Response of Aspirin-Allergic Patients to Challenge by Some Analgesics in Common Use

Challenge tests with some analgesics in common use were performed in five aspirin-sensitive asthmatics. Marked falls in FEV₁ were observed after ingestion of paracetamol, indomethacin, mefenamic acid, and dextropropoxyphene in some subjects. The mechanisms of analgesic-induced asthma are discussed: it is believed to be a non-immunological process of great practical importance when prescribing analgesics to asthmatics.     

Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study

Background

The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005–2010 compared with 1998–2004, including estimation of possible substitution effects by other analgesics.

Methods and Findings

We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005–2010 compared with 1998–2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of −21 deaths (95% CI −34 to −8) per quarter, equating to approximately 500 fewer suicide deaths (−61%) over the 6 years 2005–2010, and −25 deaths (95% CI −38 to −12) per quarter, equating to 600 fewer deaths (−62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed.

Conclusions

During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics. Please see later in the article for the Editors'' Summary     

Letter: The clinical course of patients with analgesic nephropathy.

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity.     

Analgesic Nephropathy: Clinical Syndrome and Prognosis

Over a five-year period 86 patients presented to a renal unit with a history of prolonged analgesic abuse and no other obvious cause of renal damage. Anaemia and peptic ulceration were common, and neurological states suggestive of chronic analgesic intoxication occurred in 22 patients. Thirty-two patients died during follow-up, but the prognosis was much better in patients who ceased abuse of compound analgesics, and improvement could occur even in advanced renal failure. While 84 patients had taken mixtures containing both aspirin and phenacetin, papillary necrosis was also found in two patients who had abused only aspirin, and when phenacetin was withdrawn from several leading compound analgesics, renal function continued to deteriorate in patients ingesting those preparations.     

Prescribing at the hospital-general practice interface. II: Impact of hospital outpatient dispensing policies in England on general practitioners and hospital consultants.

OBJECTIVE--To assess the impact on general practitioners and hospital consultants of hospital outpatient dispensing policies in England. DESIGN--Postal questionnaire and telephone interview survey of general practitioners and hospital consultants in January 1991. SETTING--94 selected major acute hospitals in England. PARTICIPANTS--20 general practitioners in the vicinity of each of 94 selected hospitals and eight consultants from each, selected by chief pharmacists. MAIN OUTCOME MEASURES--Proportions of general practitioners unable to assume responsibility for specialist drugs and of consultants wishing to retain responsibility; association between dispensing restrictions and the frequency of general practitioners being asked to prescribe hospital initiated treatments. RESULTS--Completed questionnaires were obtained from 1207 (64%) of 1887 general practitioners and 457 (63%) of 729 consultants. 570 (46%) general practitioners felt unable to take responsibility for certain treatments, principally because of difficulty in detecting side effects (367, 30%), uncertainty about explaining treatment to patients (332, 28%), and difficulty monitoring dosage (294, 24%). Among consultants 328 (72%) wished to retain responsibility, principally because of specialist need for monitoring (93, 20%), urgent need to commence treatment (64, 14%), and specialist need to initiate or stabilise treatment (63, 14%). The more restricted the drug supply to outpatients, the more frequently consultants asked general practitioners to prescribe (p less than 0.01) and complete a short course of treatment initiated by the hospital (p less than 0.001). CONCLUSIONS--Restrictive hospital outpatient dispensing shifts clinical responsibility on to general practitioners. Hospital doctors should be able to retain responsibility for prescribing when the general practitioner is unfamiliar with the drug or there is a specialist need to initiate, stabilise, or monitor treatment.     

Effect on prescribing of the limited list in a computerised group practice.

The prescribing of drugs in the therapeutic classes that are affected by the government''s limited list was investigated in a computerised group practice of just over 3,000 patients. Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list. A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics. The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change.     

