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Biomedical subjects

L H Booij

Publications and source records attributed to L H Booij.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neuromuscular transmission and its pharmacological blockade. Part 2: Pharmacology of neuromuscular blocking agents.

Clinically, neuromuscular blockade is induced with either depolarizing or non-depolarizing relaxants. Suxamethonium is the only depolarizing relaxant still in use. It is hydrolysed in the plasma by pseudo-cholinesterase (plasma cholinesterase). In some patients and in particular diseases the plasma cholinesterase activity is low and hence the effect of suxamethonium prolonged. Suxamethonium is characterized by side-effects such as myalgia, fasciculations and increase in intraocular, intracranial and intragastric pressure. More serious adverse reactions are masseter muscle spasm and potassium release, in patients with some neuromuscular diseases and increase in extrajunctional acetylcholine receptors. As non-depolarizing muscle relaxants benzylisoquinolines and steroidal compounds are mainly used. Each relaxant has its own pharmacological characteristics. The effect of most relaxants depends on liver and renal function because the pharmacokinetic behaviour is strongly dependent on these organs. Also, acid base balance disturbances, change in temperature, and neurological diseases have an effect on the profile of the relaxants. A number of drugs (anaesthetics, antibiotics, antiepileptics, etc.) have an effect on neuromuscular transmission, and thus interact with the relaxants. Some non-depolarizing relaxants cause histamine release and cardiovascular effects.

Body Temperature↗
PubMed1997

Neuromuscular transmission and its pharmacological blockade. Part 3: Continuous infusion of relaxants and reversal and monitoring of relaxation.

Continuous infusion is an attractive method of administration when muscle relaxation is needed for a longer period. The pharmacokinetic behaviour of a drug is an important determining factor for the suitability of relaxants for continuous infusion. At present mainly intermediately long acting relaxants are used for this purpose. At the end of surgery residual curarization may exist and thus anaesthesiologists prefer to be able to reverse the relaxants. The anticholinesterases neostigmine, pyridostigmine, and edrophonium are used clinically for this reason. Their effect is prolonged in patients with renal failure, and also affected during acid-base disturbances. Some other drugs have been used experimentally for the reversal of neuromuscular blockade, but are inadequate. Special problems can arise when reversal of a mivacurium-induced or antibiotic-induced blockade is wanted, or mivacurium was administered. Monitoring neuromuscular transmission is an important feature to determine the effect of relaxant administration or to detect residual curarization. It is based on stimulation of peripheral nerves with either single twitch, train of four, tetanic or double burst stimulation. The evoked response can be quantitated with mechanomyography, electromyography, or accelerography. The response of the various muscles to nerve stimulation varies due to the different characteristics of the muscles. Clinically, the use of the adductor pollicis muscle is advised.

Electromyography↗
PubMed1997

Neuromuscular transmission and its pharmacological blockade. Part 1: Neuromuscular transmission and general aspects of its blockade.

Blockade of neuromuscular transmission is an important feature during anaesthesia and intensive care treatment of patients. The neuromuscular junction exists in a prejunctional part where acetylcholine is synthesized, stored and released in quanta via a complicated vesicular system. In this system a number of proteins is involved. Acetylcholine diffuses across the junctional cleft and binds to acetylcholinereceptors at the postjunctional part, and is thereafter metabolized by acetylcholinesterase in the junctional cleft. Binding of acetylcholine to its postjunctional receptor evokes muscle contraction. Normally a large margin of safety exists in the neuromuscular transmission. In various situations, apart from up-and-down regulation of acetylcholine receptors, adjustment of acetylcholine release can occur. Pharmacological interference can interrupt the neuromuscular transmission and causes muscle relaxation. For this reason both depolarizing and non-depolarizing muscle relaxants are clinically used. The characteristics of an ideal clinical muscle relaxant are defined. In the description of the pharmacology of the relaxants the importance of pharmacodynamic and pharmacokinetic parameters are defined. Stereoisomerism plays a role with the relaxants. Toxins and venoms also interfere with neuromuscular transmission, through both pre- and postjunctional mechanisms.

Down-Regulation↗
PubMed1997

Neuromuscular transmission and its pharmacological blockade. Part 4: Use of relaxants in paediatric and elderly patients, in obstetrics, and in the intensive care unit.

