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Biomedical subjects

M F Roizen

Publications and source records attributed to M F Roizen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine.

Opioid compounds are commonly used analgesics. After opioid administration, troublesome subjective effects, such as dysphoria, dizziness, nausea, and pruritus, have been reported. While some if not all of these are believed to occur due to central nervous system effects of opioids, the anecdotal reports heard from volunteers in our other studies suggest that a peripheral opioid antagonist reduced some of these effects. In this double-blind randomized placebo-controlled study, we evaluated the efficacy of oral methylnaltrexone, a selective peripheral opioid receptor antagonist, to decrease subjective effects after administering morphine to normal human volunteers. After intravenous morphine injection (0.05 mg/kg), significant increases in subjective ratings were obtained on 'nauseous', 'skin itch', 'stimulated', and 'flushing'. Oral methylnaltrexone 19.2 mg/kg significantly decreased these four ratings. Plasma methylnaltrexone concentrations at two different oral doses were also measured to correlate between pharmacological effects of the compound and its plasma levels. Our results suggested that methylnaltrexone has a potential therapeutic value in decreasing some undesirable subjective effects associated with opioid medications.

Administration, Oral↗
PubMed1998

Gut motility and transit changes in patients receiving long-term methadone maintenance.

This study was conducted to survey gut motility and transit in 19 volunteers receiving methadone maintenance who were opioid-dependent, and to measure the oral-cecal transit time in these individuals using the lactulose hydrogen breath test. None of these patients reported constipation problems before use of illicit drugs. During current long-term methadone therapy, 58% of patients experienced some degree of constipation, and two of these 19 patients reported that constipation was a very serious problem. Mean +/- standard deviation (SD) oral-cecal transit time in these individuals was 159+/-49.2 minutes, which is significantly longer than the transit time recorded in two previous studies of healthy volunteers (P < 0.01). These results indicate that tolerance to opioids does not appear to extend to gastrointestinal motility and transit. It seems that patients receiving long-term methadone therapy are a good model for use in evaluating gastrointestinal effects of opioid antagonists.

Adult↗
PubMed1998

Prevention of apomorphine- or cisplatin-induced emesis in the dog by a combination of methylnaltrexone and morphine.

PURPOSE: Morphine can have either an emetic or an antiemetic effect. The emetic effect of morphine can be blocked by methylnaltrexone (MNTX), a quaternary opioid antagonist with peripheral action. In this study, we tested the hypothesis that administering MNTX to block the peripheral emetic effect of morphine would unmask the central antiemetic effect of the morphine. The net result, we hypothesized, would be a reduction in apomorphine- or cisplatin-induced emesis. METHODS: MNTX 0.25 mg/kg and morphine 1 mg/kg were administered to conscious dogs which were then challenged with the potent emetic agents apomorphine or cisplatin. Emesis was assessed by the presence of characteristic retching motions accompanied by the regurgitation of gastric contents. RESULTS: We observed that apomorphine challenges of 0.1 mg/kg and of 0.03 mg/kg produced 100% emesis in control animals. After pretreatment with MNTX and morphine, the frequency of emesis with the larger dose of apomorphine was reduced to 50% and with the smaller dose to 22%. MNTX alone did not block apomorphine-induced emesis. In animals challenged with cisplatin 3 mg/kg, the emetic response was 100%. Emesis did not occur in animals pretreated with MNTX 0.25 mg/kg and morphine 1 mg/kg before cisplatin. CONCLUSIONS: Our results demonstrate that MNTX combined with morphine reduces apomorphine-induced emesis and blocks cisplatin-induced emesis. These results support the hypothesis that the emetic effect of morphine is peripheral and its antiemetic action is central. In combination, MNTX and morphine may have a clinical role in the treatment of chemotherapy-induced emesis.

Administration, Oral↗
PubMed1998

Improving the efficiency of survey research in postoperative patients.

STUDY OBJECTIVE: To increase the contact rate with eligible patients for quality assurance/improvement surveys by modifying survey rounds to accommodate the schedules of individual nursing units. DESIGN: Two-phase, interventional time series study. SETTING: Postoperative inpatients at a university hospital. PATIENTS: 498 adult postoperative inpatients who remained hospitalized during the second postoperative day. INTERVENTIONS: Between the first and second measurement periods, efforts were made to learn the schedule of each nursing unit and to improve the efficiency of survey rounds so that a larger proportion of patients could be contacted. MEASUREMENTS AND MAIN RESULTS: The contact rate for eligible patients was improved from 66% to 80% (p < 0.01). Improvement during the second period was attributed to fewer patients being away from the nursing unit (20% vs. 12%, p < 0.05) or otherwise occupied by attending physicians on rounds (9% vs. 4%, p < 0.05). CONCLUSION: Strategies individualized to patient care units can improve the efficiency and credibility of inpatient survey research. We describe the strategies most helpful in improving the efficiency of survey rounds at one medical center.

Adult↗
PubMed1998

A compelling rationale for using preoperative visits to complete adult immunizations.

Immunization is a safe and cost-effective method to protect adult patients against many diseases, including hepatitis B, pneumococcal infections, and influenza. Despite this fact, only 10% to 40% of adults in the United States who would benefit have been immunized. Approximately 62% to 92% of patients who develop a disease preventable by vaccination have visited an outpatient clinic at least once in the 3 years preceding their illness. Efforts to educate providers about immunization guidelines have not increased immunization rates. In this report, we propose using the preanesthesia clinic as an alternative site to screen, identify, and immunize adults at risk. We also discuss three vaccines that could be offered to patients and analyze the efficacy of the vaccines.

Adult↗
PubMed1998

Review of the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction.

