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Biomedical subjects

C H Wilder-Smith

Publications and source records attributed to C H Wilder-Smith.

At least 19 recordsLinked to original sources
PubMed2004

Esomeprazole 40 mg i.v. provides faster and more effective intragastric acid control than pantoprazole 40 mg i.v.: results of a randomized study.

BACKGROUND: Oral esomeprazole 40 mg provides greater acid control than oral pantoprazole 40 mg. AIM: To compare the effects on intragastric acid control of esomeprazole 40 mg administered intravenously with pantoprazole 40 mg intravenously. METHODS: Healthy Helicobacter pylori-negative male and female subjects were enrolled into this single-centre, open, randomized, two-way crossover study. Esomeprazole 40 mg intravenously and pantoprazole 40 mg intravenously were administered as 15-min infusions once daily at 09:00 hours for 5 days. Continuous 24-h intragastric pH monitoring was carried out at baseline and on days 1 and 5. RESULTS: pH-data were available for all 25 subjects who completed the study. Esomeprazole 40 mg intravenously resulted in 8.3 and 13.9 h with an intragastric pH > 4 on days 1 and 5 compared with 5.3 and 9.0 h, respectively for pantoprazole 40 mg intravenously (day 1: P < 0.001, day 5: P < 0.0001). During the first 4 h of dosing on day 1 corresponding values were 1.7 and 0.6 h respectively (P < 0.0001). A mean median pH above 4 on day 5 was only attained with esomeprazole 40 mg intravenously. CONCLUSIONS: Once-daily dosing with esomeprazole 40 mg intravenously provides faster and more pronounced intragastric acid control than pantoprazole 40 mg intravenously.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls.

BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.

Adult↗
PubMed2001

Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.

Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.

Adult↗
PubMed2000

Analgesic action of i.v. morphine-6-glucuronide in healthy volunteers.

The pharmacodynamics of morphine-6-glucuronide (M-6-G) i.v. were assessed in 12 healthy male volunteers in an open study. After a single bolus dose of M-6-G 5 mg i.v., we measured antinociceptive effects, using electrical and cold pain tests, and plasma concentrations of M-6-G, morphine-3-glucuronide (M-3-G) and morphine. Pain intensities during electrical stimulation (at 30, 60 and 90 min after injection) and ice water immersion (at 60 min) decreased significantly (P < 0.005) compared with baseline. Mean plasma peak concentrations of M-6-G were 139.3 (SD 38.9) ng ml-1, measured at 15 min. Our data demonstrate that M-6-G has significant analgesic activity.

Adult↗
PubMed2000

Helicobacter pylori and gastric erosions. Results of a prevalence study in asymptomatic volunteers.

BACKGROUND/AIMS: Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers. METHODS: 175 asymptomatic subjects underwent upper gastrointestinal endoscopy. Antral biopsies were taken for bacterial cultures, histology and quick urease (CLO) test. A (13)C-urea breath test was performed after endoscopy. NSAID intake, alcohol consumption and smoking habits were also recorded in each subject. RESULTS: 33 (19%) of 175 asymptomatic volunteers had macroscopic lesions on upper gastrointestinal endoscopy, 7 were H. pylori positive, 26 were H. pylori negative. Gastric erosions occurred in 8% (14 subjects) of all volunteers. 10 subjects were H. pylori negative and 4 H. pylori positive. In 11 volunteers, gastric erosions were restricted to the prepyloric antrum. Only 1 of 14 subjects had a history of NSAID intake and 6 subjects were alcohol abstainers. CONCLUSION: We conclude that gastric erosions occur in a considerable amount of asymptomatic volunteers. They are predominantly localized in the prepyloric antrum and are most likely not associated with H. pylori infection, NSAID intake, smoking or alcohol consumption.

Adolescent↗
PubMed1999

Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis.

