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

The analgesic activities of paracetamol (100, 178, 316 and 562 mg kg-1), caffeine (10, 18, 32 and 56 mg kg-1) and combinations of these doses were tested on a pain-induced functional impairment model in the rat. Dysfunction of the right hind limb was induced by an intra-articular injection of 30% uric acid in the knee. Drugs were given orally and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol alone induced a dose-dependent analgesic effect whereas caffeine alone did not show any activity at the assayed doses. Combinations of 316 mg kg-1 paracetamol with either 10, 18, 32 or 56 mg kg-1 caffeine yielded analgesic effects significantly greater than that of paracetamol alone. The highest potentiation was observed with a paracetamol-caffeine mixture of 316-32 mg kg-1. Caffeine coadministration, however, did not significantly change paracetamol plasma levels. No potentiation was obtained with other combinations. Paracetamol plasma levels and analgesic effect observed with administration of 316 mg kg-1 paracetamol alone or 316-32 mg kg-1 of paracetamol-caffeine were fitted to the sigmoidal Emax model according to the Hill equation. The curves obtained were parallel, but that of the combination was shifted to the left. It is concluded that caffeine is able to potentiate the analgesic effect of paracetamol by a pharmacodynamic mechanism, but this only occurs at certain dose combinations.
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PMID:Characterization of the analgesic effect of paracetamol and caffeine combinations in the pain-induced functional impairment model in the rat. 810 58

mu-Opioid receptor agonists, e.g. morphine, produce analgesia that can be potentiated by restraint stress. Adenosine receptor agonists, e.g. 5'-N-ethylcarboxamidoadenosine (NECA), also produce analgesia. To determine if adenosine-induced analgesia is also potentiated by stress, dose- and time-effect curves for NECA (0.01-0.1 mg/kg s.c.) were generated in adult male Sprague-Dawley rats either unrestrained or restrained in Plexiglas cylinders, using the tail-flick assay. Morphine (1.0-5.6 mg/kg s.c.) was also tested for comparison. Both compounds produced dose-dependent increases in tail-flick latencies. This effect of both drugs was potentiated in restrained rats. The opioid receptor antagonist, naltrexone (1.0 mg/kg s.c.) blocked completely the effect of morphine in both groups and attenuated the stress-induced potentiation of NECA-induced analgesia. The adenosine receptor antagonist, caffeine (10.0 mg/kg s.c.), blocked the analgesic effect of NECA but not that of morphine. These results indicate that adenosine-mediated analgesia is potentiated by restraint stress and suggest a role for endogenous opioids in the mediation of stress-induced potentiation of analgesia.
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PMID:Restraint stress potentiates analgesia induced by 5'-N-ethylcarboxamidoadenosine: comparison with morphine. 822 92

The present study examined the spinal antinociceptive effects of adenosine analogs and inhibitors of adenosine kinase and adenosine deaminase in the carrageenan-induced thermal hyperalgesia model in the rat. The possible enhancement of the antinociceptive effects of adenosine kinase inhibitors by an adenosine deaminase inhibitor also was investigated. Unilateral hindpaw inflammation was induced by an intraplantar injection of lambda carrageenan (2 mg/100 microl), which consistently produced significant paw swelling and thermal hyperalgesia. Drugs were administered intrathecally, either by acute percutaneous lumbar puncture (individual agents and combinations) or via an intrathecal catheter surgically implanted 7-10 days prior to drug testing (antagonist experiments). N6-cyclohexyladenosine (CHA; adenosine A1 receptor agonist; 0.01-1 nmol), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680; adenosine A2A receptor agonist; 0.1-10 nmol), 5'-amino-5'-deoxyadenosine (NH2dAdo; adenosine kinase inhibitor: 10-300 nmol), and 5-iodotubercidin (ITU; adenosine kinase inhibitor; 0.1-100 nmol) produced, to varying extents, dose-dependent antinociception. No analgesia was seen following injection of 2'-deoxycoformycin (dCF; an adenosine deaminase inhibitor; 100-300 nmol). Reversal of drug effects by caffeine (non-selective adenosine A1/A2 receptor antagonist; 515 nmol) confirmed the involvement of the adenosine receptor, while antagonism by 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A1 receptor antagonist; 242 nmol), but not 3,7-dimethyl-1-propargylxanthine (DMPX; adenosine A2A receptor antagonist; 242 nmol), evidenced an adenosine A1 receptor mediated spinal antinociception by NH2dAdo. dCF (100 nmol), which was inactive by itself, enhanced the effects of 10 nmol and 30 nmol NH2dAdo. Enhancement of the antinociceptive effect of ITU by dCF was less pronounced. None of the antinociceptive drug regimens had any effect on paw swelling. These results demonstrate that both directly and indirectly acting adenosine agents, when administered spinally, produce antinociception through activation of spinal adenosine A1 receptors in an inflammatory model of thermal hyperalgesia. The spinal antinociceptive effects of selected adenosine kinase inhibitors can be significantly augmented when administered simultaneously with an adenosine deaminase inhibitor.
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PMID:Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an inflammatory thermal hyperalgesia model in the rat. 952 Feb 38

