give rise to problems. The current edition of the British National Formulary lists several propri- Table 1-Main differences between British approved name3 and intemational non-proprietary name4 of various etary oral preparations of morphine sulphate, drugs including liquid, sustained release, and non- sustained release preparations, which may result British International non- British International non- in confusion. approved name proprietary name approved name proprietary name Confusion between sustained release and non- Acepifylline Acefylline Hydroxyurea Hydroxycarbamide sustained release morphine sulphate tablets and Acinitrazole Aminitrozole lodipamide Adipiodone morphine sulphate liquid can result in two Acrosoxacin Rosoxacin Ipodate lopodate different outcomes: high initial peak plasma con- Actinomycin C Cactinomycin Ironedetate Feredetate centrations of morphine and inadequate dura- Actinomycin D Dactinomycin Isobuzole Glysobuzole tion of analgesia will result if liquid or Epinephrine Lignocaine non-sustained release tablets are given instead of Aloxidone Allomethadione Methadyl acetate Acetylmethadol sustained release tablets, while accumulation of Ametazole Betazole Metharbitone Metharbital morphine and potential toxicity will occur with Amethocaine Tetracaine Methimazole Thiamazole repeated dosing if a sustained release tablet is Amylobarbitone Amobarbital Methohexitone Methohexital given instead of a non-sustained release prepara- Anoxynaphthonate Anazolene Methoin Mephenytoin Azetepa Azatepa Methotrimeprazine tion. Balipramine Depramine Methsuximide Mesuximide There are two other potential sources of Barbitone Barbital Methyl benzoquate Nequinate confusion. Firstly, the proprietary name MST Bendrofluazide Bendroflumethiazide Methyl cysteine Mecysteine has been misinterpreted as being an abbreviation Benzathine penicillin Benzathine benzylpenicillin Methylphenobarbitone Methylphenobarbital for morphine sulphate rather than a formulation Benzhexol Trihexyphenidyl Methyprylone Methyprylon of the drug. Secondly, Oramorph liquid is also Benztropine Mitozantrone Mitoxantrone available in unit dose vials, which have been Bindazac Bendazac Mustine Chlormethine reported to have been confused with injectable Bismuth glycollylarsanilate Glycobiarsol Nealbarbitone Nealbarbital preparations and given intravenously or intra- Bromodiphenhydramine Bromazine Nicoumalone Acenocoumarol muscularly in error.2 Buniodyl Bunamiodyl Nitrofurazone Nitrofural To minimise such errors in our hospital we Amfebutamone Noradrenaline Buthalitone Buthalital Norbutrine Norbudrine aim to ensure that prescriptions for solid oral Butoxamine Butaxamine Octacosactrin Tosactide formulations of morphine sulphate include both Carbolonium Hexcarbacholine Oxethazaine Oxetacaine the brand name and the approved name-for Chlophedianol Clofedanol Oxpentifylline Pentoxifylline example, morphine sulphate sustained release Chlorbutol Chlorobutanol Pentacosactride Norleusactide (MST) or morphine sulphate (Sevredol). When Chlordantoin Clodantoin Pentaerythritol Pentaerithrityl these items are dispensed by the pharmacy, the Chlorfenvinphos Clofenvinfos Pentobarbitone Pentobarbital containers are labelled with both the proprietary Chlorhexadol Chloralodol Pentolinium Pentolonium and approved names. As the liquid morphine Chlormethiazole Clomethiazole Phanquone Phanquinone sulphate preparation listed in our formulary is Chlorpheniramine Chlorphenamine Phenobarbitone Oramorph liquid (not in unit dose vials) we have Colistin sulphomethate Colistimethate Phenyl aminosalicylate Fenamisal decided not to include Oramorph sustained Cyclobarbitone Cyclobarbital Plasmin Fibrinolysin Cysteamine Mercaptamine Polyoxyl (8,40) stearate Macrogol ester release tablets, to minimise potential confusion Deoxycortone Desoxycortone Povidone Polyvidone between liquid and tablet formulations. Desferrioxamine Deferoxamine Pramoxine Pramocaine The guidelines put forward by the expert Diamthazole Dimazole Promethoestrol Methestrol working group will aid decision making in the Diatrizoate Amidotrizoate Proquamezine Aminopromazine prescribing of . Doctors and pharma- Diazinon Dimpylate Quinalbarbitone Secobarbital cists, however, have an important role in Dichlorphenamide Diclofenamide Rolicypram Rolicyprine ensuring that the range ofproducts available and Dicyclomine Dicycloverine Secbutobarbitone Secbutabarbital the accuracy with which the prescription is writ- Diethylpropion Amfepramone Solapsone Solasulfone ten reduce to a minimum the risk of patients Dipenine Diponium Stanolone Androstanolone receiving the wrong formulation of morphine Dipyrone Stilboestrol Diethylstilbestrol