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Biomedical subjects

P A Routledge

Publications and source records attributed to P A Routledge.

At least 19 recordsLinked to original sources
PubMed2004

The effects of acute ethanol intake on isoniazid pharmacokinetics.

AIM: To assess effects of acute ethanol intake on the pharmacokinetics of isoniazid in healthy male volunteers. METHODS: Sixteen healthy male, drug-free subjects were studied. Each received in the fasting state, on two occasions separated by at least 1 week, isoniazid (200 mg orally). On one occasion (assigned randomly), subjects received ethanol 0.73 g/kg, 1 h before isoniazid, followed by 0.11 g/kg ethanol orally every hour thereafter for 7 h. Plasma isoniazid and acetylisoniazid concentrations were measured by means of high-performance liquid chromatography. Blood ethanol concentrations were measured hourly by breath analysis. Plasma concentrations of isoniazid and acetylisoniazid were analysed using TOPFIT software. RESULTS: Peak concentrations of isoniazid were reached within 90 min, in both the ethanol-treated and control groups. The ethanol dosage regimen used resulted in peak blood ethanol concentrations between 78 mg/l and 103 mg/l. There was no significant difference in area under the curve, half-life of elimination or the ratio of acetylisoniazid to isoniazid (AcINH/INH) in the sample withdrawn 3 h after isoniazid dose. Acetylator phenotype for patients was the same in both phases, whether assessed by half-life of isoniazid or the AcINH/INH ratio at 3 h. CONCLUSIONS: Acute ethanol intake at this dose is unlikely to affect results of acetylation studies in which isoniazid is used as a substrate, whether the half-life of isoniazid or the AcINH /INH ratio at 3 h is used to phenotype patients.

Acetylation↗
PubMed2004

Adverse drug reactions in elderly patients.

Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication is crucial, and prescribers should develop an effective therapeutic partnership with the patient and with fellow health professionals. Undergraduate and postgraduate education in evidence-based therapeutics is also vitally important. The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. "Rational" or "obligatory" polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

The involvement of nurses in reporting suspected adverse drug reactions: experience with the meningococcal vaccination scheme.

AIMS: In order to aid the monitoring of the new Meningococcal serogroup C Conjugate (Men C) vaccine, the Yellow Card Scheme was extended to allow nurses for the first time to report any suspected adverse reactions associated with these vaccines. We have analysed the Yellow Cards received by the Committee on Safety of Medicines (CSM) Wales from nurses reporting a suspected reaction in association with these vaccines during the first 16 months of the programme. METHODS: CSM Wales receives Yellow Cards from healthcare professionals in Wales. Details of Yellow Cards reporting a suspected adverse reaction associated with Men C vaccines during the study period were extracted from the CSM Wales database and analysed according to health professional category [nurses, General Practitioners (GP), hospital doctors or pharmacists]. RESULTS: During the study period 534 117 doses of Men C vaccines were administered in Wales; in the same period CSM Wales received 1095 Yellow Cards containing 1952 suspected reactions. Nurses completed 529 [48.3%, 95% confidence interval (CI) 43.6, 53.1] Yellow Cards compared with 294 (26.8%, 95% CI 22.7, 30.8) from GPs, 262 (23.9%, 95% CI 20.1, 27.6) from hospital doctors and 10 (0.91%, 95% CI 0.43, 1.73) from others, which include hospital pharmacists, community pharmacists and health visitors. The proportion of Yellow Cards sent by nurses was significantly higher than those sent by GPs and hospital doctors. Ninety-five percent CIs for differences in proportions (CI diff prop) were (0.175, 0.254) and (0.204, 0.282), respectively. The majority (90.9%, 95% CI 88.7, 93.5) of the Yellow Cards from nurses reported suspected reactions children in over the age of 5 (95% CI diff prop 0.861, 0.917). The spectrum of suspected adverse drug reactions (ADRs) involved the skin and subcutaneous tissue, central nervous system, general reactions, and the gastrointestinal tract. Of the suspected reactions reported by nurses, GPs and hospital doctors, 13.4% (95% CI 10.5, 15.8), 12.9% (95% CI 9.6, 16.8) and 9.1% (95% CI 6.5, 11.8), respectively, were of serious reactions. Nurses reported 52.5% (95% CI 45.4, 60.6) of all the suspected serious reactions, which was statistically more significant than hospital doctors [chi2 = 5.864, degree of freedom (DF) = 1, P < 0.05] but not GPs (chi2 = 0.066, DF = 1, P > 0.05). CONCLUSIONS: Nurses were the health professionals who provided the largest proportion of reports of suspected ADRs and almost half of all reports during the Men C vaccination campaign. Their reports contained an equal proportion of serious suspected ADRs and the reports were documented as completely as those from GPs and hospital doctors.

