Gm Peterson

Toenail onychomycosis: an important global disease burden

Onychomycosis is a fungal infection of the nail plate or nail bed. It does not usually cure itself and it can trigger more infectious lesions in other parts of the body. The reported prevalence of onychomycosis is increasing in Western countries, presumably due to lifestyle changes and the ageing of the population. Approximately 10% of the general population, 20% of the population aged >60 years, up to 50% of people aged >70 years and up to one‐third of diabetic individuals have onychomycosis. Care should be taken for the accurate diagnosis and timely treatment of toenail onychomycosis to prevent complications. Current treatment options have relatively limited therapeutic success, particularly long‐term. Oral medications are associated with high recurrence rates and treatment failure, and are not suitable for many cases due to potential adverse effects. Topical medications are recommended only for mild to moderate cases. The cost of therapies may also be prohibitive in some cases. In the light of these issues, more research is warranted for the investigation and development of more effective and economical options for the treatment and prophylaxis of toenail onychomycosis. In patient populations such as diabetic individuals, where onychomycosis can provoke lower extremity complications, professional podiatry care of toenails and feet should be encouraged.

Overuse of proton pump inhibitors

Background: There have been concerns raised about the potential adverse effects of proton pump inhibitors, especially with long‐term use. In particular, their potent action can suppress the features and delay the diagnosis of gastric cancer, while prolonged exposure may hasten the development of gastric carcinoids.

The Pharmacy Diabetes Care Program: assessment of a community pharmacy diabetes service model in Australia

Aim  To assess the impact of a community pharmacy diabetes service model on patient outcomes in Type 2 diabetes.

Plasma levels of morphine and morphine glucuronides in the treatment of cancer pain: relationship to renal function and route of administration

SummaryThere is growing evidence that renally-impaired patients receiving morphine therapy are at greater risk of developing opiate toxicity, due to the accumulation of an active metabolite, morphine-6-glucuronide (M6G), which is usually excreted by the kidneys. This study examined the relationships between morphine dosage, renal function, and trough plasma concentrations of morphine and its glucuronide metabolites in 21 patients (aged mean: 68.5 years; 11 males) receiving either oral or subcutaneous morphine for terminal cancer pain. The median daily morphine dosages (mg · kg−1) were: orally 1.87 (range 0.37–6.82) and subcutaneously 1.64 (range 0.22–3.60).The median plasma concentrations of morphine, morphine-3-glucuronide (M3G), and M6G (ng · ml−1) were: 36.0, 1035.2, and 142.3, respectively. The plasma concentrations of morphine, M3G and M6G were each significantly related to the daily morphine dosage (n=21, Spearman r=0.79, 0.91, and 0.88 respectively). Accumulation of the morphine glucuronides was dependent on renal function. The plasma concentrations of M3G and M6G, when divided by the morphine concentration, were significantly related to the caluclated creatinine clearance of the patient. Patients receiving oral morphine had higher plasma concentration ratios of glucuronide/morphine than those receiving subcutaneous therapy, presumably due to first-pass glucuronidation.The results of this study confirm that accumulation of the pharmacologically active M6G is related to renal function, which probably explains the observation that morphine dosage requirements are generally reduced in patients with renal impairment.

Pharmacists' attitudes towards dispensing errors: their causes and prevention

Objective: To assess the attitudes of pharmacists towards the issue of dispensing errors.

A Randomised Trial of Strategies to Improve Patient Compliance with Anticonvulsant Therapy

Summary: Fifty‐three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance‐improving strategies: patient counselling, a special medication container, self‐recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.

