FAM001159-0001
intervals of 4-7 days to usual dose of 75-100 mg Dolmatil® (Sanofi-Synthelabo) ~ 100 rag/5 mL, thioridazine 100 rag/ per course and max. 4 injections; max. duration of daily according to response; CHILD not recom- Tablets, both scored, sulpiride 200 rag, net price ’ net price 300 mL = £7.14. Label: 2 treatment 2 weeks---if maintenance treatment mended 100-tabpack=£13.85;400mg(f/c), 100-tab ! fNote. These suspensions should not be diluted but the necessary change to an oral antipsychotic 2-3 Short-term adjunctive management of severe pack = £36¯29. Label: 2 .: :~t~a preparations may be mixed with each other to days after last injection, or to a longer acting anti- anxiety, 15-20rag daily in divided doses; max. Sulpltil® (Pharmacia) I~ ~0iovid¢ intermediate strengths psychotic depot injection given concomitantly 40 mg daily; CHILD not recommended Tablets, scored, sulpiride 200 rag. Net price 28-tab "ff~-~p, brown, thioridazine (as hydrochloride) with last injection of zuclopenthixol acetate; By deep intramuscular injection, psychoses, mania, pack = £4.29; 112-tab pack = £12.85. Label: 2 ~ff.~5"~mg/5 mL, net price 300 mL = £1.98. Label: 2 CHILD not recommended prochlorperazine mesilate 12.5-25 mg 2-3 times Sulpor® (Rosemont) IPoMI Clopi~ol Acuphase® (Lundbeck) daily; CHILD not recommended Oral solution, sugar-free, lemon- and aniseed-fla. LUOPERAZINE Injection (oily), zuclopenthixol acetate 50 mg/mL. By rectum in suppositories, psychoses, mania, the voured, sulpiride 200 mg/5 mL, net price 150 mL (’~’n~ications: see under Dose; anti-emetic (section Net price I-mL amp = £5.20; 2-mL amp = £10.03 equivalent of prochlorperazine maleate 25 mg 2- = £27.00. Label: 2 3 times daily; CHILD not recommended ~,6) ... . , .~autions: see notes anove ZUCLOPENTHIXOL THIORIDAZlNE Contra-indications: see notes above DIHYDROCHLORIDE Preparations , b’qdc;-effects: see notes above; extmpyramidal Indications: under specialist supervision, second. Indications: schizophrenia and other psychoses, Section 4.6 more frequent, especially at doses line treatment of schizophrenia in adults (see 6 mg daily; pancytopeniai thrombocy- particularly when associated with agitated, Contra-indicationa, below) aggressive, or hostile behaviour PROMAZINE HYDROCHLORIDE Cautions: see notes above; avoid in porphyria Cautions: see notes above; ECG screening and by mouth (reduce initial doses in elderly by Indications: see under Dose electrolyte measurement before treatment, after (section 9.8.2) each dose increase and at 6-month intervals; also Contra-indications: see notes above; apathetic or Cautions: see notes above; also cerebral arterio- Schizophrenia and other psychoses, short-term monitor for visual defects on prolonged use; withdrawn states sclerosis ldjunctiv¢ management of psychomotor agita- avoid in porphyria (section 9.8.2) Slde-effects: see notes above; urinary frequency Contr’a-indications: see notes above tion; excitement, and violent or dangerously Contra-indications: see notes above or incontinence; weight loss (less common than impulsive behaviour, initially 5 mg twice daily, or Side-effects: see notes above; also haemolytic weight gain) " " ’ CARDIOTOXIClTY, Thioridazine is associated with QT- 10rag daily in mod fled-release form, jncreased anaemia interval prolongation and increased risk of ventriculat 5 mg after 1 week, then at intervals of 3 days, Dose: initially 20-30mg daily in divided doses, Dose: by mouth, short-term adjunctive manage- arrhythmias. The CSM has advised that thioridazinc increasing to a max. of 150 mg daily if necessary; ~¢ording to the response; CHILD Lip to 12 years, ment of psychomotor agitation, 100-200mg 4 should be restricted to second-line treatment of schizo- usual maintenance dose 20-50 mg daily; ELDERLY phrenia in adults under specialist supervision. Thiorid. up to 5mg daily in divided doses, times daily; CHILD not recommended (or debilitated) initially quarter to half adult dose; Agitation and restlessness in elderly, 25-50 mg 4 azine is contra-indleated in patients with: according to response, age, and body- ¯ significant cardiac disease, such as angina, brady- CHILD not recommended times daily eardia, second- or third-degree heart block, cardiac adjunctive management Of severe By.intramuscular injection, short-term adjunctive failure; Clopixol® (Lundbeck) ~,Laaxiety, 2--4 mg daily in divided doses or 2--4 mg management of psychomotor agitation, 50mg ¯ history of ventricular arrhythraia; " Tablets, all fi’c, pink, zuclopenthixol (as dihydro- ,iSd,ai’iy in modified-release form, increased if nec- (25 mg in elderly or debilitated), repeated if nec- ¯ QT-interval prolongation or a family history of th~ chloride) 2 mg, net price 20.