ent-dextilidine and Pain

This review provides an overview of the basic knowledge of drug pain therapy in the palliative situation. Pain is one of the main symptoms in 60 to 90 % of cancer patients. Pain also develops with neurological and other diseases that occur in end-of-life situations. To address this symptom, a holistic strategy is required that encompasses all physical, psychological, social, and spiritual aspects of the multi-dimensional pain experience ("total pain" concept).Drug treatment for cancer pain has been based on a stepwise approach for many years, starting with non-opioid analgesics, followed by moderate and strong opioids. In contrast, today's pain management is determined more by the actual intensity of this aversive event.The pain assessment should be tailored to identify a nociceptive vs. neuropathic pain component that needs to be challenged by the most appropriate drug therapies. Non-opioid analgesics are ideal substances for relieving nociceptive pain. Antidepressants and anticonvulsants reduce the intensity of new neuropathic pain. Opioids are suitable for all types of pain, but are restricted to a second line choice. Among all opioids are tilidine and tramadol prodrugs, which only relieve pain after activation in the liver. Drug-drug interactions may also block this activation. Rapid release opioids should be used for cancer breakthrough pain. Transdermal opioid applications are recommended for swallowing disorders, but usually not to initiate pain control. An opioid switch can be performed if side effects such as hallucinations for the selected opioid are more pronounced than the pain reduction.. Dieser Beitrag bietet einen Überblick zu Basiswissen in medikamentöser Schmerztherapie in der Palliativsituation. Schmerz ist eines der führenden Symptome bei 60–90 % aller Krebspatienten. Schmerzen entstehen auch bei neurologischen oder anderen Krankheiten, die am Lebensende auftreten. Um dieses Symptom zu behandeln, ist eine ganzheitliche Strategie vonnöten, die alle körperlichen, psychologischen, sozialen und spirituellen Aspekte der multidimensionalen Schmerzerfahrung („Total Pain“-Konzept) umfasst.Die Behandlung von Krebsschmerzen basierte viele Jahre auf einem Stufenschema, beginnend mit nichtopioiden Analgetika, gefolgt von mittelstarken und starken Opioiden. Im Gegensatz dazu wird die heutige Schmerzbehandlung mehr von der tatsächlichen Intensität dieses aversiven Ereignisses bestimmt.Die Schmerzbeurteilung sollte darauf zugeschnitten sein, eine nozizeptive vs. neuropathische Schmerzkomponente zu identifizieren, die durch die geeignete Arzneimitteltherapie gelindert werden muss. Nichtopioid-Analgetika sind ideale Substanzen zur Linderung nozizeptiver Schmerzen. Antidepressiva und Antikonvulsiva reduzieren die Intensität neuer neuropathischer Schmerzen. Opioide sind für alle Arten von Schmerzen geeignet, sollten jedoch als zweite Wahl eingesetzt werden. Tilidin und Tramadol sind Prodrugs, die erst nach Aktivierung in der Leber schmerzlindernd wirken. Arzneimittelwechselwirkungen können diese Aktivierung blockieren. Schnellwirksame Opioide sollten bei Tumor-Durchbruchschmerzen eingesetzt werden. Transdermale Opioid-Anwendungen werden bei Schluckstörungen empfohlen, normalerweise jedoch nicht, um die Schmerzkontrolle einzuleiten. Wenn Nebenwirkungen wie Halluzinationen für das ausgewählte Opioid auftreten, kann ein Opioid-Wechsel durchgeführt werden.

