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PubMed1988

Analgesic profile of rimazolium as compared to different classes of pain killers.

1,6-Dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazol (rimazolium, MZ-144) proved to be effective in all the analgesic assays used (independently of the nociceptive stimulus applied) (hot plate, tail flick, writhing tests, Randall-Selitto test, tail clip, surgical pain) differing in this respect from the nonsteroidal antiinflammatory analgetics. The analgesic, antiinflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared. The prostaglandin (PG) mediated pain (acetylcholine-, adenosine triphosphate- and acetic acid-induced writhing) was inhibited by all the three types of compounds, however, pain reaction where PGs are not involved (MgSO4-writhing) was inhibited only by rimazolium and morphine but not, or only slightly, by PG synthesis inhibitors. While the analgesic effect of rimazolium alone was not reversed by naloxone, the full analgesia evoked by the ineffective doses of morphine and rimazolium combinations was completely naloxone reversible (pA2 = 8.6). In addition, rimazolium produced weak analgesia by intrathecal administration, and its concomitant s.c. administration enhanced the analgesic effect of intrathecally administered morphine. Furthermore, chronic treatment with rimazolium failed to influence its analgesic activity, and no tolerance developed and no naloxone precipitated withdrawal syndrome could be seen. In addition, rimazolium did not substitute for morphine in morphine dependent rats, after morphine withdrawal, thus indicating that rimazolium lacks the capacity of producing opiate-like physiological dependence. Also rimazolium fails to show any indication of narcotic-like abuse liability by any of clinical assessments. Rimazolium, morphine and indometacin inhibited the carrageenin-induced edema formation. Gastrointestinal lesions produced by indometacin were depressed by rimazolium and enhanced by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1978

Analgesic studies of codeine and oxycodone in patients with cancer. II. Comparisons of intramuscular oxycodone with intramuscular morphine and codeine.

The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.

Adult↗
PubMed1986

Analgesic use by leprosy patients.

We questioned 235 subjects with leprosy regarding the consumption of analgesic preparations, and 46 subjects (19.5%) admitted to having consumed more than 2 kg of analgesics; the main reason for consumption was neuritic pain. The commonly consumed analgesics are paracetamol (acetaminophen) and local proprietary compound analgesics containing aspirin, phenacetin, and caffeine. Intravenous urograms were done on 28 of the 46 subjects, but none showed evidence of renal papillary necrosis. The reasons for this lack of renal papillary necrosis are postulated. Excessive ingestion of analgesics may be a contributory factor in the development of interstitial nephritis in patients with leprosy.

Acetaminophen↗
PubMed1979

[Causes and consequences of long term consumption of phenacetin-containing analgesics, from the urologist's point of view (author's transl)].

In the last two decades reports concerning analgesic nephropathies have been presented from most industrial countries. Today, there is no doubt concerning a causal association between long-term consumption of analgesics and renal failure. In a group of 274 urological patients, the reasons and consequences of long-term intake of phenacetin-containing compounds are herewith demonstrated. The reason for chronic consumption of analgesics is mainly headache, due to psychosomatic causes which had not been adequately treated. After an average latency period of 20 years, renal (papillary necrosis, chronic interstitial nephritis) and extrarenal manifestations appeared. Despite slow progression and low gradient symptoms, severe alterations could be determined at the first examination. Course and prognosis primarily depend on a successful cessation of analgesics and the elimination of the accompanying infection. In the last decade, an increase of transitional cell carcinoma induced by analgesics has been observed. 22 of our patients presented a tumor of the urothelium (i.e. 8%). A further increase of these specific cases is expected.

Analgesics↗
PubMed1985

[Characteristics of terminal analgesics-induced nephropathy].

The diagnosis of analgesic-associated nephropathy (AAN) may be missed because of the patients denial or regular analgesic intake. We therefore performed a cross-sectional study of the 144 patients of our hemodialysis center to investigate differences between the 48 patients with AAN (33%) and patients with other kidney diseases who served as controls. The aim was to find other attributes of analgesic users relating to social history, habits and morbidity. Dialysis patients with AAN were significantly older (60 +/- 10 versus 52 +/- 15 years) and more frequently women (65% versus 37%) compared with controls; they often had a family history of analgesic abuse. Comparison with an age-matched control group of hemodialysis patients with other kidney diseases showed that AAN patients smoked, used hypnotics and laxatives, and required prescriptions significantly more frequently; they were less frequently willing to undergo renal transplantation. With regard to accompanying diseases, they suffered significantly more often than the age-matched controls from anemia, renal osteodystrophy, peptic ulcer disease, diverticulosis, hemorrhoids, atrial fibrillation, coronary heart disease, hyperlipidemia, carpal tunnel syndrome, and urinary tract infections. The characteristic pattern of habits, social history and accompanying diseases may facilitate the diagnosis of AAN even in cases where analgesic consumption is denied.

