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

A transdermal fentanyl patch for the treatment of chronic cancer-related pain is available in four dosages (25, 50, 75, and 100 microg/hr). Fentanyl is released from a 72-hour reservoir by diffusion through a controlled-release membrane to the skin, through which it is absorbed into the microcirculation. The pharmacokinetics of fentanyl differ markedly as a function of the route of administration. Unlike intravenous administration, in which peak plasma levels occur within minutes and the plasma elimination half-life is 2 to 3 hours, after initial transdermal fentanyl patch application, peak levels occur within 14 hours and the elimination half-life exceeds 24 hours. When compared with oral morphine at doses effecting the same degree of pain relief, fewer gastrointestinal disturbances (nausea, vomiting, and constipation) and better alertness and sleep quality have been reported in two studies. The transdermal fentanyl patch is as effective as oral opioids in relieving cancer-related pain, with a safety and side effect profile equal to or better than that of oral opioids. The convenient, once-every-72 hours dosing regimen is easily adjusted to the individual's need for around-the-clock pain control, and provides stable and predictable therapeutic drug plasma concentrations. Patient acceptability is high and the cost is lower than other methods required to deliver parenteral opioids. The recent development of an oral transmucosal fentanyl citrate delivery system for the treatment of breakthrough pain will further expand the use of transdermal fentanyl patches for the treatment of chronic pain.
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PMID:Factors influencing quality of life in cancer patients: the role of transdermal fentanyl in the management of pain. 967 31

The aim of this study was to evaluate results of completion gastrectomy for severe postgastrectomy gastric stasis. A total of 51 women and 11 men underwent completion gastrectomy for gastric stasis between 1985 and 1996; follow-up was complete in 98% at 5.4 +/- 5 years. All patients had modified Visick scores preoperatively of grade III (37%) or IV (63%). Presentation included combinations of nausea, vomiting, postprandial pain, chronic abdominal pain, and chronic narcotic use. All had undergone prior vagotomy and had a median of four previous gastric operations. Hospital mortality was zero. Complications occurred in 25 patients (40%) and included the following: narcotic withdrawal syndrome (18%), ileus (10%), wound infection (5%), intestinal obstruction (2%), and anastomotic leak (5%). All or most symptoms were relieved in 43% (Visick grade I or II), but 57% of the patients remained in Visick grade III or IV. Nausea, vomiting, and postprandial pain were reduced from 93% to 50%, 79% to 30%, and 58% to 30%, respectively (P<0.05), but chronic pain, diarrhea, and dumping syndrome were not significantly affected. Univariate analysis revealed no preoperative characteristic to be predictive of good outcome. Logistic regression analysis suggested that the combination of nausea, need for total parenteral nutrition, and retained food in the stomach predicted a poor outcome (P<0.05). Completion gastrectomy is successful in 43% of patients. The combination of nausea, need for total parenteral nutrition, and retained food at endoscopy are negative prognostic factors.
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PMID:Near-total completion gastrectomy for severe postvagotomy gastric stasis: analysis of early and long-term results in 62 patients. 1045 19

A water-soluble phosphoramidate prodrug (L-758,298, compound I) of the potent and selective human Substance P receptor antagonist L-754, 030 (compound II) is under development as an i.v. drug for treatment of emesis, migraine, and chronic pain. Compound I undergoes hydrolysis readily to II under acidic conditions. In the studies reported herein, we investigated the stability of I in blood and hepatic subcellular fractions from rats, dogs, and humans as well as the conversion of I to II in rats and dogs after i.v. dosing. Compound I was converted to II rapidly in rat blood but was stable in dog and human blood. However, the conversion was rapid in liver microsomes prepared from dogs and humans. As expected from the results of in vitro studies, the in vivo conversion of I to II was rapid after i.v. dosing of I to rats and dogs. The relative extent of exposure of II after i.v. dosing of I was estimated by comparing the dose-adjusted area under the plasma concentration versus time curve values of II after i.v. dosing of I with those after i.v. dosing of II. In rats, the extent of exposure was estimated to be approximately 90 and approximately 100% at 1 and 8 mg/kg, respectively; in dogs, that was approximately 59% at 0.5 mg/kg. A nonproportional increase in the area under the concentration versus time curve value of II with dose was observed after i.v. administration of I in dogs from 0.5 to 32 mg/kg, suggesting that the elimination of II might have been saturated at higher doses.
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PMID:Substance P receptor antagonist I: conversion of phosphoramidate prodrug after i.v. administration to rats and dogs. 1053 23

