Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tramadol is a centrally acting analgesic that has been shown to be effective in a variety of acute and chronic pain states. Unlike other centrally acting analgesics, it exerts a dual action by binding to the opioid receptor site in the central nervous system and by weakly inhibiting the reuptake of biogenic amines. Tramadol is rapidly and almost completely absorbed, with an onset of action occurring within 1 hour of oral administration. The recommended dosage is 50 to 100 mg every 4 to 6 hours; however, regular administration is an alternative, particularly for chronic pain states such as osteoarthritis, where the use of the recently developed sustained release formulation may represent an important advantage. Published studies specifically evaluating the use of tramadol in this disease support its effectiveness. Nausea, drowsiness, constipation, dizziness, and sweating have been reported in association with tramadol use. Nausea occurs early in the course of administration, and may be reduced by slowly titrating the dose of tramadol against response. Tramadol would appear to be particularly useful in the elderly population affected by osteoarthritis because, unlike nonsteroidal anti-inflammatory drugs, it does not aggravate hypertension or congestive heart failure, nor does it have the potential to cause peptic ulcer disease. Compared with narcotics, tramadol does not induce significant respiratory depression, constipation, or have significant abuse potential.
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PMID:Pharmacology and clinical experience with tramadol in osteoarthritis. 891 98

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.
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PMID:Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine. 980 Jan 45

As has been demonstrated in binding studies the two opioids tilidine (CAS 27107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site. Therefore it is of interest to evaluate whether such a difference in opioid affinity is also seen in the pharmacological effects of clinically relevant doses in man. Following institutional approval by the local ethical committee and informed consent, 12 volunteers received oral doses of tramadol (100 mg), tilidine/naloxone (100 mg) and placebo, respectively, in a randomized, double-blind cross-over design. In order to determine the degree of constipation, oral-caecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripheral and central mediated effects were compared to placebo. Tramadol as well as tilidine/naloxone induced a significant (p < 0.05) prolongation of oral-caecal transit when compared to placebo. However, prolongation of oral-caecal transit was significantly longer in the tilidine/naloxone (p < 0.05) than in the tramadol group. Compared to tramadol, the pronounced constipating effect of tilidine/naloxone is likely to be due to the 10 fold higher affinity of that drug to the peripheral opioid receptor sites in the intestinal tract, which are responsible for normal propulsion. Such difference in binding is underlined by a central effect, the pupillary light reflex response. The amount of constriction of the iris to light was reduced after both opioids. Again, tilidine/naloxone significantly reduced (p < 0.001) the pupillary light reflex when compared to tramadol. Other side effects such as tiredness, nausea, emesis and dry mouth were more often reported after tilidine/naloxone than after tramadol (40% versus 15%; p < 0.05). Vertigo and perspiration were more often reported after tramadol than after after tilidine/naloxone (58% and 78% versus 8%; p < 0.01). All these data support the findings that while tramadol is considered an opioid, it does not mediate its main clinical relevant properties via binding at the opioid receptor. More likely, due to its monoaminergic reuptake mechanism, to a lesser extent opioid-like effects are induced.
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PMID:Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex. 1068 12

It is well accepted that long-term administration of opioids results in a dose-related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid-related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro-cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro-cecal transit and inhibition of the pupillary light reflex.
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PMID:Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. 1121 27

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

A variety of evidence suggests that endogenous opioid peptides play a role in the short-term control of eating. More recently, opioid receptor antagonists like naltrexone have been approved as a treatment for alcohol dependence. Here we review the evidence for a role of opioid peptides in both normal and abnormal eating and drinking behaviours and in particular try to identify the nature of the role of opioids in these behaviours. Particular attention is paid to the idea that opioid reward processes may be involved both in the short-term control of eating and hedonic aspects of alcohol consumption, and parallels are drawn between the effects of opiate antagonists on food pleasantness and the experience of drinking alcohol. The review also explores the extent to which data from studies using opiate antagonists and agonists provide evidence for a direct role of endogenous opioids in the control of ingestive behaviour, or alternatively whether these data may be better explained through non-specific effects such as the nausea commonly reported following administration of opiate antagonists. The review concludes that the present data suggests a single opioid mechanism is unlikely to explain all aspects of ingestive behaviour, but also concludes that opioid-mediated reward mechanisms play an important control in hedonic aspects of ingestion. The review also highlights the need for further empirical work in order to elucidate further the role of opioid peptides in human ingestive behaviour.
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PMID:Opioid peptides and the control of human ingestive behaviour. 1247 44

