Eudragit-based transdermal delivery system of pentazocine: Physico-chemical, in vitro and in vivo evaluations.

The present study was aimed to develop a matrix-type transdermal formulation of pentazocine using mixed polymeric grades of Eudragit RL/RS. The possible interaction between drug and polymer used were characterized by FTIR, DSC and X-RD. X-RD study indicates a change of state of drug from crystalline to amorphous in the matrix films prepared. The matrix transdermal films of pentazocine were evaluated for physical parameters and in vitro dissolution characteristic using Cygnus' sandwich patch holder. Irrespective of the grades of Eudragit polymer used, the thickness and weight per patch were similar. In vitro dissolution study revealed that, with an increase in the proportion of Eudragit RS (slightly permeable) type polymer, dissolution half life (t(50%)) increases and dissolution rate constant value decreases. Selected formulations were chosen for these pharmacokinetic studies in healthy rabbits. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2,) K(el), and MRT) were evaluated statistically. In vitro dissolution profiles (DRC and t(50%)) and pharmacokinetic parameters showed a significant difference between test products (P<0.01). Quantitatively good correlation was found between the percentage of drug absorbed from the transdermal patches and AUC((s)).

[Continuous intravenous administration of fentanyl reduces tenesmus after transurethral resection of the prostate (TUR-P)].

BACKGROUND: The relief from tenesmus is important after transurethral resection of the prostate (TUR-P). We evaluated the effect of continuous intravenous administration of fentanyl on the tenesmus. METHODS: Eleven patients receiving fentanyl infusion (fentanyl group) were compared with fourteen patients without fentanyl infusion (control group) retrospectively. All patients underwent TUR-P under spinal anesthesia with hyperbaric 0.5% bupivacaine 2.2-2.8 ml. In the fentanyl group, fentanyl infusion 25 microg x hr(-1) was started followed by fentanyl 50 microg administration postoperatively. RESULTS: In the fentanyl group, NSAIDs were needed in only one patient. Eleven patients in the control group, however, required NSAIDs and three of them needed additional pentazocine administration. The required amount of NSAIDs per patient was significantly smaller in the fentanyl group (Mann-Whitney U test, P < 0.01). In the fentanyl group, one patient had slight nausea but needed no care. Other side effects, such as respiratory depression, hypotension, bradycardia and somnolence were not observed. CONCLUSIONS: Continuous intravenous administration of fentanyl was very effective and safe enough for the tenesmus after TUR-EP.

Synthesis and evaluation of 3-(4-chlorobenzyl)-8-[11C]methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one: a PET tracer for imaging sigma(1) receptors.

3-(4-Chlorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1), a putative dopamine D(4) receptor antagonist (k(i) = 8.7 nM), was labeled by positron-emitter (11C) and its pharmacological evaluation was carried out with in vitro quantitative autoradiography and positron emission tomography (PET). 11C-Methylation of a corresponding desmethyl precursor (2) with [11C]CH(3)I gave [11C]1 with >or=98% of radiochemical purity after HPLC purification and 67-90 GBq/micromol of specific activity at the end of synthesis. The in vitro autoradiography using rat brain sections demonstrated that [11C]1 shows no specific binding to the D(4) receptors, but a high specific binding to sigma(1) receptors (IC(50) = 105 nM). In the PET study with monkey brain, [11C]1 was highly taken up by the brain and trapped in the brain for at least 90 min. The distribution pattern of radioactivity in the brain was striatum > thalamus > frontal cortex > cerebellum, which was same as the result of in vitro autoradiography. Pre-treatment with non-radioactive 1 (1 mg/kg) produced a significant reduction of radioactivity in all the regions including the cerebellum. Pre-treatment with (+)pentazocine (1 mg/kg), a selective sigma(1) receptor agonist, also reduced the radioactivity in the same regions to a similar extent. These results indicate that [11C]1 may have some specific binding to the sigma(1) receptors, which is consistent with the result of in vitro autoradiography.

[Anesthetic management of patients undergoing irrigation and drainage of chronic subdural hematoma--retrospective analysis of analgesia and sedation under locoregional anesthesia].

