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Biomedical subjects

G D Olsen

Publications and source records attributed to G D Olsen.

At least 55 records · Page 3Linked to original sources
PubMed1980

The effects of methadone on respiration and ventilation in Pygmy goats.

The respiratory effects of dl-methadone administered i.v. were examined in awake of Pygmy goats. Three castrated males and three anestrus females received i.v. injections of methadone in increasing sequential saline treatments 10 days before the methadone injections. Serum dl-methadone was measured by radioimmunoassay. The PACO2 and PaCO2 decreased significantly (P < .001) following administration of methadone, while arterial blood pH, respiratory frequency, VE, VA, VO2, VE/VO2, and VA/VO2 significantly increased (P < .05). These results are consistent with relative hyperventilation. The changes were sex-related except for the increases in pH and VO2. There was a strong correlation between increasing serum methadone concentration and increasing ratio of VA/VO2. Naloxone did not antagonize the methadone effects. Since methadone induces hypoventilation in many species including man, the pygmy goat provides an interesting example of a sharply contrasting species difference in narcotic effects. The mechanism of the drug-induced hyperventilation and the possible role of female sex hormones in the potentiation of the ventilatory effects should be explored.

Animals↗
PubMed1978

Gentamicin binding to serum and plasma proteins.

Gentamicin binding to serum proteins was studied by equilibrium dialysis at 37 degrees C and pH 7.4 in the presence of both physiologic and adjusted concentrations of ionized calcium and magnesium. The percentage of bound drug was inversely related to the concentration of these two divalent cations, raning from 27% bound with no calcium and magnesium present to 17% bound in the presence of four times physiologic concentrations. No significant difference in the extent of drug-protein binding was noted in a comparison of sera from healthy and uremic subjects. Heparin also was found to affect gentamicin binding. Increasing heparin concentration in serum increased apparent gentamicin-protein binding to 34% in the presence of physiologic amounts of calcium and magnesium. Buffered heparin solutions without plasma proteins bound up to 65% of total drug concentration. Gentamicin-protein binding may have implications regarding pharmacokinetics and renal cortical uptake.

Blood Proteins↗
PubMed1978

Conjugate lateral gaze nystagmus and free phenytoin concentrations in plasma: lack of correlation.

Electrooculographic recordings during left and right conjugate lateral gaze fixation from 10 degrees to 50 degrees were made in 29 patients being treated with phenytoin. At the time of electrooculographic recordings, venous blood samples were drawn for analysis of total and free phenytoin plasma concentrations. Rhythmic horizontal nystagmus occurred in 7 patients, and only at extreme (40 degrees, 50 degrees) later gaze in 6 of these. Measurable free phenytoin levels in the 29 patients ranged from 0.2 to 3.2 mug/ml, and in the 7 patients with nystagmus were 0.6, 0.8, 1.0, 1.0, 1.7, 1.8, and 3.2 mug/ml. Neither the occurrence of nystagmus nor the degree of lateral gaze at onset could be correlated with free phenytoin concentrations in plasma.

Adolescent↗
PubMed1978

Stereospecific antibodies to methadone. II. Synthesis of d- and 1-methadone antigens.

Diastereomeric methadols were prepared by reduction of the methadone enantiomers. Resulting methadols, after purification and characterization by mass spectrometry, were succinylated. The hemisuccinyl derivatives were conjugated with thyroglobulin via carbodiimide condensation. The conjugates of d- and of 1-methadol hemisuccinyl-thyroglobulin were employed as the antigens for immunization of white New Zealand rabbits in order to obtain specific anti d- and anti 1-methadone antisera.

Animals↗
PubMed1978

Methadone-induced respiratory depression in the dog: comparison of steady-state and rebreathing techniques and correlation with serum drug concentration.

The respiratory effect of di-methadone administered subcutaneously was examined in awake, unsedated female Labrador retrievers in which a chronic tracheostomy had been established. Respiratory depression was determined from the change in ventilatory response to carbon dioxide. Two methods for assessing the response were evaluated and compared, namely the classical steady-state and rebreathing techniques. Maximal methadone-induced respiratory depression after administration of 2 mg/kg of dl-methadone occurred by 1 hr as detected by both methods, but the magnitude of the response as detected by the steady-state technique was significantly greater. At 8 hr significant respiratory depression was still detectable by the steady-state but not by the rebreathing technique. At comparable serum drug levels, the rebreathing method consistently detected a smaller degree of drug-induced respiratory depression. Methadone administration produced a decrease in slope of the ventilation-response curve which was significant at 1 and 2 hr for both methods. Slopes of the response curves obtained at pretreatment control measurements were markedly different for the two techniques, being significantly greater for the rebreathing method. Serum dl-methadone concentration was measured by radioimmunoassay. The mean serum half-life of methadone was 4.7 hr. There was excellent correlation between the logarithm of serum drug concentration and drug-induced respiratory depression as measured by either technique.

Animals↗
PubMed1977

New gas chromatogrphic assay for the quantification of methadone. Application in human and animal studies.