= 62p; 10 rag, 20 = essary after 6-8 hours; CHILD not recommended condition; - = "~ e~ay to 6mg daily; CHILD 3-5 years up to I mg £1.73; 25 mg, 20 = £3.47. Label: 2 ¯ uncorrected hypokalaemia or hypomagnesaemia; _~d~’!y, 6-12 years up to 4 mg daily Depot injection (zuclopenthixol decanoate): sec- ¯ concomitant use with other drugs known to cause tion 4.2.2 Promazine (Non-proprietary) . QT-interval prolongation; : :; ~’~;ifluop’erazine (Non-proprietary) Tablets ~, coated, promazine hydrochloride ¯ reduced cytochmme P450 21)6 activity; ,(Tablets, coated, trifluoperazine (as hydrochloride) ¯ concomitant use with drugs that inhibit or are metab- 25 mg, net price 20 = 49p; 50 mg, 20 = 87p. : -iil mg, net price 20 = 57p; 5 mg, 20 = 87p. Label: 2 Atypical antipsychotics ¯ olised by cytochrome P450 2D6. Label: 2 rJWailable from most genetic manufacturers The ’atypical antipsychotics’ amisulpride, cloz- Side-effects: see notes above; less sedating than Available from Biorex =pral solution, trifluoperazine (as hydrochlo~’ide) apine, olanzapine, quetiapine, risperidone, and chlorpromazine, and extrapyramidat symptoms Oral solution ~, pr0mazine hydrochloride ~mg/5 mL. Net price 200-mL = £11.07. Label: 2 zotepine may be better tolerated than other antipsy- and hypothermia rarely occur; more likely to 25 mg/5 mL, net price 150 mL = £ 1.60; 50 mg/ ~..rAy~lable from Rosemont (sugar-free) chotics; extrapyramidal symptoms and prolactin induce hypotension and increased risk of cardio- 5mL, 150mL =£2.06. Label: 2 oStelazine® (Goldshield) elevation may be less frequent than with older anti- toxicity and prolongation of QT interval (see i A’,;ailable from Rosemont Tablets, both blue, f/c, tfifluoperazine (as hydro- psychotics. above); pigmentary retinopathy (with reduced Injection, promazine hydrochloride 50 mg/mL. chl0ride) I mg, net price 20 = 61p; 5 mg, 20 = The atypical antipsychotics may be used as first- visual acuity, brownish colouring of vision, and Net price 1-mL amp = 30p ~: Label: 2 line treatment for schizophrenia, but clozapine is impaired night vision) occurs rarely with high Note. May be difficult to obtain licensed for the treatment of schizophrenia only in doses; sexual dysfunction, particularly retrograde ; dark blue, light blue, and white pellets, patients unresponsive to, or intolerant of, conven- ejaculation, may occur tional antipsychotic drugs. It can cause agranulo- SULPIRIDE Dose: 50-300 mg daily (initially in divided doses); £4.36; 10 mg, 30-cap pack = £2.83; cytosis and its use is restricted to patients registered max’. 600mg daily (in hospital patients only); Indications: schizophrenia !.mg~ 30-cap pack = £4.27. Label: 2, 25 with the Clozaril Patient Monitoring Service (see CHILD not recommended Cautions: see notes above; also excited, agitated, trifluoperazine (as under Clozapine, below). or aggressive patients (even low doses may mg/5 mL. Net price 200-mL Sertindole has been suspended following reports aggravate symptoms) Thioridazlne (Non-proprietary) 2 of arrhythmias and sudden cardiac death; it remains Contra-indications: see notes above; also por- Tablets, coated, thioridazine hydrochloride 25 mg~ available on a named-patient basis (from Lund- phyria (section 9.8.2) net price 20 = 35p; 50 mg, 20 = £1.02; 100 rag, 20 ZUCLOPENTHIXOL ACETATE beck~erdolect~) for patients already stabilised on Side-effects: see notes above; also hepatitis = £1.57. Label: 2 the drug in whom other antipsychotics are inappro- Available from Alpharma, DDSA (Rideril~), Hillemss, Indications: short-term management of acute psy- Dose: 200-400 mg twice daily; max. 800mg daily priate. IVAX .’ chosis, mania, or exacerbations of chronic psy- in predominantly negative symptoms, and 2.4 g Oral solution, thioridazine (as hydrochloride) CAUTIONS AND CONTRA-INDICATIONS. daily in mainly positive symptoms; ELDEaLY, 25 mg/5 mL. Net price 500-mL = £2.67. Label: 2 Cautions: see notes above; avoid in porphyria While most atypical antipsychotics have not gener- lower initial dose, increased gradually according Available from Hillcross, Rosemont c;: ally been associated with prolongation of the QT to response; CHILD under 14 years not recom- (section 9.8.2) Plelleril® (Novartis) IPoHI COntra-indications: see notes above interval, caution should be exercised if they are pre- mended Tablets, all f/c, thioridazine hydrochloride 10 mg, Side-effects: see notes above scribed with other drugs known to increase the QT net price 84-tab pack = £ 1.01 ; 25 mg, 84-tab pack ~DOse: by deep intramuscular injection into the glu- interval. Atypical antipsychotics should be used Sulpiride (Non-proprietary) = £1.66; 50mg, 84-tab pack = £3.23; 100 rag, 84- ,,teal muscle or lateral thigh, 50-150mg (elderly with caution in patients with cardiovascular disease, Tablets. sulpiride 200 mg, net price 100-tab pack = tab pack = £6.24. Label: 2 ~,50-100 mg), if necessary repeated after 2-3 days or a history of epilepsy; they should be used with £ 14.12; 400 mg, I OO-tab pack = £36.29¯ Label: 2 Suspension 25 rag/5 mL, thioridazine 25 rag/5 mL, H(I additional dose may be needed 1-2 days after caution in the elderly; inleraetions: Appendix I Available from Alpharma. APS. CP. Generics. WAX net price 300mL = £1.96. Label: 2 the first injection); max. cumulative dose 400 mg (antipsychotics). FAM001159-0002 4.2. I AnttpsychoUc arugs i ~ t 176 4.2. I Antipsychotic drugs Injection, chlorpromazine hydrochloride 25 rag/ and lens opacities, and purplish pigmentation of the Fluphenazine, haloperidol, and trifluoperaziae c0ntra-lndications: see notes above mL. net price I-mL amp = 60p; 2-mL amp = 60p skin, cornea, conjunctiva, and retina are also of value but their use is limited by the high "Side.effects: see notes above Available from Antigcn Overdosage: for poisoning with phenothiazines incidence of extrapyramidal symptoms. Hal0. i~ose-" 0.25-1.5 mg daily in divided doses, adjusted