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Biomedical subjects

T Mellstrand

Publications and source records attributed to T Mellstrand.

At least 19 recordsLinked to original sources
PubMed1988

CSF and plasma pharmacokinetics of pethidine and norpethidine in man after epidural and intrathecal administration of pethidine.

The disposition of pethidine and its main metabolite, norpethidine, in cerebrospinal fluid (CSF) and plasma was studied in 11 thoracic surgery patients after lumbar epidural (100 mg; n = 6) or lumbar intrathecal (25 mg; n = 5) administration of pethidine. Pethidine appeared more slowly in plasma after intrathecal than after epidural administration (tmax 2.3 h and 14 min, respectively), but systemic bioavailability was similar. The CSF concentrations of pethidine were higher than those in plasma after both routes of administration. The maximal CSF/plasma concentration ratio was 6000 to 45,000 after intrathecal administration but was only 26 to 97 after the epidural route. Pethidine was rapidly distributed in CSF; nine to ten h after the intrathecal and epidural injections the CSF/plasma concentration ratios were 12 to 89 and 2 to 33, respectively. The calculated bioavailability in CSF of epidural pethidine was 10.3%. The terminal elimination half-life of pethidine was 6.0 h (CSF) and 5.4 h (plasma) after intrathecal administration and 8.6 h (CSF) and 8.8 h (plasma) after epidural injection. The volume of distribution of unchanged pethidine in the subarachnoid space was 13 ml.kg-1 and clearance from the CSF was 15 microliters.kg-1.min-1. In all patients receiving intrathecal pethidine and in some patients after epidural pethidine, CSF norpethidine concentrations were higher than those in plasma; the maximum CSF norpethidine was 102 to 1211 ng.ml-1 and 14 to 210 ng.ml-1 and the maximum CSF/plasma norpethidine concentration ratios were 21 to 652 and 0.6 to 14 times after intrathecal and epidural administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Pharmacokinetics of different epidural sites of morphine administration.

In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy - in 10 ml saline in the lumbar epidural interspace (n = 5), in 10 ml saline in the thoracic epidural interspace (n = 5), in 2 ml saline in the thoracic interspace (n = 8) and in 10 ml saline in the lumbar epidural interspace (n = 5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogeneously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Systemic absorption of adrenaline after aerosol, eye-drop and subcutaneous administration to healthy volunteers.

Adrenaline is the drug of choice for management of the anaphylactic reaction. The objective of this study was to compare systemic absorption of adrenaline after administration by different routes to healthy volunteers. Ten puffs (1.5 mg as adrenaline base) with 10-15 s intervals between them followed 2 h later by 20 puffs (3 mg) of adrenaline from a pressurized aerosol (Medihaler-Epi, 3M Riker, 14.0 mg/ml adrenaline acid tartrate) were sprayed into the cheek pouch or inhaled through the mouth or the nostrils. Adrenaline was also administered to the eyes by giving 2 drops (1 mg) of Isopto-Epinal (Alcon, 10 mg X ml-1). Finally, 0.5 ml (0.5 mg) of adrenaline was given subcutaneously in the upper arm of the same individuals. The systemic absorption was determined by measuring plasma adrenaline levels and effects on blood pressure, heart rate and finger tremor before and 5, 15, 30, 60, 90, and 120 min after adrenaline administration. Adrenaline given as eye-drops did not have any significant effect on these parameters. Subcutaneously administered adrenaline caused within 5 min a significant increase of plasma adrenaline level (from 1.0 +/- 0.2 to peak of 6.5 +/- 1.2 nM) which gradually decreased during 2 h. This mode of adrenaline administration increased the systolic blood pressure by a maximum of 11 +/- 3.5 mmHg, heart rate by 9 +/- 2.2 beats X min-1, tremor ratio by 4 +/- 0.6 and reduced the diastolic blood pressure by 18 +/- 4.7 mmHg. The cardiovascular effects were approximately maximum 15 min after administration and lasted almost 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1987

Loperamide--an opiate receptor agonist with gastrointestinal motility effects.

Loperamide is an opiate agonist, also exerting activity by inhibiting the action of calmodulin. The mode of action in the clinic is probably mainly due to its action on opiate receptors, since the effects of loperamide can be reversed by naloxone. The exclusive action in the gut is explained by the specific distribution of loperamide with extensive distribution to the gut and minimal influence on opiate receptors in CNS. Loperamide is well absorbed after oral administration and extensively metabolized. The pharmacokinetic properties are linear over a wide dose range.