Topics: Administration, Cutaneous; Analgesics; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents; Breakthrough Pain; Drug Substitution; Hallucinations; Humans; Neoplasms; Neuralgia; Pain; Pain Measurement; Palliative Care; Terminal Care; Tilidine; Tramadol

Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices.. A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation.. Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine/naloxone and predominantly in the region of Berlin. Dependency on tramadol or tilidine/naloxone is reported only rarely from addiction counseling centers. One third of the patients surveyed in an addiction clinic reported experiences with tramadol or tilidine/naloxone, but mostly with duration of less than 4 weeks and with a medical prescription based on a reasonable indication. Also, occasional illegal use of opioid analgesics as a substitute of heroin was reported. An evaluation of pooled data from statutory health insurance companies found 2.5% of persons receiving at least 1 prescription of tramadol or the combination of tilidine and naloxone in 2009 (1.6% with tramadol and 1.0% with tilidine/naloxone). High usage with more than 180 DDDs per year was found in 8.6% of patients treated with tramadol and 17.2% of patients with tilidine/naloxone.. In conclusion, the subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice. Considerable less information is available for the combination of tilidine and naloxone. However, the cumulation of evidence indicated a higher risk of misuse, abuse, and dependency for tilidine/naloxone solution, but not for slow-release tablets.

Topics: Analgesics, Opioid; Drug Therapy, Combination; Fraud; Germany; Humans; Incidence; Naloxone; Opioid-Related Disorders; Pain; Self Medication; Tilidine; Tramadol

Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Cyclooxygenase 2 Inhibitors; Humans; Naloxone; Osteoarthritis; Pain; Risk Factors; Tilidine; Tramadol

The cold pressor test (CPT) is widely implemented and offers a simple, experimental acute pain model utilizing cold pain. Previous trials have frequently paired the CPT with opioids in order to investigate the mechanisms underlying pharmacological analgesia, due to their known analgesic efficacy. However, opioid side effects may lead to unblinding and raise concerns about the safety of the experimental setting. Despite the established clinical efficacy of dipyrone (metamizole), its efficacy, tolerability, and safety in cold pressor pain has not been systematically addressed to date. This pooled analysis included data of 260 healthy volunteers from three randomized, placebo-controlled, double-blind substudies using the CPT following a pre-test-post-test-design. These substudies allow for comparing a single dose of 800 mg dipyrone with two different doses of the opioid tilidine/naloxone (50/4 mg and 100/8 mg, respectively). Outcomes included pain intensity ratings, pain tolerance, medication-attributed side effects, as well as changes of blood pressure and heart rate. We demonstrate that both opioid doses and dipyrone had a comparable, significant analgesic effect on cold pressor pain. However, dipyrone was associated with significantly less self-reported adverse effects and these were not significantly different from those under placebo. These results indicate that the combination of dipyrone and the CPT provides a safe, tolerable, and effective experimental model for the study of pharmacological analgesia. In combination with a CPT, dipyrone may be useful as a positive control, or baseline medication for the study of analgesic modulation.

Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cold Temperature; Dipyrone; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Naloxone; Pain; Pain Measurement; Tilidine; Treatment Outcome; Young Adult

The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management.. In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day.. Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia.. All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.

Topics: Acute Disease; Aged; Aged, 80 and over; Amides; Analgesics, Opioid; Anesthetics, Local; Catheterization; Female; Femoral Neck Fractures; Femoral Nerve; Humans; Male; Methimazole; Middle Aged; Models, Organizational; Naloxone; Narcotic Antagonists; Nerve Block; Pain; Pain Measurement; Pain, Postoperative; Prilocaine; Prospective Studies; Ropivacaine; Tilidine

335 patients (51% female, 49% male, mean age 56 years) with chronic pain and multimorbidity have been included in a multi-center 2-years' study with slow release Tilidine/Naloxone for efficacy and safety which included detailed laboratory examinations. 316 patients had already been treated with analgesics. 159 patients (47.5%) finished the study as planned, 176 patients finished the study earlier.. Parameters of quality of life such as persistent pain, sleep, mood and activity have improved. Tolerance has not been observed. In 85 patients (25%) adverse events had occurred (nausea, vomiting, dizziness) which are related to the study-medication. Constipation was documented in only 4 patients. After 2 years of therapy with Tilidine/Naloxone there has been no relevant changes in laboratory findings. There has been no sign of organ damage or interactions with concomitant medication.. Tilidine/Naloxone is an effective and safe analgesic (WHO II) suitable for the longterm treatment of patients with chronic pain.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Disease; Comorbidity; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Pain; Pain Measurement; Quality of Life; Tilidine; Treatment Outcome

