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At least 19 recordsLinked to original sources
PubMed2003

Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline.

All previous studies of intra-articular (IA) analgesic drugs for postarthroscopy pain have administered test-drugs at the end of the arthroscopic procedure, before any baseline pain could be assessed. Assay sensitivity has often not been documented or has been assumed to be present if a placebo control group had significant pain during the observation period. We present an improved study design employing an IA catheter for test-drug administration only in patients with moderate-to-severe baseline pain within 2h postoperatively. Using this technique we explored the incidence of moderate-to-severe pain and possible predisposing factors for pain through a close follow-up of all patients. The study incorporated an explanatory study of IA ketamine. A double-blind, double-dummy technique was used. Summed pain intensity differences 0-120 min after test medication was the primary outcome variable. Of 77 patients assessed for inclusion, only 45 had moderate or severe pain. Significantly more women (78%) than men (45%) had moderate-to-severe pain (P<0.005). Those not included continued to have no or mild pain and consumed less rescue analgesics than those who had high baseline pain. Mean baseline pain in the patient group with moderate or severe pain was 50mm on a 0-100 m visual analogue scale (VAS) (SD=15.1)(n=45). Mean VAS in the patient group with no or mild pain was 7.5mm (SD=8.7)(n=32). The new method for IA analgesic trials solves the problem with undesirable inclusion of patients with no or mild pain. We observed rapid onset and significant pain relief after IA injection of 10 ml saline with or without ketamine 10mg, but no difference between these two test medications. Intra-muscular ketamine 10mg showed significantly better early pain relief, global evaluation, and longer time to rescue analgesic, compared with IA ketamine 10mg.

Analgesics↗
PubMed1986

The analgesic problem in the Federal Republic of Germany: analgesic consumption, frequency of analgesic nephropathy and regional differences.

The recent withdrawal of phenacetin from the pharmaceutical market in the FRG has stimulated the discussion of the extent of analgesic abuse and analgesic nephropathy (AN). Data from wholesale statistics, given here, revealed in the FRG population a high yearly per-capita consumption of analgesics (18.2 g), mostly used in mixed compounds. According to standardized data, the FRG ranks first among the north European countries. We suggest that the prevalence data given from the EDTA-registry (4.6% of the endstage renal population) underestimates the real extent of AN. AN in the FRG shows a north-to-south decline and is most prevalent in northern areas and West Berlin. It is assumed that the analgesic dilemma in the FRG is identical to the dilemma in Switzerland and Belgium.

Adolescent↗
PubMed1994

Analgesic nephropathy in Belgium is related to the sales of particular analgesic mixtures.

Analgesic nephropathy, a chronic progressive renal disease induced by the abuse of drugs containing analgesics and potentially addictive substances (e.g. caffeine, codeine), continues to be a serious problem in Belgium. A recent investigation (1990) of Belgian dialysis patients, including 54 of the 55 dialysis centres, established that 15.6% of the patients had analgesic nephropathy, showing a small decrease in prevalence compared to the 1979 and 1984 estimates. Considerable changes were observed in the sales figures of analgesic during the period 1983-1991. Phenacetin completely disappeared from the market and single analgesics, particularly paracetamol, gained large market shares. The total sales of single analgesics slowly increased, whereas the sales of analgesic mixtures decreased from 12.5 million to 8 million packages per year. In recent years the composition of most analgesic mixtures has been reduced to a single analgesic component in combination with caffeine and/or codeine. In comparing the geographical distribution of the sales of different analgesic products (1983) with the prevalence of analgesic nephropathy (1990), a strong correlation could be observed with particular analgesic mixtures, whereas this was not the case with single analgesics. This observation suggests that a careful analysis of sales data showing a high volume of analgesic mixtures sold, containing two analgesic substances combined with potentially addictive components, is a pharmacoepidemiological indicator for the presence of analgesic nephropathy in a given population.

Adult↗
PubMed1996

Combination analgesic involvement in the pathogenesis of analgesic nephropathy: the European perspective.