Suppositories, chlorpromazine 100 rag. Label: 2, II and related compounds, sce Emergency Treatment peridol may be preferred for the rapid control of according to the response; ELDERLY (or debili- ’Special order’ [unlicensed] product; contact Martindale of Poisoning. p. 26. hyperactive psychotic states. It is less hypotensive ~tated) initially half adult dose; CHILD not recom- or regional hospital manufacturing unit than chlorpromazine and is therefore also popular Largactil® (]lawgrcen) 135~3] CLASSIFICATION OF ANTIPSYCHOTICS. The Tablets, all off-white, f/c, chlorpromazlne hydro- for agitation in the elderly, despite the high incl. ) ’--,® tConcord) phenothlazlne derivatives can be divided into 3 dence of extrapymmidal side-effects. chloride 10 rag. Net price 56-tab pack = 71p; main groups. Thioridazine is associated with rare reports of ~ qte~ts benperidol 250 micrograms. Net price 25 mg, 56-tab pack = 9gp; 50 mg, 56-tab pack = ventricular arrhythmia and it is now restricted for (i00-tab pack = £26.13. Label: 2 £2.05; 100 rag, 56-tab pack = £3.81. Label: 2, II Group I: chlorpromazine, levomepromazine use as second-line treatment for schizophrenia in Syrup. brown, chlorpromazine hydrochloride (methotrimeprazine), and promazine, generally adults; it should be prescribed under specialist ~"~-ORP RO MAZIN E 25 mg/5 mL. Net price 100-mL pack = £1.1 I. characterised by pronounced sedative effects and supervision only. Label: 2, I 1 moderate antimuscarinic and extrapyramidal side- . HyDROCHLORIDE Suspension forte, orange, sugar-free, chlorprom- effects. Prnmazine is not sufficiently active by mouth to WARNING. Owing to the r sk of contact sensit.isation, phar- azine hydrochloride 100 mg (as embonate)/5 mL. be used as an antipsychotic drug; it has been used to ~.cistS, nurses, and other health workers should avoid Net price 100-mL pack = £2.56. Label: 2, 11 Group 2: pericyazine, pipotiazine, and thioridazine, treat agitation and restlessness in the elderly (see ~eet contact with chlorpromazine; tablets should not be Injection, chlorpromazine hydrochloride 25 rag/ generally characterised by moderate sedative Other uses, below). crushed and solutions shouId be handled with care Indications: see under Dose; antiemetic in pallia- effects, marked antimuscarinie effects, but fewer Loxapine causes relatively little sedation; in mL. Net price 2-mL amp = 67p t,~tive care (section 4.6) extrapyramidal side-effects than groups I or 3. overdosage it has a high potential for serious neuro- Cautions: see notes above; also patients should logical and cardiac toxicity. FLUPENTIXOL ’,~emain supine and the blood pressure monitored Group 3: fluphenazine, perphenazine, prochlorper- (Flupenthixol) ~’-’-for 30 minutes after intramuscular injection azine, and trifluoperazine, generally characterised OTHER USES. Nausea and vomiting (section 4.6), Indications: schizophrenia and other psychoses, ~ontra-lndications: see notes above by fewer sedative effects, fewer antimuscarinic choreas, motor tics (section 4.9.3), and intractable particularly with apathy and withdrawal but not ~ide-effects: see no~es above; also intramuscular effects, but more pronounced extrapyramidal side- hiccup (see under Chlorpromazine Hydrochlorid¢ mania or psychomotor hyperactivity; depression ’i "; injection may be painful, cause hypotension and effects than groups 1 and 2. and under Haloperidol). Benperldol is used in devi- (section 4.3.4) ant antisocial sexual behaviour but its value is not ¯ i ~’tachycardia, and give rise to nodule formation Cautions: see notes above; avoid in porphyria i~ose: by mouth, Drugs of other chemical groups tend to resemble established. (section 9.8.2) "i~Schizophrenia and other psychoses, mania, short- the phenothiazines of group 3. They include the Psychomotor agitation and, in the elderly, agita- Contra-indications: see notes above; also excita- [,i~term adjunctive management of severe anxiety, butyrophenones (benperidol and haloperidol); tion and restlessness, should be investigated for an ble and overactive patients diph enylbutylpiperldin es (pimozide); thlo- underlying cause; they can be managed with low i psychomotor agitation, excitement, and violent or Side-effect: see notes above; less sedating but ’dangerously impulsive behaviour initially 25 mg xanthenes (flupentixol and zuclopenthixol); sub- doses of chlorpromazine or haloperidol used for ~ extrapyramidal symptoms frequent ¯ " 3 times daily (or 75 mg at night), adjusted accord- stituted benzamldes (sulpiride); oxypertine; and short periods. The use of promazine for agitation Dose: psychosis, initially 3-9mg twice daily Cing to response, to usual maintenance dose of 75- Ioxapine. and restlessness in the elderly has declined. Olanza- adjusted according to the response; max. 18mg For details of the newer antipsychotie drugs ami- ~.