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PubMed2002

The efficacy of combination analgesic therapy in relieving dental pain.

BACKGROUND: An experience of poorly managed pain related to dental treatment can lead patients to avoid or postpone treatment. The development of new pain management strategies equips dental clinicians with additional treatment options that can provide more effective pain relief LITERATURE REVIEWED: The author reviewed dental and medical literature dealing with the safety, efficacy and mechanisms of action of common analgesic treatments. CONCLUSIONS: For the treatment of mild to moderate pain, acetaminophen and non-steroidal anti-inflammatory drugs, or NSAIDs, continue to be the most appropriate options. The use of cyclo-oxygenase2-inhibitor NSAIDs should be strongly considered for use with patients at risk of experiencing gastrointestinal toxicity. The pathophysiology of pain is a complex central and peripheral nervous system process, and the use of combination analgesics that act at multiple pain sites can improve pain relief after a dental procedure. For moderate to moderately severe pain, tramadol or combination medications such as tramadol with acetaminophen or codeine with acetaminophen are appropriate. For severe pain, use of opioids or opioid combinations is advised. CLINICAL IMPLICATIONS: Providing appropriate treatment after dental surgery requires a careful medical history and an educated anticipation of the level of pain the patient may encounter. New analgesic options are available and should be considered, particularly combination analgesics, which can provide faster onset and prolonged duration of action and can combat pain at multiple sites of action.

Acetaminophen↗
PubMed2003

Racial and ethnic disparities in emergency department analgesic prescription.

OBJECTIVES: We examined racial and ethnic disparities in analgesic prescription among a national sample of emergency department patients. METHODS: We analyzed Black, Latino, and White patients in the 1997-1999 National Hospital Ambulatory Medical Care Surveys to compare prescription of any analgesics and opioid analgesics by race/ethnicity. RESULTS: For any analgesic, no association was found between race and prescription; opioids, however, were less likely to be prescribed to Blacks than to Whites with migraines and back pain, though race was not significant for patients with long bone fracture. Differences in opioid use between Latinos and Whites with the same conditions were less and nonsignificant. CONCLUSIONS: Physicians were less likely to prescribe opioids to Blacks; this disparity appears greatest for conditions with fewer objective findings (e.g., migraine).

Adolescent↗
PubMed1997

Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients.

The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.

Analgesics↗
PubMed2000

Effect of gender on anti-inflammatory and analgesic actions of two kappa-opioids.

The higher incidence of inflammatory and painful disorders in women and recent reports that have emphasized the importance of gender in nociceptive sensitivity and responsiveness to analgesics prompted us to investigate gender as a factor in the variability in response to opioids. We studied the anti-inflammatory and antinociceptive effects of two kappa-opioid agonists in adjuvant-induced arthritis, one that acts both peripherally and centrally (PNU50488H; 20 mg/kg/day), the other which is peripherally selective (asimadoline; 5 mg/kg/day). Both drugs had equally powerful anti-inflammatory effects in both male and female rats (reducing measures by 60-80%). In contrast, there were gender-based heterogeneities in their analgesic actions, contingent on the method of stimulation (mechanical or thermal); males were insensitive to the analgesic effects of asimadoline with thermal but not mechanical nociceptive stimuli. We also sought evidence for gender influences on the joint content of Substance P (SP), a peptide suggested to have a role in producing inflammation and found that levels were higher in the untreated arthritic females, although there were no gender differences in disease sensitivity or nociception in arthritic animals receiving no drugs. Paradoxically, both drugs elevated SP concentrations in the joints, perhaps as a consequence of an action of kappa-opioids to suppress SP release from peripheral nerves, but the gender differences remained. Further experiments are required to determine exact mechanisms responsible for the gender distinction in analgesic response to kappa-opioids that may involve differential activation of primary afferents.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2002

Can ketamine potentiate the analgesic effect of epidural morphine, preincisional or postincisional administration?