Tramadol and morphine were compared for treatment of severe chronic pancreatitis pain and their interaction with gut motor function. Oral tramadol or morphine doses were titrated double-blinded and randomized for five days in 25 patients and pain, side effects, bowel function, orocecal and colonic transit, anal resting pressure, and rectal distension thresholds were measured. Pain intensities (mean+/-SD, 0 = none, 100 = unbearable) before treatment and on day 4 were 75+/-19 and 8+/-13 with tramadol (P < 0.001), and 65+/-21 and 5+/-6 with morphine (P < 0.001). On day 4, 67% of patients with tramadol and 20% with morphine rated their analgesia as excellent (P < 0.001) with mean respective doses of 840 mg (range: 80-1920) and 238 mg (20-1125). Orocecal transit was unchanged after five days of tramadol, but increased with morphine (P < 0.05). More patients had prolonged colonic transit times with morphine by day 5 (P < 0.05). Rectal distension threshold pressures increased only with tramadol (P < 0.01). It is concluded tramadol and morphine are potent analgesics in severe chronic pancreatitis pain when individually titrated. Tramadol interfered significantly less with gastrointestinal function and was more often rated as an excellent analgesic than morphine.

Adult↗
PubMed1999

Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery.

BACKGROUND: Chronic nociceptive input induces sensitization and changes in regulatory reflexes in animal models. In humans, postoperative somatic and visceral sensitization and the secondary effects on reflex gut motility are unclear. METHODS: Somatic and visceral sensation and gastrointestinal motility were evaluated after abdominal hysterectomies in 50 patients who were randomized to receive double-blinded postoperative 48-h infusions of morphine or tramadol. Pain scores, rectal distension, skin electric sensation and pain tolerance thresholds, and gastrointestinal transit were assessed before and after operation, during and after analgesic infusions. RESULTS: Pain intensity scores decreased similarly with morphine and tramadol infusions (total doses, 66.8+/-20 mg and 732.4+/-152 mg [mean +/- SD], respectively). Skin pain tolerance thresholds in the incisional dermatome remained similar with morphine and tramadol throughout the study. During morphine infusions, pain tolerance thresholds on the shoulder increased (P<0.05) and then decreased after discontinuation on day 4 (P<0.02) compared with before operation. Rectal distension pain tolerance pressure thresholds increased after operation during morphine infusions (P<0.05). Similar but nonsignificant trends occurred with tramadol. Orocecal and colonic transit times increased after operation with both morphine and tramadol (P<0.005), but gastric emptying was prolonged only with morphine (P = 0.03). AU motility and sensory parameters had returned to preoperative levels by 1 month after operation. CONCLUSIONS: Pain control was equally effective with morphine and tramadol infusions. No somatic or visceral sensitization was evident during morphine and tramadol infusions, but pain tolerance thresholds as markers of antinociception were increased more during morphine infusions. The significant sensitization seen only after morphine discontinuation may be due to convergent visceral input. Gut motility was prolonged significantly by visceral surgery itself and also by morphine.

Adult↗
PubMed1998

The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers.

AIMS: Dihydrocodeine is metabolized to dihydromorphine via the isoenzyme cytochrome P450 2D6, whose activity is determined by genetic polymorphism. The importance of the dihydromorphine metabolites for analgesia in poor metabolizers is unclear. The aim of this study was to assess the importance of the dihydromorphine metabolites of dihydrocodeine in analgesia by investigating the effects of dihydrocodeine on somatic and visceral pain thresholds in extensive and quinidine-induced poor metabolizers. METHODS: Eleven healthy subjects participated in a double-blind, randomized, placebo-controlled, four-way cross-over study comparing the effects of single doses of placebo and slow-release dihydrocodeine 60 mg with and without premedication with quinidine sulphate 50 mg on electrical, heat and rectal distension pain tolerance thresholds. Plasma concentrations and urinary excretion of dihydrocodeine and dihydromorphine were measured. RESULTS: In quinidine-induced poor metabolizers the plasma concentrations of dihydromorphine were reduced between 3 and 4 fold from 1.5 h to 13.5 h after dosing (P < 0.005) and urinary excretion of dihydromorphine in the first 12 h was decreased from 0.91% to 0.28% of the dihydrocodeine dose (P < 0.001). Dihydrocodeine significantly raised the heat pain tolerance thresholds (at 3.3 h and 5 h postdosing, P < 0.05) and the rectal distension defaecatory urge (at 3.3 h and 10 h postdosing, P < 0.02) and pain tolerance thresholds (at 3.3 h and 5 h postdosing, P < 0.05) compared with placebo. Premedication with quinidine did not change the effects of dihydrocodeine on pain thresholds, but decreased the effect of dihydrocodeine on defaecatory urge thresholds (at 1.5 h, 3.3 h and 10 h postdosing, P < 0.05). CONCLUSIONS: In quinidine-induced poor metabolizers significant reduction in dihydromorphine metabolite production did not result in diminished analgesic effects of a single dose of dihydrocodeine. The metabolism of dihydrocodeine to dihydromorphine may therefore not be of clinical importance for analgesia. This conclusion must however, be confirmed with repeated dosing in patients with pain.

