Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate (SRMS) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution (IRMS) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer. Of 33 patients entered, 27 completed the study and were included in the efficacy and safety analysis. Patients were initially randomized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose, every 4 hours. After 2 days, a crossover was performed, and patients received the alternate treatment for 3 days. Pain and side effects were assessed using a standard 100 mm visual analogue scale (VAS). There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness, nausea, depression, and anxiety. The incidence of breakthrough pain was similar for both treatment groups, as was the incidence of confusion and constipation. The results demonstrated that SRMS is a safe, effective analgesic preparation for patients who require oral opioids for cancer pain. The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours.
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PMID:A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer. 159 Feb 84

The aim of the regional administration of opioids is to provide an efficient and prolonged analgesia. Then, opiates can be useful for postoperative analgesia and for the treatment of chronic pain of malignant origin. Analgesia is correlated with several adverse effects of which the most frequent are nausea and itching and the most severe is respiratory depression. Beside the adverse effects, other properties of opiates could be responsible of favourable effects which can be taken in advantage in specific indications. In the postoperative period, epidurally administered opioid can attenuate the neuroendocrine and metabolic responses to surgery and pain. This effect is responsible of a reduction of the resistance to insulin and of a better nutritional balance, especially after major abdominal surgical procedures. Opioids also act by a reduction of the motor functions of the bowel, which perhaps could reduce the incidence of anastomotic breakdowns. Finally, other effects have been reported, as anecdotes, such as the treatment of spasm after bilateral replantation of the ureters, neurologic bladder dysfunctions and enuresis. Spinal administration of opioids has also been used as a treatment of premature ejaculation.
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PMID:[Non-analgesic effects of opioids]. 167 72

Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides. Stimulation of these receptors by their appropriate ligands such as endogenous (e.g. enkephalis, endorphins) or exogenous opioids, clonidine, serotonin, somatostatin inhibits the release of excitatory neurotransmitters and relieves pain. There are at least 3 different opioid receptors, called mu-, kappa- and delta-receptors in the spinal cord. These can be differentiated from one another by their specific affinity toward different endogenous or exogenous opioids and the pure narcotic antagonist, naloxone. It appears that the nociferous impulses transmitted by parallel pathways equipped with different inhibitory receptors have to be integrated to produce pain sensation and partial inhibition of transmission in different pathways or complete inhibition in one of the pathways may relieve pain. In recent years the concept of "selective spinal analgesia" has been applied clinically for the relief of postoperative, obstetrical and chronic pain. At first it was expected that the intrathecal or peridural administration of morphine will produce analgesia without the side effects of systemically administered morphine. It soon became evident, however, that intrathecally and peridurally administered morphine after several hours of delay reaches the fourth ventricle and by stimulating mu-receptors may cause respiratory depression and other undesired effects (e.g. nausea, vomiting, pruritus). Several different approaches are being investigated for the production of selective spinal analgesia without side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha 2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.
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PMID:Pain control with intrathecally and peridurally administered opioids and other drugs. 168 73

Activation of the sympathetic nervous system appears to be relevant in some patients with unexplained pain after cholecystectomy, particularly those who show increases in plasma transaminase activity after challenge with morphine (morphine responders). In this study, the hypothesis that dexamethasone would improve chronic biliary pain, perhaps by suppressing activation of the sympathetic nervous system, was tested in a double-blind, placebo-controlled, cross-over trial in 20 patients, 10 morphine responders and 10 nonresponders. Before treatment with dexamethasone and placebo, urinary excretion of norepinephrine (NE) was significantly higher (p less than 0.05) in morphine responders than in nonresponders. During treatment with dexamethasone, 1 mg each night for 4 weeks, neither morphine responders nor nonresponders showed a significant improvement in pain or nausea or a significant reduction in sympathoadrenomedullary activity as assessed by urinary excretion of catecholamines. At the dose administered, dexamethasone was unhelpful for chronic pain after cholecystectomy and did not result in suppression of the sympathetic nervous system as assessed by urinary excretion of NE.
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PMID:Placebo-controlled trial of dexamethasone for chronic biliary pain after cholecystectomy. 180 45

Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes.
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PMID:Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. 183 Dec 48

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosage of clomipramine hydrochloride are described, and clinical studies of the use of clomipramine in treating obsessive-compulsive disorder (OCD), other psychiatric conditions, and chronic pain are reviewed. Clomipramine hydrochloride, a tricyclic antidepressant, is a potent inhibitor of serotonin reuptake and may affect dopaminergic neurotransmission, suppress rapid eye movement sleep, produce changes in electrocardiograms, and elevate plasma prolactin. The drug is well absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism. Peak plasma concentrations occur three to four hours after a 150-mg oral dose. The mean elimination half-life is 39 hours. Some 66% of a dose is excreted in the urine, the remainder being eliminated in the feces. In clinical trials, clomipramine was significantly more effective than placebo, clorgiline, amitriptyline, imipramine, and doxepin in ameliorating the symptoms of OCD. Initial effects are seen at four weeks; improvement may continue for up to 18 weeks. Clomipramine may also be effective in treating panic attacks, phobias, depression, and chronic pain. The most common adverse effects of clomipramine are anticholinergic; others include nausea, seizures, and sexual difficulties. Interactions between clomipramine and barbiturates, haloperidol, monoamine oxidase inhibitors, and cigarette smoking have been documented. The usual initial adult dosage is 25-50 mg/day, titrated gradually to 250 mg/day if necessary. Clomipramine hydrochloride is a welcome new agent for the treatment of obsessive-compulsive disorder. Although its adverse-effect profile is like that of other tricyclic antidepressants, sexual dysfunction and seizures may be more frequent with this agent and limit its use.
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PMID:Clomipramine: an antiobsessional tricyclic antidepressant. 218 Jun 23