A randomized controlled trial was conducted to determine the effect of adding epidural ketamine to epidural morphine comparing between giving ketamine at preincisional time and postincisional time on postoperative analgesia in patients undergoing gynecological operations. Eighty patients scheduled for gynecological operation under combined epidural-general anesthesia were randomly divided into 4 groups. Group 1 received epidural morphine 3 mg before skin incision. Group 2 received epidural morphine 3 mg after skin incision. Group 3 received epidural morphine 3 mg and ketamine 30 mg before skin incision. Group 4 received epidural morphine 3 mg and ketamine 30 mg after skin incision. Lidocaine 2 per cent with epinephrine 1:200,000 was used as the main anesthetic agent during the operation in all groups. Postoperative analgesics were pethidine 1 mg/kg intramuscularly or paracetamol 1,000 mg oral. The time to the first analgesic requirement and pain during 48 h were recorded. The amount of pethidine and paracetamol required and the time to the first dose of analgesic requirement were not significantly different among the groups. There were no differences in the incidences of pruritus, nausea, vomiting and nightmare. We concluded that adding ketamine to epidural morphine either by preincisional or postincisional administration did not potentiate the analgesic effect of epidural morphine.

Adult↗
PubMed2002

Evaluation of analgesic, antipyretic and anti-inflammatory activity of spirobarbitunylphenothiazines in rodents.

Analgesic, antipyretic and anti-inflammatory activities of newly synthesized spirobarbitunylphenothiazines viz 10-[7, 11-Di(4-4' dimethoxphenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5.5] undecane 1, 5 dione] acetylphenothiazine (test drug A) and 10-[7, 11-Di (N.N-dimethylaminophenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5, 5] undecane-1, 5 dione] acetylphenothiazine (test drug B) have been screened in Swiss mice and Wistar rats. The peripheral analgesic activity of test drugs A and B was investigated by acetic acid induced writhing test in Swiss mice while the central analgesic action was assessed by hot-wire (tail flick test) of the analgesiometer and tail-clip test in Wistar rats. Antipyretic activity was assessed on Brewer's yeast induced pyrexic model while antiinflammatory activity was seen on carrageenan induced hind paw oedema. Analgesic activity was found to be only of peripheral type as there was reduction of 66% in writhing responses by test drugs A and B in dose of 80 mg/kg in mice. No change in the tail flick responses was observed on analgesiometer or by tail clip by both the test drugs. Reduction of 1.5 to 2.0 degrees C in rectal temperature was observed in pyretic rats by test drugs A and B in dose of 80 mg/kg. 80% reduction in paw volume was noted in 80 mg/kg dose of both the test drugs which was comparable to the anti-inflammatory activity of 300 mg/kg, p.o. of phenylbutazone.

Analgesics↗
PubMed2003

Free radicals after painful stimulation are influenced by antioxidants and analgesics.

OBJECTIVES: To study the balance between the pro-oxidative and antioxidative defence system after repeated painful stimulation in rats and the efficacy of the administration of different antioxidants (vitamins C, E, A, and selenium), analgesics (acetylsalicylic acid, morphine), and their combinations. METHODS: Mechanical clamping of both hind limbs was applied for 10 min for 5 consecutive days in adult male Wistar rats. The tail-flick latency was measured before and after a 5-day nociceptive stimulation with or without the substance application. The reactive oxygen species (ROS) were determined in the sensorimotor cortex. RESULTS: Painful stimulation increased lipoperoxidation which persisted for up to 15 days after it had been discontinued. A simultaneous injection of antioxidants decreased the levels of TBARS, SOD and GSHPx; however, antioxidants applied one week prior to the painful stimulation were ineffective. A simultaneous injection of analgesics reduced stress-induced analgesia caused by the nociceptive stimulation, but did not affect lipoperoxidation. CONCLUSIONS: A combination of antioxidants with analgesics normalized both the oxidative stress and functional (the tail-flick latency) indicators. These results suggest that the administration of antioxidants in pain treatment may be employed to decrease the doses of analgesics and to prevent the negative impact of reactive oxygen species on nociception.

Analgesics↗
PubMed2004

Weak opiate analgesics: modest practical merits.