Adult↗
PubMed1998

Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing.

BACKGROUND: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant. METHODS: The dose-dependent effects of adjuvant preoperative epidural tramadol on postoperative analgesia (pain scores and patient-controlled analgesia (PCA) use) and pain processing (heat pain thresholds) were prospectively studied in a double-blind, randomised, placebo-controlled 5-day trial. Forty patients undergoing knee or hip surgery received anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous PCA tramadol in all patients. RESULTS: Postoperative pain scores were similar in all groups. The time to first PCA use was shorter, the total dose and duration of PCA use greater, and side-effects more common with 20 mg tramadol than with 100 mg or placebo (P < 0.05). There were no differences in PCA doses required or side-effects between the tramadol 100 mg and placebo treatment groups. Heat pain tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively compared to baseline and placebo (P = 0.01). CONCLUSIONS: Preoperative adjuvant epidural tramadol does not improve postoperative analgesia after lidocaine epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti-analgesia and increased side-effects. While tramadol 100 mg depresses postoperative pain-processing, as measured by heat pain tolerance thresholds, this is not reflected in improved clinical pain measures.

Analgesia, Epidural↗
PubMed1998

Pain treatment in multimorbid patients, the older population and other high-risk groups. The clinical challenge of reducing toxicity.

The prevalence of pain is high in multimorbid patients and they can experience a multitude of painful conditions. The changes in physiology and homeostasis associated with multimorbidity and increasing age and the immature metabolism of neonates all increase the risk of toxicity from analgesics. Altered pharmacokinetics and metabolism influence drug pharmacodynamics and therapeutic windows. Imbalances in local homeostatic mechanisms increase local toxicity. The gastrointestinal organs and the kidney have a major role in the absorption, metabolism and excretion of analgesics and changes in their function predispose individuals to adverse effects. Knowledge of such compromise should influence the choice of analgesic, the administration regimen and the mode of application. The mainstay of chronic pain treatment are 3 classes of drugs: nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and a host of so-called adjuvant drugs, which are used to enhance the analgesic action of the classic analgesics. In each class a wide range of drugs are available, that differ in pharmacokinetic and pharmacodynamic characteristics. These differences can be exploited to either increase analgesic efficacy and reduce toxicity, or to minimise the interference of pain therapy with daily life. Clinically important differences in analgesic and toxic effects between drugs in each analgesic class will be discussed in this article from the perspective of reducing adverse effects. New knowledge concerning the mechanism of action of analgesics and their metabolites is making the specific selection of NSAIDs and opioids to reduce adverse effects in multimorbid, chronic pain patients possible.

Aged↗
PubMed1997

The analgesic tramadol has minimal effect on gastrointestinal motor function.

AIMS: The analgesic tramadol, an opioid agonist and monoaminergic reuptake blocker, has been assumed to interfere less with gastrointestinal motor function than other opioid analgesics, but this has not been specifically investigated. In this study we examined the effect of tramadol on variables of gastrointestinal motor function. METHODS: Ten healthy volunteers participated in a two-arm, placebo-controlled, double-blind, randomized, cross-over study comparing tramadol 50 mg and placebo solutions given four times a day for 10 days. Oro-caecal (lactulose H2-breath test) and colonic (solid markers) transit times and anal sphincter pressures were measured after 10 days dosing. RESULTS: Median oro-caecal transit time was 90 min (interquartile range: 75-105) with placebo and 90 min (60-105) with tramadol (not significant). The median total colonic transit time increased from 45.6 h (25.2-64.8) with placebo to 58.8 h (50.4-78.0) with tramadol (not significant), which is still within the normal range (< 60 h). Anal sphincter resting pressures were not significantly changed by tramadol compared with placebo. CONCLUSIONS: Tramadol has a minor delaying effect on colonic transit, but no effect on upper gastrointestinal transit or gut smooth muscle tone. Tramadol may be a useful analgesic where interference with gut motor function is undesirable.