The use of spinally administered opioids to manage pain is discussed. Central action on opioid receptors of the substantia gelatinosa allows opioids to be administered spinally for pain originating anywhere inferior to the cranial nerves. Spinal opioids are most commonly administered for intractable midline sacral and perineal pain. The best candidates for spinal opioids are patients in whom appropriate "conventional" therapy no longer provides adequate relief, patients who experience severe adverse effects from conventional therapy, and patients for whom alternative anesthetic procedures are inappropriate or have failed. A reasonably safe initial dose is morphine sulfate 1 mg intrathecally. The availability of preservative-free, concentrated morphine sulfate enables larger doses to be safely and comfortably administered. Increased dosage requirements may result from tolerance, progression of disease, increased systemic absorption, or slippage of the catheter tip. As with systemically administered opioids, care must be exercised when discontinuing spinal opioid therapy. Adjuvant drugs used with spinal opioids include systemically administered analgesics, antidepressants, corticosteroids, and spinal local anesthetics. The administration of spinal opioids with systemic opioids or other CNS depressants may result in excessive sedation, respiratory depression, nausea, vomiting, constipation, pruritus, and other adverse effects. Spinally administered opioids can be used to manage severe chronic pain effectively, safely, and comfortably.
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PMID:Pain management with spinally administered opioids. 220 8

This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients.
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PMID:Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study. 229 42

In order to investigate the efficacy and safety of long-term treatment with flupirtine in patients with chronic pain, in particular arthrosis and arthritis, a study was planned which, when completed, will encompass the treatment of 200 patients over a 12-month period. The present paper is a preliminary report of this ongoing study. The report deals with 104 patients: 55 of whom completed the 12-month treatment period and a 2-week follow-up phase, during which flupirtine was replaced by placebo in order to be able to detect drug-withdrawal effects. Forty nine patients withdrew from the study. Most of the patients were suffering from degenerative rheumatic arthrosis or inflammatory rheumatic arthritis. The average daily dosage was 300 mg. The incidence of drop-outs was highest in the first months with hardly any patients withdrawing in the last six months. Fifteen patients dropped out because of side effects (dizziness, nausea, sleep disturbances, and headache). Ten patients dropped out because of ineffectiveness, seven because of side effects plus ineffectiveness, and three because of side effects and other reasons. The remaining 14 patients dropped out because of other or non-medical reasons. For the 55 patients who completed the study, the analgesic took effect within 45 minutes to 2 hours, the duration of effect was 4-6 hours. Three-quarters of the patients responded to the drug, one-quarter did not. The analgesic effect remained constant during the 12-month treatment, as did the average number of capsules taken per month. There was no evidence that tolerance developed. The most frequent side effects were drowsiness (9% of patients), dizziness (11%), dry mouth (5%) and pruritus (9%). The withdrawal symptom scale completed every month during treatment (to determine baseline values) and every day throughout the 2-week placebo post-treatment phase showed no changes in the median. The mean value increased during the withdrawal phase, however, indicating that the symptomatology was more pronounced in some subjects. After withdrawal, the non-specific symptoms increased to a greater extent than symptoms from the opiate scale. The symptoms were present throughout the withdrawal phase. If the withdrawal phenomena had corresponded to the flupirtine's terminal half-life, then the symptoms ought to have been present mainly in the first few days. There was a slight trend for lowering systolic blood pressure but no changes in diastolic blood pressure or heart rate, nor changes in the ECG or laboratory analysis that could be related to flupirtine. These preliminary data suggest that flupirtine is safe when given for a period of one year.
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PMID:On the adverse reactions and efficacy of long-term treatment with flupirtine: preliminary results of an ongoing twelve-month study with 200 patients suffering from chronic pain states in arthrosis or arthritis. 245 18

In a randomised double-blind study of 20 patients with chronic pain, epidural morphine 5 mg in 5 ml of saline was compared with epidural clonidine 150 micrograms in 5 ml of saline. Thirteen patients had a clinical and radiological diagnosis of arachnoiditis, 6 had low back pain and 1 had post-operative scar pain. There were 18 females and 2 males with an average age of 52 years, range 22-76 years. There was no difference found between the 2 solutions in the resultant analgesia measured by the visual analogue scale for pain, pain relief or the pain word score during the 3 h period of the study. No difference was found in the patient's mood which was also measured with the visual analogue scale. Two patients had no analgesia from either injection, 2 patients did not obtain any relief from clonidine and another 2 obtained no relief from morphine. Six patients reported that clonidine was better than morphine, 5 reported that morphine and clonidine were the same and 3 reported that morphine was better than clonidine. The duration of analgesia from the clonidine varied from 6 h to 1 month; the duration of analgesia from morphine varied from 6 to 24 h. Clonidine was associated with sedation and a fall in blood pressure of greater than 20 mm Hg in all patients, 1 patient required ephedrine to treat hypotension. Twelve patients had pruritus, 7 nausea and 2 vomiting following the morphine. Statistically there was no difference found between morphine and clonidine for short-term (3 h) analgesia in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A double-blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. 317 51


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