-300 mg daily (but up to I g daily may be required pine and risperidone may be effective for agitation !in psychoses); ELDERLY (or debilitated) third to daily; ELDERLY (or debilitated) initially quarter to sulpride, clozapine, olanzapine, quetiapine, risperi- and restlessness in the elderly [unlicensed]¯ half adult dose; CHILD not recommended done, sertindole, and zotepine, see under Atypical half adult dose; CHILD (childhood schizophrenia Equivalent doses of oral antipsychotics ~- and autism) I-5 years 500 micrograms/kg every antipsychotics, p. 181. Depixol® (Lundbeck) 4-45 hours (max. 40 mg daily); 6-12 years third to These equivalences are intended only as an approx- Tablets, yellow, s/c, flupentixol 3 mg (as dihydro- CHOICE. As indicated above, the various drugs imate guide; individual dosage instructions should half adult dose (max. 75 mg daily) chloride). Net price 20 = £2.99. Label: 2 Intractable hiccup, 25-50 mg 3-4 times daily differ somewhat in predominant actions and side- also be checked; patients should be carefully moni- Depot injection (flupentixol decanoate): section tored after any change in medication By deep intramuscular injection, (for relief of acute effects. Selection is influenced by the degree of 4.2.2 symptoms but see also Cautions and Side- sedation required and the patient’s susceptibility to Antipsychotic effects), 25-50mg every 6-8 hours; CHILD, 1-5 extrapyramidal side-effects. However, the differ- Daily dose FLUPHENAZINE HYDROCHLORIDE ences between antipsychotic drugs are less impor- years 500 micrograms/kg every 6-8 hours (max. Chlorpromazine l O0 mg Indications: see under Dose 40mg daily); 6-12 years 500micrograms/kg tant than the great variability in patient response; Clozapine Cautions: see notes above SO mg every 6-8 hours (max. 75 mg daily) moreover, tolerance to secondary effects such as Haloperidol 2-3 mg Contra-indications: see notes above Induction of hypothermia (to prevent shivering), sedation usually develops. The atypical antipsy- Loxapine 10-20 mg Side-effects: see notes above; less sedating and by deep intramuscular injection, 25-50 mg every chotics may be appropriate if extrapyramidal side- Pimozide 2 mg fewer antimuscarinic or hypotensive symptoms, effects are a particular concern (see under Atypical Risperidone 0.5- I mg 6-8 hours; CHILD 1-12 years, initially 0.5-1 mg/ Sulpiride but extrapyramidal symptoms, particularly dys- Antipsychotics, below). Clozapine is used for 200 mg kg, followed by maintenance 500 micrograms/kg tonic reactions and akathisia, more frequent; sys- Thioridazine :i schizophrenia when other antipsychotics are inef- 100 mg every 4~ hours Trifluoperazine S mg temic lupus erythematosus fective or not tolerated. By rectum in suppositories as chlorpromazine base 100 mg every 6-8 hours [unlicensed] Dose: schizophrenia and other psychoses, mania, Prescribing of more than one antipsychotic at the Important. These equivalences must not be extrapolated initially 2.5-10rag daily in 2-3 divided doses, beyond the max. dose for the drug. Iligher doses require ¯ Note. For equivalent therapeutic effect I00mg chlor- same time is not recommended; it may constitute a adjusted according to response to 20mg daily; careful titration in specialist units and the equivalences promazine base given rectally as a suppository --- 20- hazard and there is no significant evidence that doses above 20 mg daily (10 mg in elderly) only shown here may not be appropriate. 25 mg chlorpromazine hydrochloride by intramusctdar side-effects are minimised. injection =- 40-50 mg of chlorpromazine base or hydro- with special caution; CHILD not recommended Chlorpromazine is still widely used despite the DOSAGE.: After an Initial period of stabilisation, In chloride b)’ mouth Short-term adjunctive management of severe wide range of adverse effects associated with it. It most patients, the long half-life of antipsychoticI anxiety, psychomotor agitation, excitement, and has a marked sedating effect and is useful for treat- !:ii drugs allows the total daily oral dose to he given as a I Chlorpromazine (Non-proprietary) violent or dangerously impulsive behaviour, ini- ing violent patients without causing stupor. Agi- "single dose. For the advice of The Royal College of Tablets, coated, chlorpromazinc hydrochloride tially I mg twice daily, increased as necessary to tated states in the elderly can be controlled without Psychiatrists on doses above’ the BNF Upper limit, IOmg, net price 56-tab pack = 71p: 25 mg. 28-tab 2 mg twice daily; CHILD not recommended confusion, a dose of I0 to 25 mg once or twice daily see P" 174" ! i l pack : 96p; 50 rag. 2g-lab pack - 95p: I O0 rag. usually being adequate. 28-tab pack : £ I. 15. I.abcl: 2. I I Hoditen" (Sanofi-Synthclabo) Flupentixol (flupenthixol) and pimozide (see BENPERIDOL A’,ailablc flom Antigen. APS. I)I)SA 1( 7d,J,util" L l lill- Tablets, all sic. t’luphccazinc hydrochloridc I mg CSM advice p. 179) are less sedating than chlor- Indications: control of deviant antisocial sexual cross. I V)’. X (pink), nct price 20 : t~ 1 06; 2.5 mg (yellow), 20 - promazine. bchaviour (but see notes above) ()rod s~doti,m, chlorpronlazinc hydrochluridc £1.33; 5rag, 20 = I~1.77. Label: 2 Sulpiride in high doses controls florid positive Cautions: see notes above; also manu[~lCltlrer 251112/5 ml.. net price 150 ml. - t~ 1.35. I t)() rag/ Hodecate:~ symptoms, but in lower doses it has an alerting advises regular blood counts and liver l~.mction 5 mL~. 