BACKGROUND: Topical capsaicin is known to be a safe and effective pain management adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic neuropathy. However, studies and case reports in the literature have indicated that other conditions may also benefit from capsaicin: painful or itching cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or inflammation of the airways and urinary tract. METHODS: To determine the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966-96) on the efficacy of capsaicin. Outcome measures consisted of the response rate and degree of pain relief. Results from placebo-controlled trials were pooled when possible; effect of treatment was estimated by the method of DerSimonian and Laird. RESULTS: Pain relief for postmastectomy syndrome and cluster headache was greater with capsaicin than with placebo; also, psoriasis and pruritus responded better to capsaicin. Uncontrolled studies and case reports have indicated that pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin. CONCLUSIONS: Capsaicin is effective for psoriasis, pruritus, and cluster headache; it is often helpful for the itching and pain of postmastectomy pain syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck pain, amputation stump pain, and skin tumor; and it may be beneficial for neural dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and rhinopathy). A universal problem for many of the studies analyzed was the absence of a "burning placebo" such as camphor.

Capsaicin↗
PubMed1998

Effects of low-dose morphine on gastric emptying in healthy volunteers.

Appropriate preoperative pain therapy for patients undergoing surgery may be withheld due to the fear that opioids will inhibit gastric emptying and increase the risk of aspiration. Previously, doses of 5 to 10 mg of morphine have been shown to delay gastric emptying time. However, the effect of lower doses of morphine on gastric emptying in humans has not been reported. In this study, the effects of intravenous morphine 0.05 mg/kg-3.5 mg for 70-kg body weight, a dose that can cause analgesia--on gastric emptying were evaluated in a double-blind, randomized, placebo-controlled study in 15 healthy human volunteers using the acetaminophen test. Our data indicated that this low dose of morphine significantly prolonged the gastric emptying time. Thus, even small doses of morphine inhibit gastric emptying. This effect may be important in patients undergoing surgery, in patients receiving other oral medications after surgery in ambulatory settings, and in instances of patient-controlled analgesia.

Acetaminophen↗
PubMed1997

The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time.

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastrointestinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique after lactulose ingestion. Morphine significantly increased oral-cecal transit time from 114.6 +/- 37.0 minutes (mean +/- SD) to 158.6 +/- 50.2 minutes (p < 0.001). Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time (110.4 +/- 45.0 minutes; not significant compared with baseline; p < 0.005 compared with morphine alone). These sessions were then followed by single-blind evaluations of descending doses of methylnaltrexone. We observed that 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time (p < 0.005 compared with morphine alone), and a dose-dependent response was obtained. There was no correlation between oral methylnaltrexone effects on the transit time and the drug plasma concentration, suggesting direct preferential luminal effects of oral methylnaltrexone. Oral methylnaltrexone may have a clinical value in the prevention and treatment of constipation induced by long-term opioid use.

Administration, Oral↗
PubMed1997

Haemolysis after etomidate: comparison of propylene glycol and lipid formulations.

We sought to determine if the solvent in the formulation of etomidate is responsible for haemolysis in patients. In a randomized, prospective, double-blind study of 49 patients undergoing otolaryngological surgery, patients received etomidate dissolved in propylene glycol or in lipid emulsion. Concentrations of free haemoglobin and haptoglobin were measured before and for up to 360 min after injection of etomidate. Free haemoglobin concentrations increased by 216.8 mg litre-1 in patients who received the propylene glycol formulation and by 11.8 mg litre-1 in the lipid emulsion group (P < or = 0.0004). Correspondingly, reductions in haptoglobin concentrations were significantly greater in the propylene glycol group (P < or = 0.002). We conclude that with respect to haemolysis, lipid emulsion is superior to propylene glycol as a solvent for etomidate.

Anesthetics, Intravenous↗
PubMed1997

Pharmacokinetics and pharmacodynamics of propofol in a new solvent.

UNLABELLED: Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation. IMPLICATIONS: Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.

Adult↗
PubMed1997

Safety and tolerance of methylnaltrexone in healthy humans: a randomized, placebo-controlled, intravenous, ascending-dose, pharmacokinetic study.

N-methylnaltrexone bromide (methylnaltrexone) is a quaternary opioid antagonist with a limited ability to cross the blood-brain barrier. In animal models it reverses at peripheral receptors such side effects of opioids as decreased gastrointestinal motility, emesis, and cough suppression without affecting the desired analgesic effect mediated by central nervous system receptors. Methylnaltrexone thus may be a clinically useful compound for the prevention and treatment of opioid-induced side effects. This study was designed to examine the safety and tolerance of methylnaltrexone in healthy human participants over a range of doses and to identify any adverse effects or toxicity associated with methylnaltrexone and the doses at which these adverse effects occur. Healthy male volunteers received intravenous methylnaltrexone in six ascending doses with a placebo randomly inserted into the sequence. Each participant was observed for subjective and hemodynamic changes. Electrocardiogram and laboratory studies were also performed. The dose-limiting adverse effect of methylnaltrexone was orthostatic hypotension at 0.64 mg/kg (n = 3) or 1.25 mg/kg (n = 5), which was transient and self-limiting. Plasma levels of methylnaltrexone in excess of 1,400 ng/mL were observed to be associated with orthostatic hypotension. There were no significant subjective changes, no release of histamine, and no changes in physical examination or laboratory studies during the course of the study. Pharmacokinetic analysis revealed an elimination half-life of 117.5 minutes (+/-53.2), and a clearance of 38.8 L/hr (+/-17.4) with a methylnaltrexone dose of 0.64 mg/kg. Our results indicate that methylnaltrexone is well tolerated at doses of 0.32 mg/kg in healthy humans.

Adult↗