(1) The first-line drugs for mild to moderate pain are non opiate analgesics, namely paracetamol and nonsteroidal antiinflammatory drugs (NSAIDs). (2) Codeine, dextropropoxyphene and tramadol are weak opiates; they are often used with paracetamol in fixed-dose combinations, in order to reinforce the analgesic effect of paracetamol. (3) These analgesic combinations have only been evaluated in a few situations associated with chronic and acute pain. And the endpoints used in clinical trials are designed more to show statistically significant differences than clear clinical differences. (4) In acute pain, available meta-analyses confirm that the first-line drug is paracetamol, or, if necessary, ibuprofen, a NSAID. (5) The paracetamol + codeine combination slightly increases the analgesic effect of paracetamol, but causes more adverse effects. Combinations of paracetamol + dextropropoxyphene and paracetamol + tramadol are even less useful. (6) The few available clinical trials fail to demonstrate that combining paracetamol with a NSAID is any more effective than either drug given alone, while adverse effects are increased. (7) Paracetamol is also the first-line treatment for chronic non cancer pain, such as low back pain or pain due to osteoarthritis of the hip. NSAIDs have no advantages over paracetamol in these settings. We found no trials of paracetamol + NSAID combinations. Combinations of paracetamol and weak opiates have been inadequately studied in this situation, and are only second-line options.

Acetaminophen↗
PubMed1983

The effect of antihistaminics on cataleptogenic action of analgesics and haloperidol.

We investigated the effect of benzhydramine, thenalidine, mepyramine (H1 receptor antagonists) and cimetidine (H2 receptor antagonist) on cataleptogenic action of morphine, codeine, fentanyl, and haloperidol. Benzhydramine antagonized the catalepsy induced by analgesics (particularly by codeine). The antagonistic effect of thenalidine was weaker (but also very prominent for codeine catalepsy). Mepyramine did not affect the catalepsy induced by analgesics. All three H1 receptor antagonists attenuated the catalepsy induced by haloperidol. Cimetidine, injected intraventricularly, did not affect the catalepsy induced either by analgesics or by haloperidol. It is suggested that the antagonistic action of benzhydramine and thenalidine against analgesic catalepsy is related rather to their antiserotonin properties, while the anticataleptic activity of all three H1 receptor antagonists against haloperidol catalepsy is caused by their anticholinergic and antiserotonin properties.

Analgesics↗
PubMed1995

[Poisonings due to analgesics during a period of 14 years in Denmark--a registry study of the period 1979-1992].

The study describes consumption of and poisoning by analgesic drugs in Denmark during the period 1979-1992. During this period, fatal poisonings from analgesics almost doubled to 200 deaths per year (40% of all drug related deaths in Denmark). The annual consumption of opioids increased at the beginning of the period, but during 1985-1992 it was relatively constant at 20 million defined daily doses (DDD) and associated with 600 hospital admissions and 150-170 deaths due to poisoning per year. Within the opioid group dextropropoxyphene consumption and poisonings decreased following a National Board of Health initiative in 1985-1987. As for the weak analgesics, consisting mainly of paracetamol or salicylates, the total consumption increased gradually and reached 145 million DDD in 1992, corresponding to 160 tablets per inhabitant per year. This consumption was associated with approximately 750 hospital admissions and 40 deaths due to poisoning. As judged from the mortality per dose the weak analgesics are 20-30 times safer than the opioids.

Analgesics↗
PubMed1995

Analgesic administration, pain intensity, and patient satisfaction in cardiac surgical patients.

BACKGROUND: Pain can adversely affect a patient's physiological and psychological recovery, yet little is known about the pain experience of cardiac surgical patients. OBJECTIVES: To examine nursing practice regarding analgesic administration and measure pain intensity and patient satisfaction with pain management practices. METHODS: To establish baseline nursing practice regarding analgesic administration, charts were reviewed retrospectively in 50 adult cardiac surgical patients, and the same information was collected concurrently for a prospective sample of 51 patients. The subjects completed visual analogue scales as a measure of pain intensity twice daily while in the cardiothoracic intensive care unit and Pain Relief Satisfaction Questionnaires on the day after transfer from the unit. RESULTS: Patients in the prospective group received significantly more analgesia. Pain intensity was moderate (4 or greater on the Visual Analogue Scale). Women had higher overall visual analogue scale scores than did men, 4.57 versus 3.70. Patients in whom an internal mammary artery had been used as a bypass graft had significantly higher scores compared with patients with vein grafts. The Pain Relief Satisfaction Questionnaire responses indicated that 96% of the patients experienced effective pain management in the cardiothoracic intensive care unit. CONCLUSIONS: Despite receiving analgesic doses twice those reported elsewhere for similar populations, the patients in this study reported moderate pain intensity. This finding was confounded by the fact that 96% expressed satisfaction with their pain management in the cardiothoracic intensive care unit. Frequent assessment and documentation of both pain and pain relief from interventions are necessary if the healthcare team is to implement an individualized analgesic regimen.