Postdural puncture headache (PDPH) is the most common complication of accidental or deliberate dural puncture. It also occurs after epidural or spinal analgesia for labor and delivery. Treatment may be conservative with analgesics and/or caffeine. Definitive treatment can be accomplished with an epidural blood patch (EBP). We present a case of postpartum convulsions which were temporally related to a caffeine infusion and an EBP.
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PMID:Treatment for postdural puncture headache associated with late postpartum eclampsia. 1041 50

Cigarette smoking remains highly prevalent in most countries. It can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms. Enzymes induced by tobacco smoking may also increase the risk of cancer by enhancing the metabolic activation of carcinogens. Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1, CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. There are genetic polymorphisms in the inducibility of CYP1A1, with some evidence that high inducibility is more common in patients with lung cancer. CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens. Caffeine demethylation, using blood clearance or urine metabolite data, has been used as an in vivo marker of CYP1A2 activity, clearly demonstrating an effect of cigarette smoking, CYP2E1 metabolises a number of drugs as well as activating some carcinogens. Our laboratory has found in an intraindividual study that cigarette smoking significantly enhances CYP2E1 activity as measured by the clearance of chlorzoxazone. In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. Similarly, although inhibitory effects of the smoke constituents carbon monoxide and cadmium on CYP enzymes have been observed in vitro and in animal studies, the relevance of this inhibition to humans has not yet been established. The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Drugs for which induced metabolism because of cigarette smoking may have clinical consequence include theophylline, caffeine, tacrine, imipramine, haloperidol, pentazocine, propranolol, flecainide and estradiol. Cigarette smoking results in faster clearance of heparin, possibly related to smoking-related activation of thrombosis with enhanced heparin binding to antithrombin III. Cutaneous vasoconstriction by nicotine may slow the rate of insulin absorption after subcutaneous administration. Pharmacodynamic interactions have also been described. Cigarette smoking is associated with a lesser magnitude of blood pressure and heart rate lowering during treatment with beta-blockers, less sedation from benzodiazepines and less analgesia from some opioids, most likely reflecting the effects of the stimulant actions of nicotine. The impact of cigarette smoking needs to be considered in planning and assessing responses to drug therapy. Cigarette smoking should be specifically studied in clinical trials of new drugs.
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PMID:Drug interactions with tobacco smoking. An update. 1042 67

Adenosine is a modulator that has a pervasive and generally inhibitory effect on neuronal activity. Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors. Relief from this tonic inhibition by receptor antagonists such as caffeine accounts for the excitatory actions of these agents. Characterization of the effects of adenosine receptor agonists and antagonists has led to numerous hypotheses concerning the role of this nucleoside. Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use.
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PMID:The role and regulation of adenosine in the central nervous system. 1128 4

