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[Changes in intraocular pressure in anesthesia induced with althesin and maintained with methoxyflurane].

Intraocular pressure and arterial blood pressure were studied in 27 patients undergoing anaesthesia induced by 0,6-1 mg/kg of Althesin iv and maintained by methoxyflurane-N2O-O2 on spontaneous ventilation. All patients were scheduled to undergo various types of eye surgery, including open-eye surgery. Patients with glaucoma and cataract were administered 20% mannitol two hours prior to surgery. In all cases premedication was based on meperidine, promethazine and atropine sulphate im. During the entire period of anaesthesia the intraocular pressure and, generally, arterial blood pressure appeared to be lowered.

Adolescent↗

Defluorination of methoxyflurane by a glutathione-dependent enzyme.

Partial purification from rat liver of an enzyme which catalyzes defluorination of methoxyflurane is described. Fractionation of liver homogenates by protamine sulfate and ammonium sulfate precipitation and by Sephadex G-100 chromatography results in a 10-fold purification with 53% recovery. The enzyme requires glutathione for activity, and other sulfhydrhyl compounds cannot be substituted. The enzyme appears to be a glutathione S-transferase, possibly one of several which have recently been characterized.

Animals↗

Effect of methoxyflurane anesthesia on serum uric acid in man.

Serum uric acid levels were significantly increased on the first and third postoperative days following methoxyflurane anesthesia in subjects undergoing various surgical procedures. The increment on each of these days was significantly correlated with the duration of the anesthesia. No such changes were found following halothane or nitrous oxide-oxygen and relaxant anesthesia.

Halothane↗

Serum fluoride concentration, renal, and hepatic function test results in dogs with methoxyflurane anesthesia.

Effects of 3 hours of methoxyflurane anesthesia in 20 dogs were determined by blood urea nitrogen (BUN), serum creatinine (SC), serum alanine aminotransferase (ALT), serum alkaline phosphatase (ALP). sulfobromphthalein (BSP), phenosulfonphthalein (PSP) clearance test, 24-hour water intake and urine excretion, and serum inorganic fluoride (SIF) evaluation. Values for BUN, SC, serum ALT, BSP, and PSP after the anesthetic were not significantly different (P less than 0.05) from the base-line values. The serum ALP values were significantly increased (P less than 0.001). Water intake and urine excretion showed a peak increase 48 hours after anesthesia. Serum inorganic fluoride concentration increased significantly (P less than 0.001) compared with the base line. The SIF 20 minutes before anesthesia was 4.54 +/- 0.82 mumol/L, at 90 minutes of surgical anesthesia 92.35 +/- 8.91 micronmol/L, at 20 minutes after anesthesia 132 +/- 12.55 micronmol/L, and at 1, 3, and 6 days after anesthesia they were 105.60 +/- 8.93, 42.10 +/- 6.90, and 12.65 +/- 1.32 micronmol/L. Clinical signs of renal or hepatic failure were not detected in any of the treated dogs during 7 day post-anesthetic observation period.

Anesthesia, Inhalation↗

Action of methoxyflurane on intraocular pressure (IOP) and acid-basic equilibrium in the dog.

MEthoxyflurane pulmonary inhalation administered to dogs, 2 ml/10kg/5 min, after 10 minutes caused a significant increase (13.3 mmHg) in intraocular pressure as well (6 mmHg) in venous pressure and a significant fall, of 23.3 mmHg, in arterial pressure and in respiratory frequency, of 3.2 per min and amplitude of 7.1 mm. On the other side, as acid-basic equilibrium alterations in blood, were observed a fall of 0.13 of pH and an increase of 18.3 mmHg of pCO2 and of 2.7 mEq/l of bicarbonate concentration.

Acid-Base Equilibrium↗

PKQuest: volatile solutes - application to enflurane, nitrous oxide, halothane, methoxyflurane and toluene pharmacokinetics.

BACKGROUND: The application of physiologically based pharmacokinetic models (PBPK) to human studies has been limited by the lack of the detailed organ information that is required for this analysis. PKQuest is a new generic PBPK that is designed to avoid this problem by using a set of "standard human" default parameters that are applicable to most solutes. RESULTS: PKQuest is used to model the human pharmacokinetics of the volatile solutes. A "standard human" value for the lipid content of the blood and each organ (klip) was chosen. This set of klip and the oil/water partition coefficient then specifies the organ/blood partition for each organ. Using this approach, the pharmacokinetics of inert volatile solute is completely specified by just 2 parameters: the water/air and oil/water partition coefficients. The model predictions of PKQuest were in good agreement with the experimental data for the inert solutes enflurane and nitrous oxide and the metabolized solutes halothane and toluene. METHODS: The experimental data that was modeled was taken from previous publications. CONCLUSIONS: This approach greatly increases the predictive power of the PBPK. For inert volatile solutes the pharmacokinetics are determined just from the water/air and oil/water partition coefficient. Methoxyflurane cannot be modeled by this PBPK because the arterial and end tidal partial pressures are not equal (as assumed in the PBPK). This inequality results from the "washin-washout" artifact in the large airways that is established for solutes with large water/air partition coefficients.PKQuest and the worked examples are available on the web www.pkquest.com.

Journal Article↗

Effects of methoxyflurane and flurothyl in mice trained to discriminate pentylenetetrazol from saline.

A procedure is described for training mice to discriminate 30mg/kg pentylenetetrazol (PTZ) from saline when lever pressing was maintained under a fixed-ratio 20 schedule of milk presentation. To define the pharmacological profile of the PTZ stimulus in mice, generalization testing was conducted with oxazepam and Ro 15-4513 (sarmazenil). Consistent with data obtained by others in rats, oxazepam (1mg/kg) blocked the PTZ stimulus whereas Ro 15-4513 substituted for PTZ, but only at a dose (2mg/kg) that also decreased rates of responding. The effects of both a depressant and excitatory vapor in this model were also determined. The volatile anesthetic methoxyflurane (1000-2000 ppm) blocked the discriminative stimulus effects of PTZ in a concentration-dependent manner, while the convulsant vapor flurothyl (900 ppm) produced greater than 90% PTZ-lever responding without disrupting rates of responding. The PTZ-like discriminative stimulus effects of flurothyl were dose-dependently blocked by oxazepam (0.03-1.0mg/kg). As has been shown in numerous previous studies in rats, PTZ could be established as a discriminative stimulus in mice. PTZ discrimination could be blocked by a benzodiazepine agonist and shares some properties with a benzodiazepine inverse agonist. Substitution and antagonism studies can also be performed with vapors, illustrating the utility of this model for comparing their behavioral effects to those of more widely studied drugs.

Journal Article↗