Analgesic nephropathy (AN) is a chronic renal disease characterized by renal papillary necrosis and interstitial nephritis caused by excessive consumption of analgesic mixtures. In a recent study, diagnostic criteria for AN, based on a computed tomography scan investigation without contrast, were presented. The observation of a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications was found to have a high diagnostic performance. Although several case control studies and two prospective studies demonstrated the association between analgesic abuse and nephropathy, the nephrotoxicity of the different analgesic products had not been clearly established. Analgesic abuse can be defined as a daily consumption of analgesic mixtures over a several-year period. Abuse of single analgesics is rare; it has been clearly demonstrated that abusers prefer analgesic mixtures. In Belgium, the prevalence of AN was positively related to the sales of analgesic mixtures containing two analgesic components plus caffeine and/or codeine. This relationship could not be observed for analgesics containing only one analgesic component plus caffeine and/or codeine. Moreover, during a European multicenter study, nephrotoxicity of different combinations of analgesic mixtures (all containing caffeine and/or codeine) could be documented in the absence of any previous phenacetin consumption. Epidemiologic observations in Sweden, France, and Belgium regarding incidence of AN, sales figures of analgesics, and legislative measurements concerning analgesic consumption supported the previous observations.

Analgesics↗
PubMed1999

Analgesic nephropathy: is it caused by multi-analgesic abuse or single substance use?

Analgesic nephropathy is a slowly progressive renal disease, characterised by renal papillary necrosis. Recently, diagnostic criteria for this disease have been defined based on renal computed tomography scanning performed without contrast. The observation of a decreased renal mass of both kidneys, combined with either bumpy contours or papillary calcifications, has been found to have high diagnostic specificity and sensitivity. However, the question remains as to what kind of analgesics can cause analgesic nephropathy. In the majority of early reports about this condition, phenacetin was singled out as the nephrotoxic culprit. However, during the last decade the nephrotoxic potential of nonphenacetin-containing preparations has become apparent. It is clear that people who abuse analgesics prefer combination analgesics containing 2 analgesics combined with caffeine and/or codeine. In contrast, abuse of products containing only aspirin (acetylsalicylic acid) or paracetamol (acetaminophen) is seldom described and associated renal disease is only occasionally reported. Experimental evidence of the nephrotoxicity of analgesic preparations is not well established. The results of studies involving analgesic administration in animals remain contradictory. Clinical evidence linking high consumption of analgesic preparations with analgesic nephropathy is overwhelming. Most patients who admit to over-consuming analgesics have taken preparation containing more than one compound. In recent years, it has become more apparent that preparations not containing phenacetin also have the potential to cause nephrotoxicity manifesting as identical renal lesions. Further epidemiological evidence of the nephrotoxic potential of analgesic combinations has come from case-control studies published during the last decade and from 2 prospective cohort studies. Effective prevention of analgesic nephropathy consists of the prohibition of over-the-counter sales of preparation containing at least 2 analgesics associated with caffeine and/or codeine.

Analgesics↗
PubMed1995

Impact of legislative measures on the sales of analgesics and the subsequent prevalence of analgesic nephropathy: a comparative study in France, Sweden and Belgium.

In a number of European countries (e.g. Belgium), analgesic nephropathy continues to be a highly prevalent renal disease, whereas in other countries (e.g. Sweden) the problem has been resolved after legislative measures were taken. In still other countries, e.g. France, the official prevalence of analgesic nephropathy has always been low. The aim of the present study is to detect whether specific legislation in particular countries has played a role in the prevalence of analgesic nephropathy. Hence, we compared analgesic legislation in Belgium, France and Sweden, and then compared it with the respective sales data of non-narcotic analgesics and with the prevalence data of analgesic nephropathy in the dialysis population. Each investigated country represents a different evolution pattern in the prevalence of analgesic nephropathy. This study indicates that legislation restricting the over-the-counter availability of the majority of analgesic components and resulting in the absence of analgesic mixtures--containing two analgesic substances and one potentially addictive substance--on the market, has effectively resulted in a substantially lower prevalence of analgesic nephropathy. Moreover, it shows that permissive legislation could be associated with very different sales data, depending on the marketing strategy of the pharmaceutical industry and the subsequent purchasing behaviour of the population. These findings indicate that, in order to eradicate analgesic nephropathy, there is a need to elaborate legislation that prohibits the availability of analgesic mixtures containing two analgesic components and at least one potentially addictive substance.