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.
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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

Opioid-related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid-associated constipation in an intraindividually controlled manner. Twenty-two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention ('control period'). Then, oral naloxone was started and titrated individually between 3x3 to 3x12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, patients were observed for further 6 days ('naloxone period'). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the 'naloxone period' due to death, operation, systemic opioid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day 'naloxone' compared to the 'control period', the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the 'naloxone period' was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.
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PMID:Oral naloxone reverses opioid-associated constipation. 1060 78

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.
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PMID:Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. 1066 59

Two subtypes of cannabinoid receptors have been identified to date, the CB1 receptor, essentially located in the CNS, but also in peripheral tissues, and the CB2 receptor, found only at the periphery. The identification of delta9-tetrahydrocannabinol (delta9-THC) as the major active component of marijuana (Cannabis sativa), the recent emergence of potent synthetic ligands and the identification of anandamide and sn-2 arachidonylglycerol as putative endogenous ligands for cannabinoid receptors in the brain, have contributed to advancing cannabinoid pharmacology and approaching the neurobiological mechanisms involved in physiological and behavioral effects of cannabinoids. Most of the agonists exhibit nonselective affinity for CB1/CB2 receptors, and delta9-THC and anandamide probably act as partial agonists. Some recently synthesized molecules are highly selective for CB2 receptors, whereas selective agonists for the CB1 receptors are not yet available. A small number of antagonists exist that display a high selectivity for either CB1 or CB2 receptors. Cannabinomimetics produce complex pharmacological and behavioral effects that probably involve numerous neuronal substrates. Interactions with dopamine, acetylcholine, opiate, and GABAergic systems have been demonstrated in several brain structures. In animals, cannabinoid agonists such as delta9-THC, WIN 55,212-2, and CP 55,940 produce a characteristic combination of four symptoms, hypothermia, analgesia, hypoactivity, and catalepsy. They are reversed by the selective CB1 receptor antagonist, SR 141716, providing good evidence for the involvement of CB1-related mechanisms. Anandamide exhibits several differences, compared with other agonists. In particular, hypothermia, analgesia, and catalepsy induced by this endogenous ligand are not reversed by SR 141716. Cannabinoid-related processes seem also involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists may induce biphasic effects, for example, hyperactivity at low doses and severe motor deficits at larger doses. Intriguingly, although cannabis is widely used as recreational drug in humans, only a few studies revealed an appetitive potential of cannabimimetics in animals, and evidence for aversive effects of delta9-THC, WIN 55,212-2, and CP 55,940 is more readily obtained in a variety of tests. The selective blockade of CB1 receptors by SR 141716 impaired the perception of the appetitive value of positive reinforcers (food, cocaine, morphine) and reduced the motivation for sucrose, beer and alcohol consumption, indicating that positive incentive and/or motivational processes could be under a permissive control of CB1-related mechanisms. There is little evidence that cannabinoid systems are activated under basal conditions. However, by using SR 141716 as a tool, a tonic involvement of a CB1-mediated cannabinoid link has been demonstrated, notably in animals suffering from chronic pain, faced with anxiogenic stimuli or highly motivational reinforcers. Some effects of SR 141716 also suggest that CB1-related mechanisms exert a tonic control on cognitive processes. Extensive basic research is still needed to elucidate the roles of cannabinoid systems, both in the brain and at the periphery, in normal physiology and in diseases. Additional compounds, such as selective CB1 receptor agonists, ligands that do not cross the blood brain barrier, drugs interfering with synthesis, degradation or uptake of endogenous ligand(s) of CB receptors, are especially needed to understand when and how cannabinoid systems are activated. In turn, new therapeutic strategies would likely to emerge.
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PMID:Behavioral effects of cannabinoid agents in animals. 1080 37