Age Factors↗
PubMed1985

[Analgesic asthma].

Analgesics-induced asthma (AIA) is quite often unidentified and then is a severe danger to the patients affliced. In a case-control-study 1042 asthmatic patients selected by random were investigated. In 18.9% of patients the presence of AIA was recorded. Woman accounted for 71% of the AIA patients. Coincidence of AIA with nasal polyposis, paranasal sinus diseases, chronic rhinitis, alcohol intolerance and severe bronchial asthma was recorded with high significance. Chronic hyperplastic changes in the upper airways were exhibited by about 64% of the AIA patients. AIA is a non-allergic form of asthma, resembling immediate allergic type I reaction. Analgesics-based acute bronchoconstriction will typically develop within 45 min. following intake of the analgesic. Triggering threshold doses may differ strongly by individuals. Oral exposure test is connected with a high risk of complications. A case history usually is sufficient for save diagnosis. Analgesics without inhibiting action on cyclooxygenase usually are tolerated. The causes of AIA should be ascribed to changes in the release and conversion of arachidonic acid (Aa) from membrane phospholipids. The inhibition of Aa release (phospholipase-A2-reaction) by protease inhibitors or the inhibition of Aa transformation to bronchoconstrictive lipoxygenase products by lipoxygenase inhibitors were shown in vitro (isolated guinea pig lung strips and human bronchi). Paraaminomethylbenzoic acid also was found to be effective in clinical experiments preventing analgesics-induced bronchoconstriction. Both seem to be principal ways for modulation of bronchoconstriction.

Analgesics↗
PubMed1977

Investigations of the analgesic and morphine-like properties of azidomorphine.

In equianalgesic doses, azidomorphine is reported by J. Knoll, S. Fürst and K. Kelemen (The pharmacology of azidomorphine and azidocodeine. J. Pharm. Pharmacol. 25: 929-939, 1973) to be less likely than morphine to cause physical dependence. As the separation of the analgesic from the dependence-producing properties would represent an important contribution to the development of potent analgesic drugs, we have compared the effects of azidomorphine and morphine in a number of experiments in laboratory animals. In analgesic studies, azidomorphine was more potent than morphine in all tests and by every route of administration. However, the differences between the analgesic effects of azidomorphine and morphine were much smaller after oral than after parenteral administration. In the rhesus monkey, the programmed administration of azidomorphine over a period of 9 weeks produced physical dependence. In addition, azidomorphine was self-administered by the rhesus monkey over 3 weeks producing marked opiate-like physical dependence. It is concluded that the introduction of the azido group into the morphine molecule leads to a marked increase in analgesic activity compared with the parent drug but which does not decrease the ability to produce physical dependence.

Analgesics↗
PubMed1972

Evidence for the nephrotoxicity of analgesics.

Analgesic nephropathy in man is a definite but complex and probably multifactorial disorder, which largely follows long-term abuse of mixed analgesics. In North America the disorder has been almost entirely associated with heavy ingestion of the combination acetylsalicylic acid (ASA), phenacetin and caffeine. There is less clinical and experimental evidence for the nephrotoxicity of single analgesics; however, evidence for the nephrotoxicity of ASA alone is greater than that for phenacetin. In view of the evidence for nephrotoxicity of most mild analgesics, removal of phenacetin from the market would be unlikely to eliminate the problem of analgesic nephropathy.

Analgesics↗
PubMed1965

Drug interaction in the field of analgesic drugs.

The evidence for believing that mixtures of aspirin, phenacetin, and caffeine provide advantages over the individual components of these mixtures is reviewed, and doubt expressed as to the rationale for the use of these mixtures in ordinary medical practice. The syndrome of ;analgesic nephropathy' is also reviewed, and on the basis of experiments in healthy volunteers it is suggested that individual ingredients of analgesic mixtures be scrutinized more carefully in an attempt to track down the agents responsible for toxic effects.The use of phenothiazine compounds, alone or in mixture with narcotics, is reviewed, and the opinion expressed that methotrimeprazine has special analgesic attributes.The narcotic antagonists represent an extremely interesting group of drugs which possess analgesic activity as well as the ability to antagonize certain effects of morphine and other narcotic agents. The patterns of respiratory effect, psychotomimesis, and abstinence phenomena seen with these antagonists illustrate the possibility of dissociating certain effects usually assumed to be linked inseparably in drugs possessing the analgesic power of morphine.

Analgesics↗
PubMed1983

A new method for the rapid measurement of analgesic activity in rabbits.

