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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patient controlled analgesia (PCA) is a drug delivery system aimed to control acute pain using negative feedback technology in a closed loop system in which the patient plays an active role. It overcomes the inadequacies of traditional analgesic protocols due to marked differences in pharmacokinetic and dynamy of analgesis between patients. Moreover, doctors and nurses frequently underprescribe opioids in patients with severe pain for fear of dangerous side-effects. A safe and effective delivery of these drugs on patient demand can be achieved using various delivery systems, modes and dosing parameters. Most devices provide both demand dosing, where a constant predetermined dose is self administered, and constant rate infusion plus demand dosing, where the minimum administration rate is determined by the doctor, but can be supplemented by patient demand. Morphine sulphate remains the drug most commonly used in PCA therapy, but meperidine hydrochloride, alfentanil, nalbuphine and buprenorphine are also sometimes administered. The doctor determines the incremental dose per demand, the lockout interval, and the maximum dose per time unit, possibly also the loading dose and the minimum dose rate when a continuous flow is used. PCA provides improved analgesia, which is immediate and independent of nurse availability. This technique decreases opioid requirements, and the required total amounts are lowered. PCA gives patients both behavioural and decisional control. They can titrate the analgesic dose in such a way as to balance pain relief with the degree of side-effects, the patient is willing to tolerate. Patients often choose less than the available total dose of analgesic. The risks consists in the usual opioid side-effects, mainly respiratory depression. These may be due to mechanical problems, machine failure, or user incidents (misprogramming, or miscalculation of doses). Standards help to ensure consistent care and avoid errors that can occur even with handwritten orders. The principles of demand analgesia are now being investigated using other agents, such as local anaesthetics, and other routes of administration, mainly epidural injection. In most patients, even in children, PCA can replace intramuscular injections, which are the standard route for opioid administration. Today PCA and spinal opioids are the two main methods of analgesia for postoperative pain management.
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PMID:[Patient-controlled analgesia]. 185 55

The antinociceptive activities of intraperitoneal (i.p.) ketamine in combination with subcutaneous (s.c.) morphine or fentanyl were studied using the mouse tail flick test, an acute pain model. Morphine and fentanyl exhibited dose-dependent effects, with respective ED50s (95% confidence limits) of 1.3 (1.2-1.4) mg/kg and 6.8 (6.2-7.4) mcg/kg. Ketamine (1, 5, 10 and 20 mg/kg) showed relatively weak antinociceptive effects with no apparent dose-response relationship. In mice pretreated with i.p. ketamine 0.1 mg/kg (no effect on the tail flick reaction time) and 1 mg/kg (antinociceptive), the effects of s.c. morphine (1.5 mg/kg) were enhanced but this was significant only at the higher ketamine dose, whereas fentanyl (6 mcg/kg, s.c.) antinociception was significantly enhanced in both pretreatment groups. The antinociceptive effects of i.p. ketamine (10 and 20 mg/kg) were also studied in mice pretreated with s.c. morphine 0.1 and 0.5 mg/kg or fentanyl 0.5 and 2.5 mcg/kg. Morphine dose-dependently enhanced ketamine antinociception, being significant only at the higher pretreatment dose level. Fentanyl (0.5 mcg/kg) pretreatment significantly enhanced ketamine (20 mg/kg) activity, with no apparent effect on ketamine 10 mg/kg. At 2.5 mcg/kg, fentanyl pretreatment significantly enhanced ketamine antinociception. These results suggest that ketamine may not be as effective in acute pain as opioids are, and that after systemic administration, the net effect of ketamine-opioid combination is a simple additive one.
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PMID:Antinociceptive effects of ketamine-opioid combinations in the mouse tail flick test. 804 51

Neuropathic pains have often been classified as opioid resistant. Here, the ability of systemic (i.p.), intracerebroventricular (i.c.v.) and intrathecal (i.th.) morphine to inhibit mechanical allodynia were studied in a nerve ligation (L5, L6 nerve roots) model of neuropathic pain in rats. Morphine administered i.p. or i.c.v. produced dose-dependent antiallodynia which was readily antagonized by naloxone (5 mg kg-1, i.p. at -10 min). In contrast, i.th. morphine at doses up to 100 micrograms was without effect. These data suggest that the failure of i.th. morphine to produce antiallodynic effects may be due, in part, to the lack of available functional spinal opioid mu-receptors which may occur following nerve injury. In contrast, the antiallodynic actions of i.p. or i.c.v. morphine appear to depend on supraspinal activation of opioid (mu?) receptors and subsequent activation of descending modulatory systems. The inconsistent data seen clinically with morphine in neuropathic pains may be related to the lack of supraspinal/spinal synergy that is normally associated with morphine efficacy in conditions of acute pain.
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PMID:Characterization of the antiallodynic efficacy of morphine in a model of neuropathic pain in rats. 858 Apr 22

