Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A once-daily dose of PF-402 60 mg and twice-daily doses of sustained-release morphine sulfate tablets (MSC) 30 mg were repeatedly administered in cancer patients in a cross-over design. Their plasma concentrations were measured, and the pharmacokinetics of PF-402 and MSC were compared. A total of 7 subjects in the study were taking commercially sold MSC 60 mg daily (30 mg twice-daily) prior to the study and had "mild" or "no" pain at the start of the study. Plasma morphine concentrations of PF-402 were longer-lasting and showed smaller fluctuations than those of MSC. Repeated administration of the same daily doses of PF-402 and MSC produced similar plasma concentrations for periods of 24 hr and 12 hr. PF-402 administration produced a Tmax of 7.4 hr, and an MRT of 9.8 hr, all longer than those with MSC. Moreover, no significant difference was observed in AUC between PF-402 and MSC. These results indicate that the sustained-release characteristics of PF-402 are superior to those of MSC, and that the two drugs have a similar absorption pattern. Adverse drug reactions (ADRs) were observed in all 7 subjects and consisted of 6 incidences of constipation, 3 incidences of nausea, 2 incidences of itching, and 1 incidence each of vomiting and somnolence. Study drug administration was not discontinued in any case due to ADRs, and no symptoms indicating physical or psychic drug dependence were observed. No abnormal laboratory values related to study drug administration were observed. The above results indicate that once-daily administration of PF-402 is sufficient to maintain plasma concentrations obtained with twice-daily administration of MSC. As the safety of PF-402 is confirmed, the drug is considered to be a useful sustained release formulation in the treatment of cancer pain.
 ...
PMID:[Pharmacokinetics of PF-402, sustained-release morphine capsule, in cancer patients with pain]. 972 Mar 27

Fentanyl has been incorporated into a transdermal therapeutic system (TTS) containing a rate-limiting membrane that provides constant release of the opioid. TTS fentanyl provides continuous opioid delivery for up to 72 hr without the need for special equipment. After Institutional Review Board approval, 53 patients with cancer pain requiring 45 mg or more of oral morphine daily were admitted into an open-label, prospective, multicenter evaluation of TTS fentanyl for the relief of pain. After a 1-week stabilization on oral morphine, patients were transferred from morphine to an appropriate dose of TTS-fentanyl (25, 50, 75, or 100 micrograms/hr) administered as a transdermal patch every 3 days. TTS fentanyl was titrated to pain relief, and patients were followed up for as long as 3 months. Pain relief and the side effects of the medications were assessed daily. Twenty-six men and 27 women with a mean (+/- SD) age of 61 (+/- 12) years entered the study; 23 patients completed the full 84-day study. The mean duration of TTS fentanyl use was 58 +/- 32 days. The mean (+/- SEM) daily morphine dose during the last 2 days of stabilization was 189 (+/- 20) mg, and the mean initial fentanyl patch dose was 58 (+/- 6) micrograms/hr. The mean daily morphine dose taken "as needed" for breakthrough pain at study completion was 35 mg. The mean final fentanyl dosage at study completion was 169 (+/- 29) micrograms/hr. Pain relief was rated as good or excellent by 82% of patients during the treatment period. When asked to compare pain relief during the first month of TTS-fentanyl use to that provided by their last analgesic before study entry, 63% preferred TTS fentanyl. Side effects considered related to the fentanyl patch were nausea (13%), vomiting (8%), skin rash (8%), and drowsiness (4%). Thirty percent of patients reported adverse experiences related to the fentanyl patch, and 17% had to be discontinued from the study. We conclude that TTS fentanyl administered every 3 days for the treatment of cancer pain is effective, safe, and well tolerated by most patients.
 ...
PMID:A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain. 973 1

Eighteen inpatients receiving morphine for cancer pain in a palliative care unit were recruited to a study employing a range of neuropsychological tests to assess cognitive function. The tests employed were National Adult Reading Test, Williams Delayed Recall Test, Immediate Memory for Digits, Trailing Making Test, and the Digit Symbol Substitution Test. These data were correlated with biochemical tests of renal and hepatic function, morphine dose, route of administration, plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations. Despite having no clinical evidence of impairment of cognitive function, the level of current intellectual functioning (Symbol Digit Substitution Test) was on average two standard deviations below normal. Immediate memory appeared to be well preserved, but Delayed Recall and Trailing Making Test scores were significantly above normal. There was no significant correlation between morphine dose, or plasma morphine and M3G and M6G concentrations, and the neuropsychological test results, although a weak correlation was found between plasma morphine concentration and digits forward (r = -0.47, p < 0.05) and Digit Symbol Substitution scores (r = -0.46, p < 0.05). Seven patients had some degree of nausea or vomiting, ascribed as an opioid adverse effect, and had higher serum creatinine concentrations, worse neuropsychological performance, and significantly higher plasma M3G concentrations (p < 0.05). These data provide some evidence to suggest that cognitive functioning in patients with advanced cancer receiving morphine may be significantly impaired despite apparent clinical normality. From these data it is not possible to determine what relative causal contribution the disease and the drug made to these observations, although renal function, plasma morphine, and M3G concentrations may be important. Future research should address a broad range of neuropsychological testing to assist in the modification of practices aimed at enhancement of quality of life, such as opioid substitution or rotation.
 ...
PMID:Neuropsychological and pharmacokinetic assessment of hospice inpatients receiving morphine. 973 2