sulphate. Dothiepin Streptonicozid Streptoniazid GILLIAN F CAVELL Dyclocaine Dyclonine Sulfametopyrazine Sulfalene Principal pharmacist Epithiazide Epitizide Sulphaurea Sulfacarbamide King's College Hospital, Ethopropazine Tetracosactrin Tetracosactide London SE5 9RS Ethybenztropine Tetrahydrozoline Fenchlorphos Fenclofos Thiacetazone 1 Expert Working Group ofthe European Association for Pallia- tive Care. Morphine in cancer pain: modes of administra- Fluopromazine Thialbarbitone Thialbarbital tion. BMJ 1996;312:823-6. (30 March.) Flurandrenolone Fludroxycortide Thiopentone Thiopental 2 Cousins D, Upton D. errors. Oral solutions can be Frusemide Thymoxamine injected. Pharmacy in Practice 1995;5:76-7. Gestronol Gestonorone Triacetyloleandomycin Troleandomycin Glycalox Glucalox Tribavirin Ribavirin Halopyramine Chloropyramine Trimeprazine Alimemazine Heptabarbitone Heptabarb Trimustine Trichlormethine Naming of drugs Hexachlorophane Hexachlorophene Troxidone Trimethadione Hexamine Methenamine Vinbarbitone Vinbarbital Differences between nomenclatures are Hexobarbitone Hexobarbital Vinylbitone Vinylbital much greater than editorial suggested Hydroxamethocaine Hydroxytetracaine Viprynium Pyrvinium ED1TOR, C F George discusses the difficulties that will result from the European Commission's includes some widely used drugs, such as name.5 This may be the same as the international directive which states that the international actinomycin D, bupropion, chlorpheniramine, non-proprietary name but different from the non-proprietary name, not the British approved dipyrone, hydroxyurea, nicoumalone, plasmin, British approved name (for example, phenobarbi- name, must appear on the labels and leaflets of povidone, and thiopentone. tal) or vice versa (povidone), or it may be different medicinal products from January 1998.' George The World Health Organisation's inter- from both of these (for example, isoproterenol, underestimates the problem, however, in asserting national non-proprietary name programme was whose British and international name is isoprena- that "in total, 41 drugs have a British approved implemented to overcome this problem of syno- line). In extreme cases the same drug has three name that is significantly different to their nyms. In practice, however, it has not achieved names, as with aminitrozole, whose British recommended international non-proprietary this objective, fundamentally because no single approved name is acinitrazole and United States name." I recently reviewed this issue and compared official organ is responsible for selecting the valid approved name is nithiamide). In the European the official listings of the British approved names terms. The World Health Organisation publishes Union, which has 11 official languages, the and the international non-proprietary names.2 If the international non-proprietary names in five situation is more complex, because several we ignore differences in spelling, such as languages (Latin, English, French, Spanish, and countries have their own list of approved names. cyclosporin (whose international non-proprietary Russian), but many developed countries have Whatever solution is adopted as a result of the name is ciclosporin) and oestradiol (estradiol), the their own nomenclature committees. new directive in 1998, clearly none of the mem- number of important differences between the two In the English speaking world, for example, the ber states ofthe European Union can, in the long nomenclatures is well over 100 (table 1); this figure United States has its own United States adopted term, expect to maintain an official name differ-

688 BMJ VOLUME 313 14 SEPTEMBER 1996 ent from the international non-proprietary 1 George CF. Naming of drugs: pass the epinephrine, please. quoted) and the values do not seem to be BMJ 1996;312:1315-6. (25 May.) name. On the other hand, the World Health 2 Hawton K, Fagg J. Trends in deliberate self poisoning and self compatible with the syndrome of inappropriate Organisation cannot impose on these countries a injury in Oxford, 1976-90. BM, 1992;304:1409-1 1. secretion of antidiuretic hormone. Instead, they name that they consider to be unacceptable. The 3 Spooner JB, Harvey JG. overdosage-facts not suggest more that simple (severe) water intoxica- most logical solution would be to set up bilateral misconceptions. Pharm J 1993;250:706-7. tion was the cause of cerebral oedema. 4 Reynolds JEF, ed. Martindale: the extra pharmacopoeia, 31st ed. discussions between the organisation's experts London: Pharmaceutical Press, 1996. T M COOK and the national nomenclature committees with 5 Ritter JM, Lewis LD, Mant TGK. A textbook of clinical Locum senior registrar in anaesthesia a view to the adoption of a single non- pharmacology. 