Eight patients undergoing major maxillary surgery were given sustained-release morphine (100 mg MST Continus) rectally, immediately after induction of general anaesthesia. Blood samples for assay were taken just prior to morphine administration, together with a further 11 samples over the following 24 h. Assay of the plasma for morphine, morphine-3-glucuronide and morphine-6-glucuronide was carried out using a validated high-performance liquid chromatography technique. Morphine Tmax ranged from 3 h to 12 h (median 6 h), Cmax 8.0-40.0 ng/ml and AUC0-24 90.1-429.7 ng/h/ml in subjects offering blood samples over the 24-h period. Likewise, morphine-3-glucuronide Tmax ranged from 3 h to 24 h (median 9 h), Cmax 153-370 ng/ml and AUC0-24 2776-4390 ng/h/ml. Morphine-6-glucuronide Tmax ranged from 8 h to 12 h (median 10 h), Cmax 24-59 ng/ml and AUC0-24 137-803 ng/h/ml. Morphine and morphine metabolite AUC0-24 ratios were calculated, but they did not correlate with analgesic needs. The AUC0-24 ratios were similar to those following oral and rectal dosing in other studies involving cancer patients. The wide variation of individual morphine and metabolite plasma levels, and their AUC ratios indicates considerable interpatient variability in the absorption and metabolism of rectal sustained-release morphine. This large interpatient variation may indicate that it is not suitable for acute pain, because analgesic requirements change much more rapidly than in the chronic pain situation where individual patient titration can take place.
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PMID:Rectal controlled-release morphine: plasma levels of morphine and its metabolites following the rectal administration of MST Continus 100 mg. 880 41

Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long-term treatment of severe pain. Morphine is a member of the morphinan-framed alkaloids, which are present in the poppy plant. The drug is soluble in water, but its solubility in lipids is poor. In man, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to compete for opioid receptor binding. The analgesic properties of M6G were recognised in the early 1970s and more recent work suggests that M6G might significantly contribute to the opioid analgesia after administration of morphine. The analgesic potency of M6G after intracerebroventricular (ICV) or intrathecal (IT) administration in rats is from 45-800 timer greater than that of morphine, depending on the animal species and the experimental antinociceptive test used. Furthermore, the development of a sensitive high-performance liquid chromatography (HPLC) assay for the quantitative determination of morphine, M6G and M3G has revealed that M6G and M3G were present in abundance after chronic oral morphine administration and that the area under the plasma concentration-time curve exceeded that of morphine. M3G has been found to antagonise morphine and M6G induced analgesia and ventilatory depression in the rat, which has led to the hypothesis that M3G may influence the development of morphine tolerance. M3G exhibits no analgesic effect after ICV or IT administration. Some studies do, however, indicate that M3G may cause non-opioid mediated hyperalgesia/allodynia and convulsions after IT administration in rats. These observations led to the hypothesis that M3G might be responsible for side-effects, hyperalgesia/allodynia and myoclonus seen after high-dose morphine treatment.
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PMID:Morphine metabolites. 906 Oct 94

Inadequate pain control after surgery is associated with adverse outcomes in elderly patients; for this reason, effective analgesia is an essential component of postoperative care in this patient group. However, postoperative pain management is challenging in the elderly because of concomitant disease states and physiological factors that can affect the pharmacodynamic and pharmacokinetic properties of analgesic drugs. Patient-controlled analgesia (PCA) offers advantages over traditional intramuscular analgesia in this setting, because it provides the opportunity to tailor therapy to the individual, as opposed to the average, patient. Morphine is the most widely used, and presently the most suitable, drug for use in PCA in the elderly. Studies have indicated that, after acute pain has been brought under control, PCA should be initiated at a dose of 1 or 1.5mg per dose, with a lockout period of 5 to 7 min. Continuous background infusions of opioids are contraindicated. Education of patients and healthcare professionals alike is necessary to optimise the utility of PCA in older patients. In addition, every effort should be made to avoid the development of postoperative confusion, as this is associated with an increased risk of inefficient pain relief and its deleterious consequences. In summary, close monitoring and evaluation of the patient throughout the peri-operative periods is required to ensure the appropriate and successful use of PCA in elderly patients.
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PMID:Practical guidelines on the postoperative use of patient-controlled analgesia in the elderly. 967 5

