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Biomedical subjects

R W Houde

Publications and source records attributed to R W Houde.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of opioid-induced constipation with oral naloxone: a pilot study.

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.

Adult↗
PubMed1989

Cancer pain management with a controlled-release oral morphine preparation.

An open-label pilot study was conducted to assess the efficacy and acceptability of a controlled-release oral morphine formulation, MS Contin tablets, when administered "by the clock" two to three times daily as a substitute for opioids given on request to patients with pain caused by advanced cancer. Initially, four-hourly does of standard "immediate-release" oral morphine sulfate tablets were substituted for the patients' prior analgesic medication and titrated to individual needs. Forty of the 47 patients enrolled in the study were subsequently switched to an eight-hourly MS Contin regimen (three patients became too ill to continue the study, and four left the study during the immediate-release titration phase because of adverse reactions that may have been drug related). Small "rescue" doses of standard oral morphine were available to the patients, but they were taken infrequently. Twenty-one of the 37 patients maintained on the eight-hourly schedule consented to be treated with, and were subsequently stabilized on, MS Contin administered every 12 hr, with a reduction of over 20% in their average daily morphine dose. Most of the patients rated the controlled-release medication superior to the standard oral morphine tablets in terms of both convenience and adequacy of relief.

Administration, Oral↗
PubMed1989

Guidelines for use of controlled-release oral morphine in cancer pain management. Correlation with clinical experience.

An open study of 47 patients with cancer pain treated with repeated doses of a controlled-release oral morphine tablet was conducted to assess the acceptability of this drug and develop guidelines for its use. Each patient kept a detailed record of pain, analgesic intake, side effects, and other medications. A nurse observer/clinician followed these patients on a daily basis and kept similar records. Of 47 patients who began the study, 37 were successfully stabilized with standard morphine sulfate tablets and then switched to controlled-release morphine (CRM). Twenty-one patients who completed the study took CRM every 12 h, and 16 patients received a dose every 8 h. Doses of the CRM ranged from 30 mg every 12 h to 360 mg every 8 h. Less frequent doses and uninterrupted sleep were reported advantages. All of the patients completing the study chose to continue this method of pain management and extended care data were obtained from each patient poststudy through continued monitoring.

Administration, Oral↗
PubMed1988

Sublingual absorption of selected opioid analgesics.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

Administration, Sublingual↗
PubMed1987

The Memorial Pain Assessment Card. A valid instrument for the evaluation of cancer pain.

Effective evaluation and treatment of cancer pain require valid and independent measurement of pain intensity, pain relief, and psychological distress. The Memorial Pain Assessment Card (MPAC) is a simple instrument designed to provide rapid evaluation of these subjective experiences. On the 8.5 by 11 inch card are printed the eight pain intensity descriptors, and three visual analog scales which measure pain intensity, pain relief, and mood. Experienced patients can complete it in less than 20 seconds. The authors administered the MPAC to 50 hospitalized cancer patients within 48 hours of referral to the Pain Service for inadequate pain control, together with standard measures: The McGill Pain Questionnaire, Profile of Mood States, Hamilton Depression Scale, and Zung Anxiety Scale. Correlational and multiple regression analyses revealed that the MPAC can distinguish pain intensity from pain relief and from general psychological distress, and it can provide multidimensional assessment that is practically equivalent to the full assessment battery. We conclude that the MPAC is valid and effective for clinical use, and recommend it for the assessment of individual patients, and as an outcome measure in clinical trials.

Adolescent↗
PubMed1987

Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain.

Concentrations of methadone in plasma, estimates of pain relief, and pupillary size were determined after a single intravenous dose (10 to 30 mg) of methadone hydrochloride to eight patients with chronic pain, five of whom had cancer. The pharmacokinetic parameter estimates reveal rapid and extensive distribution (Varea) and a slow apparent elimination half-life (t1/2) (mean Varea = 3.59 L/kg and harmonic mean t1/2 = 23 hours). The harmonic mean blood clearance is 106 ml/min, the harmonic mean renal clearance is 3.9 ml/min, the mean hepatic extraction ratio is 0.089, and plasma protein binding is 86% to 89%. These results suggest that only the free (unbound) fraction of methadone present in blood is extracted by the liver and that methadone can be classified as a low (hepatic)-extraction drug. The data were fit to a pharmacokinetic-pharmacodynamic model to obtain estimates of the steady-state plasma methadone concentration required to produce 50% of the maximum pain relief. This value varied from 0.04 to 1.13 micrograms/ml (mean = 0.29 micrograms/ml). These results indicate substantial interindividual variation in the relationship between changes in plasma methadone concentration and analgesia in patients with chronic pain receiving opioids. A pharmacokinetic-pharmacodynamic model may be useful for the individualization of analgesic dosage and therefore the optimization of pain management in patients with chronic pain.

Adult↗
PubMed1985

Intramuscular meptazinol and morphine in postoperative pain.