The purpose of this study was to elucidate the relationship of plasma catecholamine concentrations with experienced pain intensity and analgesic effects in the setting of an experimental pain study with human volunteers.. Plasma norepinephrine and epinephrine concentrations of 12 healthy human volunteers were analysed before and during painful electrical tooth-pulp stimulation under medication using the highly potent opioid analgesic tilidine in a fixed tilidine/naloxone combination and with the non-steroidal anti-inflammatory agent bromfenac. Catecholamine levels were compared with pharmacodynamic effects and reported adverse effects.. Catecholamine levels revealed a statistically significant increase in plasma epinephrine concentrations (but not norepinephrine concentrations) 60-90 min after administration of tilidine/naloxone. This was correlated with the onset of adverse effects involving vertigo episodes in all reported cases. In contrast, there was no obvious correspondence of epinephrine or norepinephrine plasma concentrations to the experience of pain and analgesia. For comparison, under medication with the non-opioid analgesic bromfenac, only one mild adverse effects were noted, and no changes in plasma epinephrine or norepinephrine could be determined during the experimental sessions.. It is proposed that elevated plasma epinephrine concentrations are a newly determined response to opioid-induced vertigo; this has possible clinical implications.

Topics: Adult; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Electric Stimulation; Epinephrine; Female; Humans; Male; Norepinephrine; Pain; Pain Measurement; Tilidine

The analgesic efficacy and safety of single oral doses of two centrally acting compounds, the combination of 50 mg tilidine and 4 mg naloxone (Valoron N) and 50 mg tramadol (Tramal), were compared to 25, 50 and 75 mg of the non-steroidal antiinflammatory bromfenac in experimental pain.. It was a placebo-controlled double-blind 6-way crossover study design with 12 human volunteers. Acute pain was generated by electrical tooth pulp stimulation. Treatment effects were determined by recording somatosensory-evoked potentials and by subjective pain rating.. The tilidine/naloxone combination clearly was the most potent medication in this study, followed by bromfenac 75 mg, which produced an early pain relief. Tramadol produced poor analgesia, as did bromfenac 25 and 50 mg. There was no dose-response relationship for bromfenac. Control of plasma levels revealed pronounced interindividual differences in peak plasma concentrations for bromfenac, but not for tramadol. Tilidine/naloxone exerted adverse effects in 9, tramadol in 3 volunteers. Under medication with 25 and 50 mg bromfenac, respectively, only one subject reported adverse effects. No adverse effects were experienced with 75 mg bromfenac or placebo.. The results support previous conclusions about the analgesic efficacy of tilidine/naloxone and tramadol in experimental pain. Moreover, the findings suggest that 75 mg bromfenac might be suitable for fast but short relief of pain of non-inflammatory genesis.

Topics: Adult; Analgesics; Area Under Curve; Benzophenones; Bromobenzenes; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Evoked Potentials, Somatosensory; Female; Humans; Male; Naloxone; Pain; Tilidine; Tramadol

In the present study involving healthy test subjects, tilidin/naloxone (Valoron N; VAL) proved to have an analgesic effect roughly twice as pronounced as that of tramadol (TRA). Moreover, the analgesic effect of VAL showed a significantly more rapid onset than did that of TRA. This finding reflects the difference in rate of action of the active substances. In accordance with these findings, VAL is thus the most powerful analgesic presently available on the German market on simple prescription.

Topics: Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Cyclohexanols; Double-Blind Method; Drug Combinations; Humans; Naloxone; Pain; Pain Measurement; Random Allocation; Tilidine; Tramadol

