Kerry J. Breen

The effects of age and chronic liver disease on the elimination of temazepam

SummaryThe pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18–92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.

Decreased oral warfarin clearance after ranitidine and cimetidine

Oxidative metabolism inhibition of a number of drugs by Cimetidine has been attributed to its imidazole ring, a hypothesis that has been supported by reports that ranitidine does not affect drug metabolism despite being five times as potent as Cimetidine as an H2‐receptor antagonist. In five healthy subjects ranitidine at 150 mg twice daily induced a 27% fall in apparent oral warfarin clearance. In the same subjects Cimetidine at 1 gm/day induced a 36% decrease in warfarin clearance. In two of the subjects the experiment was repeated after giving 750 mg ranitidine per day and in two other subjects after 200 mg Cimetidine twice daily. In both instances there was a stepwise fall in warfarin clearance with increasing doses. The data indicate that interference with drug metabolism by H2‐receptor antagonists is not confined to Cimetidine but that on a molar basis ranitidine and Cimetidine are roughly equivalent in inhibiting warfarin clearance and that the effects are related to dose.

Misconduct in medical research: whose responsibility?

Abstract

A Prospective study of septic complications of endoscopic retrograde cholangiopancreatography

Abstract Prophylactic antibiotics are used in an attempt to avoid the septic complications of endoscopic retrograde cholangiopancreatography (ERCP). We prospectively performed blood cultures and surveyed patients for complications. The aims were first, to determine the incidence of bacteraemia associated with ERCP, second, to assess the incidence of clinical sepsis following the procedure and third, to evaluate the effectiveness of our antibiotic prophylaxis.

Cimetidine impairs the elimination of chlormethiazole.

SummaryCimetidine impairs the systemic clearance of a number of low extraction drugs and this study examines its effect on the oral clearance of the high extraction drug, chlormethiazole. Cimetidine (1 g/day for 7 days) caused the clearance of chlormethiazole to fall to 69% of pretreatment values. It also prolonged the elimination half-life by 60%. The findings indicate that the metabolism of chlormethiazole is inhibited by cimetidine and the co-administration of these drugs may lead to excess sedation and respiratory depression.

Difficult physician–patient encounters

Consultant physicians encounter patients, and families and carers of patients, who leave us feeling helpless, frustrated, irritated and even angry. There are limited opportunities for trainees and physicians to discuss how to recognize, manage, learn from and prevent these difficult physician–patient encounters. This paper addresses factors, including physician factors, that may contribute to making encounters difficult, categorizes the types of difficult encounters and provides generic and specific suggestions (based in part on published literature and in part on our personal experience) about prevention and management of many of them.

Ranitidine does not affect chlormethiazole or indocyanine green disposition

Cimetidine has been shown to inhibit hepatic mixed‐function oxidase activity and to lower hepatic blood flow. It is not known whether these effects are related to its H2‐receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2‐receptor antagonist and differs structurally from cimetidine. In our study, ranitidine, 150 mg twice daily, had no effect on oral or systemic clearance of chlormethiazole, a sedative with a high clearance, and no effect on indocyanine green elimination.

Ethical issues in the use of complementary medicines

Ethics are about how we as individuals and as a community choose to live our lives after considering all the relevant values and interests. A more detailed definition describes ethics as ‘An accumulation of values and principles that address questions of what is good or bad in human affairs. Ethics searches for reasons for acting or refraining from acting; for approving or not approving conduct; for believing or denying something about virtuous or vicious conduct or good or evil rules’1. Consideration of ethical issues has traditionally used systematic frameworks, including approaches such as utilitarian (‘the ends justify the means’), principlist or deontological (as exemplified by the US Belmont report which has become the standard means of considering ethical issues in health care under the headings of respect, benevolence, non-maleficence and justice) and other frameworks1. Derived from consideration of ethical issues are the codes of ethics to which professional groups claim allegiance. These codes have been seen as evidence of ‘professionalism’ of the professional groups. A modern definition of professionalism for medical practitioners is held to encompass a moral commitment to service, public profession of values, and negotiation of a social contract with society2. The relevance of codes of ethics and their application in regard to professional conduct is referred to below when the accountability and regulation of conventional medicine are contrasted with complementary/alternative medicine (CAM). Western societies are presently experiencing a marked increase in the use of CAM and menopausal women are among the highest users3. This review examines some important ethical issues in regard to the use and regulation of CAM.

The patient-doctor relationship in the new millennium : Adjusting positively to commercialism and consumerism

Predicting the future can only be sensibly based on a study of history, especially the emerging trends of our recent past. In Western society, the last 20 years have seen several new influences brought to bear on the patient-doctor relationship. This brief review examines some of these influences, especially in terms of their impact on the ethical conduct of medical practitioners and the regulatory responses of the medical profession. The review concludes with some suggested ways in which the future can be influenced for better outcomes for patients and the medical profession.

Research misconduct: time for a re-think?

The incidence of research misconduct appears to be increasing, drawing attention in the general media and academic literature. Concerns have been expressed about probable under‐reporting, harms arising, lack of an agreed international definition, welfare of whistleblowers and the adequacy of the investigation processes and any subsequent sanctions. A fully satisfactory approach to prevention, detection, investigation and adjudication has yet to emerge. While the definition of research misconduct contained in the Australian Code for the Responsible Conduct of Research is comprehensive, universities and other research institutions at times struggle in their task of investigating and adjudicating allegations of research misconduct. A more centralised, independent process of oversight and monitoring of this role played by the universities and institutions would help support those institutions and help maintain community confidence in the research endeavour.