A new gas chromatographic assay utilizing 2-dimethylamino-4,4-diphenyl-5-nonanone as the internal standard was developed for the quantification of methadone. The method involved extraction of methadone with 1-chlorobutane from tissue at pH 9.8, re-extraction of an aliquot of the organic solvent with 0.5 M sulphuric acid, alkalinization and final extraction into chloroform. The assay was used to determine the concentration of methadone (i) in whole blood samples from a normal volunteer following a single 9.4-mg oral dose of d-methadone hydrochloride, (ii) in whole blood, saliva and gastric juice from a methadone addict maintained on 90 mg of dimethadone hydrochloride per day, (iii) in mouse liver microsomes incubated with methadone, and (iv) in the perfusate of the isolated perfused rat liver.

Animals↗
PubMed1977

Clinical effects and pharmacokinetics of racemic methadone and its optical isomers.

The respiratory and pupillary effects of oral l-, d-, and d,l-methadone were studied in healthy male volunteers 21 to 35 yr of age. The mean half-life of drug in blood was 22 hr for racemic methadone, 24 hr for l-methadone, and 25 hr for d-methadone. The effects of d-methadone were not significantly different from the placebo response at a 7.5 mg dose, whereas a 50 and 100 mg dose slightly depressed respiration in one subject each. Both 7.5 mg of l-methadone and 15 mg of d,l-methadone induced intense and sustained respiratory depression and miosis. The changes induced by l-methadone were of longer duration than those of d,l-methadone, lasting more than 72 hr in some subjects. Whole blood drug concentration correlated well with respiratory depression and miosis for l- and d,,l-methadone. The potency ratio of l-methadone to d,l-methdone, calculated from blood drug concentration data, was found to be 3.0 for respiratory depression and 2.7 for miosis. The antiduretic effect of 15 mg of d,l-methadone was investigated in three subjects and was found to persist for as long as measurements were taken, namely 11 and 12 hr in two subjects. d,l-Methadone administered frequently for pain may have cumulative effects on respiratory control and ability to excrete a water load.

Adult↗
PubMed1977

Stereospecific antibodies to methadone. I. Radioimmunoassay of d,l-methadone in human serum.

Anti-d,l-methadone antibodies were produced in rabbits immunized with d,l-methadol-hemisuccinate thyroglobulin conjugate. Using the antiserum, a radioimmunoasay (RIA) for determination of d,l-methadone in human serum has been developed and is described. Concentration of d,l-methadone of 1.4 pmol in a native serum sample (volume 0.1 ml or less) could be measured directly by RIA. The antibodies crossreact 100% with d,l-methadone, 50% with d-methadone, 50% with l-methadone and 100% with alpha-d-methadol. No crossreactivity was found with alpha 1-methadol, morphine, meperidine, dextropropoxyphene, 2-ethyl-5-methyl-3,3-diphenyl-l-pyrroline and 2-ethylidene-l, 5-dimethyl-3,3-diphenylpyrrolidene. High sensitivity and small sample requirements make this method suitable for future monitoring of patients on methadone maintenance and for studies where other procedures have lack of sensitivity.

Animals↗
PubMed1976

Iodo-bis(quaternary ammonium) salts. Potential cartilage-selective x-ray contrast agents.

Bis(quaternary ammonium) compounds in which one or both quaternary nitrogens bear iodinated benzyl moieties and the charged centers are separated by 2, 4, 6, or 10 methylene units have been synthesized and evaluted for (a) binding to cartilaginous material, (b) radiocontrast characteristics, and (c) in vitro pharmacological effects. Also prepared was 1,5-diiodo-2,4-bis(beta-trimethylammonioethyl)benzene diiodide, an analogue in which the iodinated aryl group lies between the charged nitrogen centers. Biological studies show that these compounds bind to cartilage but at relatively slow rates and with low persistence, resulting in low and transient levels of radiopacity. In common with simpler bisquaternary compounds, these compounds block synaptic transmission.

Animals↗
PubMed1975

Morphine binding to human plasma proteins.

The interaction of (N-methyl-14C) morphine with purified human albumin and gamma globulin and with human plasma was studied by equilibrium dialysis. Morphine binds to albumin and, to a lesser extent, to gamma globulin, but probably does not bind to plasma lipoproteins. The per cent of drug bound to protein was dependent on protein concentration but independent of drug concentration in the therapeutic range of plasma morphine concentration. In this range, 34.0% to 37.5% of the drug is bound to human plasma, largely to the albumin fraction. This study is compared to an earlier one on the interaction of methadone with plasma proteins. It is likely that the lower lipid solubility of morphine compared to methadone is related to its decreased affinity for plasma proteins.

Blood Protein Electrophoresis↗
PubMed1975

Morphine and phenytoin binding to plasma proteins in renal and hepatic failure.