Gastrointestinal Motility↗
PubMed1987

Fluorine uptake in bovine enamel from various treatment agents.

Bovine tooth enamel with a low and uniform fluorine content was used for the study of fluorine uptake by the Micro-Acid-Drop enamel biopsy technique from different treatment agents commonly used in Sweden. The fluorine concentration in the enamel was also measured after an exposure of the treated test surfaces in artificial saliva for 90 minutes. Sodium fluoride 0.2% and 2%, ferric aluminum fluoride solution and Duraphat varnish showed a high uptake of fluorine in the enamel with the highest concentration in the surface layer. Fluor Protector and the toothpastes showed a considerably lower fluorine uptake. After immersion in artificial saliva of the specimens, the concentration of fluorine in the enamel decreased.

Acid Etching, Dental↗
PubMed1987

Stability of PABA after UV irradiation in vivo and in vitro.

Sunscreens are widely used for the prevention of acute and chronic sun damage. One of the most widely used sunscreens is para-aminobenzoic acid (PABA). It has been reported that PABA decomposes on exposure to air and light as well as exposure to high doses of UVB. In the present study we found that PABA was stable during long-term storage. PABA seems to be stable after irradiation of physiological doses of UVA and UVB in vitro. However, the in vivo studies demonstrate that significantly less PABA could be extracted from UVA-irradiated sites compared to controls.

4-Aminobenzoic Acid↗
PubMed1986

Characterization of the antinociceptive effects of some adenosine analogues in the rat.

The antinociceptive effects of the stable adenosine analogues N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamidoadenosine (NECA) were investigated in conscious rats using cutaneous thermal tests (hot plate and tail flick). Subcutaneous administration of the adenosine analogues induced a dose-dependent antinociceptive response for all agents. However, NECA was approximately 15 times more potent than PIA and CHA. Approximately the same potency order and response was seen when the adenosine analogues were administered intrathecally at the lumbar level. By this route of administration, the adenosine analogues were approximately 10-20 times more potent than after S.C. administration. Intracerebroventricular administration (lateral ventricles), however, induced a variable response, in most cases a slight hyperalgesia. The nonspecific adenosine antagonist theophylline (S.C.) rapidly reduced the antinociceptive effect induced by PIA (S.C.) but enprofylline, a bronchodilating xanthine with low ability to antagonize adenosine did not influence PIA-induced antinociception. It is concluded that stable adenosine analogues and presumably adenosine itself have potent antinociceptive effects via specific adenosine receptors in the rat. The effects seem to be mediated mainly by a spinal mechanism of action.

Adenosine↗
PubMed1986

Extradural morphine: influence of adrenaline admixture.

The influence of the addition of adrenaline on extradural morphine analgesia and pharmacokinetics was investigated in a double-blind study. Morphine 2 mg was administered to 14 patients undergoing thoracotomy. In addition, adrenaline 50 micrograms added to the extradural solution, was administered to half of the patients, selected randomly. Morphine concentrations in serial plasma and cerebrospinal fluid (CSF) samples were measured. Postoperative analgesia was estimated by determining the requirement for additional analgesics. Following extradural administration of plain morphine, the peak morphine concentrations in CSF were 22 +/- 5 (SEM) times those in plasma; during the elimination phase the CSF concentrations exceeded those in plasma by about 150 times. The area under the concentration v. time curve (AUC) was 162 +/- 27 (SEM) times larger in CSF than in plasma. The admixture of adrenaline with the extradural morphine increased the individual variability in CSF and plasma concentrations. However, compared with the plain morphine group, adrenaline did not significantly increase the concentrations of morphine in CSF, nor were the morphine concentrations in plasma significantly decreased. The duration of analgesia was related to the amount of morphine in CSF, that is AUC (P less than 0.05) and peak concentrations of morphine in CSF (P less than 0.05).

Aged↗
PubMed1986

Does alcohol absorb to activated charcoal?

Activated charcoal seldom is used in pure-alcohol poisoning since it is absorbed rapidly from the gut. Furthermore in early reports activated charcoal was found to adsorb alcohol poorly. However, in 1981 North et al. [North, D. S., Thompson, J. D. & Peterson, C. D. (1981). Am. J. Hosp. Pharm., 38, 864-866] demonstrated in dogs that charcoal given at the same time as alcohol can reduce the blood alcohol concentration significantly. To study whether charcoal is of value in a clinical situation, a randomized cross-over study in two phases was conducted. Each person drank 88 g of alcohol and 30 min after either 20 g of activated charcoal was taken or the same volume of water was drunk. There were no significant differences in plasma alcohol concentrations with or without charcoal.