3rd ed. London: Edward Arnold, 1995. Southmead Hospital, proprietary name for those drugs for which Bristol BS1O SNB discrepancies exist. ***The BMys index uses the medical subject headings published by the United States 1 Matthai SM, Sills JA, Davidson DC, Alexandrou D. Cerebral FERNANDO A NAVARRO National Library of Medicine. These headings oedema after ingestion of MDMA ("ecstacy") and Clinical pharmacologist in Index Medicus and and are unrestricted intake of water. BMY 1996;312:1359.(25 F Hoffmann-La Roche, are used Medline May.) CH-4070 Basle, Switzerland an international standard; it is appropriate to use an international standard because the BMJ is 1 George CF. Naming of drugs: pass the epinephrine, please. points out, BMJ 1996;312:1315-6. (25 May.) read worldwide. As Nick Bradley 2 Navarro FA. La nomenclatura de los farmacos. II. Las however, the headings do not always reflect cur- denominaciones comunes internacionales en Espansa. Med rent usage, and so at the beginning of this year Hyponatraemia must be treated with low Clin 1995;105:382-8. we decided to make some changes; thus, for water input 3 Commission. British approved names. London: HMSO, 1990. instance, the index now refers to cars instead of 4 World Health Organisation. Dinominations communes interna- automobiles and, indeed, to paracetamol instead EDITOR,-S M Matthai and colleagues have rightly tionales (DCI) pour les substances pharmaceutiques. Inter- of acetaminophen.-ED1rOR brought our attention again to hyponatraemia as a national nonproprietary names (INN) for pharmaceutical complication of ingesting 3, 4-methylenedioxy- substances. Geneva: WHO, 1992. (Cumulative list No 8.) methamphetamine (MDMA or "ecstasy"), adding 5 Fleeger CA, ed. USAN and the USP dictionary ofdrugs names. 31st ed. Rockville: USP, 1993. two cases' to at least four previously described. The Cerebral oedema after MDMA syndrome ofinappropriate secretion ofantidiuretic ("ecstasy") and unrestricted hormone has been proposed as the cause in five of these six cases.' water intake I am unconvinced that the clinical and BMJ should use "paracetamol" instead of biochemical details presented in these cases point "acetaminophen" in its index Values for plasma osmolality may have indisputably to the syndrome of inappropriate EDrrOR,-One drug is notably absent from C F been wrong secretion of antidiuretic hormone. In this syn- George's editorial on the naming of drugs.' drome the inappropriateness is not that the urine is Paracetamol is widely used for pain and fever EDITOR,-S M Matthai and colleagues report concentrated in the presence of dilute plasma, from cradle to grave. It is also the substance most two cases of cerebral oedema associated with the because this can occur in other diseases such as syndrome of inappropriate secretion of antidiu- hyponatraemic dehydration complicating diar- commonly taken in deliberate self poisoning,2 of 3, causing 150 deaths a year in Britain.3 It is a retic hormone after ingestion rhoeal illness, but rather that water is inappropri- medicine that people travelling abroad take with 4-methylenedioxymethamphetamine (MDMA ately conserved by the kidney in the presence of them or buy when they get to their destination, or "ecstasy").' Their letter is, however, some- total body water overload. Overhydration explains so everyone should know what to call it. Yet it what misleading. the natriuresis and high urine sodium concentra- still has two names: paracetamol and acetami- In case 1 the patient was reported to have a tion that usually accompanies the true syndrome of nophen. This creates two problems, one for the plasma sodium concentration of 119 mmol/l and inappropriate secretion of antidiuretic hormone, general public and one for doctors and medical a plasma osmolality of 156 mmol/kg. Some time despite the hyponatraemia. Natriuresis was not editors. later the urine sodium concentration was 6 present in case 1,' the urine sodium concentration Acetaminophen is the United States adopted mmol/l and urine osmolality 655 mmol/kg. In of 6 mmol/l suggesting avid renal sodium name,4 and in the United States the substance is case 2 the patient was reported to have a plasma conservation; it was also not documented in three always and only called acetaminophen. Paraceta- sodium concentration of 112 mmol/Il and a ofthe four previous cases mentioned.' In case 2 the mol is the recommended international non- plasma osmolality of 142 mmol/kg. Urinary stated urine osmolality (184 mmol/kg) is proprietary name,4 the British approved name,4 sodium concentration was 99 mmol/l and urine accounted for