Analgesics↗
PubMed1998

An investigation into compound analgesic prescribing in South Africa, with special emphasis on meprobamate-containing analgesics.

The primary aim of the study was to analyse the prescribing patterns of compound or combination analgesics in four metropolitan areas in South Africa. Prescription data from 50 medical practices in each area were obtained from a medical aid scheme, and were retrospectively analysed for 1995. One-third (33.1%) of all prescriptions for central nervous system (CNS) drugs was for compound analgesics. Compound analgesics represented 81.2% of the total number, and 72.1% of the total cost, of all non-opioid analgesic prescriptions. Children younger than 10 years received 30.2% of all compound analgesics. The most frequently prescribed combination product was an analgesic capsule consisting of paracetamol, codeine phosphate, caffeine and meprobamate. Nearly half of all the meprobamate-containing analgesics prescribed, contained exactly the same dosages of active ingredients. Meprobamate-containing analgesics represented 29.6% of the total number of analgesic prescriptions. Most patients using meprobamate-containing analgesics (48.4%) were females between the ages of 30 and 59 years. Further studies on compound analgesic prescribing should be undertaken, especially in relation to the diagnoses for which they are prescribed, as well as to other medication taken concurrently with analgesic products.

Journal Article↗
PubMed2000

Effect of chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache.

OBJECTIVE: To investigate the effects of chronic analgesic exposure on the central serotonin system and the relationship between the serotonin system and the analgesic efficacy of nonnarcotic analgesics. METHODS: Paracetamol was administered daily to adult male Wistar rats for a period of 15 or 30 days. Analgesic efficacy was measured by the tail flick test. After completion of the treatment protocol, the rats were humanely killed, and the frontal cortex and brain stem were isolated. Characteristics of the specific binding of the 5-HT2A serotonin receptor and the serotonin transporter were studied using a radioligand binding technique. Platelet serotonin was determined by high-performance liquid chromatography. RESULTS: Chronic paracetamol administration resulted in a significant decrease in the maximum number of 5-HT2A binding sites and an increase in the maximum number of 5-HT transporter binding sites in frontal cortical membrane (P<.001). Changes in the central 5-HT system were associated with a rise in platelet 5-HT levels. The degree of receptor downregulation, as well as transporter upregulation, became less evident after more prolonged drug administration. Readaptation of serotonin receptors and transporters coincided with the decrease in the analgesic efficacy of paracetamol, as well as a fall in platelet 5-HT levels. CONCLUSIONS: These findings provide further evidence in support of an involvement of the 5-HT system in the antinociceptive activity of simple nonnarcotic analgesics. Plasticity of this neurotransmitter system after chronic analgesic exposure may lead to the loss of analgesic efficacy and, in its more extreme form, may produce analgesic-related painful conditions, for example, analgesic abuse headache.

Acetaminophen↗
PubMed1976

Post-transplantation analgesic dependence in patients who formerly suffered from analgesic neophropathy.

Twenty-two patients with functioning grafts who originally developed renal failure due to analgesic nephropathy ("analgesic" group), and 84 patients with various other causes of renal failure ("non-analgesic" group) were studied over one year to assess the extent of analgesic use and abuse. On each occasion that one of these patients reported to hospital a urine sample was collected and analyzed for N-acetylparaminophenol (NAPA). Of the "analgesic" group of patients, 14% had consistently negative urine samples while 41% showed NAPA in more than half the urines collected. In the "non-analgesic" group 29% of patients had entirely negative urine tests, and in only 7% were more than half of the urines NAPA-positive. Patients in the "non-analgesic" group readily admitted taking anaglesics at frequencies compatible with the observed number of positive tests. This contrasted with the "analgesic" group in which 14 of 19 patients with NAPA-positive urines denied analgesic intake. This is considered to be a guilt manifestation in patients who have developed a psychological dependence on analgesics and have recidivated with full knowledge of the possible harm these drugs may inflict on their grafts.

