Drug advertising in medical journals.
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Biomedical subjects
Publications and source records attributed to R E Ferner.
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INTRODUCTION: Spironolactone is increasingly being used in the treatment of heart failure. However, it has been associated with cases of hyperkalaemia. The common use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-2 receptor (AT2) antagonists in heart failure increases the risk of hyperkalaemia. OBJECTIVE: To identify the risk of spironolactone withdrawal, hyperkalaemia and severe hyperkalaemia in patients prescribed spironolactone together with either an ACE inhibitor or an AT2 antagonist. METHODS: Retrospective identification and analysis of patients co-prescribed an ACE inhibitor or an AT2 antagonist with spironolactone. Patients' records were linked to their biochemical results and the doses of spironolactone, ACE inhibitor and AT2 antagonists received by them. RESULTS: We found that a higher proportion of patients in our cohort stopped taking spironolactone compared with the Randomised Aldactone Evaluation Study and a higher proportion developed hyperkalaemia, a predicted adverse effect of spironolactone combination with an ACE inhibitor or an AT2 antagonist. Patients with diabetes mellitus and those with a haematocrit below 0.36, were more likely to develop hyperkalaemia than those without these traits. CONCLUSIONS: Spironolactone is a common cause of hyperkalaemia when used in combination with either an ACE inhibitor or an AT2 antagonist. This reinforces the need for care when extrapolating the results of clinical trials to daily clinical practice.
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UNLABELLED: The pharmacokinetics of venlafaxine in therapeutic doses is well established. It is metabolized by the cytochrome P450 enzymes including CYP2D6. The toxicokinetics in overdose is less well known. CASE REPORT: A 33-year-old Caucasian female who ingested 3.0 g venlafaxine, and 210 mg zolpidem. The patient remained symptomatic for the following 24 h. Plasma pharmacokinetic analysis demonstrated a prolonged elimination half-life of venlafaxine, estimated to be 15.3 h. We postulate that the patient was a slow metabolizer of substrates for CYP2D6, an enzyme known to exhibit polymorphism.
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AIMS: We studied the international classification of disease (ICD) hospital discharge codes to find unreported adverse drug reactions (ADRs), and asked doctors about their attitudes to reporting some of these cases. METHODS: We examined the ICD codes assigned on discharge to identify ADRs and compared these with spontaneous reports made to the Committee on Safety of Medicines (CSM). Doctors involved were sent brief résumés of cases and asked if they would report them. RESULTS: 49 of 21 365 patient episodes were coded on discharge as ADRs, of which 33 were 'reportable'. Fourteen spontaneous reports were received by the CSM during the same period. The two groups did not overlap. 25 of 60 doctors responded to our questionnaire, and would have reported only 8 of 75 cases outlined. CONCLUSIONS: The ICD coding allowed us to identify important ADRs which most doctors would not report spontaneously.
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.
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CASE REPORT: A 40-year-old schizophrenic man was found unconscious, with constricted pupils, sinus tachycardia, and twitching of the limbs. There were signs of lung infection, which was treated with antibiotics, and mild rhabdomyolysis. He regained consciousness over 8 hours, and reported taking 3-4 g clozapine. Recovery was uneventful. Measured peak clozapine and norclozapine concentrations were 3.53 mg/L and 0.70 mg/L, respectively. The concentration-time curves were biphasic, with secondary peaks at approximately 36 hours postadmission. Terminal elimination half-lives were 16.9 hours and 22.5 hours for clozapine and norclozapine, respectively. CONCLUSION: Clozapine and its metabolite norclozapine can show biphasic plasma concentration-time curves after overdosage.