Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advances in basic and clinical research have greatly expanded the options for analgesic pharmacotherapy. There are three broad categories of analgesic medications: (1) nonopioid analgesics, which includes the nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, dipyrone, and others; (2) a diverse group of drugs known as the "adjuvant analgesics," which are defined as "drugs that have primary indications other than pain but may be analgesic in selected circumstances;" and (3) opioid analgesics. The advent of highly selective COX-2 inhibitors has generated excitement because of the possibility that these new NSAIDs will be much safer than previous COX inhibitors. However, the cost-benefit of using these relatively more expensive drugs versus other NSAIDs plus gastro-protective therapies needs to be determined. Adjuvant analgesics can be grouped into four major classes according to their use: multipurpose, neuropathic pain, musculoskeletal pain, and cancer pain. There has been a dramatic increase in the number of these drugs during the past two decades and they now play an important role in the management of chronic pain. Pain specialists are now using opioids for chronic nonmalignant pain in addition to the traditional use for acute and cancer pain. This change in practice evolved from recognition that selected patients with chronic noncancer-related pain can experience sustained analgesia and function better with these drugs, without developing an addictive disorder. The combination of opioids and other drugs, such as an N-methyl-D-aspartate-receptor antagonist, may improve the balance between analgesia and adverse effects.
 ...
PMID:Current pharmacotherapy of chronic pain. 1068 34

The PSIs include acetaminophen, NSAIDs, and salicylates. They can be used alone for the treatment of mild pain or as an adjunct to opioid analgesia. In children, most experience is with acetaminophen and ibuprofen. For the treatment of mild to moderate pain, these agents can be administered as needed or at fixed intervals. The latter dosing scheme may provide a more consistent serum level, thereby improving analgesia. The major advantages of acetaminophen are its availability as a suppository for PR administration and its lack of effects on renal and GI function, adverse effects that may be seen with the NSAIDs. Many of the effects on platelet functioning, RBF, and the GI tract may be eliminated with the introduction of NSAIDs that selectively inhibit COX II without effects on COX I, the enzyme present in the GI tract, renal system, and platelets. Future evaluations with these agents in the pediatric population are needed. For more severe pain, the NSAID salicylate or acetaminophen can be combined with a weak opioid, such as codeine, oxycodone, or hydrocodone. When using oral analgesics, factors that may interfere with effective analgesia include a child's refusal to take the medication, ineffective doses and dosing regimens, decreased bioavailability following PO administration, inability to tolerate PO medications because of nausea or vomiting, altered GI motility, and a delayed onset caused by slow absorption. With such caveats in mind, the PO route provides an effective and cost-effective means for many patients. It should be considered as the primary route for pediatric patients in the treatment of mild to moderate pain, even in the hospital setting.
 ...
PMID:Weak analgesics and nonsteroidal anti-inflammatory agents in the management of children with acute pain. 1083 89

Postoperative pain, arising due to surgical tissue injury, is most frequent type of pain found in clinical practice. In postoperative analgesia opioids still constitute the fundamental form of pain treatment, but the development of neurophysiology and neuropharmacology has allowed for the optimization of postoperative analgesia. Therefore, in order to potentialize the pain relief effect of opioids and/or inhibit the nociception process and its consequences, diverse drugs and therapies are used. The procedure is called multimodal analgesia and consists in the administration of opioids in conjunction with NMDA antagonists, COX inhibitors, cholecystokinin antagonists, agonists of muscarine receptors, agonists of alpha-2 receptors or cytokine inhibitors. An alternative or supplementary therapy in the postoperative period relies on local anaesthetic techniques or TENS. There also exists pre-emptive analgesia, whose aim is to safeguard the central nervous system from increased afferent nociceptive stimulation during the operation.
 ...
PMID:[Postoperative pain treatment]. 1096 35

COX-2 selective inhibitors provide analgesia and blunt inflammation while also sparing the gastrointestinal tract from classic NSAID toxicity. Therapeutic effects are thought to result from inhibition of the inflammatory COX-2 isoform. Organ sparing is considered the result of preservation of homeostatic COX-1 enzyme function. Similar roles of the COX isoforms in the kidney would reduce NSAID-associated nephrotoxicity. However, human kidney tissue expresses COX-2 enzyme, suggesting a role for this isoform in maintenance of physiological renal processes. Available clinical data on the renal effects of COX-2 selective inhibitors in humans also demonstrate nephrotoxic potential.
 ...
PMID:COX-2 selective inhibitors: analysis of the renal effects. 1290 60

To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain.
 ...
PMID:Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen. 1532 4

Paracetamol produces analgesia in the mouse writhing test through a central action which is paralleled by a reduction in brain PGE(2) concentrations. In contrast, diclofenac has a peripheral analgesic action in this test. Paracetamol-induced hypothermia is also accompanied by a reduction in brain PGE(2) concentrations in C57/Bl6 mice. This hypothermic effect of paracetamol was reduced in COX-1 but not in COX-2 gene-deleted mice. These results support the view that analgesia and hypothermia due to paracetamol are mediated by inhibition of a third COX isoenzyme (designated COX-3). In cultured mouse macrophages, COX-2 is induced by treatment with LPS or with high concentrations of diclofenac. Diclofenac-induced COX-2 is inhibited with low concentrations of paracetamol, whereas LPS-induced COX-2 is insensitive to paracetamol inhibition. The mechanisms of induction and possibly the functions of these two COX-2 enzymes are also different.
 ...
PMID:COX-3 and the mechanism of action of paracetamol/acetaminophen. 1562 90

