摘要:

Computer-based patient care information systems (PCIS) have emerged as an integral component of healthcare organisations. Currently, 4 models of PCIS exist: the centralised model, the hub-and-spoke model, the network model, and the distributed model.The centralised model has the advantage of a central patient database; however, a major disadvantage of this model is the inability to easily interface with other software packages.The hub-and-spoke model links satellite or feeder systems into a mainframe computer; thus, each satellite has the ability to work independently. This system is limited by the ability to interface satellite systems with the mainframe computer.The network model works via a local area network (LAN) using client server technology which allows for high speed data access and transfer. The network model does not provide an integrated view of patient information and can access only 1 host system at a time.The distributed model is similar to the network model in design but provides for data and system integration via relational databases. This allows for the creation of a central data repository and support for decision-support tools.Computer-assisted decision-support has the potential to significantly improve clinical decision-making. Six types of computer-assisted decision-support have been defined: alerting, interpreting, assisting, critiquing, diagnosing and managing. Software representing each type of decision-support software has been incorporated into clinical practice; however, with the exception of drug interaction programs, widespread incorporation of decision-support software into PCIS is uncommon.Clinical pharmacokinetic programs are a category of pharmacy-related decision-support software, and current clinical pharmacokinetic software systems can be categorised as interpreting, assisting or critiquing decision-support. Despite the potential for significant clinical contributions, the integration of clinical pharmacokinetic software into PCIS is uncommon. Most packages are available only as stand alone programs or as a module of a pharmacy information system. These packages usually maintain theirown centralised database and require special file transfer protocols for integration.Although PCIS are becoming more commonplace, the integration of commercial clinical pharmacokinetic packages into PCIS is limited. New technology using standardised and relational databases should allow for easier integration in the future.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