In recent papers (8, 12, 13) it has been shown that the analysis of event related brain potentials has become a powerful tool in attempts to quantify pain experience in man. However, the following conditions have to be fulfilled when cerebral potentials are used to measure experimentally induced pain, as well as pain relief under pharmacological treatments: 1) randomization of stimulus intensities to minimize effects of habituation within and between sessions (3), 2) randomization of interstimulus intervals with a minimum distance of about 15 seconds to avoid overlapping effects, and 3) control of the power spectral density of brain activity immediately before the stimulus is applied. In searching for pain related cerebral potentials a principal component analysis was utilized. The grand mean of all evoked potentials (analysis period 500 ms) was built, and the brain potentials were decomposed into basic waveforms for the different experimental conditions (painful-nonpainful; different kinds of skin stimuli). Two components were found as correlates of the painfulness in a sample of 8 healthy untreated subjects (4). In order to demonstrate the usefulness and sensitivity of the here described methods to quantify analgesic effects in man, the opioide tilidine and the opiate antagonist naloxone were orally administered in different combinations. In detail, the 5 treatments: tilidine (100 mg), naloxone (32 mg), tilidine (100 mg) + naloxone (8 mg), tilidine (100 mg) + naloxone (32 mg), and placebo, were given double blind (3 replications of 5 X 5 Latin squares) in 15 healthy subjects, each participating in 5 sessions with exactly 3 days intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesics; Brain; Drug Evaluation; Evoked Potentials; Humans; Naloxone; Pain; Tilidine

The effects of the opioid tilidine and the opiate antagonist naloxone on somatosensory evoked potentials (SSEP) and pain ratings (E), elicited by electrical skin stimuli with randomized intensities, were investigated for different, orally administered tilidine and naloxone combinations in a double-blind Latin square design in 15 healthy humans. A high correlation between SSEP amplitudes and E was found for all treatments investigated. Tilidine (100 mg) decreased both SSEP amplitudes and E by about 25% compared to the placebo. No significant differences were found between the analgesic effects of tilidine and TN8 (tilidine 100 mg; naloxone 8 mg). The effects of both treatments were significantly different from those of the naloxone, placebo and TN32 treatments (tilidine 100 mg; naloxone 32 mg), indicating a marked naloxone-induced reversal of tilidine analgesia. Naloxone (32 mg) increased the SSEP amplitudes. No naloxone-induced hyperalgesia was seen in the pain ratings.

Topics: Adult; Analysis of Variance; Cyclohexanecarboxylic Acids; Evoked Potentials, Somatosensory; Humans; Male; Naloxone; Pain; Sensory Thresholds; Tilidine

Pain rating, withdrawal reflex and skin resistance reaction upon electrical skin stimuli were studied on 15 male volunteers under placebo, tilidine and prazepam. Tilidine (Valoron) is an orally applicable narcotic analgesic, with a mode of pain relief presumably similar to morphine; the tranquilizer prazepam (Demetrin) belongs to the benzodiazepine group. Significant reduction in all measured reaction amplitudes was found under tilidine, whereas prazepam reduced significantly only the skin resistance reaction. The relative drug-induced changes in reaction amplitudes, related to the corresponding placebo value, were independent of stimulus intensity for all investigated reactions. Therefore, fitted power functions re = a . Sn between reaction amplitudes re and stimulus intensity S showed a decrease in parameter a under the investigated drugs, whereas the exponent n remained constant. High correlations between parameters a and corresponding reciprocal threshold currents could be shown for all reactions measured. Furthermore the drug-induced changes of withdrawal reflex amplitude and of subjective estimation were found to be correlated over subjects. In contrast, no correlations were found between variations in skin resistance reaction and magnitude estimation due to the selected drugs, i.e., the influence of the drugs on the sensory component of pain sensation and on the skin resistance reaction were independent effects.

Topics: Analgesia; Cyclohexanecarboxylic Acids; Electric Stimulation; Humans; Male; Pain; Prazepam; Reflex; Sensory Thresholds; Skin; Tilidine

Topics: Adult; Analgesics; Cyclohexanecarboxylic Acids; Drug Evaluation; Female; Humans; Male; Pain; Pentazocine; Postoperative Complications; Tilidine

Topics: Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Male; Middle Aged; Pain; Placebos; Propiophenones; Tilidine