Adolescent↗
PubMed2002

Erythrocyte thiopurine methyl transferase assessment prior to azathioprine use in the UK.

BACKGROUND: Individuals with low activity of a key metabolic enzyme, thiopurine methyl transferase (TPMT), are more susceptible to azathioprine-induced myelosuppression. AIM: To determine the pattern of use of TPMT activity estimation, with respect to azathioprine use, by medical practitioners in the UK. DESIGN: Retrospective analysis of assay use. METHODS: We analysed all test results (n=3291), and patient and practitioner details, from inception of TPMT assay in 1990 to the end of December 2000, held at the Purine Research Laboratory, Guy's Hospital, London. Patient details were anonymized. Repeat analyses and requests from outside the UK were excluded. RESULTS: The male:female ratio was approximately equal and the mean age was 46.6 (range 0.5-97) years. Thirteen different medical specialities requested assays; Dermatology and Gastroenterology were the most frequent users, together accounting for 86% of requests. The numbers of centres requesting the assay varied widely both within and between different specialities. Some 80% of individuals had normal TPMT activity, 9% enzymic activity above normal, and 10% low activity. Fifteen had no detectable enzymic activity: 0.45% (1:220) of the study population. DISCUSSION: This incidence of undetectable enzyme activity is significantly higher than the previously reported level of 1:300 derived from smaller studies, and makes the economics of screening more attractive.

Adolescent↗
PubMed2001

Random and systematic medication errors in routine clinical practice: a multicentre study of infusions, using acetylcysteine as an example.

AIMS: The nature and incidence of errors in prescribing and giving medicines have previously been estimated by trained observers, or by retrospective analysis of incidents in which patients have come to harm. We have examined prospectively in routine clinical practice the concentrations of intravenous infusions of a drug (acetylcysteine) which is given according to a complicated dosing schedule. METHODS: We prospectively collected samples before and, where possible, after the infusion of acetylcysteine in 66 anonymous patients requiring treatment for acetaminophen (paracetamol) overdose in four centres in the United Kingdom. We measured the concentration in each infusion bag, and deduced from the weight of the patient the percentage of the anticipated dose that had actually been given. RESULTS: The experimentally determined dose was within 10% of the anticipated dose in 68 of 184 individual bags (37%), and within 20% of the anticipated dose in 112 bags (61%). Doses in 17 bags were more than 50% from the anticipated doses. In three patients, values in all three bags appeared to be systematically wrong by 50% or more; in a further seven cases, individual bags differed by 50% or more from the anticipated value. The median difference between pre- and post-infusion samples was 0% [interquartile range -5.2% to +14.6%], but 9% showed a disparity of greater than +/- 50%. CONCLUSIONS: Our data suggest that there is large random variation in administered dosage of intravenous infusions. Systematic calculation errors occur in about 5% [95% confidence interval 2, 8%] of cases, and major errors in drawing up in a further 3% [1, 7%], with inadequate mixing in 9% [4, 14%]. While we have no evidence that patients were adversely affected, and while the regime of administration of the drug studied (acetylcysteine) is complicated, these data suggest that the delivered dose often deviates from the intended dose, and that methods of quality control are needed.

Acetaminophen↗
PubMed2001

Colchicine induced rhabdomyolysis.

A case of colchicine induced rhabdomyolysis is reported. A 73 year old man with ischaemic heart disease, atrial fibrillation, chronic congestive cardiac failure, and chronic gout presented with diffuse muscle pain. He had been taking an increased dose of colchicine (1.5 mg daily) for an exacerbation of gout for six weeks before the presentation. Investigations confirmed the diagnosis of rhabdomyolysis and discontinuation of colchicine resulted in resolution of clinical and biochemical features of rhabdomyolysis. Although neuromuscular adverse effects of colchicine are well recognised, rhabdomyolysis is rare and this is only the fourth reported case of colchicine induced rhabdomyolysis in the literature.