Administration, Oral↗
PubMed1997

Perioperative magnesium infusion and postoperative pain.

BACKGROUND: NMDA receptor activation is considered one of the mechanisms involved in postoperative pain and hypersensitivity. Magnesium is the physiological blocker of the NMDA-receptor-complex-associated calcium ionophore. The aim of this study was to determine if a pre-, intra- and postoperative infusion of magnesium would reduce postoperative pain. METHODS: In a prospective, randomised, double-blinded and placebo-controlled study, 24 patients undergoing elective hysterectomy in standardised general anaesthesia received a 5 h infusion of either placebo or magnesium laevulinate (initial bolus 8 mmol: then 8 mmol/h) starting with induction of anaesthesia. Postoperative analgesia was by PCA morphine for the first 48 h and patients were followed for 5 d with regular assessment of pain and side-effect scores. RESULTS: Overall, pain scores were similar with magnesium and placebo infusion, although patients in the magnesium group experienced more episodes of severe or unbearable pain (placebo = 6%, magnesium = 16%, P = 0.02). Median pain scores were higher in the magnesium group only at 3 h postoperatively (P = 0.04): afterwards there were no significant differences. Except for the first postoperative hour (placebo = 12.8 +/- 4.7 mg, magnesium = 9.3 +/- 3.2 mg, P = 0.04), cumulative morphine consumption was similar. Gastrointestinal complication rates and patient satisfaction were similar in both groups. CONCLUSIONS: Perioperative magnesium infusion does not improve postoperative analgesia. At the doses used in this study, the use of magnesium is associated with short-term decreases in postoperative analgesia.

Adult↗
PubMed1996

Characterization of the genetic polymorphism of dihydrocodeine O-demethylation in man via analysis of urinary dihydrocodeine and dihydromorphine by micellar electrokinetic capillary chromatography.

The genetic polymorphism of dihydrocodeine O-demethylation in man via analysis of urinary dihydrocodeine (DHC) and dihydromorphine (DHM) by micellar electrokinetic capillary chromatography is described. Ten healthy subjects which are known to be extensive metabolizers for debrisoquine ingested 60 mg of DHC and collected their 0-12 h urines. In these samples, about 1% of the administered DHC equivalents are shown to be excreted as DHM. Premedication of 50 mg quinidine sulfate to the same subjects is demonstrated to significantly reduce (3-4 fold) the amount of O-demethylation of DHC, a metabolic step which is thereby demonstrated to co-segregate with the hydroxylation of debrisoquine. Thus, in analogy to codeine and other substrates, extensive and poor metabolizer phenotypes for DHC can be distinguished. Using the urinary DHC/DHM metabolic ratio to characterize the extent of O-demethylation, the metabolic ratio ranges of extensive and poor metabolizers in a frequency histogram are shown to partially overlap. Thus, classification of borderline values is not unequivocal and DHC should therefore not be employed for routine pharmacogenetic screening purposes. Nevertheless, the method is valuable for metabolic research and preliminary data demonstrate that the same assay could also be used to explore the metabolism of codeine.

Codeine↗
PubMed1995

Sedation with intravenous infusions of propofol or thiopentone. Effects on pain perception.

The aim of this study was to investigate pain perception during thiopentone or propofol infusions for sedation. Thirty ASA 1 or 2 patients received a two step infusion of either thiopentone (step 1: 1.25 mg.kg-1 followed by 2.5 mg.kg-1.h-1; step 2: 1.25 mg.kg-1 and 12.5 mg.kg-1.h-1; n = 15) or propofol (step 1: 0.5 mg.kg-1, 1 mg.kg-1.h-1; step 2: 0.5 mg.kg-1, 5 mg.kg-1.h-1; n = 15) for sedation. At control and 10 min after the start of each infusion dosage, reaction times and thermal pain detection thresholds were determined. We found no clinically or statistically significant depression of thermal pain detection thresholds during propofol or thiopentone infusions and these are, therefore, unlikely to be associated with clinically relevant hyperalgesia.

Adolescent↗
PubMed1995

Individual and group dose-responses to intravenous omeprazole in the first 24 h: pH-feedback-controlled and fixed-dose infusions.

