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Biomedical subjects

K M Foley

Publications and source records attributed to K M Foley.

At least 37 records · Page 2Linked to original sources
PubMed1993

Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics.

BACKGROUND: The transdermal therapeutic system (fentanyl), or TTS(fentanyl), continuously delivers fentanyl for up to 72 h. The transdermal therapeutic system (fentanyl)-100 delivers approximately 100 micrograms/h. The repeated dose pharmacokinetics of this drug using the recommended dosing interval have not been evaluated previously and were determined in the present study. METHODS: Blood samples were obtained from ten opioid-tolerant cancer patients who received five applications of TTS(fentanyl) at 72-h intervals. A sample of venous blood was taken before each dose; multiple samples were taken during and after the fifth application. A gas chromatographic/mass spectrometry method was used to assay fentanyl (limit of detection 0.2 ng/ml). RESULTS: For the fifth dose, the mean (SD) maximum concentration was 2.6 (1.3) ng/ml and the mean (SD) area under the serum fentanyl concentration-time curve (0-72 h) was 116.9 (59.9). Following removal of the system, the mean (SD) apparent half-life was 21.9 (8.9) h. There were no differences among the serum fentanyl concentrations measured before the second through fifth doses. Fentanyl absorption was 47% complete at 24 h, 88% complete at 48 h, and 94% complete at 72 h. The mean (SD) dose delivered during the 72-h period was 4.3 (1.1) mg. A first-dose trough concentration predicted from fifth-dose kinetics and the actual first-dose trough concentration were very similar. Adverse effects ascribed to the transdermal system were minimal. CONCLUSIONS: These results suggest that steady-state serum concentrations are approached by the second dose of TTS(fentanyl) and that the kinetics are stable with repeated dosing. The apparent half-life following system removal is relatively long, indicating ongoing absorption from a subcutaneous depot.

Administration, Cutaneous↗
PubMed1993

Opioids.

The major clinical uses for opioids are to control pain, suppress cough, and to treat diarrhea. These drugs, however, have the potential for abuse. It is postulated that the significant mood-altering effects of opioids combined with their pharmacology, in which tolerance and physical and psychological dependence occur, account for their abuse liability. A classification of the groups of patients that commonly present with complications of opioid use is reviewed briefly before discussing the clinical pharmacology of the opioids and their acute and toxic effects.

Humans↗
PubMed1992

The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function.

Morphine-6-glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. Although accumulation of morphine-6-glucuronide in patients with renal insufficiency has been implicated in morphine toxicity, the contribution of the metabolite to morphine analgesia in patients with normal renal function has not been established. To evaluate this contribution, we repeatedly sampled blood and assessed effects during and after a loading infusion with morphine (mean duration, 168 minutes) in 14 patients with chronic pain, all of whom had normal serum creatinine levels. Plasma concentrations of morphine and morphine-6-glucuronide were assayed by use of high performance liquid chromatography with electrochemical detection. Patients were divided into three groups on the basis of the molar concentration ratio of morphine-6-glucuronide:morphine from the start of the infusion until 240 minutes later: Group 1 (n = 5) had a mean ratio greater than or equal to 0.7:1; group 2 (n = 4) had a mean ratio less than 0.7:1 but greater than or equal to 0.4:1; and group 3 (n = 5) had a mean ratio less than 0.4:1. Time-effect plots revealed that average and peak relief were greater in group 1 than group 2 and greater in group 2 than group 3. For all patients, mean morphine-6-glucuronide:morphine ratio throughout the study was significantly correlated with mean pain relief (r = 0.611, p less than 0.02). These data suggest that morphine-6-glucuronide contributes to morphine analgesia in patients with normal renal function. The role of the metabolite should be considered when morphine is used clinically.

Adult↗
PubMed1992

Central pain from cerebral abscess: thalamic syndrome in AIDS patients with toxoplasmosis.

We describe two patients with acquired immunodeficiency syndrome (AIDS) who developed classic thalamic syndrome (TS) due to Toxoplasma abscesses in the thalamic region. Treatment with amitriptyline provided substantial relief in both patients. Postmortem examination in one case revealed a lesion in the internal capsule and thalamic reticular nucleus. These observations indicate that (1) TS can result from an isolated lesion in the internal capsule and reticular nucleus of the thalamus, (2) cerebral abscess can cause classic TS, (3) central pain can be added to the many pain syndromes that afflict AIDS patients, and (4) an analgesic response to amitriptyline is possible in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The relationship of pain and symptom management to patient requests for physician-assisted suicide.

Uncontrolled pain and multiple adverse symptoms compel some cancer patients with advanced disease to consider suicide or to request physician-assisted suicide as their only option. Any debate that focuses on the options to terminate life in patients with advanced disease must give adequate consideration to the existing level of care for patients with these distressing symptoms. Numerous studies have described the educational, attitudinal, and legislative barriers that exist and prevent patients from receiving acceptable pain and symptom management during their illness. Lack of knowledge about the use of analgesics, coupled with the lack of sophistication in diagnosing and treating the psychological complications of cancer, are examples of such educational barriers. Existing continuing care programs, like hospice, that manage symptoms in patients with far-advanced disease are currently insufficient to meet the needs of this large population. We need to address the access to expert care of distressing symptoms including pain and psychological distress as well as the quality of life of this patient population before we can fully address the options for terminating life.