Two separate trials compared controlled-release (CR) oral oxycodone (administered every 12 hours) with immediate-release (IR) oxycodone (4 times a day) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation. In one study, 48 patients with cancer pain were randomized to open-label titration with either CR or IR oxycodone (maximum dose, 400 mg/day) for a period of up to 21 days. In a study of similar design, 57 patients with low back pain were titrated with either CR or IR oxycodone (maximum dose, 80 mg/day) for a period of up to 10 days. The majority of patients in both studies were converted to oxycodone from other opioid analgesics. Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control, the time to achieve stable pain control, and the degree of pain control achieved. Among cancer patients, 85% achieved stable analgesia, 92% with the CR formulation and 79% with the IR formulation. Among noncancer patients, 91% achieved stable pain control, 87% with the CR formulation and 96% with the IR formulation. The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids: nausea, vomiting, constipation, somnolence, dizziness, and pruritus. Nausea and vomiting were the most frequently cited reasons for treatment discontinuations. These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic, moderate to severe pain.
 ...
PMID:Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control? 1053 67

Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability. The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials. In general, TTS fentanyl produces the same adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients. Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.
 ...
PMID:Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. 1066 59

The occurrence of undesirable side effects due to opioids (delirium, confusion, myoclonus, nausea, emesis) is one of the major complications in the management of pain, especially in chronic cancer pain states. Methadone, as an alternative to morphine, has been proposed in the control of opioid-induced toxicity. Methadone is a synthetic opioid, with mu and delta receptor activity, associated with the capacity to inhibit N-methyl-D-aspartate receptors. Questions have arisen concerning its equianalgesic ratio since its rediscovery over the past few years and are certainly related to its receptor interactions. Aspects of its pharmacology, indications, and switching modalities are discussed here. Opioid rotation is a new tool in the management of cancer pain, deserving more attention.
 ...
PMID:Opioid switch to oral methadone in cancer pain. 1088 15

In the medical environment, information disclosure to patients and respect of autonomy have spread rapidly. Today, many terminally-ill cancer patients wish to spend as much time at home as possible. In such situations the patient who has been informed that curative treatments are no longer expected to be beneficial can now hope to receive home care and visiting care from hospice/palliative care services. The essential concepts of hospice/palliative care are symptom management, communication, family care and a multidisciplinary approach. These concepts are also important in the outpatient department. In particular, medical staff need to understand and utilize management strategies for common symptoms from which terminally-ill cancer patients suffer (ex. cancer pain, anorexia/fatigue, dyspnea, nausea/vomiting, constipation, hypercalcemia and psychological symptoms). They also need to know how to use continuous subcutaneous infusion for symptom management in the patients last few days. The present paper explains the clinical practices of hospice/palliative care in the outpatient department. Also discussed is support of individual lives so that maximum QOL is provided for patients kept at home.
 ...
PMID:[Hospice and palliative care in the outpatient department]. 1105 18

Patients with moderate to severe cancer pain and insufficient pain relief from nonopioid analgesics were treated with slow-release tramadol for initial dose finding and as a long-term treatment. Immediate-release tramadol was provided for the treatment of breakthrough pain and a standard nonopioid analgesic (1000 mg naproxen daily) was given as suggested for step 2 of the WHO analgesic ladder. Ninety of 146 patients (62%) completed the 6-week trial period. Drop-outs were due to adverse events (20%), inadequate pain relief (9%), or both (2.5%), death due to the underlying disease (4%), low patient compliance (2%) or other reasons. Average and maximal pain intensity decreased from day 1 to day 4. The number of patients with good and complete pain relief increased from 43% after week 1 to 71% after week 6 with maximum daily doses of tramadol up to 650 mg. However, 70% of the patients still needed less than 400 mg tramadol per day in week 6. Most patients (86%) experienced adverse events during the study period. Some common side effects of opioids, such as fatigue, dizziness, and constipation, decreased in frequency over the 6 weeks. The frequency of other adverse events such as nausea, vomiting and sweating did not change. Slow-release tramadol provided fast and efficient pain relief in almost two-thirds of patients both during initial dose finding and during long-term treatment, improving treatment options in step 2 of the WHO analgesic ladder.
 ...
PMID:Slow-release tramadol for treatment of chronic malignant pain--an open multicenter trial. 1114 43

Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.
 ...
PMID:Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. 1151 84

An appropriate medical treatment and care during the final phase can make a calm and peaceful dying possible. Aim of this review is to show the symptoms and treatment of patients with a far advanced disease in the last three days of life and to standardise terms used to describe the last period of life. There are definitions worked out for rehabilitation in palliative medicine, for the terminal phase and the final phase. We know that the final phase is a very dynamic process with sometimes a lot of symptoms and problems. Reasons for an "active" medical treatment in the last three days of life are, that new symptoms may occur or previous good controlled symptoms like pain, dyspnoea, vomiting, fear etc. can reappear, which could make a change or finishing of treatment necessary. The aim of palliative medicine is to improve the quality of life especially in the terminal phase. If we focus on the terminal phase most patients - even with cancer pain - can die peacefully and under good symptom control. The dynamic situation in the final phase and the ethical decisions force us to draw our attention to these patients and stay with them until they die. Humanity is besides a funded medical care essential in accompanying the patient in his last days of life. Until now there are not many clinical studies which can help us to find guidelines for the treatment in the last three days of live.
 ...
PMID:[Symptom control in the terminal phase]. 1181 Mar 78


<< Previous 1 2 3 4 5 6 7 8 9 Next >>