Aged↗
PubMed2000

Community exposures to chemical incidents: development and evaluation of the first environmental public health surveillance system in europe.

OBJECTIVE: To describe the frequency, nature and location of acute chemical incidents in Wales, and the morbidity in employees, emergency responders and the general public who were exposed. DESIGN: Active multi-agency community-based surveillance system. SETTING: Wales, 1993-5. MAIN OUTCOME MEASURES: Frequency, nature and location of incidents, populations potentially exposed and with symptoms. RESULTS: Most of the 402 incidents identified were not associated with sites governed by the Control of Industrial Major Accident Hazard Regulations but with smaller industrial sites and commercial premises. About two in every thousand of the estimated 236 000 members of the public considered to be at risk from exposure reported symptoms, which were mainly nausea, headaches, and irritation of the eye, skin and respiratory tract. The most commonly reported chemicals that members of the public were exposed to were smoke toxins, miscellaneous organics, toxic gases and flammable gases. A health authority was reported to be involved in only 34 (8%) of the incidents and in only 3 of the 29 incidents where more than 100 members of the public were exposed. CONCLUSION: A geographically defined, multi-agency surveillance system can identify high risk locations and types of incidents, together with the chemicals most likely to be involved. Such ongoing surveillance information is essential for appropriate policy making, emergency planning, operational management and training.

Environmental Exposure↗
PubMed1999

Spontaneous reporting of suspected adverse reactions to antihistamines: a national and international perspective.

Twenty-one sedative and five non-sedating antihistamines are presently available on the UK market. Analysis of spontaneous reports of suspected adverse drug reactions was performed for those drugs with more than 90 reported reactions on the UK ADROIT database to the period ending 31 December 1997. Thus nine antihistamines, (four sedative antihistamines and five non-sedating antihistamines) were included. For each of the four sedative agents (azatidine, chlorpheniramine, diphenhydramine and trimeprazine), reactions associated with the cardiovascular, gastrointestinal, central nervous systems, the skin, general and psychiatric reactions made up more than 70% of total reported reactions. For all four agents, fatal reactions constituted less than 2.5% of total reactions. For each of the five non-sedating agents (acrivastine, astemizole, cetirizine, loratidine and terfenadine), reactions associated with the cardiovascular, gastrointestinal central nervous systems, the skin, general and psychiatric disorders together made up more than 75% of total reported reactions. For all five non-sedating agents, fatal reactions constituted less than 1% of total reactions. However, there were 21 reports of fatality in association with terfenadine, 11 (52%) of which were either sudden deaths or those associated with a cardiac rate of rhythm reaction. Analysis of the WHO database for non-sedating drugs showed a similar pattern, with terfenadine being associated with the highest frequency of reports of potentially serious arrhythmias and of sudden death and death related to disturbances of cardiac rate and rhythm combined. Despite the limitations of spontaneous reporting systems, comparison of the benefit-risk profiles of drugs using this data within a class of drugs can provide valuable information, and pharmacovigilance of antihistamines (and all other agents) using this and other means should continue for the lifetime of their use in humans.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

1,2-dibromoethane--a toxicological review.

DBE is transported in the UK in road tankers and there is always the possibility of an accident. The consequences could be serious, since this chemical is absorbed by all routes, rapidly penetrates clothing and there is no effective antidote. Severe cases of poisoning are difficult to treat and there is a high mortality. Prevention of exposure is therefore essential.

Animals↗
PubMed1998

The impact of nationally distributed guidelines on the management of paracetamol poisoning in accident and emergency departments. National Poison Information Service.

OBJECTIVE: To assess the impact of the treatment guidelines on the management of paracetamol self poisoning in accident and emergency (A&E) departments. METHODS: 24 A&E departments in Wales and England provided details of their management of paracetamol poisoning before and after the distribution of national treatment guidelines to all A&E departments in the United Kingdom. RESULTS: Significant increases were seen in the availability of formal written policies, the display of treatment nomograms, the recommendation to treat beyond 16 hours after ingestion, and to use a lower line on the treatment nomogram for patients at special risk of paracetamol induced liver damage. CONCLUSIONS: Regularly updated guidelines in the management of paracetamol poisoning should be displayed in A&E departments so that medical and nursing personnel have access to the best current information on the treatment of poisoning with this frequently used drug.