We retrospectively investigated the relationship between intraoperative hemodynamic variability and variables including patient background, anesthetic profile, and operative profile in 108 patients undergoing irrigation and drainage of chronic subdural hematoma under locoregional anesthesia. Patients were divided into two groups according to the degree of changes in mean arterial blood pressure (MAP) and heart rate (HR) during operation. Group A (n = 66) had MAP and HR changes < 20%, and Group B (n = 42) had MAP or HR changes > or = 20% of preoperative baseline values. Age was significantly higher in group B than Group A (mean +/- SD; 70 +/- 12 vs. 62 +/- 14 years, P < 0.01). In respect to additional anesthetic agents used (none; no additional anesthetic agents, enough; pentazocine > or = 0.3 mg.kg-1 and droperidol > or = 0.05 mg.kg-1, pentazocine > or = 0.5 mg.kg-1 or droperidol > or = 0.15 mg.kg-1, little; less than "enough"), ratio of "little" administered in Group B was significantly higher than that in Group A (64.3% vs. 37.9%, P < 0.05). These findings suggest that intraoperative hemodynamic variability under locoregional anesthesia in patients with chronic subdural hematoma is associated with age and insufficient use of hypnotic and/or analgesic agents.

Dilatation of radiation-induced esophageal strictures under sublingual buprenorphine analgesia: a pilot study.

BACKGROUND: Pain during dilatation of radiation strictures is a troublesome complaint. There is little information on sedation and analgesia during this procedure. We performed a pilot study to compare the analgesic efficacy of sublingual buprenorphine and intravenous pentazocine during dilatation of radiation-induced esophageal strictures. METHODS: Thirty-one patients with esophageal cancer who had radiation-induced strictures were randomized to receive either buprenorphine 0.2 mg sublingually two hours before dilatation (n = 17) or pentazocine 30 mg intravenously five minutes before dilatation (n = 14). Dilatation was considered successful if it could be performed to 12 mm diameter or more. Pain experienced during dilatation was graded as mild, moderate or severe. RESULTS: Sixteen patients in the buprenorphine group and 12 in the pentazocine group were dilated to > 12 mm size (p = ns). Twelve and nine patients respectively in the two groups experienced mild or no pain; ten and six patients had minor side-effects (p = ns). CONCLUSION: Buprenorphine is useful for sedoanalgesia during dilatation of radiation-induced strictures of the esophagus.

Analgesia for the reduction of Colles fracture. A comparison of hematoma block and intravenous sedation.

OBJECTIVE: An alternative to general anesthesia was tested against conventional sedation by a double-blind, randomized clinical trial in reduction of Colles fracture. SETTINGS: A large teaching hospital where cases of Colles fracture are not different from those seen in district hospitals. PATIENTS: Sixty-six out of 80 consecutive cases with this fracture were selected from March to August 1990 on the basis of: 1) informed consent; 2) no contraindication to any method of analgesia; 3) no analgesic during the past 8 hours; 4) injury duration less than 96 hours; 5) no mental, auditory, or visual impairment; and 6) no associated injury. INTERVENTIONS: Patients were randomized into 2 equal groups. After tests for Xylocaine (Astra brand of lidocaine hydrochloride) sensitivity in both groups, the A group received 30 mg of pentazocine with 5 mg of diazepam intravenously on the dorsum of the affected wrist (sedation group), whereas the B group received 20 cc of 1.5% Xylocaine into the fracture hematoma. Five minutes later the fracture was reduced and immobilized by Lakhtakia or A. Singh. MAIN OUTCOME MEASURES: Thirteen to 15 hours later Manglik, blinded to the analgesia status of the patient, recorded pain before, during, and after reduction using Visual Analogue Scale (VAS). MAIN RESULTS: Statistically, randomization and blinding were found to be effective. The pain scores during reduction in the local anesthetic group (median = 1.8) were significantly less than those in the sedation group (median = 8.7), P < 0.001 using the Wilcoxon rank sum test. The difference persisted in regression analysis. The 2 methods proved comparable in safety and other measures of effectiveness. CONCLUSIONS: Hematoma block by local anesthetic is a safe and effective alternative to sedation in reduction of Colles fracture.

[Analgosedation as an adjuvant during surgery under local anesthesia]. / Analgosedierung als adjuvante Massnahme bei Eingriffen in Lokalanästhesie.

Twelve systemically healthy patients each (ASA risk groups 1-2) who required oral surgery under local anesthesia received the short-acting benzodiazepin Midazolam for analgosedation as well as the analgesics Pentazocin or Piritramid. Both i.v. medications are suitable as adjuvants for local anesthesia since neither clinically relevant respiratory and circular depression nor major sleepiness were observed.

Cortical and thalamic effects of local application of pentazocine to the rat somatosensory cortex.