1511 ml. - C3.76. Labcl: 2. I I Suction 4.2.2 effect on apathetic ’.,,ithdrawn schizophrenics. tests during long-term treatment Available lrom thlltsto~,s, I~.oscnl’,~nl FAM001159-0003 174 4.2 Drugs used in psychoses and related disorders ease, hepatic impairment; Interactions: Appen- 4.2. I Antipsychotic drugs 175 dix I (barbiturates and primidone) ’4.2 :/’:i~ Drugs .used in normal activity and social behaviour. Patients with and the depot preparations. They are easy to recog- DRIVrNG. Drowsiness may persist the next day and affect acute schizophrenia generally respond better than nise but cannot be predicted accurately because ’ ~" psychoses and related performance of skilled tasks (e.g. driving); effects of those with chronic symptoms. they depend on the dose, the type of drug, and on alcohol enhanced ...... : disorders ~. Long-term treatment of a patient with a definite individual susceptibility. Contra-indic.ations: insomnia caused by pain; diasnosis of schizophrenia may be necessary even 4.2. I Antipsychotic drugs Extrapyramidal symptoms consist of: porphyria (section 9.8.2), pregnancy, breast-feed- after the first episode of illness in order to prevent 4.2.2 Antipsychotic depot injections ¯ parkinsonian symptoms (including tremor), ing; children, young adults, elderly and debili- - " the manifest illness from becoming chronic. With- 4.2.3 Antimanic drugs which may occur more commonly in adults or tated patients, also patients with history of dreg or drawal of drug treatment requires careful surveil- the elderly and may appear gradually; alcohol abuse lance because the patient who appears well on Advice of Royal College of Psychiatrists On doses ¯ dystonia (abnormal face and body movements) medication may suffer a disastrous relapse if treat- Side-effects: include hangover with drowsiness, above BNF upper limit and dyskinesia, which occur more commonly , ment is withdrawn inappropriately. In addition the dizziness, ataxia, respiratory depression, hyper- Unless otherwise stated, doses in the BNF are licensed in children or young adults and appear after need for continuation of treatment may not become sensitivity reactions, headache, particularly in doses--any higher dose is therefore unlicensed (for an only a few doses; explanation of the significance of this, see p. 1). ? immediately evident because relapse is often elderly; paradoxical excitement and confusion ¯ akathisia (restlessness), which characteristi- delayed for several weeks after cessation of treat- occasionally precede sleep; overdosage: see I. Consider alternative approaches including adjuvant cally occurs after large initial doses and may therapy and newer or atypical neuroleptins such as ment. Emergency Treatment of Poisoning, p. 25 resemble an exacerbation of the condition clozapine. ,Antipsychotie drugs are considered to act by being treated; and Dose: see under preparations below 2. Bear in mind risk factors, including obesity~artie. interfering with dopaminergic transmission in the ular caution is indicated in older patients especially ¯ tai’dive dyskinesia (rhythmic, involuntary brain by blocking dopamine D2 receptors, which those over 70. i! may ¯give rise to the extrapyramidal effects movements of tongue, face, and jaw), which 3. Consider potential for drug interactions---see inter- usually develops on long-term therapy or with Amytal~ (Flynn) I~ actions: Appendix I (antipsychoties). described below, and also to hyperprolactinaemia. high dosage, but it may develop on short-term 4. Carry out ECG to exclude untoward abnormalities Antipsychotic drugs may also affect cholinergic, Tablets, amobarbital (amylobarbitone) 50 mg, net treatment with low doses--short-lived tardive such as prolonged QT inten, al; repeat ECG periodi- alpha-adrenergic, bistaminergic, and serotonergic pride 20 = £1.84. Label: 19 cally and reduce dose if prolonged QT interval or receptors. dyskinesia may occur after withdrawal of the Dose: 100-200 mg at bedtime (Important:but see also other adverse abnormality develops. drug. - 5. Increase dose slowly and not more often than once contra-indications) : ’ ’CAUTIONS AND, CONTRA-INDICATIONS. Parkinsonian symptoms remit if the drug is With- weekly. should,be used with .caution in drawn and may be suppressed by the adminiStration Sodium Amytal® (Flyun) ~ 6. Carry out regular pulse, blood pressure, and tempera- ture checks; ensure that patient maintains adequate with hepatic impairment (Appendix’2), of antimuscarini¢ drugs (section 4.9.2). However, routirie administration of such di’ugs is’not jusiified Capsules, both bhie, amobarbital (amylobarbitone) fluid intake. impairment (Appendix 3), cardiovascular dis- sodium 60rag, net price 20 = £3.43; 200 mg, 20 = 7. Consider high
170 4.1.1 Hypnotics For guidelines on benzodiazepine withdrawal, see abrupt withdrawal thereafter); Interactlonsr p. 166. Chloral Elixir, Paedlatrlc, BP IPol’4i Icohol Appendix I (anxiolytics and hypnotics) (Chloral Oral Solution, Paediatric) ,hol is a poor hypnotic because its diuretic Elixir, chloral hydrate 4% in a suitable vehicle DRIVING. Drowsiness may persist the next day and affect DIAZEPAM performance of skilled tasks (e.g. driving); effects of interferes with sleep during the latter part of with a blackcurrant flavour. Extemporaneous Indications: short-term use in anxiety or insomnia, alcohol enhanced night. With chronic use, alcohol disturbs sleep adjunct in acute alcohol withdrawal; status epi- preparations should be recently prepared accord- Contra-indications: acute pulmonary insuffi. patterns and causes insomnia; interactions: ing to the following formula: chloral hydrate tepticus (section 4.8.2); febrile convulsions (sec- ciency; alcohol-dependent patients who continue ~/~ppendix I (alcohol). 