Dihydroetorphine (DHE) is one of the strongest analgesic opioid alkaloids known; it is 1000 to 12000 times more potent than morphine. Several in vitro and in vivo studies have shown that DHE is a selective mu-opioid receptor (OP(3)) agonist that also binds and activates all human recombinant mu-, delta-, and kappa-opioid receptors (OP(3), OP(1), and OP(2)). The onset of the analgesic effect of DHE in rodents is rapid, 5 to 15 min after parenteral administration; the duration of action is short, the analgesic effect disappears within 120 min after administration. By oral administration much higher doses of DHE are required to produce analgesic effects. These characteristics are accounted for by the pharmacokinetic properties of DHE in the rat, namely, by rapid distribution of DHE from the injection site to the brain and rapid metabolism by glucuronidation in the gut and liver followed by elimination into the bile. Continuous infusion and repeated administration of DHE lead to the development of tolerance to analgesia, physical dependence, and a rewarding effect in normal rats but not in animals with formalin-induced inflammation. Although formalin-induced inflammation is only one type of pain stimulus, these findings suggest that DHE addiction would be observed only in the case of pain-free conditions. Clinical reports in China show that sublingual doses of DHE, 20 to 180 microg, produce a potent analgesic effect with only mild side effects, including dizziness, somnolence, nausea, vomiting, constipation, and shortness of breath. To improve the short-lasting effect following sublingual administration, transdermal delivery of DHE via a patch has been investigated. The patch formulation of DHE produces continuous analgesic effect with minimal physical dependence and rewarding effect in rats suffering from chronic pain. This patch formulation, which is very suitable for DHE, may be viable for the treatment of severe pain and is likely to improve patients' quality of life.
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PMID:Dihydroetorphine: a potent analgesic: pharmacology, toxicology, pharmacokinetics, and clinical effects. 1248 Nov 94

Cough is an important defensive reflex of the airway and a common symptom of respiratory disease. After an upper respiratory tract virus infection, cough is transient, but is more persistent with conditions such as asthma, rhinosinusitis, gastroesophageal reflux, chronic obstructive pulmonary disease (COPD) and lung cancer. Treatment directed at these conditions may improve cough, but there remains a need to control cough directly. The most effective antitussives are opioids, such as morphine, codeine or pholcodeine, but they produce side effects including drowsiness, nausea, constipation and physical dependence. Opioids such as k- and d-opioid receptor agonists, non-opioids such as nociceptin, neurokinin and bradykinin receptor antagonists, vanilloid receptor VR(1) antagonists, blockers of sodium-dependent channels, and maxi-K calcium-dependent channel activators of afferent nerves may all represent novel antitussives and this needs to be confirmed in clinical trials.
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PMID:Current and future prospects for drugs to suppress cough. 1291 74

Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.
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PMID:Pharmacotherapy of alcohol dependence: a review of the clinical data. 1518 19

Perioperative management of geriatric patients is becoming an important component in anaesthetic practice in the 21st century. This phenomenon is due to the fact that people aged 65 and over are the segment with the fastest growing population. Thus, it is estimated that by the year 2025 20 % of the population in the western hemisphere will be > 65 years of age. Currently, elderly patients comprise one-third of all operations, and one out of two patients older than 65 years of age will undergo an operation in their lifetime. The dramatic change in demographics of surgical patients will have a tremendous impact on the use of anaesthetics. Older patients facing surgery can generally be expected to be a more complex case than their younger counterparts. They have more systemic diseases (e. g. cardiac, pulmonary, endocrine), and usually these diseases have advanced to more serious stages. These patients may suffer disability, both physical and mental, and may show differences in the pharmacokinetic as well as the pharmacodynamic of compounds such as opioids. While neuronal numbers, dendrites and synapses decline with age and the ventricular volume triples, cerebral circulation is similar to young adults, although there is a reduction in cerebral blood flow (CBF). This is because of the lower unit weight, lower CBF and CMRO (2), which are tightly coupled in aging where autoregulation is preserved. However, because of a decline in dopaminergic, serotonergic, cholinergic and GABAergic transmitters, anticholinergic compounds (atropine, scopolamine) as well as some anaesthetics such as ketamine, benzodiazepines or even propofol may produce delirium and/or an increase in efficacy when given together with opioids. Therefore it is mandatory to consider a pharmacologic interaction with a potentiation and/or an addition in effects of other drugs when judging the net action of opioids in the elderly. Physicians and nurses treating geriatric patients tend to have an unfounded level of fear of complications associated with treating perioperative pain. Although it is known that inadequate analgesia may delay recovery, the treatment of perioperative pain in the geriatric patient remains inadequate, even relative to younger patients. It is well established that there is increased responsiveness to the effects of opioids in the elderly. This may result in an increased risk of respiratory depression, while especially the elderly female patient demonstrates an increase in the duration of effects, but the risk of nausea is not augmented. Increased sensitivity of older patients to systemic opioids mostly involves pharmacokinetic factors such as a higher proportion of unbound and active substances as well as changes in drug redistribution. Because of a 40 % reduction in stroke volume in the elderly, there is a protracted redistribution of opioids to the liver. This results in a prolonged metabolisation, a lesser inactivation over time followed by an increase in duration of effects, mainly impairment of respiration. To a much lesser extent, pharmacodynamic factors with an increased response at opioid receptor sites have to be considered. Although the mechanisms causing differences of opioid action in the elderly may be complex, the clinical implications are not. They include slow titration of opioids to allow for long circulation times, lower total doses because of increased sensitivity, and anticipation of a longer duration of action because of reduced clearance. Since elderly patients present multimorbidity, therapy of chronic pain has to be considered in the light of multidrug intake, which, due to interaction, results in marked side-effects, and a prolonged duration of action. Those opioids should be used which, due to their pharmacokinetic properties, have a reduced volume of distribution, present a low plasma protein binding and finally result in the formation of no pharmacologically active metabolites.
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PMID:[Use of opioids in the elderly -- pharmacokinetic and pharmacodynamic considerations]. 1533 29


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