The pharmacodynamic and pharmacokinetic characteristics of the non-depolarizing muscle relaxants are dependent on age. Thus differences are found between paediatric patients, adults, and elderly patients. Muscle relaxants cross the placenta and thus may cause problems in the fetus. Many of the potential adverse effects of relaxant administration are seen more pronounced in intensive care patients. Prolonged effects and problems in wearing patients from the ventilator are observed when muscle relaxants are used in such patients. Critical illness neuropathy is a syndrome different from relaxant induced neuromyopathy, but may be enhanced by relaxant administration.

Adult↗
PubMed1997

Regional metabolism of articaine in 10 patients undergoing intravenous regional anaesthesia during day case surgery.

AIMS: To study the pharmacokinetics of articaine and its metabolite articainic acid, in patients undergoing intravenous regional anaesthesia. METHODS: Ten patients (three male, seven female, ASA class 1-2), scheduled for surgery of the hand or forearm were included in the study. Articaine (40 ml, 0.5% solution (200 mg) was injected over 30 s. In total fifteen arterial blood samples were taken; one before injection and then at 10 min intervals, starting 10 min after completion of injection, until the tourniquet was released; thereafter blood samples were drawn at intervals of 1, 5, 10, 15, 20, 25, 30, 45, 60, 75 and 90 min. The tourniquet was released 30 min after completing the injection. RESULTS: During tourniquet application and regional analgesia of 30 min duration, 55% of articaine was hydrolysed by plasma (20%) and tissue (35%) esterase activity to the metabolite articainic acid. After releasing the tourniquet, articaine and its metabolite appeared in the blood; articaine was rapidly eliminated with a t1/2z of approximately 60 min. The plasma concentration of the metabolite articainic acid was the sum of the amount formed during IVRA (55%) and the amount formed after tourniquet release (45%). CONCLUSIONS: Articaine is a safe agent for intravenous regional anaesthesia (IVRA) with rapid onset of good surgical anaesthesia. During tourniquet application and regional analgesia, 55% of the administered dose is already hydrolysed, thus reducing the chance of side effects after tourniquet release.

Anesthesia, Intravenous↗
PubMed1997

Repeated enflurane anaesthetics and model predictions: a study of the variability in the predictive performance measures.

We quantified the total variability (reproducibility) and the within-patient but between repeat anaesthetics variability (repeatability) in measures which are used to judge the predictive performance of our physiological model. We studied 14 patients who received enflurane closed-circuit anaesthesia on two occasions. The end-tidal concentrations measured and those predicted served to calculate the predictive performance measures of the model: root mean squared error (rmse = total error), bias (systematic error) and scatter (error around the bias). The overall results were: rmse 15 (7)%, bias 0 (14)% and scatter 9 (3)% (grand mean (total SD)). The within-patient SD values were smaller for the rmse (4%) and bias (10%), but not for scatter (3%). The repeat rmse values and biases were linked to the first results. This implies that these performance measures depended partly on the patient. As there was no association between the personal performance measures and age, sex, body weight, body surface area or body mass index, these characteristics cannot be used to further tune the model.

Adolescent↗
PubMed1997

Comparison of the disposition kinetics of lidocaine and (+/-)prilocaine in 20 patients undergoing intravenous regional anaesthesia during day case surgery.