Cortical and thalamic somatosensory evoked activity was studied following local application of 3% pentazocine to the primary somatosensory SI area (PSA) or to the parietal association area (PAA) of the rat cerebral cortex. At cortical level pentazocine affected the responsiveness of the two cortical areas in a way at least in part opposite. In PSA it essentially depresses the negative wave of the responses, whereas in PAA it increases both the positive and the negative components of the evoked potentials. The changes observed were restricted to the cortical region on which the drug was applied. At thalamic level, administration of pentazocine to the PSA or the PAA did not modify the bioelectrical activity recorded from the center median-parafascicular complex. It is concluded that pentazocine has a direct influence on cortical neurons involved in somatosensory processes. The failure of pentazocine-induced cortical changes to modulate neuronal activity at thalamic level is discussed.

Sedation for outpatient conservative dentistry. A trial of pentazocine supplementation to diazepam and local analgesia techniques.

Pentazocine 30 mg. or 15 mg or a placebo, was administered randomly to forty-nine patients undergoing conservative dental treatment in combination with a local analgesic block and intravenous diazepam. Simple cardiorespiratory measurements were made throughout the treatment period. Patients in the 30 mg pentazocine group required some 6 mg diazepam less than the placebo (control) group (P less than 0.05). Patients receiving 15 mg pentazocine also required less diazepam compared to the control group, but this difference was not statistically significant. There were no significant differences between the three groups either in recovery times or the cardiorespiratory measurements.

[Methodological variants of neuroleptanalgesia (author's transl)]. / Varianten der Neuroleptanalgesie.

A survey is presented of the variations of neuroleptanalgesia. Modification of the injection technique, the hypnotic, the analgesic or the neuroleptic partial effect of the drug combinations produces four variations. The principles of the classical type of neuroleptanalgesia, namely the ability to selectively influence the single components of anaesthesia and the predominant use of a strong analgesic must remain unaltered in the definition of a variant. The use of clear nomenclature is used in an attempt to overcome the confusion which still exists in this field.

[Analgesic effect of pentazocine and its action on nociceptive afferent pathway].

Nociceptive stimulus was applied to the skin of adult cats by pinching with a serrated forceps or by radiant heat with Pain meter. This stimulation caused motor or emotional responses such as movements of the head and trunk, vocalization, escape and attack. After the administration of pentazocine, these responses disappeared and the animals behaved normally. Analgesic action appeared approximately 15 min after the administration and lasted more than 90 min. Effects of pentazocine on pain-afferent pathways were studied and the evoked potential was recorded by tibial nerve stimulation. Though pentazocine did not influence the evoked potential recorded from somatic sensory area I and mesencephalic central gray, the evoked potential in pre-central association area, nucleus centralis lateralis, nucleus suprageniculatus-limitans and reticularis pontis caudalis was reduced by pentazocine.

Induction of physical dependence in rats by short interval medication.

Rats were intermittently medicated at one hour intervals through an implanted intravenous cannula. Physical dependence on morphine and codeine was developed rapidly and it was detectable with the maintenance dose as low as 9.6 mg/kg/day. Physical dependence on pentazocine was also developed with the maintenance dose of 96 mg/kg/day, but was not with 9.6 mg/kg/day. In the pentazocine-treated rates, body weight loss was observed after the abrupt withdrawal, and abstinence signs were precipitated by naloxone 1 mg/kg. Cross physical dependence between morphine and pentazocine was demonstrated. Pentazocine suppressed the abstinence signs of rats weakly dependent on morphine, and morphine suppressed those of pentazocine-dependent rats. ID-1229, a new benzomorphan analgesic, did not produce dependence in this test and did not suppress the abstinence signs of morphine- and pentazocine-dependent rats.

The value of associating pentazocine with drugs used in accepted intravenous techniques.

Pentazocine, a systemic analgesic, can be utilized in local analgesic and intravenous techniques to provide better operating conditions in difficult cases, a reduction in the dosage of other agents employed, and a smoother recovery period.

[Trial of analgesia by acupuncture]. / Essais d'analgésie par acupuncture

The clinical trial involved 31 cases, 10 in stomatology. Acupuncture may produce analgesia after simple premedication. Of 21 abdominal operations, in 5 completion of effect using local infiltration of a few millilitres of lignocaine or intravenous pentazocine was required. In 7, general anaesthesia was required to complete the operation. All patients not receiving supplementary general anaesthesia were able to eat normally as soon as they were back in bed, passed flactus the same day and had a bowel movement the next day. Ten stomatological operations may be considered to be successful. Further pursual of these trials is justified.