1. Individual responses to intravenous boli of omeprazole have shown considerable variability. Data on the individual responses to the new omeprazole infusion formulation are lacking. 2. Individual dose-responses in the first 24 h of fixed-dose and pH-feedback-controlled infusions of omeprazole were assessed in two randomised, third-party blinded, cross-over studies, using two separate groups of eight healthy subjects. In study A, feedback-controlled infusions of omeprazole (target pH 5, dose range 0-12 mg h-1) and fixed-dose infusions (8 mg h-1) were compared, both with an initial bolus of 80 mg. Omeprazole plasma concentrations were measured. Study B assessed the effect on individual pH-control of a loading bolus of either 40 mg or 80 mg omeprazole, followed by feedback-controlled infusions. 3. Study A: the median % time of pH > 5 was 71.2 (total range: 48.9-83.2) with feedback infusions and 57.9 (28.0-95.3) with fixed-dose infusions (P = 0.06). The mean 24 h infusion doses were 173.1 mg (44.5-253.1) in the feedback group and 192 mg in the fixed-dose group. The AUC of omeprazole plasma concentrations ranged widely, but correlated with the % time of pH > 5 during fixed-dose infusions. Study B: initial boli of 40 mg and 80 mg of omeprazole resulted in similar 24 h median % of time with pH > 5, 69.2 (49.9-78.8) and 69.6 (44.4-87.7), respectively. Mean omeprazole doses infused by feedback pump were 187.6 mg (83.1-253.6) after 40 mg boli and 159.9 mg (61.8-227.0) after 80 mg boli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing?

BACKGROUND/AIMS: Prolonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of ranitidine and omeprazole for a period of 72 hours. METHODS: Twelve healthy volunteers received individually titrated 72-hour intravenous infusions of omeprazole, ranitidine, or placebo in a double-blind, crossover study. Gastric pH and dosing requirements were compared. RESULTS: The median percentage of time with pH > 4 (interquartile range) was 93% (88%-95%) on day 1 and 96% (94%-99%) on day 3 with omeprazole and 67% (56%-78%) and 43% (31%-51%), respectively, with ranitidine (both P < 0.001 vs. omeprazole). The mean doses (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44 mg and 134.0 +/- 37 mg (P < 0.0001), and ranitidine doses were 502.5 +/- 76 mg and 541.8 +/- 25 mg, respectively (P = 0.05). CONCLUSIONS: Omeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding is inappropriate.

Acids↗
PubMed1994

Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain.

BACKGROUND: Opioid and spinal monoaminergic agonists have distinct analgesic properties, which may potentiate each other. Tramadol has both opioid and monoaminergic agonist actions. This initial study compared the analgesic and toxic effects of tramadol and morphine in patients with strong cancer pain. PATIENTS AND METHODS: Pain control and side-effects with tramadol and morphine were compared in 20 cancer patients hospitalised for the treatment of strong pain. Doses of oral solutions of tramadol or morphine were individually titrated in the double-blind, randomized, cross-over study. Cross-over was after day 4, the day of statistical evaluation. RESULTS: The mean pain intensity (+/- SD) on a verbal rating scale (0 = none, 4 = unbearable) was similar with morphine (1.6 +/- 1.2, n = 17) and with tramadol (1.5 +/- 1.3, n = 16) on the fourth day of dosing. The mean daily doses on day 4 were 101 +/- 58 mg of morphine and 375 +/- 135 mg of tramadol, indicating a relative potency of 4:1 with oral dosing. The total number of side-effects per person was lower on the fourth day with tramadol (p < 0.05), as was the severity of nausea (p < 0.05) and constipation decreased with tramadol (p < 0.05). Three patients dropped out of the morphine group due to side-effects and 4 out of the tramadol group due to inadequate analgesia. Overall, 8 patients (40%) preferred morphine, 3 (15%) favoured tramadol and 9 (45%) expressed no distinct choice. Nurses rated pain control better with morphine (p < 0.03), but the tolerability of tramadol was judged superior (p < 0.002). CONCLUSIONS: In certain cancer patients with strong pain, tramadol achieved good pain control with fewer side-effects than morphine. The non-opioid mode of action may result in a different spectrum of analgesia and side-effects. Longterm studies are required to confirm this study of brief duration.

Administration, Oral↗