Adult↗
PubMed1998

[Staged analgesic therapy in tumor pain].

Overall, pain is one of the most common symptoms associated with cancer and often produces greater anticipatory distress than other features of the disease. Drug selection depends on the intensity of pain rather than on the specific pathophysiology. Mild to moderate pain can often be treated effectively by so-called "weak" opioids. Non-opioid analgesics, like acetyl-salicylic acid or paracetamol can be added according to the "analgesic ladder" proposed by the World Health Organization (WHO). Opioids should be given on a fixed time schedule thereby, preventing pain from recurring. Additional rescue doses (approximately 50 degrees, of baseline single dose) are given for breakthrough pain. Noninvasive (oral, rectal, sublingual, transdermal and intranasal) routes of application should be maintained as long as possible to preserve independence and mobility. When treatment by infusion therapy (subcutaneous, intravenous, epidural) has been elected, the addition of patient controlled analgesia (PCA), which permits patients to administer a preset amount of narcotic at preset intervals, is an effective means to manage breakthrough and incident pain in selected patients. Antidepressants, anticonvulsants and some antiarrhytmics are used as co-analgesics. Oral medication alone can guarantee pain relief in about 95% of the patients. The WHO analgesic ladder has proven effective in all settings of patients care.

Analgesics↗
PubMed1983

Analgesic nephropathy. An uncommon cause of end-stage renal disease.

The frequency of analgesic nephropathy as a cause of end-stage renal disease varies considerably, not only between countries but also between different areas in the same country. We questioned 277 hemodialysis patients in the Washington, DC, area regarding the consumption of analgesic preparations. Only eight (2.8%) of the patients consumed excessive quantities of analgesic compounds prior to institution of hemodialysis. In addition, three of the eight patients had other causes for their end-stage renal disease. We conclude that analgesic nephropathy is an unusual cause of end-stage renal disease in the greater Washington, DC, area.

Adult↗
PubMed2002

Frequency of analgesic use and risk of hypertension in younger women.

BACKGROUND: In addition to their antipyretic, anti-inflammatory, and pain-relieving effects, analgesics may interfere with blood pressure regulation. However, little prospective information is available on the association between analgesic use and the risk of hypertension. METHODS: We performed a prospective study of 80 020 women aged 31 to 50 years who participated in the Nurses' Health Study II and had no previous history of hypertension. Frequency of use (in days per month) of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was collected by mailed questionnaire in 1995. Incident cases of physician-diagnosed hypertension were identified by self-report on the 1997 biennial questionnaire. RESULTS: During 164 090 person-years of follow-up, 1650 incident cases of hypertension were identified. At least 1 d/mo, 51.2% of the cohort used aspirin, 76.7% used NSAIDs, and 72.5% used acetaminophen. After adjusting for age, all 3 classes of analgesics were associated with an increased risk of incident hypertension (P<.001 for trend). After further adjustment for all 3 analgesics and other potential risk factors, only NSAIDs and acetaminophen (P<.001 for trend for both) were significantly associated with risk of hypertension. Compared with nonusers, the relative risk of hypertension for women taking NSAIDs 22 d/mo or more was 1.86 (95% confidence interval, 1.51-2.28) and for those taking acetaminophen 22 d/mo or more was 2.00 (95% confidence interval, 1.52-2.62). CONCLUSIONS: Use of NSAIDs and use of acetaminophen were significantly associated with increased risk of hypertension, but aspirin use was not. A substantial proportion of hypertension in the United States, and the associated morbidity and mortality, may be due to the use of these medications.

Acetaminophen↗
PubMed2004

Lifetime nonnarcotic analgesic use and decline in renal function in women.