The transdermal 7-day buprenorphine matrix patch provides a constant and user-friendly pain management when chronic musculoskeletal pain requires opioids. This analysis of clinical routine data evaluated the benefit of this treatment for patients previously receiving oral long-term treatment with weak opioids alone. Data of 310 patients previously treated with tramadol or tildate/naloxone and part of a multicentre observational study with 3295 patients were analyzed. In 89.7% of the 310 patients oral treatment with weak opioids was replaced by the 7-day buprenorphine patch due to insufficient analgesia. During treatment with the 7-day buprenorphine patch there was a clinically significant decrease of the mean pain intensity at rest during the day from 5.7 to 2.9, on physical effort during the day from 7.3 to 3.8 and at night from 5.2 to 2.3 (11-point NRS scale, p < or = 0.001). In addition, quality of life aspects such as mobility, self-reliance and quality of sleep improved, which are relevant for individual patient satisfaction with pain management. For patients with previous long-term tramadol or tilidate/naloxone treatment the switch to the 7-day buprenorphine matrix patch proved to be effective and safe for the management of chronic pain. The user-friendly 7-day application interval contributes to improving compliance and a reducing exposure to tablets.

Topics: Activities of Daily Living; Administration, Cutaneous; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Disease; Drug Substitution; Female; Germany; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Pain; Pain Measurement; Prospective Studies; Quality of Life; Tilidine; Tramadol

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Pain; Tilidine; Time Factors

Topics: Analgesics, Opioid; Chronic Disease; Delayed-Action Preparations; Humans; Musculoskeletal Diseases; Pain; Pain Measurement; Tilidine; Treatment Outcome

Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Humans; Middle Aged; Naloxone; Narcotic Antagonists; Pain; Patient Satisfaction; Surveys and Questionnaires; Tilidine; Time Factors

Topics: Analgesics, Opioid; Chronic Disease; Cross-Sectional Studies; Health Surveys; Humans; Pain; Pain Measurement; Tilidine; Treatment Outcome

Topics: Analgesics, Opioid; Humans; Naloxone; Narcotic Antagonists; Pain; Pain, Intractable; Tilidine

50 patients with incurable chronic pain states were treated for a period of between six months and 14 years (median: 31 months) with tilidine-naloxone, and the results of tumor recorded. Amelioration of pain was achieved in an average of 60.7% of the cases. The 16 patients of this series suffering from neuropathic pain who received a somewhat lower dose responded equally as well (60.3% amelioration) as the overall group. In 24 patients suffering from pain, the daily dose remained unchanged throughout the course of treatment, had to be increased in 19, and was reduced in seven patients. In two patients, acceptable side-effects were indicated; in no case were there any signs of drug-induced organic damage.. The results show that tilidine-naloxone is a highly effective opioid analgesic with a remarkably favorable benefit-risk ratio for use in long-term treatment.

Topics: Adult; Aged; Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Middle Aged; Pain; Pain Measurement; Tilidine

Topics: Animals; Drug Therapy, Combination; Humans; Naloxone; Pain; Tilidine

After 70 treatments with extracorporeal shock wave lithotripsy (ESWL), using a combination of dipotassiumclorazepate p.o. 12 h before treatment and tilidin-naloxon 45 min before ESWL, 56 patients reported to be painfree or only minor, well-tolerable pain. Informed consent was obtained in all patients for this pilot study, leaving the possibility of further pain medication. 7 patients asked for an additional analgesic (fentanyl) and another 7 patients required a sedative (midazolam). No further anesthesiologic procedures were necessary. Nausea was observed in one patient as a possible side-effect of tilidin. To confirm these preliminary results, a prospective randomized study is currently conducted.

Topics: Administration, Oral; Adult; Aged; Anti-Anxiety Agents; Clorazepate Dipotassium; Cyclohexanecarboxylic Acids; Epidural Space; Female; Humans; Injections; Lithotripsy; Male; Middle Aged; Naloxone; Pain; Tilidine

Topics: Adult; Female; Humans; Mediastinal Emphysema; Oxygen Inhalation Therapy; Pain; Radiography; Thorax; Tilidine