Valproate: a simple chemical with so much to offer

The debate exists amongst clinical pharmacologists as to unlimited supplies of which drug would be most useful when stranded on a deserted island. The tricyclic antidepressants have always rated highly because of their variety of useful therapeutic effects, but valproate also deserves to be high on the list. Of course, it will protect against seizures, if they arise, but it could also be useful for analgesia, preventing migraine and stabilizing the mood particularly if one becomes mentally unbalanced on the island. It might even help to prevent the development of cancer. It would not be an overstatement to suggest that valproate is truly a remarkable drug – a multitude of therapeutic effects from such a simple chemical structure (2-propylpentanoic acid; Fig. 1) – with a remarkable story; it was discovered by chance and is now well-established in the management of a number of neurological conditions and psychiatric disorders. An American chemist (Burton) first synthesized valproate as an organic solvent in 1882 (1). It is a clear, colourless to pale yellow liquid at room and body temperature, and only slightly soluble in water, but highly soluble in organic solvents. The current generic name (valproic acid) was derived from the more descriptive name 2-propylvaleric acid (2). Valproate had been used infrequently as a solvent until its therapeutic properties were serendipitously discovered in 1962 by French researchers, when it was being used as a solvent for other compounds (khelline derivatives) that were being tested for potential anticonvulsant activity (2–4). Eynard and colleagues had encountered difficulty in dissolving some of the derivatives in water or common organic solvents. Valproate was then used to solubilize these compounds and anticonvulsant activity was subsequently observed for the entire test compounds at all doses. Laboratory studies demonstrated anti-seizure activity with valproate (5) and the first clinical trial in epilepsy using the sodium salt of valproic acid was reported in 1964 (6, 7). It was released in France in 1967 (as ‘Depakine’), in Great Britain in 1973 and was approved by the US Food and Drug Administration (FDA) in 1978. It was the only new anticonvulsant drug marketed for many years, beforehand and afterwards. Valproate is currently marketed in over 100 countries and is well established as a first-line and widely used antiepileptic agent, with a very broad spectrum of activity against both generalized and partial seizures in adults and children (4, 8, 9). It is effective against absences and myoclonic, and generalized tonic-clonic seizures. In addition, the drug is useful in the treatment of partial seizures, with or without secondary generalization (2–4, 8, 9). Intravenous valproate has also been shown to be effective against status epilepticus (10). Results from numerous clinical trials suggest that valproate probably has the widest spectrum of anticonvulsant activity of all current antiepileptic drugs in adults and children with epilepsy (4, 8, 9). Received 9 May 2005, Accepted 19 May 2005 Correspondence: Gregory Peterson, Unit for Medication Outcomes Research and Education, School of Pharmacy, University of Tasmania, Locked Bag 26, Hobart TAS 7001, Australia. Tel.: 61 3 62262197; fax: 61 3 62267627; e-mail: g.peterson@utas.edu.au OH H3C H3C

Doctors’ beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention

Abstract

Drug-related admissions to an Australian hospital

This study was conducted to determine the prevalence of drug‐related hospital admissions in southern Tasmania, Australia. The causes of consecutive admissions to medical wards of the Royal Hobart Hospital were reviewed. Comprehensive data were collected over a 10‐week period on 691 admissions (median age: 67 years and range: 11–97 years; 50.8% males). Sixty‐eight (9‐8%) of the admissions were classified as being either probably or definitely drug‐related. Most of these admissions were attributable to intentional overdose (38.2%) or an adverse drug reaction (30.9%). The overdoses often involved benzodiazepines or antipsychotics. Gastrointestinal bleeding related to the use of nonsteroidal anti‐inflammatory drugs was the most common adverse drug reaction (38.1% of all reactions). Other drug‐related admission categories were poor compliance (14.7%), dosage decrease or therapy cessation by a doctor producing an exacerbation of symptoms (7.4%), substance abuse (4.4%) and drug interaction (4.4%). Patients with a drug‐related admission were, on average, younger than the other medical admissions, with no significant difference in gender. Patients admitted due to an overdose or substance abuse were younger than other drug‐related admissions and non‐drug related admissions. In conclusion, this study has determined that almost 10% of medical admissions to the hospital are drug‐related and it is estimated that 40 to 50 elderly people are admitted each year suffering from gastrointestinal bleeding related to nonsteroidal anti‐inflammatory drugs.

Accuracy and clinical utility of the CoaguChek XS portable international normalised ratio monitor in a pilot study of warfarin home-monitoring.

Aim: To evaluate the accuracy of the CoaguChek XS international normalised ratio (INR) monitor compared with the laboratory method. Methods: The accuracy and ease of use of the recently marketed CoaguChek XS portable INR monitor was evaluated in 17 patients involved in a trial of warfarin home monitoring. INR results from the monitor were compared with those from the laboratory method. Clinical applicability was measured by discrepant INR values, defined in the literature by expanded and narrow agreement criteria, and by the proportion of INR values differing by >15% and by >20% from those derived by the laboratory method. Results: Participants provided 59 comparison INR measurements for analysis. The paired results were highly correlated (r = 0.91). Expanded and narrow agreement between paired INR values occurred 100% of the time. Only three CoaguChek XS (5.1%) results differed by >15% compared with the laboratory method; no results differed by >20% or were discrepant by >0.5 INR units. Conclusions: In the hands of patients the CoaguChek XS showed good correlation with laboratory determination of INR and compared well with expanded and narrow clinical agreement criteria. Both patients and doctors were highly satisfied with the accuracy and ease of use of the CoaguChek XS.