It is well-known that morphine is the king of analgesics. It is widely used, and administered in various ways for the control of acute and chronic pain states. There are, however, certain types of pain and certain clinical conditions in which morphine cannot be used due to the risk of possible complications. These are usually pain states associated with intracranial hypertension, the presence of serious respiratory problems, the onset of major opioid tolerance, persistent vomiting, and so on. The search for "alternative analgesics" has been in progress for a decade, alternatives that could be used alone or in combination for spinal administration in the treatment of complex chronic pain states and with a low incidence of secondary effects. Today, research is carefully assessing the clinical effectiveness and the side effects of a series of drugs for spinal administration, that is, epidural or intrathecal, such as the new narcotics, alpha-2 agonists, central muscle relaxants, calcitonin, and local anesthetics. In this alternative analgesic category we have to mention the somatotrophin-release inhibiting factor (SRIF), which is an ubiquitous native hormone with widespread, predominantly inhibitory actions, and octreotide, its synthetic analogue. In this article we review the literature on the natural drug and its synthetic analogue, paying particular attention to the problems connected with intraspinal administration and analgesic properties.
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PMID:The epidural and intrathecal administration of somatotrophin-release inhibiting factor: native and synthetic analogues. 1099 19

Traditionally, acupuncture is embedded in naturalistic theories that are compatible with Confucianism and Taoism. Such ideas as yin-yang, qi, dampness, and wind represent East Asian conceptual frameworks that emphasize the reliability of ordinary, human sensory awareness. Many physicians who practice acupuncture reject such prescientific notions. Numerous randomized, controlled trials and more than 25 systematic reviews and meta-analyses have evaluated the clinical efficacy of acupuncture. Evidence from these trials indicates that acupuncture is effective for emesis developing after surgery or chemotherapy in adults and for nausea associated with pregnancy. Good evidence exists that acupuncture is also effective for relieving dental pain. For such conditions as chronic pain, back pain, and headache, the data are equivocal or contradictory. Clinical research on acupuncture poses unique methodologic challenges. Properly performed acupuncture seems to be a safe procedure. Basic-science research provides evidence that begins to offer plausible mechanisms for the presumed physiologic effects of acupuncture. Multiple research approaches have shown that acupuncture activates endogenous opioid mechanisms. Recent data, obtained by using functional magnetic resonance imaging, suggest that acupuncture has regionally specific, quantifiable effects on relevant brain structures. Acupuncture may stimulate gene expression of neuropeptides. The training and provision of acupuncture care in the United States are rapidly expanding.
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PMID:Acupuncture: theory, efficacy, and practice. 1237 83

The three-step analgesic ladder, originally proposed for cancer pain relief by the World Health Organization (WHO), is now widely employed for all types of pain, including the chronic pain of musculoskeletal disease. Tramadol, an analgesic with weak opioid receptor affinity and possessing monoaminergic activity, has proved suitable for use at Step 2 of the WHO ladder. Owing to its pharmacological properties, tramadol is more appropriate than NSAIDs for patients suffering from gastrointestinal and renal problems. Importantly, the analgesic potency of tramadol is greater than that of NSAIDs and of other weak opioids (codeine, dextropropoxyphene). It also causes fewer opioid-type adverse effects, e.g. nausea, drowsiness, vomiting, dry mouth and constipation. In chronic musculoskeletal pain it is recommended that tramadol should be given by mouth and by the clock; the initial dose should be titrated upward gradually to reach the individual level required for suitable pain control. This dosage strategy will also minimise the usual opioid-type adverse effects encountered with tramadol. Four recent publications are reviewed to illustrate the efficacy of tramadol, alone or in conjunction with an NSAID, in the management of low back pain, osteoarthritis pain and breakthrough pain.
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PMID:Tramadol in musculoskeletal pain--a survey. 1195 1


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