BACKGROUND: Analgesics are commonly used and may impair kidney function. However, limited prospective information is available on the long-term effects of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen on renal function. METHODS: A total of 1697 women participating in the Nurses' Health Study provided information on a mailed questionnaire in 1999 about lifetime use of acetaminophen, aspirin, and NSAIDs and provided blood samples in 1989 and 2000. The main outcome was change in estimated glomerular filtration rate (GFR) in 11 years. Multivariate logistic regression was used to determine the odds of developing the outcome according to lifetime analgesic intake. RESULTS: The mean +/- SD estimated GFR decreased from 88 +/- 17 to 79 +/- 17 mL/min per 1.73 m(2). There were no substantial differences in the unadjusted or estimated GFR levels among the categories of lifetime intake for the 3 analgesic groups at baseline or after 11 years. Acetaminophen use was associated with an increased risk of a GFR decline of at least 30 mL/min per 1.73 m(2) (P trend =.01) and a GFR decline of 30% or greater (P trend<.001), but aspirin and NSAID use were not. Compared with women consuming less than 100 g of acetaminophen, multivariate-adjusted odds ratio (95% confidence intervals) for a decline in GFR of at least 30 mL/min per 1.73 m(2) for women consuming more than 3000 g was 2.04 (1.28-3.24). CONCLUSIONS: Higher lifetime use of aspirin and NSAIDs is not associated with renal function decline, but high acetaminophen use may increase the risk of loss of renal function. The absolute risk of renal function decline due to even high lifetime analgesic intake seems to be modest.

Acetaminophen↗
PubMed1998

Intestinal absorption and analgesic activity of aminopeptidase-resistant cellobiose-coupled leucine enkephalinamide.

Leucine enkephalinamide (LEamide), aminopeptidase-degradable opioid peptide, was coupled with cellobiose (cellobiose-coupled LEamide, CcpLEamide). CcpLEamide was absorbed from the rat small intestine in vitro, whereas LEamide was not. CcpLEamide on the mucosal side was more stable than aminopeptidase-resistant cellobiose-coupled leucine enkephalin (CcpLE) in the presence of inhibitors of enkephalinase and angiotensin converting enzyme, and much more stable than LEamide. The absorption rate (clearance) of CcpLEamide was comparable with that of CcpLE in the presence of these peptidase inhibitors. Analgesic activities of these enkephalins were tested by the acetic acid writhing assay and hot-plate assay after subcutaneous administration to mice. Both assays indicated CcpLEamide-induced analgesia. On the other hand, the analgesic activity of LEamide was not observed, but pretreatment with amastatin (a peptidase inhibitor) produced LEamide-induced analgesia. These results indicate that CcpLEamide is stable in the body and has analgesic effects without pretreatment with peptidase inhibitors, and was stable enough to be absorbed from the small intestine. We propose CcpLEamide as an orally active analgesic peptide candidate.

Aminopeptidases↗
PubMed2000

Analgesic and antiinflammatory activities of an extract from Parkia biglobosa used in traditional medicine in the Ivory Coast.

In the Ivory coast, Parkia biglobosa (Mimosaceae) is used in traditional medicine as an analgesic drug, especially against dental pain. Of the three extracts obtained from the plant bark, the hexane fraction was studied to determine its analgesic and/or antiinflammatory activities. The results show that this extract possesses a marked analgesic activity when evaluated with the abdominal writhing test in mice, but, like paracetamol, was ineffective with the hot-plate method, a feature suggesting a peripheral mechanism of action. This activity was accompanied by an antiinflammatory effect, somewhat weaker than the analgesic one.

Analgesics↗
PubMed2004

Amide derivatives of [6-(5-methyl-3-phenylpyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acids as potential analgesic and anti-inflammatory compounds.

In this study, amide derivatives of [6-(5-methyl-3-phenyl-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were synthesized and tested for their in vivo analgesic and anti-inflammatory activity by using the p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a, 6d, 6e, 6g, 6h and 6m were more potent than that of aspirin as an analgesic and indomethacin as an anti-inflammatory drug, respectively. The other derivatives generally resulted in comparable activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro human whole blood assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and other mechanisms might be involved.

Acetates↗