Analgesics↗
PubMed2001

Opioid analgesic prescribing and use - an audit of analgesic prescribing by general practitioners and The Multidisciplinary Pain Centre at Royal Brisbane Hospital.

AIMS: This study evaluated the use of and need for opioids in patients attending the Multidisciplinary Pain Centre at the Royal Brisbane Hospital (RBH). METHODS: All consecutive in-patient admissions in 1998 were reviewed. A 10-point scoring system based on the World Health Organization (WHO) analgesic ladder was devised to facilitate comparison of analgesic prescribing on admission and at the time of discharge. A conversion table was used to standardize opioid analgesic doses to an oral morphine equivalent. RESULTS: Of the 370 patients reviewed, 233 (81%) were by their general practitioners. Records of 288 (78%) were available for full review and 270 (94%) of these had noncancer pain. On admission, 239 (83%) were taking an opioid analgesic, with 135 (47%) taking strong opioids (e.g. morphine, oxycodone, methadone). There was a significant decrease in the mean total daily oral morphine equivalent prescribed on discharge 36.9 mg (95% CI: 33.4, 40.4) compared with that on admission 88.7 mg (95% CI: 77.6, 99.8) (P < 0.001). There was a significant decrease (P < 0.05) in the proportion of patients taking a primary opioid on discharge 153 (58%) compared with admission 239 (83%), although the proportion of patients taking a strong opioid on discharge 150 (52%) compared with admission 135 (47%) was not significantly different (P > 0.05). The proportion of patients taking a laxative showed a significant increase on discharge 110 (73%) compared with admission 38 (28%) (P < 0.05). CONCLUSIONS: Our analgesic prescribing scoring system and opioid conversion table have the potential to be developed further as tools for assessing opioid analgesic prescribing. The significant decrease in total daily oral morphine equivalents signifies the value of prescribing in accordance with the WHO analgesic ladder, and the necessity of general practitioner education. The management of chronic pain is complex, and it requires interventions additional to pharmacological therapy. Evaluation by a multidisciplinary team, coupled with experience in and an understanding of analgesic prescribing and rehabilitation provides an effective basis for improving the management of patients with chronic pain.

Acetaminophen↗
PubMed2000

Transdermal delivery of the potent analgesic dihydroetorphine: kinetic analysis of skin permeation and analgesic effect in the hairless rat.

Dihydroetorphine is an extraordinarily strong opioid analgesic. To assess its effectiveness after topical application in hairless rats we have examined the kinetic analysis of skin permeation through excised skin and the in-vitro reservoir effect of skin, and have investigated the predictability of plasma concentration and analgesic effect following in-vivo transdermal application. Dihydroetorphine was moderately permeable from an aqueous suspension through excised hairless rat skin. Dihydroetorphine flux from drug-dispersed pressure-sensitive adhesive tape was threefold that from the applied aqueous suspension. The fluxes through the abdominal and the dorsal skin during tape application fitted the Fickian diffusion equation well after the tape was removed peeling off the outer layer of the stratum corneum. The relationship between the plasma concentration and the analgesic effect was examined for four different rates of infusion of dihydroetorphine. A non-linear pharmacokinetic disposition was observed. Following abdominal (0.28 cm2, 20 microg) and dorsal (0.50 cm2, 35 microg) applications of the dihydroetorphine tape, plasma concentration (0.2-0.8 ng mL(-1)) and analgesic effect were maintained at a suitable level, for more than 8 h, until removal of the tape. These profiles were predictable using the combined equation for percutaneous absorption, disposition and the analgesic effect, but the analgesic effect was slightly lower than the predicted value. The results show that it was possible to control the plasma concentration and the analgesic effect of dihydroetorphine by topical application of the analgesic using pressure-sensitive adhesive tape in the hairless rat. It was possible to predict the result using mathematical modelling.