Effects of an educational outreach campaign (IMPACT) on depression management delivered to general practitioners in one primary care trust

Objective An educational outreach initiative with general practitioners (GPs) within Walsall, led by pharmacists and aimed at delivering evidence-based guidance on stepped care management of clinical depression.Methods Standardised educational material was produced with key messages and contributions by experts on prescribing principles and management of clinical depression based on NICE guidance. The primary care pharmacists together with a psychiatrist or other professional delivered the training through initial face-to-face meetings with GP practices and carrying out follow-up visits.Evaluation Analysis of prescribing data (PACT) on antidepressants, which included prescribing of defined daily doses (DDD) and net ingredient cost (NIC) of commonly prescribed antidepressants for the whole of Walsall teaching Primary Care Trust (tPCT) and comparison with prescribing data for the West Midlands and for England during the period June 2000 to June 2006.Results The use of Fluoxetine increased slightly and the prescribing of Dosulepin continued to fall. The prescribing of Escitalopram, which had steadily increased prior to the launch of campaign, showed decline, resulting in savings of over ￡50K in the year 2005 to 2006. This was in comparison to a relative increase in the prescribing for Escitalopram for the same time period in the West Midlands and nationally. Prescribing of Dosulepin continued to fall. The total cost of prescribing for the four antidepressants fell and theses changes were sustained over the following year.Conclusions The educational outreach campaign successfully influenced prescribing behaviour in terms of adhering to NICE guidance and cost-effective prescribing, and also facilitated improved communication among clinicians at the primary-secondary care interface.     

Hospital formularies: need for continuous intervention.

The effects of introducing a hospital formulary alone and with active intervention were compared prospectively with regard to drug costs and the quality of prescribing. Intervention comprised feedback on prescribing habits, peer comparison, and information on drugs. Aspects of prescribing that were not subjected to intervention did not alter. In the year in which intervention occurred generic prescribing rose by 50%; inappropriate prescribing and overall use of third generation cephalosporins fell; and compliance with the recommended list of drugs was good. Overall, drug costs remained static, compared with a projected increase of 0.25 m pounds; in a comparative control hospital drug costs rose by 18%. During the next year, when no form of intervention took place, previous gains were eroded and drug costs rose. Continuous intervention, review, and feedback are required if a formulary is to continue to achieve its objectives.     

Significance of GABAergic systems in the action of improgan, a non-opioid analgesic

Improgan is the prototype drug from a new class of non-opioid analgesics chemically related to histamine and histamine antagonists, but the mechanism of action of these compounds has not been identified. Because several classes of analgesics act in the brain by reducing GABAergic inhibition of endogenous pain-relieving circuits, and because the activity of these substances is abolished by the GABA(A) agonist muscimol, the present study assessed the effects of muscimol on improgan antinociception in rats. Intracerebroventricular (icv) improgan (80 microg) and morphine (20 microg) both induced 80-100% of maximal analgesic responses on the tail flick test 10 to 30 min later. However, muscimol pretreatment (0.5 microg, icv) completely eliminated the antinociceptive activity of both compounds. Since improgan in vitro lacks activity at opioid and GABA(A) receptors, these findings: 1) confirm earlier literature showing that muscimol inhibits morphine analgesia, and 2) suggest that improgan activates a supraspinal, descending analgesic pathway, possibly via inhibition of GABAergic transmission. Since muscimol is the first compound discovered which inhibits improgan analgesia, muscimol will be a useful tool for the further characterization of this new class of pain-relieving substances.     

Defining inappropriate practices in prescribing for elderly people: a national consensus panel

OBJECTIVE: To develop a consensus-based list of inappropriate practices in prescribing for elderly people. DESIGN: Mail survey of a 32-member national panel. SETTING: Academic medical centres across Canada. PARTICIPANTS: Thirty-two specialists selected arbitrarily, including 7 clinical pharmacologists, 9 geriatricians, 8 family practitioners and 8 pharmacists. OUTCOME MEASURES: Consensus that the practice would introduce a substantial and significant increase in the risk of serious adverse effect and is common enough that its curtailment would decrease morbidity among elderly people, ranking of clinical importance of the risk, and availability of equally or more effective and less risky alternative therapy. RESULTS: The 32-member national panel developed a list of 71 practices in prescribing for elderly people and rated the clinical significance of each on a scale of 1 (not significant) to 4 (highly significant). The practices in prescribing identified fell into 3 categories: drugs generally contraindicated for elderly people, drug-disease interactions and drug-drug interactions. The mean significance rating was greater than 3 for 39 practices. For each practice, alternative therapies were recommended. There was surprising congruence among the specialists on the significance rating and the suggested alternative therapies. CONCLUSION: The authors have developed a valid, relevant list of inappropriate practices in prescribing for elderly people, to be used in a practice-based intervention study.