A simple and rapid method is described for the screening of narcotic and non-narcotic analgesics in conscious rabbits. This method is based upon the increase in threshold by electrical stimulation of the ears of rabbit, by analgesics. A reliable dose-response and time-response relations were observed for both groups of analgesics. Naloxone did not produce a hyperalgesia when given alone. It antagonized, however, the analgesic activity of morphine without altering that of aspirin. From these results it is concluded that nociception induced by electrical stimulation of rabbit ears is a simple and rapid method for the screening of analgesics as well as their interactions with specific antagonists.

Analgesics, Opioid↗
PubMed1983

GABA-opiates interactions in the activity of analgesics.

The influence of compounds which reduce or potentiate GABA-ergic inhibition on the effect of analgesics of various structures was studied. The effect was estimated according to the analgesic activity (experiments in rats) and the suppression of the impulse summation in the central nervous system (experiments in rabbits). It was shown that GABA-negative agents (bicucullin, thiosemicarbazide) markedly decreased the effect of morphine, hydrocodone and the enkephaline analogs: Tyr-D-Ala-Gly-Phe-NH2 and Tyr-D-Ala-Gly-Phe(NO2)NH2. The action of bicuculline was close to that of naloxone, an opiate receptor blocker. GABA-positive agents (muscimol, GABA cetyl ether, valproate) potentiated the activity of the mentioned narcotic analgesics. The effect of GABA-positive agents was blocked not only by GABA-negative compounds, but also by naloxone. The obtained data are interpreted in terms of the assumed mutual complementary of GABA-ergic and opioidergic systems. It was shown that the effects of the analgesics of a different structure: phenylpiperidine derivatives (trimeperidine, fentanyl), diphenylacetic acid derivative (dimenoxadol) and 3-benzazocine tricyclic derivative (pentazocine) were unchanged by the studied GABA-ergic analyzers. The reasons for those dissimilarities between analgesics of different structures are discussed.

Aminooxyacetic Acid↗
PubMed1984

Mode of action of peripheral analgesics.

Peripheral analgesics amount to more than 95% of the analgesic market. The most important drugs of this group, salicylates, p-aminophenol derivatives, and nonacidic pyrazoles, have been used in therapy for about 100 years, their mode of action remaining unclear until today. This brief review gives a survey on the current knowledge of the therapeutic mechanisms and the molecular causes of the effects and the most important side effects of peripheral analgesics. At present, two theories cannot be rejected on the basis of current knowledge. The first and very popular concept postulates that peripheral analgesics act by inhibiting the formation of arachidonic acid metabolites. The alternative hypothesis relates the effects of the salicylates and related drugs to inhibition of various cell functions by unspecific, concentration-dependent incorporation of drug molecules in the cellular membrane. These two concepts are discussed, and the importance of the physiochemical characteristics and the pharmacokinetic behaviour of peripheral analgesics for the understanding of their effects and side effects is pointed out.

Analgesics↗
PubMed1984

Caffeine as an analgesic adjuvant.

Thirty clinical studies involving more than 10,000 patients conducted during the last 20 years have been analyzed to assess the value of caffeine as an analgesic adjuvant. Although most studies included patients with postpartum uterine cramping or episiotomy pain, some involved patients with pain from oral surgery or headache. In 21 of 26 studies, the relative potency estimates of an analgesic with caffeine to an analgesic without caffeine is greater than one. The pooled relative potency estimates in each of several major categories of combination analgesics are significantly greater than one. The overall pooled relative potency estimate is 1.41, with 95% confidence limits of 1.23 to 1.63; that is, to obtain the same amount of response from an analgesic without caffeine requires a dose that is approximately 40% greater than one with caffeine.

Acetaminophen↗
PubMed1983

[Pharmacological studies of dl-2[3-(2'-chlorophenoxy)phenyl]propionic acid. I. Analgesic and antipyretic effects].

Analgesic and antipyretic effects of dl-2[3-(2'-chlorophenoxy)phenyl] propionic acid (CPP) were studied in mice, rats and guinea-pigs. CPP produced a dose dependent inhibition of acetic acid-induced writhing syndrome. Its ED50 values 1 and 3 hr after oral administration were 47 and 31 mg/kg, respectively. CPP had a potent analgesic effect on bradykinin-induced nociceptive response in rats, and its ED50 value was 15 mg/kg 2 hr after oral administration. The analgesic activity of CPP in these experiments was less potent than that of indomethacin, but it was approximately equivalent to ibuprofen and 10 to 20 times as potent as aspirin. CPP had no analgesic effect on both the tail pinch and hot plate tests in mice, while CPP potentiated the analgesic effect of codeine on these tests. CPP had no effect on the nociceptive response induced by intradermal injection of bradykinin and/or EDTA in guinea-pigs. On the other hand, when CPP was given orally in a dose range of 1.25 to 5 mg/kg, it produced an antipyretic effect on yeast-induced fever in rats. The antipyretic activity of CPP was equivalent to ibuprofen and 10 to 15 times as potent as aspirin.