200 mg, water 0.1 mL, blackcurrant syrup I mL, tion 4.8.3); muscle spasm (section 10.2.2); pefi- to drink L~ syrup to 5 mL. Net price 100 mL = 95p. Label: I, operative use (section 15. 1.4.1 ) Side-effects: nasal congestion and irritation 27 Anxiolytics (increased nasopharyngeal and bronchial secre; Cautions: respiratory disease, muscle weakness Dose: up to I year 5 mL, taken well diluted with water at (Benzodiazepine anxiolytics can be effective in (special care in myasthenia gravis), history of bedtime lions), conjunctival irritation, headache; rarely, paradoxical excitement, confusion, dependence, ~lleviating anxiety states. Although these drugs are drug or alcohol abuse, marked personality disor- Welldorm® (S&N Hlth.) ~ gastro-intestinal disturbances, rash, urticaria, bul- i~ffen prescribed to almost anyone with stress- der, pregnancy and breast-feeding (Appendixes 4 Tablets, blue-purple, f/c, cloral betaine 707 mg and 5); reduce dose in elderly and debilitated, and lous eruption, anaphylaxis, alterations in liver !i’~l’ated symptoms, unhappiness, or minor physical (=- chloral hydrate 414 mg). Net price 30-tab pack enzymes 7d.~sease, their use in many situations is unjustified. in hepatic impairment (avoid if severe, Appendix = £2.43. Label: 19, 27 Dose: severe insomnia in the elderly (short-terni i tiff particular, they are not appropriate for treating 2), renal impairment (Appendix 3); avoid pro- Dose: I-2 tablets with water or milk at bedtime, max. 5 longed use (and abrupt withdrawal thereafter); use), I-2 capsules (or 5-10 mL syrup) at bedtime; -:depression or chronic psychosis. In bereavement, tablets (2 g chloral hydrate) daily CHILD not recommended ! ~;y~:hological adjustment may be inhibited by special precautions for intravenous injection (sec- Elixir, red, chloral hydrate 143.3 mg/5 mL. Net Restlessness and agitation in the elderly, 1 cap- ibenzodiazepines. In children anxiolytic treatment tion 4.8.2); porphyria (section 9.8.2); interac- price 150-mL pack = £2.05. Label: 19, 27 sule (or 5 mL syrup) 3 times daily should be used only to relieve acute anxiety (and tions: Appendix 1 (anxiolytics and hypnotics) Dose: 15-45 mL (0.4-1.3 g chloral hydrate) with water Alcohol withdrawal, initially 2-4 capsules, if nec- ,"related insomnia) caused by fear (e.g. before sur- DRIVING. Drowsiness may affect performance of skilled or milk, at bedtime, max. 70 mL (2 g chloral hydrate) tasks (e.g. driving); effects of alcohol enhanced daily; CHILD 1-1.75 mL/kg (30-50 mg/kg chloral essary repeated after some hours; "gery). h" Anxiolytic treatment should be limited to the lowest Contra-indlcatlons: respiratory depression; acute hydrate), max. 35 mL (I g chloral hydrate) daily day 1 (first 24 hours), 9-12 capsules in 3-4 pulmonary insufficiency; sleep apnoea syndrome; . divided doses; ., ~x~ssible dose for the shortest possible time (see CSM day 2, 6-8 capsules in 3--4 divided doses; ’ ~lvice, section 4.1 ). Dependence is particularly likely severe hepatic impairment; not for chronic psy- TRICLOFOS SODIUM day 3, 4-6 capsules in 3-4 divided doses; then in patients with a history of alcohol or drug abuse and chosis; should not be used alone in depression or Indications: insomnia (short-term use) " gradually reduced over days 445; total treatinent [. in:patients with marked personality disorders. in anxiety with depression; myasthenia gravis; avoid injections containing benzyl alcohol in Cautions: see Chloral Hydrate for not more than 9 days 3’Anxiolytics, particularly the benzodiazepines, neonates (see under preparations below) Contra-indlcations: see Chloral Hydrate Note. For an equivalent therapeutic effect I capsule -= have been termed "minor tranquillisers’. This term Side-effects: see Chloral Hydrate but less gastric 5 mL syrup ~:ismisleading because not only do they differ mark- Side-effects: drowsiness and lightheadedness the irritation ¢’edly from the antipsychotic drugs (’major tmn- next day; confusion and ataxia (especially in the ~ q~illisers’) but their use is by no means minor. Dose: see under preparation below Heminevrin® (AstraZeneca) elderly); amnesia; dependence; paradoxical Capsules, grey-brown, clomethiazole base 192 mg !:[Antipsychotics, in low doses, are also sometimes increase in aggression (see also section 4.1); used in severe anxiety for their sedative action but muscle weakness; occasionally: headache, Trlclofos Oral Solution, Bp FFg’~ in an oily basis. Net pric:e 60-cap pack = £4.34. Label" 19 ’ "long-term use should be avoided in view ofa possi- vertigo, hypotension, salivation changes, gastro- (Triclofos Elixir) i: ble risk of tardive dyskinesia (section 4.2.1). intestinal disturbances, visual disturbances, dys- Oralsolution, triclofos sodium 500 rag/5 mL. Net Syrup, sugar-free, clomethiazole edisilate 250 mg/ 5 mL. Net price 300-mL pack = £3.63. Label: 19. :D Some antidepressants (section 4.3) are licensed arthria, tremor, changes in libido, incontinence, price 300 mL - £28.23. Label: 19 t’0r use in anxiety and related disorders; see sect on urinary retention; blood disorders and jaundice Available from Celltech i 4.3. for a comment on their role in generalised reported; skin