This paper describes a series of experimental prerequisites in assessments to measure the efficacy of analgesic drugs in healthy man. Of course, there is no doubt that an analgesic has to prove its validity exactly where it ought to help; i.e. in the patient suffering from pain. But to objectify the mode of action, or to measure dose-response functions, to evaluate the optimal therapeutic dosage, or to compare the relative efficacy of the drug tested with known substances--all these investigations can best be performed in a sample of healthy, informed, intelligent and cooperative volunteers, as homogenous as possible. Various kinds of stimuli used in the experimental pain laboratory will be compared with respect to their usefulness in algesimetry; for example the CO2 laser stimulus and the intracutaneous electrical shock. New examples in the analysis of cerebral potentials evoked by painful stimuli will be presented, such as the principal component analysis, the maximum entropy method, and procedures of cerebral potential mappings. It will be shown that frequency transformation of stimulus-induced changes in the electroencephalogram can result in a powerful tool to verify effects even of the so-called weak analgesics, such as acetyl salicylic acid (Aspirin).

Topics: Adult; Aspirin; Electric Stimulation; Electroencephalography; Evoked Potentials; Humans; Methods; Naloxone; Pain; Tilidine

Systemic administration of opioids is one of the traditional, but by no means optimized therapeutic procedures in cancer pain. Besides the underlying pathophysiology, appropriate treatment has to take into account the psychodynamics and behavior of the patient as well as his life expectancy. In view of this, therapy with centrally acting analgesics can be considered after administration of analgesics with peripheral action first and then of psychoactive agents. Nefopam is a centrally (but not spinally) acting analgesic with a novel activity profile. Its advantages and disadvantages in the treatment of carcinoma pain are outlined. The opiate agonist-antagonist principle has the advantage of a lower dependence and tolerance potential. In addition, the preparations pentazocine, tilidine plus naloxone, and buprenorphine deviate from the morphine derivatives in various constituent effects. Their actions and side effects are outlined. The optimization of control of cancer pain is not possible without taking into account the time dimension. In 50 pain patients with advanced cancer, the following main errors were observed in previous treatment of pain syndromes: (1) too early parenteral administration in the course of the disease; (2) underdosage; (3) application intervals that were too long; and (4) use of analgesics as needed by the patient or on request and not according to a time schedule.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Middle Aged; Morphine; Nefopam; Neoplasms; Pain; Pentazocine; Tilidine; Tramadol

In an open study in patients with tumour-induced pain the analgetic effects of the prostaglandin-inhibiting compound diflunisal and the centrally-acting analgetic tilidine N were compared. A dosage of 1 g diflunisal was found to be equivalent to 50 drops of tilidine N and to be subjectively well-tolerated. In the pain-relieving therapy of tumour patients diflunisal appears to offer a genuine alternative to centrally-acting analgetics.

Topics: Aged; Cyclohexanecarboxylic Acids; Diflunisal; Dose-Response Relationship, Drug; Humans; Male; Neoplasms; Pain; Salicylates; Tilidine

Topics: Adolescent; Analgesics; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Drug Combinations; Female; Humans; Male; Naloxone; Pain; Pain, Postoperative; Tilidine; Wounds and Injuries

Topics: Age Factors; Burns; Cyclohexanecarboxylic Acids; Humans; Infant; Pain; Tilidine

Tilidine (Valoron) is a new strong analgesic which was introduced into the market in West Germany in 1970. In February 1978 tilidine was placed under the regulations of the German Narcotics Act because it had rapidly become an easily acquired substitute for opiates on the drug scene. Cases have become known where tilidine dependence developed during the treatment of pain in patients without any preceding addiction to other drugs. The relevant literature on tilidine is reviewed in regard to pharmacological, epidemiological and clinical aspects of tilidine dependence and abuse.

Topics: Adult; Cyclohexanecarboxylic Acids; Drug and Narcotic Control; Germany, West; Humans; Iatrogenic Disease; Pain; Respiration; Substance-Related Disorders; Tilidine

Topics: Cyclohexanecarboxylic Acids; Delirium; Female; Humans; Male; Pain; Self Medication; Substance Withdrawal Syndrome; Substance-Related Disorders; Tilidine

Topics: Adult; Analgesics; Cyclohexanecarboxylic Acids; Humans; Male; Pain; Substance-Related Disorders; Tilidine