We studied spinal analgesic and antiallodynic effects of endomorphin-1 and endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2 (2.5, 5, 10 microg i.t.) increased the tail-flick latency and, to the lesser extent, the paw pressure latency. The range of potencies in both those models of acute pain was as follows: DAMGO > morphine = endomorphin-1 > endomorphin-2. In a model of inflammatory pain, the number of formalin-induced flinching episodes was decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pain model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.) dose-dependently antagonized allodynia. Those effects of endomorphins were antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In conclusion, our results show a strong analgesic action of endomorphins at the spinal cord level. The most interesting finding is a strong, stronger than in the case of morphine, antiallodynic effect of endomorphins in rats subjected to sciatic nerve crushing, which suggests a possible use of these compounds in a very difficult therapy of neuropathic pain.
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PMID:Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic pain in rats. 1007 92

Opioids are the most commonly used medication for patients with acute pain. Morphine is the prototype with which all other opioids are compared. Synthetic and semisynthetic derivatives of morphine have unique properties, allowing for the use of a larger selection of medication. An understanding of the mechanisms of action, adverse effects, and routes of administration of the various potent opioids is important for good postoperative pain management.
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PMID:Analgesic agents for the postoperative period. Opioids. 1035 54

We have previously shown that methadone maintenance patients are hyperalgesic. Very little is known about the antinociceptive effects of additional opioids in these patients. This study (1) compared the intensity and duration of antinociceptive responses, at two pseudo-steady-state plasma morphine concentrations (C(SS1) and C(SS2)), between four patients on stable, once daily, doses of methadone and four matched control subjects; and (2) determined, in methadone patients, whether the antinociceptive effects of morphine are affected by changes in plasma R(-)-methadone concentration that occur during an inter-dosing interval. Two types of nociceptive stimuli were used: (1) a cold pressor test (CP), (2) electrical stimulation (ES). Morphine was administered intravenously to achieve the two consecutive plasma concentrations. Blood samples were collected, concurrently with nociceptive responses, to determine plasma morphine concentrations. Methadone patients achieved mean C(SS1) and C(SS2) of 16 and 55 ng/ml respectively; those of controls were 11 and 33 ng/ml. Methadone patients were hyperalgesic to pain induced by CP but not ES. Despite significantly greater plasma morphine concentrations, methadone patients experienced minimal antinociception in comparison with controls. Furthermore in methadone patients, the antinociception ceased when the infusion ended. In comparison, the duration of effect in control subjects was 3 h. The fluctuations that occurred in plasma R(-)-methadone concentration during an inter-dosing interval had little effect on patients' responses to morphine. Our findings suggest that methadone patients are cross-tolerant to the antinociceptive effects of morphine, and conventional doses of morphine are likely to be ineffective in managing episodes of acute pain amongst this patient group. Further research is needed to determine whether other drugs are more effective than morphine in managing acute pain in this patient population.
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PMID:Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine. 1142 27

Morphine is the preferred analgesic agent for the critically ill patient. Fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability or for patients manifesting symptoms of histamine release with morphine or morphine allergy. Hydromorphone is an acceptable alternative to morphine for patients with significant adverse affects from morphine or severe renal dysfunction. Meperidine and intravenous codeine should be avoided if at all possible. APAP and NSAIDs may be useful in the management of acute pain secondary to their opioid-sparing effects. Use of nonopioid analgesics may reduce the dose of opioid required for adequate pain control and help to minimize opioid-induced side effects. NSAIDs should be used only when the benefit-to-risk ratio is favorable. APAP should be used as an adjunct but not as the sole analgesic agent in critically ill patients. Regardless of which agent or agents are used to optimize pain control, it is imperative that caregivers recognize that the optimal analgesic dose and regimen vary widely between patients. Based on the pharmacokinetics and pharmacodynamics of the agent(s) selected, enough time for an adequate trial should be allowed before switching to other agents. Employing these principles optimizes the use of medications in the management of the complex physiologic response to pain.
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PMID:Analgesia in the intensive care unit. Pharmacologic and pharmacokinetic considerations. 1186 3


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