Analgesics↗
PubMed1981

[Comparative double-blind study of the analgesic activity of fosfosal (UR-1521) in patients with musculoskeletal and articular pain (author's transl)].

Fosfosal or 2-phosphonoxybenzoic acid is a new analgesic drug, whose analgesic activity and side effects have been determined in a double blind clinical study in comparison with placebo. The study has been done with 60 outpatients, of both sexes, which suffered musculoskeletal and arthritic pains. Patients were treated with fosfosal or placebo for eight days. The daily dose of fosfosal was 1 gram three times a day, once every 6-8 hours. The results obtained show that fosfosal has a clear analgesic activity, statistically significant versus placebo in all the parameters that were measured: pain severity, activity impairment and insomnia. The overall evaluation of the group of patients treated with fosfosal showed a marked improvement with a difference statistically significant with respect to the control group treated with placebo (p less than 0.001). The distribution of results in the fosfosal treated group was as follows: poor, 1; regular, 8; good, 10 and excellent, 6. The distribution in the placebo group was as follows: poor, 15; regular, 3; good, 2 and excellent, 0. The marked analgesic activity, the absence of side effects and the excellent gastric tolerance suggest that fosfosal is a promising new analgesic drug useful for the treatment of painful syndromes of several etiologies.

Adult↗
PubMedDate not supplied

[Intake patterns of analgesics in patients with headache who came to the neurologist].

We have analysed the pattern of analgesic use in a group of patients that came for the first time to the neurologist. We have examined the first intention analgesic use in patients with headache, before the therapeutic intervention of the neurologist. During a month, we have followed a group of 40 patients. 20 of them were admitted as ambulatory patients at a Headache Unit at a Hospital and the other 20 were attended as outpatients by a general neurologist. 'Over-the-counter' analgesics were the most commonly used (paracetamol, acetylsalicylic acid and combinations of them with other products such as caffeine). More than a half of the patients had consumed a combination of analgesics. At the time of the investigation, the mean of analgesic use were greater in the group attended at the Headache Unit than in the one attended by the general neurologist. This could depend on the fact that chronic daily headache was more frequent in the first group and that they were older than the other group. These findings could be in relation with a larger evolution of their headache.

Acute Disease↗
PubMed1995

[Registration in medical journals of prescriptions for strong analgesics prescribed by general practitioners].

The use of strong analgesics was continuously registered in 90 patients throughout 12 months via the public health authorities, who are responsible for the control of prescription of strong analgesics. After the 12 months, questionnaires were sent to the prescribing doctors about the treatment during that period. Twenty-five patients were excluded mainly due to incomplete data and non-responding GPs. Analysis of validity of the GPs' registration, with the public health authorities' registration used as the reference standard, showed 90% (95% confidence limits (CL):68-99%) agreement concerning continuing treatment with strong analgesics and 98% (CL:88-100%) regarding GPs' registration of patients not being treated with strong analgesics. In all, misclassification occurred in 5% (CL:1-13%) of the patients. Our study suggests that the GPs' information about prescriptions of strong analgesics is valid, and that it can be used in research.

Analgesics↗
PubMedDate not supplied

[Amitriptyline facilitates the analgesic effect of adrenal medulla autograft in the lumbar subarachnoid space of the rat].

OBJECTIVES: To investigate the possible enhancement of analgesic effect induced by treatment with amitriptyline (AMI) after the autografting of suprarenal medulla into the subarachnoid lumbar space in the rat. MATERIAL AND METHODS: Four experimental groups were formed (control + saline solution [SS]; control + AMI; transplant + SS and transplant + AMI). AMI (10 mg/kg i.p.) or SS was administered for 28 days after surgery. The tail-flick test, with baseline values taken before surgery, was used to measure threshold pain on days 1, 4, 7, 14, 21 and 28. RESULTS: Suprarenal medullae transplantation afforded evident analgesic effect from day 1 to day 28. Analgesic effect was enhanced in transplanted rats treated with AMI from day 4 of treatment, with more evident effect on day 28. No analgesic effect per se was observed in the control group. CONCLUSIONS: Our results confirm that grafting per se has an analgesic effect and that it can be improved by systematic treatment with AMI. These results suggest new possibilities for using suprarenal medulla grafts for pain.

Adrenal Medulla↗