reactions; on intravenous injection, Dose: 1 0-20 mL (1-2 g triclofos sodium) at bedtime; CHILD up:to 1 year 25-30 mg/kg, I-5 years 2.5-5 mL Antihistamines "aiixiety disorder and panic disorders. The use of pain, thrombophlebitis, and rarely apnoea; over- (250-500 mg triclofos sodium), 6-12 years 5-10 mL ~ ahtihistamines (e.g. hydroxyzine, section 3.4.1) for dosage: see Emergency Treatment of Poisoning, (0.5-1 g tficlofos sodium) Some antihistamines such as diphenhydramine ’i their sedative effect in anxiety is not considered to p.25 (section 3.4.1) and promethazine are on sale to the the appropriate. Dose: by mouth, anxiety, 2mg 3 times daily denotes preparationsthat ~ considered to public for occasional insomnia; their prolonged increased if necessary to 15-30mg daily in duration of action may often lead to drowsiness the Benzodiazepines divided doses; ELDERLY (or debilitated) half adult following day. The sedative effect of antihistamines dose may diminish after a few days of continued treat- Benzodlazepines are indicated for the short-term Insomnia associated with anxiety, 5-15rag at relief of severe anxiety but long-term use should be Clomethiazole ment; antihistamines are associated with headache, bedtime psychomotor impairment and antimuscarinic avoided (see p. 166). Diazepam, alprazolam, chlor- CHILD night terrors and somnambulism, 1-5 mg Clomethiazole (chlormethiazole) may be a useful effects. diazepoxide, clobazam, and clorazepate have a sus- at bedtime . rained action. Shorter-acting compounds such as hypnotic for elderly patients because of its freedom Promethazine is also popular for use in children, lorazepam and oxazepam may be preferred in By intramascular injection or slow intravenous from hangover but, as with all hypnotics, routine but the use of hypnotics in children is not usually i injection (into a large vein, at a rate of not more patients with hepatic impairment but they carry a administration is undesirable and dependence justified. than 5 mg/minute), for severe acute anxiety, con- :~ greater risk of withdrawal symptoms. occurs. It is indicated for use as a hypnotic only in trol of acute panic attacks, and acute alcohol with- In panic disorders (with or without agoraphobia) the elderly (and for very short-term use in younger PROMETHAZINE HYDROCHLORIDE drawal, I 0 mg, repeated if necessary after not less resistant to antidepressant therapy (section 4.3), a adults to attenuate alcohol withdrawal symptoms, than 4 hours benzodiazepine (Iorazepam 3-5 mg daily or clon- see section 4.10). Note. Only u~ intramuscular route when oral and intra- Indications: night sedation and insomnia (short- azepam 1-2mg daily (section 4.8.1) [both unli- venous routes not possible; special precautions for intra- term use); other indications (section 3.4.1, section :eensed])may be used; alternatively a venous injection see section 4.8.2 CLOMETHIAZOLE !benzodiazepine may be used as short-term adjunc- 4.6) By intravenous infusion----section 4.8.2 (Chlormethiazole) Cautions: section 3.4.1 ’:’"" tire therapy at the start of antidepressant treatment By rectum as rectal solution, acute anxiety and agi- Indications: see under Dose; alcohol withdrawal Contra-lndications: section 3.4.1 : to prevent the initial worsening of symptoms. tation, 500 micrograms/kg repeated after 12 hours (section 4.10) Side-effects: section 3.4.1 ¯ : Diazepam or Iorazepam are very occasionally as required; ELDERLY 250micrograms/kg; CHILD Cautions: cardiac and respiratory disease (confu- administered intravenously for the control of panic Dose: I~v mouth, 25 mg at bedtime increased to not recommended " attacks. This route is the nmst rapid but the proce- sional state may indicate hypoxia); history of 50 mg if necessary; CHILD under 2 years not rec- CHILD febrile convulsions, see p. 239 drug abuse; marked personality disorder; elderly; ommended, 2-5 years 15-20 rag, 5-10 years 20-- :" dure is not without risk (section 4.8.2) and should By rectum as suppositories, anxiety when oral route excessive sedation may occur (particularly with 25 rag, at bedtime be used only when alternative measures have tailed. not appropriate, 10-30 mg (higher dose divided); higher doses); hepatic impaimlent (especially if The intramuscular route has no advantage over the dose form not appropriate lbr less than 10mg severe since sedation can mask hepatic coma); Preparations oral roule. renal impainnent; avoid prolonged use (and Section 3.4. l FAM001159-0005
Rapifen® (Janssen-Cilag) disoquinolinium non-depolar- Atracurlum (Non-proprietary) Ultlva® (Elan) [PoHI , Injection, atracurium besilate 10 mg/mL, net price Injection, alfentanil (as hydrochloride) Injection, powder for reconstitut relaxants (except cisatracurium) are 2.5-mL amp = £1.85; 5-mL amp = £3.37; 25-mL 500 micrograms/mL Net price 2-mL amp = 72p; (as hydrochloride), net price I-m with histamine release which can cause amp = £14.45 10-mL amp = £3.31 mg vial = £11.00; 5-mg vial = £27.50 : ,. hypotension, tachycardia, broncho- Available from Faulding DBL Intensive care injection, alfentanil (as hydro- L rarely, anaphylactoid reactions. Aminos- Tracrlum® (GlaxoWellcome) chloride) 5 mg/mL. To be diluted before use. Net relaxantS are not associated with Injection, atracurium besilate 10 mg/mL, net price price l-mL amp = £2.65 IS.l,S : Muscle relaxants, : release. Drugs possessing vagolytlc can counteract any bradycardia that occurs 2.5-mL amp = £1.78; 5-mL amp = £3.23; 25-mL knownMuscle relaxants used in anaesthesia-~~!