OBJECTIVE: The aim of this investigation was to compare the pharmacokinetics of lidocaine and prilocaine in two groups of 10 patients undergoing intravenous regional anaesthesia. METHOD: The study had a randomized design. The patients were allocated to one of the two groups of 10. Each group received either lidocaine (200 mg = 0.855 mM) or prilocaine (Citanest, 200 mg = 0.909 mM), injected intravenously over a period of 30 s. Onset of the surgical analgesia was defined as the period from the end of the injection of the local anaesthetic to the loss of pinprick sensation in the distribution of all three nerves. RESULTS: The mean onset time of surgical analgesia of lidocaine was 11.2 +/- 5.1 min and that of prilocaine was 10.9 +/- 6.0 min. After releasing the tourniquet, lidocaine is bi-exponentially eliminated with a t1/2 alpha of 4.3 +/- 2.1 min and a t1/2 beta of 79.1 +/- 31.2 min. Total body clearance was 0.86 +/- 0.39 litres/min. Prilocaine is rapidly and bi-exponentially eliminated with a t1/2 alpha of 3.0 +/- 1.6 min and a t1/2 beta of 29.9 +/- 15.7 min. The total body clearance of prilocaine is higher than that of lidocaine, 4.15 +/- 1.31 vs. 0.86 +/- 0.39 litres/min, respectively (P = 0.0007). Both compounds show comparable volumes of distribution (Vd, Vss and V beta) and a comparable t1/2 alpha (4.3 +/- 2.1 vs. 3.0 +/- 1.6 min; P = 0.1780). The t1/2 beta for the two compounds were different (P = 0031); 79.1 +/- 31.2 min for lidocaine and 29.9 +/- 15.7 min for prilocaine. The mean residence time (MRT) of lidocaine (193 +/- 233 min) also differed significantly from that of prilocaine (33.4 +/- 19.9 min; P = 0.0022). CONCLUSION: Lidocaine is preferred for relatively long procedures and prilocaine for short procedures.

Adult↗
PubMed1997

Epidural metabolism of articaine to its metabolite articainic acid in five patients after epidural administration of 600 mg articaine.

The clinical pharmacokinetics, metabolism and renal excretion of articaine and its metabolite articainic acid have been investigated in man after epidural administration. (+/-)-Articaine and its metabolite (+/-)-articainic acid have different pharmacokinetic constants (P = 0.0079) except for lag-time (tlag; 0.06 min), first phase distribution of elimination (t 1/2 alpha; 0.49 +/- 0.21 h), and elimination half life (t 1/2 beta; 2.19 +/- 0.98 h), which are all the same for both compounds. The total body clearance of articaine (103 +/- 57 L h-1) is 10 times higher than that of the metabolite articainic acid (10.7 +/- 1.80 L h-1, P = 0.0079). With similar half-life (t 1/2 beta) values (2h), the volumes of distribution (V beta) are 10 times higher for the parent drug than for the metabolite ((329 +/- 212 L compared with 38.4 +/- 7.5 L, respectively; P = 0.0079). The difference between the areas under the curves for total plasma articainic acid and that formed in the plasma gives an indication of the percentage metabolism during epidural transfer (5.38 +/- 1.51%). This percentage of metabolism corresponds to a mean epidural transfer time of 5 min. The main compound in the urine is articainic acid (64.2 +/- 14.4%), followed by articainic acid glucuronide (13.4 +/- 4.97%) and the parent drug (1.45 +/- 0.77%). In total, 79.0 +/- 18.5% of the dose is recovered in the urine. The renal clearance of articaine is 22.5 +/- 13.9 mL min-1, whereas that of articainic acid is 119.6 +/- 30.1 mL min-1 (P < 0.0001). The apparent renal clearance of articainic acid glucuronide was 25.4 +/- 12.0 mL min-1. This value does not differ from that of the parent drug (P > 0.8). Articainic acid glucuronide is not present in plasma, but has an apparent renal clearance of 25 mL min-1. These results suggest that articainic acid is glucuronidated by the tubular cells and then excreted.

Adult↗
PubMed1996

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium.

We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree.

Adolescent↗
PubMed1995

Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia.

After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean apparent half-lives (+/- SD) of elimination were 10 min (0.165 h +/- 0.053 h) for 3,6-dinicotinoylmorphine and 1.77 h +/- 1.23 h for 6-mononicotinoylmorphine. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morphine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, and 4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3,6-dinicotinoylmorphine was biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine, and morphine-6-glucuronide.

Adolescent↗
PubMed1995

A system model for halothane closed-circuit anesthesia. Structure considerations and performance evaluation.