entirely by the sodium concentration and the name used for the substance throughout osmolality 184 mmol/kg. They do not state (99 mmol/l) and its attendant anion(s); the urinary the world outside the United States. Two names whether the osmolalities were measured or urea concentration cannot have been high so this for such a common over the counter drug must calculated. patient cannot have been avidly retaining water at create confusion and risk for the public travelling Plasma osmolality can be calculated from that time. I assume that the stated plasma osmola- the equation: plasma osmolality = (2 x plasma lities of 156 and 147 mmol/kg should have read to and from the United States. Ideally, the + + United States would abandon the name acetami- sodium) plasma urea concentration plasma 256 and 242 mmol/kg. Urine osmolality was also nophen and adopt paracetamol. A pragmatic glucose concentration. Some people chose to far from maximal (365 mmol/kg) in one of the first step would be to label preparations as include potassium concentration in the calcula- other cases alleged to be the syndrome ofinappro- containing the substance "acetaminophen (para- tion. To have a plasma osmolality of 156 priate secretion ofantidiuretic hormone mentioned cetamol)" in the United States and "paracetamol mmol/kg with a plasma sodium concentration of by Matthai and colleagues.' (acetaminophen)" in Britain and other coun- 119 mmolIl or an osmolality of 142 mmol/kg Severe dehydration, and presumably sodium tries. with a plasma sodium concentration of 112 depletion, caused by hyperthermia and sweating as mmol/l is extremely unlikely. In both instances part of the MDMA intoxication syndrome is well Doctors in Britain who do not know that para- in cetamol has another name could come unstuck there would need to be a drastic deficiency in known and supported by experimental evidence clinically and in their reading. Here the BMJ has anions and these values are probably not animals.23 Dehydration would explain why serum a role. Since 1992 (volume 305) the index for the compatible with life. Both values may have been antidiuretic hormone concentrations might be BMJ has said "see acetaminophen" beside the typographical errors and osmolalities in case 1 appropriately high, even had they been measured. I entry for paracetamol. It then indexes all entries and 2 were 256 and 242 mmol/kg, respectively. think that the hyponatraemia was more likely to about paracetamol under the American name, The features of the syndrome of inappropriate have been caused by a combination of sodium even though the articles use the name paraceta- secretion of antidiuretic hormone are, however, a depletion from severe sweating or vomiting, or mol. I wonder why the BMJ does this, because it low plasma osmolality and low plasma sodium both, and excessive water intake without sodium is not the usual or proper practice in Britain. The concentration with an inappropriately concen- repletion, as suggested by the title of the letter by name paracetamol appears, without reference to trated urine. There is usually a high urinary Matthai and colleagues.' acetaminophen, in the index and text of the sodium concentration due to low urine volume Though I disagree with the postulated March 1996 edition of the British National in association with low circulating aldosterone pathophysiology, I agree that unrestricted water Formulary, the 1995 indexes of the Drug and concentrations. In case 1 urine osmolality was intake is to be discouraged; sports drinks Therapeutics Bulletin and the Lancet, and the high and urinary sodium concentration low; this containing salt might be more appropriate for 1995 edition of A Textbook of Pharmacology.5 It could be produced by severe dehydration (caus- supply at "rave" parties. makes no sense for the BMJ alone to use aceta- ing appropriately raised concentrations of Cerebral oedema in cases 1 and 2' is not neces- minophen as the reference name for this drug. antidiuretic hormone) in which rehydration sarily indicative of total body water overload (the fluids were deficient in sodium (such as from person may still be dehydrated despite ingesting NICK BRADLEY copious drinking of water). Severe hyponatrae- large amounts of water). It has been postulated to General practitioner water administra- Ide Lane Surgery, mia may also occur in acute alcohol intoxication. be caused by acute ingestion (or Alphington, In case 2 the urine osmolality was not high (par- tion), leading to a sudden lowering of plasma Exeter EX2 8UP ticularly if the plasma osmolality was incorrectly osmolality with intracellular water shift.4

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