Administration, Cutaneous↗
PubMed1993

Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics.

BACKGROUND: Development of tolerance to opioid analgesics occurs often in patients with cancer-related pain. Cross-tolerance among opioid analgesics provides the physician with a major management problem. Incomplete cross-tolerance among opioid analgesics has been demonstrated to occur in animals and humans. The current study provides clinical evidence of the incomplete cross-tolerance of methadone with a number of mu-opioid agonist analgesics in patients with advanced cancer-related pain. RESULTS: Patients presented in the current study had cancer-related pain refractory to other mu--opioid receptor agonist analgesics as evidenced by inadequate analgesia despite escalation of opioid dose. All patients were adequately managed by conversion of their opioid dose to methadone. Additionally, the dose of methadone required to establish and maintain analgesia in these patients was modest compared with previous opioid dose requirements. CONCLUSIONS: Methadone is a potent opioid analgesic that demonstrates incomplete cross-tolerance with other mu-opioid receptor agonist analgesics. Conversion of the opioid-tolerant patient with cancer-related pain to methadone may represent an important therapeutic option in the management of patients with this difficult problem.

Adolescent↗
PubMed2006

Prevalence of opioid analgesic injection among rural nonmedical opioid analgesic users.

OBJECTIVE: The purpose of this study was to examine the prevalence and correlates of opioid analgesic injection (OAI) in a cohort of rural opioid analgesic users. METHODS: Cross-sectional study of 184 participants from rural Appalachian Kentucky. RESULTS: The majority of participants were male (54.9%), white (98.4%) and the median age was 30 years (interquartile range: 24-37). The self-reported lifetime prevalence of injection drug use (IDU) was 44.3%, with 35.3% of respondents reporting injection of oral opioid analgesic formulations. The prevalence of self-reported hepatitis C (HCV) was 14.8%, significantly greater than those not injecting opioid analgesics (1.7%) (p<0.001). Receptive needle sharing, distributive needle sharing and sharing of other injection paraphernalia was reported by 10.5%, 26.3%, and 42.1% of those currently injecting, respectively. CONCLUSIONS: Opioid analgesic injection was more prevalent in this rural population than has been found in previous reports. This study suggests a rising problem with injecting among rural opioid users, a problem more typically associated with urban drug users. Educating injectors of opioid analgesics on safe needle practices is necessary in order to curb the transmission of HIV, HCV, and other infectious diseases. Further study on the longitudinal course of opioid analgesic injection in this population appears warranted.

Adult↗
PubMed2000

Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.

BACKGROUND: The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD: A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy. RESULTS: The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect. CONCLUSION: The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.

Acetaminophen↗
PubMed2006

Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: report of the national analgesic nephropathy study.

Previous studies suggested that the non-contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history. Specific renal anatomic criteria were developed to determine whether a constellation of CT findings (small indented calcified kidneys [SICK]) is linked to analgesic ingestion. For approximating use before the onset of renal disease, only analgesic ingestion at least 9 yr before starting dialysis was considered relevant. Fifteen patients met the criteria for SICK. This represented 7% of the enrolled patients and approximately 1% of the total ESRD population. There was a significant increase in the estimated risk among patients with a history of heavy aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43] for > or =1 kg lifetime; OR 8.8 [95% CI 1.2 to 66] for > or =0.3 kg/yr). Total analgesic ingestion of > or =0.3 kg/yr also was significantly associated with SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by combination products that contained aspirin and phenacetin (used by three patients with SICK), which are no longer available. In addition, the CT finding of SICK was present only in a minority of heavy analgesic users, yielding a sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD population and do not occur among a sufficient proportion of heavy analgesic users to render the non-contrast-enhanced CT scan a sensitive tool to detect analgesic-associated kidney injury.

Adult↗