Acetaminophen↗
PubMed1998

Important drug-drug interactions in the elderly.

Although drug-drug interactions constitute only a small proportion of adverse drug reactions, they are important because they are often predictable and therefore avoidable or manageable. Their frequency is related to the age of the patient, the number of drugs prescribed, the number of physicians involved in the patient's care and the presence of increasing frailty. The most important mechanisms for drug-drug interactions are the inhibition or induction of drug metabolism, and pharmacodynamic potentiation or antagonism. Interactions involving a loss of action of one of the drugs are at least as frequent as those involving an increased effect. It is likely that only about 10% of potential interactions result in clinically significant events and, while death or serious clinical consequences are rare, low-grade, clinically unspectacular morbidity in the elderly may be much more common. Nonspecific complaints (e.g. confusion, lethargy, weakness, dizziness, incontinence, depression, falling) should all prompt a closer look at the patient's drug list. There are a number of strategies that can be adopted to decrease the risk of potential clinical problems. The number of drugs prescribed for each individual should be limited to as few as is necessary. The use of drugs should be reviewed regularly and unnecessary agents withdrawn if possible, with subsequent monitoring. Patients should be encouraged to engage in a 'prescribing partnership' by alerting physicians, pharmacists and other healthcare professionals to symptoms that occur when new drugs are introduced. Physicians with a responsibility for elderly people in an institutional setting should develop a strategy for monitoring their drug treatment. For those interactions that have come to clinical attention, it is important to review why they happened and to plan for future prevention. Clinicians should also report, via the appropriate postmarketing surveillance scheme, any drug-drug interactions they have encountered. Finally, multidisciplinary education about the nature of physiological aging and its effect on drug handling, and the possible presentations of drug-related disease in older patients, is an important element in reducing interactions in the elderly.

Aged↗
PubMed1997

The effect of repeated-dose activated charcoal on the pharmacokinetics of sodium valproate in healthy volunteers.

AIMS: We investigated the effects of repeated-dose charcoal administered several hours after sodium valproate on the pharmacokinetics of a single dose of the drug in healthy volunteers. METHODS: The pharmacokinetics of sodium valproate were studied in seven healthy volunteers after administration of a syrup (300 mg) on two occasions, one of which was followed by administration of repeated doses of oral charcoal starting 4 h after the drug up to 32 h (total dose 80 g). RESULTS: Valproate was rapidly absorbed with maximum concentrations 1 h after administration. The area under the plasma concentration-time curve to 48 h (AUC (0.48 h)) was 408 +/- 114.5 (s.d.) mg l-1 h in the control phase and 398 +/- 108.6 mg l-1 h after charcoal and the t1/2 elimination was 20 +/- 6.8 h in the control phase, and 22 +/- 9.2 h after charcoal (NS). CONCLUSIONS: Repeated-dose activated charcoal does not appear to enhance the rate of elimination of sodium valproate after therapeutic doses of the drug and any beneficial effect of charcoal in overdose may be to prevent absorption of valproate still present in the gut.

Adult↗
PubMed1997

The effect of intravenous aminophylline on essential tremor.

AIMS: The effects of intravenous aminophylline (375 mg) or placebo (saline) were studied in 10 patients with benign essential tremor. METHODS: This was a single-blind crossover study. Patients received aminophylline by i.v. infusion over 15 min or saline at least 1 week apart. Tremor was measured by a peizoresistive accelerometer at 15 min intervals predose and up to 2 h. Plasma theophylline concentrations were measured by h.p.l.c. RESULTS: Tremor power was significantly greater following aminophylline (5.67-6.2 Hz) than placebo (5.6-5.9 Hz). CONCLUSIONS: We conclude that intravenous aminophylline potentiates benign essential tremor when given acutely by the intravenous route in the doses required to achieve therapeutic benefits in asthma.

Adolescent↗