Adsorption↗
PubMed1985

CSF and plasma pharmacokinetics of intramuscular morphine.

Morphine concentrations in plasma and cerebrospinal fluid (CSF) were measured in 58 elderly patients after intramuscular administration of 10 mg morphine. The assay employed gas chromatography with electron capture detection. From 49 of the patients undergoing urological procedures plasma and lumbar CSF samples were obtained simultaneously as spinal analgesia was given, and in addition, repeated venous samples were obtained over 4 hours from 35 of the patients. A plasma-morphine concentration vs time plot was drawn from the mean values and a CSF-morphine vs time plot was calculated by pooling individual CSF concentrations and using the sliding mean technique. The individual CSF/plasma-morphine concentration ratio vs time was also plotted. In addition, 2 or 3 CSF and plasma samples were collected simultaneously from 3 patients undergoing thoracotomy. Large interindividual variation in the CSF concentration was found. The peak CSF level was reached after 3 h and, following pseudoequilibrium, CSF-morphine levels appeared only slightly lower than those found in plasma. The availability to spinal CSF amounted to no more than 0.005% of the administered dose. CSF-morphine concentrations were not related to plasma protein or albumin concentrations.

Aged↗
PubMed1984

Pharmacokinetics of epidural morphine in man.

Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6-7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66 +/- 8 mg/ml: mean +/- SEM) appeared within 12 +/- 3 min, and the terminal elimination half-life in plasma was 213 +/- 24 min. In CSF, morphine reached a peak (1575 +/- 359 ng/ml) after 135 +/- 40 min. The terminal elimination half-life for morphine in CSF was 239 +/- 10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9 +/- 0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.

Biological Availability↗
PubMed1984

Guanfacine in essential hypertension: effects during rest and isometric exercise.

The antihypertensive effects of guanfacine (0.5 to 4 mg daily) were investigated for 1 yr in 13 patients with essential hypertension. Blood pressure (BP) and heart rate (HR) response was measured during isometric exercise (handgrip) before starting the therapy, after 1 yr of treatment, and 2 wk after withdrawal. Guanfacine in once-daily dosage reduced BP during rest (supine BP: control, 175 +/- 6/103 +/- 4 mm Hg; 1 yr guanfacine, 161 +/- 5/91 +/- 3 mm Hg). Steady-state plasma concentrations after 1 yr were 4.1 +/- 0.59 ng/ml. Resting plasma norepinephrine (NE) and epinephrine (E) levels were lower during active therapy than 2 wk after withdrawal (guanfacine and control: plasma NE, 0.27 +/- 0.03/0.64 +/- 0.13 ng/ml; plasma E, 0.09 +/- 0.02/0.17 +/- 0.05 ng/ml). The relative reduction of plasma catecholamines (guanfacine and withdrawal) was of the same order during handgrip exercise as during supine rest. During isometric handgrip exercise, BP was lower during guanfacine therapy than before treatment and 2 wk after withdrawal, but the increment in BP during handgrip exercise was not affected by the drug despite the lower BP values on therapy. Our data indicate that the central alpha 2-agonist action of guanfacine reduces sympathoadrenal function equally during rest and isometric exercise.

Blood Pressure↗
PubMed1984

Pharmacokinetic aspects of intrathecal morphine analgesia.

Fifteen patients undergoing thoracotomy were given 0.25 or 0.50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study. Administration of morphine at the end of the operation resulted in a highly variable duration of analgesia ranging from 1-20.5 and 1-40 h for the 0.25 and 0.50 mg groups, respectively. Calculation of cumulative consumption pattern of additional analgesics given im indicated a dose-related analgesia lasting around 12 h. Morphine concentrations in the CSF were high and dose dependent. Thus, at 1 h, CSF concentrations (means +/- SEM) were 4,228 +/- 361 ng/ml and 10,447 +/- 1,538 ng/ml for the 0.25 and 0.50-mg groups, respectively. The plasma concentrations generally were very low, i.e., under 1 ng/ml. For the 0.50 and 0.25 mg groups, the terminal elimination half-life in CSF was 175 +/- 9 min and 196 +/- 13 min, respectively: the volume of CSF distribution was 0.88 +/- 0.16 ml X kg-1 and 1.06 +/- 0.17 ml X kg-1, respectively: and the clearance from CSF was 2.81 +/- 0.41 microliter X kg-1 X min-1 and 3.41 +/- 0.55 microliter X kg-1 X min-1, respectively (means +/- SEM). The study indicates that the significant pharmacokinetic parameter related to the long duration of analgesia after intrathecal morphine administration probably is the high CSF concentrations found, since the rate of elimination from CSF is similar to what is reported for morphine in plasma. Furthermore, modulation of nociceptive input in the thoracic region also may be achieved by lumbar administration, but a slower onset should be anticipated.

