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A J Bilski

Publications and source records attributed to A J Bilski.

7 recordsLinked to original sources
PubMed1998

A meta-analysis of nausea and vomiting following maintenance of anaesthesia with propofol or inhalational agents.

A number of prospective randomized comparator studies have suggested that there is a reduction in post-operative nausea and vomiting following maintenance of anaesthesia with propofol compared with inhalational agents. We analysed these studies in more detail by examining the effects of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate on the incidence of emesis. A search of the Zeneca database MEDLEY was undertaken and prospective randomized comparator studies identified. These were examined individually and independently by two of the authors and log-odds ratios, calculated from the incidence data of each individual trial, were determined and combined using a fixed-effects meta-analysis approach. Patients who received maintenance of anaesthesia with propofol had a significantly lower incidence of post-operative nausea and vomiting in comparison with inhalational agents regardless of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate.

Adult↗
PubMed1988

The pharmacology of epanolol (ICI 141292)--a new beta 1-selective adrenoceptor partial agonist.

The clinical benefit of beta-adrenoceptor partial agonists is still debated. To clarify the situation, epanolol, ICI 141,292 [N-[-2-(3-o-cyanophenoxy-2-hydroxypropylamino)ethyl]-4- hydroxyphenylactamide], has been developed to assess the role of modest beta-adrenoceptor partial agonist activity in humans. Animal studies have shown that epanolol is a potent beta-adrenoceptor partial agonist with a greater affinity for beta 1- than beta 2-adrenoceptors. In vitro, the PA2 values obtained for espanolol at atrial and tracheal beta-adrenoceptors were 8.42 and 6.33, respectively (isoproterenol as agonist), giving a selectivity ratio of 123. The potency was studied in vivo in the dog, where it was also shown that as an antagonist at the cardiac beta 1-adrenoceptor, it was 18 and 40 times more potent than atenolol and practolol, respectively. Espanolol has less partial agonist activity in the rat than pindolol, but more than practolol. In this species, it is also a classical partial agonist, exhibiting agonist activity at all beta-adrenoceptor blocking doses. This is in contrast to pindolol, which caused predominantly beta-adrenoceptor blockade at low doses and partial agonist activity at higher doses. These differences were confirmed in haemodynamic studies in the dog. In contrast to many other partial agonists, the partition coefficient, log P, of epanolol in octanol and water is low (0.92).

Adrenergic beta-Agonists↗
PubMedDate not supplied

The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551).

While specific antagonists of the beta 1-adrenoceptor, such as atenolol and betaxolol, are widely available, a potent specific antagonist selective for the beta 2-adrenoceptor has yet to be described. Previously described beta 2-selective antagonists such as butoxamine, H 35/25, and IPS 339 are lacking in potency, specificity, or appropriate beta 2-selectivity. ICI 118,551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] possesses a high degree of selectivity and specificity for the beta 2-adrenoceptor. The affinity of propranolol and ICI 118,551 for beta-adrenoceptors has been determined by comparing their antagonist potencies, expressed as pA2 values, against the actions of isoproterenol on the guinea pig atrium and uterus. ICI 118,551 had a higher affinity for the uterine beta 2-receptor than did propranolol (pA2 9.26 and 8.64, respectively) but a lower affinity for the atrial beta 1-receptor (pA2 7.17 and 8.30, respectively). Thus, the beta 2/ beta 1-selectivity ratios, in vitro, were 123 for ICI 118,551 and 2.2 for propranolol. The potency and selectivity of ICI 118,551 and atenolol on the chronotropic and vasodilator actions of isoproterenol were compared in anaesthetised dogs. The apparent K' B values at the vascular beta-adrenoceptor were 2.1 micrograms/kg for ICI 118,551 and 253 micrograms/kg for atenolol, and the potency ratio for antagonism of vascular versus atrial actions of isoproterenol was greater than 250:1. In regard to ancillary pharmacological properties, ICI 118,551 has no partial agonist activity but has a membrane-stabilising action similar to that of propranolol.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

An application of receptor models to the analysis of data on beta-adrenoceptor blockade.

1. The classical single receptor competitive occupancy model accurately describes the joint action of an agonist (isoprenaline) and a beta-adrenoceptor antagonist (propranolol) or some partial agonists (dichlorisoprenaline, practolol) on the positive chronotropic response in rats which have been depleted of catacholamines. 2. The mathematical form of the model suggests that the dissociation constants of classical competitive partial agonists may be assessed using dose ratios by exactly the same method as that currently used for agonist-antagonist interactions, provided that the log dose-response curves are first suitably normalized. 3. Close agreement between the theoretical mathematical models and the experimental data can be demonstrated by statistical fitting for certain beta-adrenoceptor antagonists (propranolol, dichlorisoprenaline, practolol). 4. The model fails to describe the behaviour of other beta-adrenoceptor antagonists (oxprenolol, pindolol). A possible extension of the model to include these drugs is proposed.

Adrenergic beta-Agonists↗