Meptazinol is an agonist-antagonist opioid analgesic believed to be unique in its selectivity for mu1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double-blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (+/- SE) times to peak effect and to remedication were 0.9 +/- 0.1 and 3.6 +/- 0.2 hours for meptazinol and 1.4 +/- 0.1 and 4.8 +/- 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32, 49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.

Adolescent↗
PubMed1985

Parenteral meptazinol: a US clinical trial.

The effectiveness and safety of i.m. meptazinol (50, 100, 200mg), a unique mu 1-selective opioid analgesic, was compared with i.m. morphine (4, 8 and 16 mg) in 128 cancer patients with moderate to severe postoperative pain; 102 patients completed the crossover study. The study design was a modification of the sequential, twin-crossover assay. Meptazinol was found to be one-fifteenth to one-twentieth as potent as morphine on a mg basis, and to provide a more rapid time to peak effect (about 40 min vs 1 h) than morphine. Morphine improved selected aspects of mood while meptazinol did not. Sleepiness was the most common side effect on morphine (n = 43), and nausea was most common on meptazinol (n = 35). The incidence of side effects appeared to be dose-related for both drugs.

Adolescent↗
PubMed1984

The pharmacokinetics of heroin in patients with chronic pain.

We measured blood concentrations of heroin and its active metabolites, 6-acetylmorphine and morphine, serially in 11 patients with chronic pain (9 of whom had cancer) after intravenous injection, intravenous infusion, intramuscular injection, and an oral dose of heroin hydrochloride. Parenteral heroin provided measureable blood levels of heroin, 6-acetylmorphine, and morphine. Blood levels of heroin and 6-acetylmorphine reached their maximal concentrations within minutes and were cleared rapidly. The mean half-life of heroin (+/- S.D.) after intravenous injection or infusion was only 3.0 +/- 1.3 minutes, and the mean clearance of heroin from the blood at apparent steady state was 30.8 +/- 2.1 ml per kilogram of body weight per minute. Morphine levels rose more gradually, and morphine was cleared much more slowly. Oral administration of heroin resulted in measurable blood levels of morphine but not of heroin or 6-acetylmorphine. The amount of circulating morphine provided by an oral dose of heroin was only 79 per cent of that available from an equal amount of morphine. We conclude that heroin is a pro-drug that serves to determine the distribution of its active metabolites. Parenteral heroin is rapidly converted to 6-acetylmorphine, which contributes to rapid pain relief. Oral heroin is converted to morphine and appears to be an inefficient means of providing morphine to the systemic circulation.

Administration, Oral↗
PubMed1983

Plasma levels and analgesia following deltoid and gluteal injections of methadone and morphine.

The objective was to determine whether deltoid as compared to gluteal injection of morphine and methadone produce differential plasma levels and analgesic effects. Thirty-two postoperative cancer patients received deltoid and gluteal injections of morphine, 8 and 16 mg, within a double-blind, twin crossover design. Forty-four patients received deltoid or gluteal methadone, 10 mg. Deltoid morphine resulted in peak plasma levels 1.8 times (P less than 0.05) those observed following gluteal morphine. Deltoid methadone resulted in peak levels 2.5 times (P less than 0.005) those following gluteal injection. Deltoid morphine resulted in an area under the drug level-time (0 to 4 hours) curve 1.4 times (N.S.) the area observed following gluteal injection. Deltoid methadone resulted in an area under the drug level-time (0 to 4 hours) curve 2.2 times (P less 0.001) the area observed following gluteal injection. Deltoid methadone, but not morphine, provided greater (1.7-fold, P less than 0.05) pain relief than gluteal injection. If more rapid and enhanced analgesia is indicated, then the deltoid site may be preferable over the gluteal site for standard doses of methadone and other lipid soluble analgesics. In addition, the relative potency of compounds of widely differing lipid solubility may depend upon the site of intramuscular injection.

Adult↗
PubMed1983

Sources of variation in analgesic responses in cancer patients with chronic pain receiving morphine.

Our objective was to identify and quantify sources of variation in the relief of chronic pain with morphine. Relief scores were extracted from records obtained during controlled trials of analgesics in cancer patients with chronic pain in which intramuscular morphine was the assay standard. Relief data from 715 patients after 565 8-mg and 538 16-mg doses were segregated according to age, race, sex, pre-drug pain intensity, character and site. Middle-aged patients obtained relief after 8 mg comparable to relief obtained by younger patients after 16 mg; oldest patients obtained relief after 8 mg comparable to relief obtained by middle-aged patients after 16 mg. Blacks receiving 8 mg obtained relief comparable to whites receiving 16 mg. Sex-related differences were not significant. Patients with moderate, as compared to severe, pre-drug pain obtained significantly greater relief only after 16 mg. Patients reporting dull pain obtained relief after 8 mg comparable to relief obtained with sharp pain after 16 mg. Patients with abdominal pain obtained relief after 8 mg comparable to relief of pain in the chest or arms after 16 mg. These results provide dose-related evidence of variation in relief with morphine in chronic cancer pain and establish particular patient and pain characteristics as variables for which controls should be provided in analgesic assays.

Adolescent↗