Ciclosporin is a lipophilic cyclic polypeptide with powerful immunosuppressive and immunomodulatory properties that has been used in veterinary medicine for two decades. It is a calcineurin inhibitor ...whose principal mode of action is to inhibit T cell activation. The drug is principally absorbed from the small intestine and is metabolised in the intestine and liver by the cytochrome P450 enzyme system. Ciclosporin is known to interact with a wide range of pharmacological agents. Numerous studies have demonstrated good efficacy for the management of canine atopic dermatitis and this has been a licensed indication since 2003. In addition to the treatment of atopic dermatitis, it has been used as an aid in the management of numerous other dermatological conditions in animals including perianal fistulation, sebaceous adenitis, pododermatitis, chronic otitis externa and pemphigus foliaceus. This article reviews the mode of action, pharmacokinetics, indications for use and efficacy of ciclosporin in veterinary dermatology.
A method is described for the simultaneous identification and quantification of opiates, amphetamines, cocainics, diazepam and nordiazepam from one hair extract (typically 10–50
mg hair). After ...decontamination by washing with shampoo, dichloromethane, isopropanol and acetone, drugs were extracted using 0.1
M HCl followed by SPE clean-up using mixed-mode extraction cartridges. The SPE extracts were submitted to a two-step derivatisation using MBTFA and MSTFA
+
1% TCMS and analysis was performed by GC–MS using both SIM and scan modes. Four deuterated standards were used to monitor 14 compounds. The limit of quantification was the total drug detected from the sample. This was 5
ng for amphetamines and 10
ng for remaining drugs which is equivalent to 0.1 and 0.2
ng/mg from a 50
mg sample.
Standard curves for the range 5–400
ng total drug concentration for all drugs had regression coefficients greater than 0.98. An authentic hair sample was used to validate the method and gave R.S.D.s <25% for both inter and intra-day reproducibility.
The results of the analysis of hair taken from four patients attending a drug treatment clinic and six hair samples including head hair, pubic hair, axial hair and beard taken at post-mortem are presented.
Abstract Data from 191 post-mortem cases where post-mortem blood beta-hydroxybutyrate (βHB) and acetone concentrations and vitreous humor glucose concentrations (where available) had been measured ...were retrospectively investigated to determine the markers required to identify and distinguish between Alcoholic Ketoacidosis (AKA), Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS). Blood βHB concentrations above 250 μg/mL were considered significant and it was shown to be the preferred marker of ketoacidosis. All cases with significant βHB detected also had acetone present (greater than 2 mg/dL) demonstrating that acetone can be used as a marker to identify ketoacidosis and can be used to indicate when βHB measurement is necessary. Vitreous humor glucose concentrations above 6.9 mmol/L were considered high and indicative of hyperglycemia prior to death. Vitreous humor glucose concentrations can be used to distinguish between DKA and ketoacidosis from other causes and to identify deaths due to HHS. The data showed that ketoacidosis can occur without a history of alcoholism or diabetes. Many diabetics are undiagnosed for many years. Therefore, DKA or HHS should be considered in sudden or unexplained deaths and glucose should be routinely measured especially in cases with risk factors for diabetes including obesity, old age, a history of mental health problems or treatment with atypical antipsychotic drugs including clozapine, olanzapine, quetiapine and risperidone.
For the final article in this series about the RCVS’ extramural studies (EMS) reforms, Sue Paterson, RCVS junior vice president, describes how a new database will act as a nexus between students, ...universities and placement providers to ensure that the right people get the right EMS placements. Two young vets who helped shape the proposals also discuss how they hope the new EMS policy will improve outcomes.
There has been a rapid increase in the number of prescriptions for baclofen (BLF), gabapentin (GBP) and pregabalin (PGL) in the UK since their introduction to therapy. Recent studies across the ...European Union and USA have shown the illicit abuse potential of these drugs and deaths have been observed. A simple, reliable and fully validated method was developed for the screening and quantification of BLF, GBP and PGL in human post-mortem (PM) blood. The analytes and their deuterated analogs as internal standard were extracted from blood using a single addition acetonitrile protein precipitation reaction followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous confirmation and quantification. The assay was linear from 0.05 to 1.00 µg/mL for BLF and 0.5 to 50.0 µg/mL for GBP and PGL, respectively with r2 > 0.999 (n = 9) for all analytes. Intra-day and inter-day imprecisions (n = 80) were calculated using one-way ANOVA; no significant difference (P > 0.99) was observed for all analytes over 8 non-consecutive days. The average recovery for all analytes was >98.9%. The limits of detection and quantification were both 0.05 µg/mL for BLF, and 0.5 µg/mL for GBP and PGL. The method was highly selective with no interference from endogenous compounds or from 54 drugs commonly encountered in PM toxicology. To prove method applicability, 17 PM blood samples submitted for analysis were successfully analyzed. The concentration range observed in PM blood for BLF was 0.08-102.00 µg/mL (median = 0.25 µg/mL), for GBP 1.0-134.0 µg/mL (median = 49.0 µg/mL) and 2.0-540.0 µg/mL (median = 42.0 µg/mL) for PGL.
Over the next few months, the RCVS will be giving us more details of its new Veterinary Graduate Development Programme (VetGDP). In this first article, chair of the education committee Sue Paterson ...explains the origins of the scheme and how the construction of the VetGDP was framed by an evidence base provided by students, new graduates and veterinary practices.
In 2010, the United Kingdom and Ireland Association of Forensic Toxicologists (UKIAFT) created forensic toxicology laboratory guidelines. This represents a revision of those guidelines as a result of ...the changing toxicological and technical landscape.
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