BACKGROUND: Previously, the authors described a physiologic model for closed-circuit inhalational anesthesia. The basic version of this system model was clinically validated for isoflurane. An extended version adopted nonpulmonary elimination causing a constant fraction of anesthetic to be irreversibly lost. This version improved the accuracy of the model for enflurane. The model's performance for other inhalational anesthetics that are not biochemically inert, such as halothane, remained to be evaluated. METHODS: The current study quantified the predictive performance of four versions of the model by comparison of the predicted and measured alveolar halothane concentration-time profiles in 53 patients. Version A did not incorporate nonpulmonary elimination, whereas version D adopted a nonlinear hepatic nonpulmonary elimination following Michaelis-Menten kinetics. A and D used fixed partition coefficients. Their counterparts, A' and D', were formulated to examine the impact of age-adjusted partition coefficients on the accuracy of our model. Each concentration measured by mass spectrometry was compared to four predicted concentrations calculated by four computer simulations (one per version). For each patient, the authors calculated the root mean squared error (rmse; typical error size), bias (systematic component), and scatter of the prediction errors. RESULTS: Fifty-three patients were anesthetized with 330 ml of liquid halothane via 426 bolus injections during more than 61 h; 21,890 alveolar concentrations (average 0.6 vol%) were measured. Version D' showed the best overall performance with an rmse of 19.6 +/- 7.2%, a bias of 0.5 +/- 15.9%, and a scatter of 13.2 +/- 3.5% (mean +/- SD). CONCLUSIONS: The model incorporating nonpulmonary elimination and age-adjusted partition coefficients (D') is sufficiently reliable and accurate to represent halothane closed-circuit anesthesia. This system model, with its various versions, is a valuable tool to predict the dynamics of isoflurane, enflurane, and halothane for clinical, educational, and research purposes.

Adult↗
PubMed1995

The bioavailability of intramuscularly administered nicomorphine (Vilan) with its metabolites and their glucuronide conjugates in surgical patients.

The kinetics of 20 mg nicomorphine intramuscularly were described in 8 patients under combined general and epidural anesthesia. The half-life of nicomorphine was 0.32 +/- 0.20 h (mean +/- SD) and is governed by the absorption-rather than the elimination rate. The half-life of 6-mononicotinoylmorphine (0.39 +/- 0.09 h) was identical to that of the parent compound (p = 0.29), suggesting it is directly related to the absorption rate of nicomorphine. Morphine had a half-life of 1.38 +/- 0.31 h. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The half-life of these 2 glucuronide conjugates was about 2.6 h (p = 0.07). A glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In urine only morphine and its glucuronides are found, with renal clearance values of 214 ml.min-1 for morphine and 132 ml.min-1 for the glucuronides. The bioavailability of this pharmaceutical formulation after intramuscular administration equals that of intravenous administration in surgical patients (at the same dose).

Adult↗
PubMed1994

Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates.

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48 +/- 0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P > 0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 ml.min-1 and for the glucuronides 81 ml.min-1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine.

Administration, Rectal↗
PubMed1994

Site- and test-dependent antinociceptive efficacy of amitriptyline in rats.

The antinociceptive efficacy of systemic- (IV), spinal- (IT), and global supraspinal (ICV)-administered amitriptyline (AMIT) was compared in three different tests for nociception: the hot-plate test, the tail-flick test, and the withdrawal reflex test. Systemic AMIT inhibited the responses in each of the three tests, with distinct dose-effect relationships. Spinal AMIT reduced in a dose-dependent fashion the force of withdrawal to noxious electrical stimulation but was ineffective in the hot-plate test and facilitated the responses in the tail-flick test. Supraspinal AMIT inhibited in dose-dependent fashion the response to the stimulus of the hot plate, reduced the force of withdrawal after a dose that was effective by the IV route, and again facilitated the responses in the tail-flick test. The results suggest that spinal sites mediate the inhibition of the withdrawal reflex and the supraspinal site the inhibition of the hot-plate test. Two conclusion are drawn: First, AMIT's site of action varies among the pain modalities; and, second, augmentation of the reactions can occur. The complex interaction accords with the clinical experience that the benefits of AMIT in pain treatment are hard to predict.

Amitriptyline↗
PubMed1994

Response to suxamethonium during propofol-fentanyl-N2O/O2 anaesthesia in a patient with active myasthenia gravis receiving long-term anticholinesterase therapy.

We describe the effect of repeated suxamethonium doses during propofol-fentanyl-N2O/O2 anaesthesia in a 29-year-old woman with active myasthenia gravis receiving chronic pyridostigmine therapy. Despite adequate pre-operative pseudocholinesterase activity, suxamethonium resistance occurred. Neither bradycardia nor residual neuromuscular block were seen after repeated doses of suxamethonium.

Adult↗