A new aminosteroidal neuromuscular blocking agent, rocuronium bromide, has recently been introduced into clinical practice. Its main advantage over other currently used drugs of this kind is its fast onset of action, which could render rocuronium the muscle relaxant of choice for rapid facilitation of tracheal intubation. A further advantage of the new compound over vecuronium bromide is the less extensive formation of breakdown products, reducing the contribution of active metabolites to the neuromuscular blocking effects of the parent compound.Thorough knowledge of the pharmacokinetics of any new drug is highly desirable for the anaesthesiologist because absorption, distribution to the tissue, as well as elimination by biotransformation and excretion, are closely related to its effects. Due to its chemical relationship to other aminosteroidal neuromuscular blocking agents such as pancuronium bromide or vecuronium, rocuronium is expected to display pharmacokinetic behaviour similar to that of its predecessors. Hepatic and renal disease may prolong the effect of rocuronium, but to a lesser extent than seen with pancuronium or vecuronium, because the plasma clearance of rocuronium is not significantly influenced by dysfunction of the liver or kidneys. On the contrary, in elderly or hypothermic patients the reduction in plasma clearance results in a prolonged duration of the action of rocuronium.All information on the pharmacokinetics of this new nondepolarising neuromuscular blocking agent which has been made available to date is presented in this review, with a discussion of the significance of these data for clinical use of the drug.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Vinorelbine (5′-noranhydrovinblastine) is a recently developed semisynthetic anticancer drug which belongs to theCatharanthusalkaloid family. Its mechanism of action is only partially known but it is assumed that it acts, like vinblastine and vincristine, as an antimicrotubule agent arresting cell division in mitosis. Clinically, vinorelbine has mainly shown activity in the treatment of advanced non-small-cell lung cancer and the treatment of metastatic breast cancer.Early pharmacokinetic data were obtained with radioactive assays (radioimmunoassay or3H-labelled vinorelbine), then with more selective high performance liquid chromatographic techniques. Vinorelbine is usually administered intravenously but there has also been some experimentation with an oral formulation. The bioavailability of a liquid filled gelatin capsule ranges between 12 and 59% with a mean value of 27% [standard deviation (SD) 12%]. Vinorelbine is rapidly absorbed with peak serum concentration reached within 2 hours.In vitro,vinorelbine is mainly distributed into the blood cells, especially platelets (78%) and lymphocytes (4.8%). The unbound blood fraction is around 2%. In lung tissue vinorelbine concentrations are much higher than in serum, by up to 300-fold 3 hours after administration.Little is known about the biotransformation of vinorelbine. Desacetylvinorelbine is considered to be a minor metabolite and is only found in urine fractions, representing 0.25% of the injected dose. Urinary excretion of vinorelbine is low, accounting for less than 20% of the dose. Faecal elimination has been demonstrated in 2 patients who were administered3H-labelled vinorelbine; the amount of radioactivity recovered in the faeces was 33.9 and 58.4% for the 2 patients, respectively.The pharmacokinetic profile of vinorelbine is often described as a 3-compartment model characterised by a long terminal half-life (t½) that varies between 20 and 40 hours and a large apparent volume of distribution (Vd) of around 70 L/kg. Systemic clearance ranges between 72.54 and 89.46 L/h (1209 and 1491 ml/min) when determined by high performance liquid chromatography and is higher than that reported by radioimmunoassay [46.2 L/h (770 ml/min)]. This could be due to the greater specificity of the chromatographic method. Vinorelbine has been administered by continuous intravenous infusion over 4 days. Steady-state was reached and the concentrations obtained were above thein vitroIC50(concentration of drug causing 50% inhibition).The effect of liver disease on vinorelbine pharmacokinetics has been studied in patients with breast cancer. Patients with massive secondary liver disease had a lower systemic clearance than those who have no liver disease or a lesser invasion.In children, vinorelbine seems to display a shorter t½ (14.7 hours) than that found in adults. In addition, the systemic clearance is highly variable [from 12 to 93.96 L/h/m2(200 to 1566 ml/min/m2)].Vinorelbine is often co-administered with cisplatin in the treatment of advanced non-small-cell lung cancer. The disposition of the alkaloid is not altered by concurrent administration of cisplatin.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions.The most important interactions affecting carbamazepine pharmacokinetics are those resulting in induction or inhibition of its metabolism. Phenytoin, phenobarbital (phenobarbitone) and primidone accelerate the elimination of carbamazepine, probably by stimulating cytochrome P450 (CYP) 3A4, and reduce plasma carbamazepine concentrations to a clinically important extent.Inhibition of carbamazepine metabolism and elevation of plasma carbamazepine to potentially toxic concentrations can be caused by stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid, metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol and (dextropropoxyphene) propoxyphene. In other cases, toxic symptoms may result from elevated plasma concentrations of the active metabolite carbamazepine-10,11-epoxide, due to the inhibition of epoxide hydrolase by valproic acid (sodium valproate), valpromide, valnoctamide and progabide.Carbamazepine is a potent inducer of CYP3A4 and other oxidative enzyme system in the liver, and it may also increase glucuronyltransferase activity. This results in the acceleration of the metabolism of concurrently prescribed anticonvulsants, particularly valproic acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine and remacemide.The metabolism of many other drugs such as tricyclic antidepressants, antipsychotics, steroid oral contraceptives, glucocorticoids, oral anticoagulants, cyclosporin, theophylline, chemotherapeutic agents and cardiovascular drugs can also be induced, leading to a number of clinically relevant drug interactions.Interactions with carbamazepine can usually be predicted on the basis of the pharmacological properties of the combined drug, particularly with respect to its therapeutic index, site of metabolism and ability to affect specific drug metabolising isoenzymes. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential, and careful dosage adjustments based on serum drug concentration monitoring and clinical observation represent the mainstays for the minimisation of risks associated with these interactions.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The metabolism of drugs to chemically reactive metabolites may play a pivotal role in the pathogenesis of idiosyncratic drug toxicity. A large number ofin vitrostudies and a limited number ofin vivostudies have demonstrated that many drugs are not toxicper se,but produce toxicity after undergoing enzyme-mediated bioactivation to chemically reactive species. Such reactive species may inflict a toxic insult on the cell either directly or indirectly by acting as a hapten and initiating an immune-mediated reaction.The enzymes responsible for bioactivation have been widely studied, both quantitatively and qualitatively, the most important being the enzymes of the cytochrome P450 (CYP) mixed function oxidase system. CYP enzymes are the most predominant drug metabolising enzymes in the liver and are also present in most other tissues of the body. The diversity of this enzyme system means that a wide range of xenobiotic substrates can be bioactivated by either a single CYP isoform or multiple isoforms of this enzyme superfamily. Other enzymes do, however, play an important role in drug bioactivation. In white blood cells, for example, myeloperoxidase has been shown to bioactivate a wide range of drugs.In other tissues low in CYP activity, prostaglandin H synthase may also be responsible for bioactivation; e.g. in the kidney paracetamol (acetaminophen) toxicity is thought to result from activation via this enzyme. The phase II or conjugation enzymes may also be important in the ultimate bioactivation of drug molecules. Whilst activation by these enzymes is, to date, apparently confined to chemicals, most drugs are also substrates for these enzymes and bioactivation by them must remain a possibility.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

To enhance the effectiveness of regional treatment in patients with liver carcinoma, cytotoxic drugs may be combined with alternative therapeutic strategies such as partial vascular blockade using degradable starch microspheres (DSM). When DSM combined with a cytotoxic drug are infused through the hepatic artery, the steep drug concentration gradient to the tumour tissue results in higher tissue drug concentrations which may elicit an increased antitumour response. The co-injected drug should therefore possess an extensive extravascular distribution and possess a suitable dose-response relationship. Furthermore, the drug of choice should also have a high total body clearance with a large component of clearance outside the target compartment, should not interact with the spheres and should be given without inducing any back-flow. Under these assumptions, a reduced systemic exposure of a co-injected drug could be translated into an increased regional extraction ratio induced by the blood flow reduction.

ISSN:0312-5963    

出版商:ADIS    

年代:1996

数据来源: ADIS