The mechanism by which COX inhibitors exert their analgesic effect is well established. However, data show no direct correlation between drug concentrations in plasma and the analgesic or adverse effects in chronic inflammatory conditions. This represents a major problem in the development of COX inhibitors, since it is difficult to predict the appropriate dosing regimen for the treatment of chronic inflammatory pain, based upon information from pre-clinical studies and eventually early clinical studies. The factors that determine response in inflammatory pain must be understood in order to make predictions about the time course of the analgesic effect. In this review the determinants of drug response and their variability will be discussed: physicochemical properties, pharmacokinetics (PK), pathophysiology and disease progression. From a mechanistic point of view, endogenous mediators of inflammation might be used as a biomarker for the analgesic effect and safety assessment. Such a biomarker can be an intermediate step between drug exposure and response. In addition, its concentration-effect relationship could be characterized by pharmacokinetic-pharmacodynamic (PK/PD) modelling. Indeed, recent investigations have shown that COX-2 inhibition, as determined by modelling of prostaglandin E2 (PGE2) levels in the whole blood assay in vitro can be used as a marker to predict drug effects (analgesia) in humans. A model-derived parameter, IC80, (total and unbound) was found to correlate directly with the analgesic plasma concentration of different COX inhibitors varying in enzyme selectivity. These findings indicate that PGE2 and thromboxane B2 inhibition can be used to predict and select efficacious doses in humans.
 ...
PMID:Pharmacokinetic-pharmacodynamic correlations and biomarkers in the development of COX-2 inhibitors. 1585 83

An integrated approach of neonatal analgesia starts with the systematic evaluation of pain and should be followed by effective interventions, mainly based on the appropriate (i.e. safe and effective) administration of analgesics. In contrast to the more potent opioids, data on the pharmacokinetics and -dynamics of non-opioid analgesics in this specific population are still rare or even lacking. We therefore evaluated various aspects of developmental pharmacology of non-opioid analgesics (paracetamol, ibuprofen, acetylsalicyl acid) in neonates. We first performed a single dose propacetamol study in preterm and term neonates. Based on these preliminary findings, a repeated dose administration scheme was developed and tested and maturational aspects from preterm till teenage were documented. Although non-selective COX-inhibitors might be effective in the treatment of postoperative or inflammatory pain syndromes in neonates, potential efficacy should be balanced against the drugs' safety profile. Neonatal renal clearance strongly depends on glomerular filtration rate (GFR) and GFR itself strongly depends on the vaso-dilatative of prostaglandins on the afferent arterioli. We therefore evaluated the impact of the administration of ibuprofen or acetylsalicylic acid on renal clearance in preterm infants and hereby used amikacin clearance as a surrogate marker. We hereby documented the negative effect of ibuprofen on glomerular filtration rate in preterm infants up to 34 weeks and we were able to show that ibuprofen and acetylsalicylic acid had an equal impact on the glomerular filtration rate.
 ...
PMID:Clinical pharmacology of non opioid analgesics in neonates. 1640 26

The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents designed for the treatment of pain and inflammation. CINODs have a multi-pathway mechanism of action that involves COX inhibition and nitric oxide donation. The anti-inflammatory and analgesic effects of COX inhibition are reinforced through inhibition of caspase-1 regulated cytokine production, while nitric oxide donation provides multiorgan protection. Whereas both conventional nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2-selective NSAIDs are associated with a variety of adverse effects on the renal system, such as hypertension and edema, CINODs may offer an improved renal safety profile. These agents are devoid of hypertensive effects in animal models and their mechanism of action suggests that they may not cause edema. CINODs also have other renal-sparing effects, being better tolerated than NSAIDs in models of kidney failure. CINODs have been shown to prevent platelet activation in vitro and exhibit anti-thrombotic activity in vivo. In animal models of ischemia/reperfusion, CINODs treatment results in improved recovery of heart contractility and reduced left ventricular end-diastolic pressure, in contrast to the effects of aspirin. The combination of improved analgesia, reduced gastrointestinal toxicity and cardiorenal protection has been established in animal models, and early clinical results suggest a favourable gastrointestinal safety profile in humans. The potential for CINODs to provide cardiorenal protection in humans is currently being investigated.
 ...
PMID:COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular and renal function. 1661 Oct 49

Due to renal COX-2 constitutive expression, meloxicam is presumably deleterious for kidney function in critical situations. The present study investigates the influence of intravenous meloxicam on renal parameters and compares it with a nonselective COX inhibitor, ketoprofen. Piglets (n = 6 in each group) were treated with ketoprofen (2 mg.kg(-1)), meloxicam (0.2 mg.kg(-1)), or saline at the beginning of anaesthesia. Under intravenous anaesthesia, pigs were instrumented for cardiovascular, respiratory, and renal function evaluation, including urinary flow (UF), glomerular filtration rate (GFR), and renal blood flow (RBF). After baseline data collection (U0), data collection consisted of six 20-minute periods (U1 to U6). In all groups, the time course of cardiovascular and respiratory parameters remained within normal ranges. A small decrease in cardiac output and an increase in mean systemic arterial blood pressure (p = 0.002) occurred in all groups. In the placebo group, a similar decrease was observed for RBF and cardiac output, with troughs of -10.1% +/- 6.8%, and -12.9% +/- 3.2%, respectively. GFR and UF, however, remained stable over time in this group. Ketoprofen significantly decreased UF (-29.3% +/- 5.5% max at U3), with similar decreases in GFR and RBF. Meloxicam induced a transient (at U2) and small decrease in UF with no difference, at any time point, with the placebo group. The renal effects of meloxicam appear minimal and transient in anaesthetized piglets. This study demonstrates the safety of meloxicam for preemptive surgical analgesia under conditions of normovolaemia. Fluid therapy appears recommended to prevent any renal dysfunction.
 ...
PMID:Renal effect of meloxicam versus ketoprofen in anaesthetized pseudo-normovolaemic piglets. 1841 47


1 2 3 Next >>