Euthanasia↗
PubMed1991

Chronic nausea and morphine-6-glucuronide.

Morphine-6-glucuronide is an active metabolite of morphine that has analgesic properties and is measurable in the plasma and cerebrospinal fluid of patients treated with this opioid. Decreased clearance of the compound has been observed in patients with renal insufficiency, and this has been associated with an increase in the ratio of morphine-6-glucuronide to morphine. Clinical effects from accumulation of morphine-6-glucuronide have not been described with the exception of case reports in which patients with renal failure were noted to develop opioid toxicity with high plasma levels of the metabolite and low levels of the parent drug. We describe a patient who experienced chronic nausea and an episode of confusion while treated with a small, stable dose of oral morphine in the setting of mild renal insufficiency. Relatively high levels of morphine-6-glucuronide were measured and all symptoms resolved promptly as the concentration of this metabolite declined. This case provides suggestive evidence that morphine-6-glucuronide can produce clinically significant effects in patients with mild renal insufficiency.

Adenocarcinoma↗
PubMed1991

Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations.

Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one-fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question.

Adult↗
PubMed1990

Character of terminal illness in the advanced cancer patient: pain and other symptoms during the last four weeks of life.

There is a great variability among advanced cancer patients in the experience of symptoms and their impact on life's activities. A subgroup of difficult patients particularly tax the clinical skills and compassion of practitioners. Although the need for information about these patients is evident, their characteristics have not been explored heretofore. We describe our experience with such patients, a group referred to the Supportive Care Program of the Pain Service at Memorial Sloan-Kettering Cancer Center. Prevalence of pain and other symptoms, patterns of opioid use and routes of drug administration, and the prevalence of suicidal ideation and requests for euthanasia are discussed.

Adult↗
PubMed1990

Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain.

To determine the relationship between changes in plasma methadone concentration and pharmacodynamic effects, plasma methadone profiles and pharmacodynamics (analgesia and sedation) were measured during and after the continuous infusion of methadone for 180 to 270 minutes in 15 patients with pain caused by cancer. An increase in plasma methadone concentration resulted in a rapid increase in pain relief or sedation. The estimates of values of 50% of maximum effect (Css50) for pain relief and sedation obtained with a pharmacokinetic-pharmacodynamic model varied tenfold to twentyfold among patients; the mean Css50 value for pain relief (0.359 +/- 0.158 [SD] micrograms/ml) was virtually the same as the mean Css50 value for sedation (0.336 +/- 0.205 [SD] micrograms/ml). Similarly, the mean gamma (slope function) for pain relief (4.4 +/- 3.8 [SD]) and sedation (5.8 +/- 5.4 [SD]) did not differ. Examination of hysteresis plots of data obtained during the infusion and for 4 to 5 hours after cessation of the infusion revealed a very rapid equilibration between plasma methadone values and the sites mediating pain relief. There was no indication of the development of tolerance to the pharmacodynamic effects of methadone during the study. This report describes a method for quantitating the pharmacokinetic-pharmacodynamic relationships of the desirable and undesirable effects of opioid analgesics.

Adult↗
PubMed1990

Neurologic pain syndromes in patients with cancer.

One third of cancer patients in active therapy and two thirds of patients with far-advanced disease have significant pain. A series of specific neurologic pain syndromes occur in this population and are unique to this pain population. Early diagnosis and treatment are critical to prevent irreversible neurologic damage and chronic neuropathic pain.

Humans↗
PubMed1989

Controversies in cancer pain. Medical perspectives.

The treatment of pain in the patient with cancer has focused attention on a series of controversial issues involving medical, social, and moral factors. The medical factors include a lack of knowledge on the part of health care professionals regarding the rational use of opioid drugs. This is coupled with real limitations in the general understanding of the mechanisms of pain and its treatment using pharmacologic, anesthetic, and neurosurgical approaches. Several pharmacologic controversies, including the choice of drug, route and method of administration, and tolerance development and risk of substance abuse, have emerged with the use of opioids on a chronic basis in the cancer population. The social and moral implications involve the issue of who will pay for high technology pain management approaches for patients either at home or in hospice care and the ethical considerations in managing pain with opioid drugs. Carefully designed studies to assess these factors, coupled with broad educational programs, will improve the care of cancer patients in pain and expand our understanding of these important issues.

Analgesics, Opioid↗
PubMed1989

Pain control in breast cancer. A panel discussion.

Pain can be a prominent finding in breast cancer patients. It may occur in the setting of the postmastectomy period, related to the disruption of normal neural pathways or the development of lymphedema. In advanced disease, the management of pain from nerve compression or bone metastases requires special approaches. In this panel discussion, the participating physicians will discuss these topics and provide an up-to-date approach to pain control in breast cancer patients.

Analgesics, Opioid↗
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

Management of pain in pancreatic cancer.

Potentially useful modalities of pain control in pancreatic cancer include antitumor therapy, pharmacotherapy, celiac plexus block, splanchnic nerve block, intercostal nerve block, and psychological intervention. These modalities are often used concurrently in treating the multiple dimensions that affect pain. Although thorough assessments are lacking, preliminary data suggest that antitumor chemotherapy and radiotherapy and celiac plexus block are especially useful modalities of pain control in these patients. The optimal time in the disease course for intervention with celiac plexus block is not known. Further studies are needed to clarify the nature of pain syndromes involved and the role of the various therapeutic modalities.

Analgesics↗