The binding of morphine and phenytoin to plasma proteins was examined in healthy subjects and in patients with renal and hepatic failure. In the uremic patients without hepatic failure, morphine binding was dependent on the concentration of total serum proteins and albumin, but not the severity of renal failure as measured by creatinine clearance. Binding of phenytoin, however, was dependent on the degree of renal failure and albumin concentration, but not on total serum protein concentration. Renal transplant in 1 patient restored the binding of both drugs to a value within the normal range. The combination of hypoalbuminemia and hyperbilirubinemia resulted in the greatest impairment to binding for both drugs. It is concluded that patients with uremia, jaundice, hypoalbuminemia, particularly in combination, are sensitive to usual clinical doses of morphine, at least in part, because of decreased binding to plasma proteins.

Bilirubin↗
PubMed1975

Binding of d-tubocurarine di (methyl-14C) ether iodide and other amines to cartilage, chondroitin sulfate and human plasma proteins.

The binding of d-tubocurarine di [methyl-14C] ether iodide (d-TCE) and other amines to bovine nasal septum, chondroitin sulfate (CS) and human plasma proteins was examined by equilibrium dialysis. Bovine nasal septum and CS bound d-TCE to a greater extent than they did morphine, d-methadone (d-ME) and l-methadone (l-ME). Cartilage, relative to an equal weight of pure CS, bound slightly more d-TCE, 50% more d-ME and l-ME, and the same amount of morphine. The amount of d-TCE bound to pure CS was similar to that of decamethonium [methyl-14C] dibromide but less than that of two new iodinated bisquaternary compounds: 1,6-bis(N,N-dimethyl-3-iodobenzylamino)hexane dichloride and 1,6-bis[dimethyl-(3-amino-4,6-diiodo-benzyl)amino]hexane dichloride. The binding of d-TCE is greater for pure CS than for impure CS which contains 26% protein, and binding to either preparation was inversely related to sodium ion concentration. In the drug concentration range explored, 30 to 40% of d-TCE is bound to plasma proteins, which is twice that of decamethonium binding but equivalent to the binding of morphine and about one-half the binding of d-ME and l-ME. In this same drug concentration range, each gram of cartilage (dry weight) can bind about 10(-7) mol of d-TCE. This study suggests that the binding of d-TCE to cartilage is an ionic type bonding to the anionic sites of the ester sulfates and glucuronate moieties of CS and that the binding of d-TCE to the protein fraction of cartilage is probably equal to, or less than, its binding to the CS fraction. It is concluded that cartilage may represent a measurable distribution pool for d-tubocurarine.

Amines↗
PubMed1972

Methadone binding to human plasma albumin.

The interaction of L-[1-(3)H] methadone with human plasma albumin was studied by equilibrium dialysis. The percent of methadone bound to albumin was relatively independent of the concentration of methadone, but was dependent on the concentration of albumin, ranging from 8.0 to 43.8 percent bound as the albumin concentration increased from 0.400 gram to 5.00 grams per 100 milliliters of solution.

Autoradiography↗
PubMedDate not supplied

Placental permeability for morphine-3-beta-D-glucuronide in the guinea pig.

The fetal Vd and the PS of the major metabolite of morphine, M3G, were studied in pregnant guinea pigs during the last half of gestation. Fetal Vd was determined to be 0.334 ml/g of fetal plus placental weight and did not vary as the gestation progressed. The mean +/- s.e. PS for M3G was 3.7 +/- 0.3 X 10(-5) ml/sec/g and was independent of anaesthesia. This value was consistent with previous studies of other hydrophilic compounds, indicating that diffusion governs the placental passage of M3G. The PS value increased with increasing fetal weight which was consistent with structural changes in the guinea pig placenta as fetal age progresses in late gestation.

Anesthesia↗
PubMedDate not supplied

Chronic in utero morphine exposure alters mu-agonist-stimulated [35S]-GTPgammaS binding in neonatal and juvenile guinea pig brainstem regions associated with breathing control.

Narcotic analgesics act acutely upon opioid receptors in the brainstem to depress respiration in neonates, whereas withdrawal from chronic in utero exposure to morphine is associated with hyperventilation in the newborn. Because of the association between breathing and exposure to exogenous opioids, opioid-stimulated [35S]-guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]-GTPgammaS) binding was examined in respiratory control areas of the brainstem in 3-, 7-, and 14-day-old guinea pigs who were exposed during the last 2 weeks of gestation by maternal subcutaneous injections of 7.5 mg/kg of morphine or an equal volume of saline twice daily. Ten micromolar D-ala(2), MePhe(4), Gly(ol)(5)-enkephalin (DAMGO), a mu-specific opioid receptor agonist, stimulated [35S]-GTPgammaS binding in the caudal and rostral ventral respiratory groups (cVRG and rVRG), nucleus tractus solitarius (NTS), and the parabrachial nucleus (PB). There were no statistically significant age-related changes in DAMGO-stimulated binding for any of the respiratory areas. However, morphine-exposed animals had decreased DAMGO-stimulated [35S]-GTPgammaS binding in these brainstem areas compared to saline-exposed animals. We hypothesize that this morphine-induced decrease in DAMGO activation of the mu-opioid receptor may be a partial explanation for the hyperventilation observed during neonatal morphine withdrawal.

Aging↗