute oral toxicities were determined for the 10 test compounds and the analgetic ED50 vs the LD50 of each compound was compared. The data confirmed the nonspecificity for writhing assays as well as a variability in activity of the test compounds against the various agonist.
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PMID:Comparative analgetic testing of various compounds in mice using writhing techniques. 58 70

In a multicentric, interindividual, double-blind study, the analgesic action, duration of effect, tolerability and side effects of the new combination preparation, Combaren (diclofenac-Na 50 mg+codeine phosphate 50 mg), were compared with those of diclofenac-Na 50 mg (Voltaren 50) in 184 patients with severe tumor-related pain. The results show that Combaren is a highly effective preparation for the treatment of severe tumor pain. The combination of diclofenac-Na with codeine phosphate leads to a clear, statistically significant, augmentation of the effectiveness of additionally used analgesics on pain severity, and the general effectiveness of the combination is more positively assessed that that of monotherapy with diclofenac (also effective). In the staged approach to the treatment of malignancy-related pain in which the aim is to provide continuous, preventive analgesia rather than ad hoc treatment of newly developing or worsening pain, this combination preparation will presumably find a permanent place in stage I/II of the generally accepted staged pain-treatment scheme.
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PMID:[Drug therapy in severe tumor pain. Comparative study of a new combination preparation versus diclofenac-Na]. 138 30

In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy.
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PMID:A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery. 151 16

In barbiturate anaesthetized spinal cats, antibody microprobes were used to measure release of immunoreactive substance P in the superficial dorsal horn following electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve. Prior microinjection of neuropeptide Y (0.2-0.6 microliters of 10(-5) mol/l solution) in the region of the substantia gelatinosa reduced the evoked release of immunoreactive substance P for up to 40 min. Microinjection of similar volumes of phosphate-buffered saline at similar sites was without effect. This action of neuropeptide Y could contribute to analgesia, particularly if this neuropeptide is co-released with noradrenaline from axon terminals in the superficial dorsal horn.
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PMID:Microinjection of neuropeptide Y into the superficial dorsal horn reduces stimulus-evoked release of immunoreactive substance P in the anaesthetized cat. 172 88

The polymorphic cytochrome P-450 DB1 (P-450 IID6) is responsible for the O-demethylation of codeine to morphine by human liver microsomes. The influence of P-450 DB1 variable activity on the bioactivation of codeine in vivo to morphine and on its analgesic effect was investigated in phenotyped healthy volunteers--7 extensive [EM] and 1 poor [PM] metabolizer of debrisoquine. After pretreatment with oral placebo or quinidine sulphate 50 mg, codeine phosphate 100 mg or placebo were administered orally according to a double-blind randomized crossover design. In EM subjects the plasma morphine Cmax was 17.9 nmol/l, whereas virtually no morphine was detectable after quinidine pretreatment (1.5 nmol/l), and in the PM subject (0.60 nmol/l). In EM codeine significantly increased subjective (VAS) and objective (R-III reflex) pain thresholds in response to selective transcutaneous nerve stimulation, whereas no significant analgesia was detected after placebo, or after codeine with quinidine pretreatment, or in the PM. In PM of genetic origin, or due to environmental alteration of the phenotypic expression (i.e. drug interaction), codeine is not activated into morphine and is an inefficient analgesic.
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PMID:Impact of environmental and genetic factors on codeine analgesia. 178 73

Hexacarbon compounds are neurotoxic to man and animals. These substances also inhibit various enzymes in vitro, including acetylcholinesterase. Since some cholinesterase inhibitors alter nociception we determined the effect of acute ip administration of 2,5-hexanedione on nociception in female Wistar rats (75-90 days old, 170-200 g; 15-17 rats in each group) using a tail-flick apparatus. The rats were injected ip with vehicle solution (120 mM NaCl containing 10 mM potassium phosphate buffer, pH 7.2) and 200, 400 or 800 mg/kg of 2,5-hexanedione in a volume of 1 ml/kg body weight. Tail-flick latencies were obtained 10, 30, 60 and 90 min after drug administration. All doses of 2,5-hexanedione caused antinociception (P less than 0.001) but the appearance and duration of the analgesia varied according to the dose of the drug. The highest dose tested (800 mg/kg) caused analgesia from 10 to 60 min, 400 mg/kg caused analgesia at 30 and 60 min, and 200 mg/kg produced antinociception only at 60 min after drug injection (P less than 0.05 for all the above comparisons). These results suggest that 2,5-hexanedione induces antinociception in rats. Whether this effect is mediated by a cholinergic mechanism is under investigation.
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PMID:Effect of acute administration of 2,5-hexanedione on nociception in rats. 179 54

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.
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PMID:Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism. 198 87

A sensitive and selective high-performance liquid chromatographic (HPLC) method for the determination of bupivacaine and its two metabolites, desbutyl- and 4'-hydroxybupivacaine, in human serum and urine is described. Bupivacaine, both metabolites and the internal standard, etidocaine, are extracted with diethyl ether and then back-extracted into an acidic aqueous phase. After subsequent extraction into diethyl ether, evaporation and reconstitution in the mobile phase, bupivacaine and the metabolites are determined by HPLC using a reversed-phase C8 column with tetrahydrofuran-potassium phosphate buffer (8:92, v/v, pH 2.4) as the mobile phase. The sensitivity of the method is 10 micrograms/l for bupivacaine and both metabolites and the extraction efficiencies are 95, 54 and 92% for bupivacaine and desbutyl- and 4'-hydroxybupivacaine, respectively. The reproducibility of the method is good, the coefficients of variation varying between 1.8 and 7.4% in the concentration range 0.10-2.00 mg/l. The procedure was applied to human serum and urine samples from two elderly women who had been operated on under epidural analgesia (plain bupivacaine, 1.5 mg/kg) because of uterine prolapse.
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PMID:Simultaneous determination of bupivacaine and its two metabolites, desbutyl- and 4'-hydroxybupivacaine, in human serum and urine. 355 65


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