Caffeine has been an additive in analgesics for many years. However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%. In vitro and in vivo pharmacological research has provided some evidence that caffeine can have anti-nociceptive actions through blockade of adenosine receptors, inhibition of cyclo-oxygenase-2 enzyme synthesis, or by changes in emotion state. Nevertheless, these actions are only considered in some cases. It is suggested that the actual doses of analgesics and caffeine used can influence the analgesic adjuvant effects of caffeine, and doses that are either too low or too high lead to no analgesic enhancement. Clinical trials suggest that caffeine in doses of more than 65 mg may be useful for enhancement of analgesia. However, except for in headache pain, the benefits are equivocal. While adding caffeine to analgesics increases the number of patients who become free from headache [rate ratio = 1.36, 95% confidence interval (CI) 1.17 to 1.58], it also leads to more patients with nervousness and dizziness (relative risk = 1.60, 95% CI 1.26 to 2.03). It is suggested that long-term use or overuse of analgesic medications is associated with rebound headache. However, there is no robust evidence that headache after use or withdrawal of caffeine-containing analgesics is more frequent than after other analgesics. Case-control studies have shown that caffeine-containing analgesics are associated with analgesic nephropathy (odds ratio = 4.9, 95% CI 2.3 to 10.3). However, no specific contribution of caffeine to analgesic nephropathy can be identified from these studies. Whether caffeine produces nephrotoxicity on its own, or increases nephrotoxicity due to analgesics, is yet to be established.
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PMID:A benefit-risk assessment of caffeine as an analgesic adjuvant. 1177 46

The objective was to evaluate the onset of action, analgesic efficacy and tolerability of Saridon*, a propyphenazone 150 mg/paracetamol 250 mg/caffeine 50 mg combination, in comparison with paracetamol 500 mg, aspirin 500 mg, ibuprofen 200 mg and placebo, by a pooled statistical analysis of eight studies. Out of 500 generally healthy patients (55.2% men, 44.8% women), average age 43.5 years, 329 (65.8%) had moderate and 171 (34.2%) severe acute dentoalveolar pain. More Saridon-treated patients reported 'pain gone/partly gone' and less 'pain unchanged or worse' compared with paracetamol, aspirin and placebo 30min (p = 0.009, p < 0.001, p = 0.001, respectively) and 60 min after dosing (p < 0.0001 for all). The difference with ibuprofen was observed 60 min after dosing (p < 0.01). Pain intensity differences 30 min and 60 min after dosing infer that Saridon has a faster onset of action than all of the other medications that it was compared with (ibuprofen at only 60 min after dosing). Total pain relief scores four hours after dosing were higher in the Saridon group compared with the paracetamol, ibuprofen, placebo (p < 0.0001 for all) and aspirin groups (p < 0.01). At the end of the study, patients assessed Saridon as more efficacious than the other study medications (p < 0.0001 for all). No serious adverse events were observed with any of the drugs studied. All medications were well tolerated. Twenty patients (4.0%) reported adverse events with no significant differences between groups. The most common adverse events were gastrointestinal disorders, followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac and general disorders. Saridon is an effective analgesic that combines the advantage of fast onset and effective analgesia as compared with paracetamol alone, ibuprofen, aspirin or placebo. The results of this pooled analysis of eight studies should be confirmed in a double-blind study, since seven of the studies included in this analysis were single blind.
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PMID:The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/ caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis). 1199 41

Back pain, chemical backache, PDPH, and neurologic deficit all may be reported after regional anesthesia for childbirth. Back pain is common during pregnancy, but epidural analgesia during labor does not increase the incidence of long-term back pain. Chemical backache caused by 2-chloroprocaine is probably a result of hypocalcemic tetany of paraspinous muscles. The mechanism is presumed to be chelation of calcium by sodium bisulfite, an antioxidant present in nesacaine-MPF. PDPH after dural puncture is caused by leakage of CSF, which causes cerebral hypotension. Cerebral hypotension leads to traction on pain-sensitive intracranial structures and cerebral vasodilation. Initial therapy includes hydration, caffeine, and sumatriptan. EBP is the most effective treatment in severe PDPH. If the first EBP fails, a second blood patch can be performed. Neurologic deficits after regional anesthesia are rare. Meticulous technique and vigilance are the keystones in avoiding major neurologic complications of regional anesthesia. Rapid diagnosis and appropriate treatment are essential to optimize a successful outcome if complications do develop.
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PMID:Backache, headache, and neurologic deficit after regional anesthesia. 1269 33

This report describes a case of isolated postpartum seizures, in an apparently healthy woman who had suffered an accidental dural puncture during epidural analgesia for labour, and was on caffeine for relief of post-dural puncture headache. Investigation failed to determine the aetiology of the seizures. The possible contribution of dural puncture and caffeine toxicity are discussed.
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PMID:Unexpected postpartum seizures associated with post-dural puncture headache treated with caffeine. 1532 81


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