Aged↗
PubMed1984

Influence of dialysis on prednisolone kinetics.

Six patients with end-stage renal disease were given prednisolone, 0.7-1.0 mg/kg/b.wt. parenterally. Prednisolone kinetics were investigated during dialysis, in 3 patients on hemodialysis and in 3 on continuous peritoneal dialysis, and also on days without dialysis. Mean plasma half-life was 250 min in five patients and 690 min in one patient who also suffered from intermittent porphyria. No change was found in prednisolone kinetics when the dialysis-free period was compared to the dialysis periods.

Half-Life↗
PubMed1984

Treatment of oral theophylline poisoning.

Two patients, 15 and 20 years old, were admitted after an overdose of theophylline in a slow-release preparation. The gradual occurrence of clinical symptoms reflected the slow gastrointestinal absorption of the drug, and therefore active treatment was not started until 10 and 12 hours after intake, respectively. Peak s-concentrations were 275 and 1295 mumol/l, respectively. One patient was treated with hemoperfusion only, whereas the more severely intoxicated patient was treated with combined hemoperfusion and hemodialysis. Only about 0.2 g theophylline was eliminated by hemodialysis in this patient compared to a calculated amount of 6.9 g by hemoperfusion. Severely theophylline-intoxicated patients should be treated with supportive therapy and hemoperfusion.

Adolescent↗
PubMed1984

Glucocorticoids and asthma. Studies of resistance and systemic effects of glucocorticoids.

Glucocorticoid resistance in asthma is genetically determined in a few individuals. Preliminary data are presented from a study showing interaction with a drug as another explanation for glucocorticoid resistance. In 6 healthy individuals, prednisolone concentrations were measured during 9 h after oral intake of 15 mg before and after 10 days' intake of 450 mg of rifampicin daily. An increased clearance of prednisolone was demonstrated. Systemic effects of inhaled glucocorticoids have also been studied. Comparison in healthy individuals between beclomethasone dipropionate given as a spray and as powder showed similar systemic effects with the two modes of administration. A new glucocorticoid for inhalation therapy, budesonide, was shown to have a weaker systemic effect than beclomethasone dipropionate. By rinsing the mouth with water after inhalation, it was possible to reduce the amount of drug swallowed, and our data showed a tendency towards less systemic effects after mouth-rinsing.

Asthma↗
PubMed1983

Pharmacokinetic aspects of epidural morphine analgesia.

Twenty patients undergoing thoracotomy were given 2, 4, or 6 mg morphine epidurally in a double-blind, randomized study for postoperative analgesia. Administration at T12-L1 or L1-L2 resulted in a dose-related analgetic duration (514 +/- 118 min, 778 +/- 207 min, and 938 +/- 155 min; means +/- SEM, respectively, for the groups). For the three groups, peak plasma morphine concentrations (range 19-34 ng/ml) were reached within 15 min. The plasma curves had a similar appearance as after an intramuscular injection and pharmacokinetic calculations showed an elimination half-life (mean +/- SEM) of 173 +/- 24 min, 200 +/- 60 min, and 213 +/- 57 min for the groups, respectively. The morphine concentrations in the CSF were considerably higher compared with plasma (45-100 times the plasma concentration at 1 h, 100-250 times at 3 h, and 125-175 times at 5 h) but the elimination half-life of morphine in the cerebrospinal fluid (CSF) was similar to that in plasma. The lumbar approach was used with similar efficacy as reported for thoracic administration. Side effects were few and nonsignificant. The authors conclude that epidural morphine administration results in a dose-dependent analgesia, as well as concentrations in the CSF that are considerably higher than in plasma. With similar elimination half-lives for morphine in CSF and plasma, the long analgetic duration probably depends on the locally high morphine concentrations achieved. For safety purposes, one may use the lumbar approach to the epidural space even for thoracic pain without reducing the efficacy.

Aged↗