~ amp = £13.88 FENTANYL as neuromuscular blocking druggetsI surgery. cific blockade of the neuromuscular junctioll 1~ Indications: analgesia during operation, enhance- CISATRACURIUM enable light levels of anaesthesia to be empl~ ment of anaesthesia; respiratory depressant in is a mixture of 10 isomers and is a with adequate relaxation of the muscles 0fl Indications: muscle relaxatiun for surgery (inter- assisted respiration; analgesia in other situations uinolinium muscle relaxant with an abdomen and d aphragm. They also relax the vo duration of actiun. It undergoes non- mediate duration) (section 4.7.2) cords and allow the passage of a tracfieal ~ metabolism which is independent of Cautions: see notes above Cautions: see section 4.7.2 and notes above Their action differs from the muscle relaxahts kidney function, thus allowing its use in Side-effects: see notes above Contra-indications: see section 4.7.2 and notes ing on the spinal cord or brain which are with hepatic or renal impairment. Cardio- Dose: by intravenous injection, intubation, above musculoskeletal disorders (sect on I0.2.2).:~ ¢g,~ , effectS are associated with significant hist- 150 micrograms&g; maintenance, 30 micr- Side-effects: see section 4.7.2 and notes above Patients who have received a muscle relax~ : release- ograms/kg approx, every 20 minutes Dose: by intravenous injection, with spontaneous should always have their respiration a~ist~,¢ ium is a single isomer of atracurium. CHILD over 2 years, initially, 100 micrograms/kg; respiration, 50-200 micrograms, then maintenance, 20 micrograms/kg approx, every 9 controlled until the drug has been inactivatdd~h potent and has a slightly longer duration 50 micrograms as required; CHILD 3- antagonised (section 15.1.6). :=’::’:.u~ than atracurium and provides greater car- minutes 5micrograms/kg, then 1 microgram/kg as . " ~:.:;£~ ~ stability because cisatracurium lacks By intravenous infusion, ADULT and CHILD over 2 required effects. years, initially, 3micrograms/kg/minute, then With assisted ventilation, 0.3-3.5 mg. then 100- Non-depolarising muscle relaxah~--~ arlum, a benzylisoquinolinium muscle after stabilisation, I-2micrograms/kg/minute; 200 micrograms as required; CHILD Nun-depolarising muscle relaxants (also know~Q short duration of action. It is metabo- dose reduced by up to 40% if used with enflurane 15micrograms/kg, then l-3micrograms/kg as competitive muscle relaxants) compete with.a~t~g cholinesterase and muscle paralysis or isoflurane required choline for receptor sites at the neuromuscularj~ac, in individuals deficient in this enzyme. CHILD under 2 years not recommended tnon and their action may be reversed,:wilh t associated with vagolytic activity or gangli- Sublimaze® (Janssen-Cilag) anticholinesterases such as neostigmine (,~:ti011 although histamine release may Nimbex® (GlaxoWellcome) Injection, fentanyl (as citrate) 50 micrograms/mL. 15.1.6). Non-depolarising muscle relaxants ma~" I~1 , with rapid injection. Injection, cisatracurium (as besilate) 2 mg/mL, net Net price 2-mL amp = 24p; 10-mL amp = £1.I 7 divided into the aminosteroid groupd~hidl price 2.5-mL amp = £2.20, 10-mL amp = £8.12 Available as a generic from Antigen an aminosteroid muscle relaxant, includes pancuronium, rocuronium and veeutgn. duration of action and is often used in Forte injection, cisatracurium (as besilate) 5 mg/ ium, and the benzylisuquinullnium gruup-whl~ mL, net price 30-mL vial = £33.43 long-term mechanical ventila- REMIFENTANIL includes atracurium, cisatracurium, gallamia¢ IIM mivacurium. . : i:~.~. :intensive care units. It lacks a histamine- Indications: supplementation of general anaes- GALl.AMINE TRIETHIODIDE Non-depolarising muscle relaxants have a slo~l’ effect, but vagolytic and sympathomi- thesia during induction and analgesia during can cause tachycardia and hyper- Indications: muscle relaxation for surgery (inter- onset of action than suxamethonium. Tbese ~,’$:~ maintenance of anaesthesia (consult product liter- can be classified by their duration of actioi~ li~ mediate duration) ature for use in patients undergoing cardiac sur- shurt-acting (15-30 minutes), intermedia~te-a~:tifi| exerts an effect within 2 minutes Cautions: see notes above gery) (30-40 minutes) and long-acting (60-120 minut~ ’,has the most rapid onset of any of the competi- Contra-indications: renal impairment Cautions: see section 4.7.2 and notes above although duration of action is dose-depeiideaL :laxants. It is an aminosteroid muscle Side-effectS: see notes above : with an intermediate duration of action. It Contra-lndicatlons: see section 4.7.2 and notes Drugs with a shorter or intermediate duratipni~bt. Dose: by intravenous injection, 80-120mg, then above action, such as atracurium and vecuronitim’ ate to have minimal histamine-releasing and 20-40mg as required; NEONATE, 600mic- Side-effects: see section 4.7.2 and notes above more widely employed than those with a lungCl’ effects; high doses produce mild mgrams/kg; CHILD, 1.5 mg/kg Dose: induction, by intravenous infusion, 0.5- duration of action such as pancuronium. ~ ." ’ 1 microgram/kg/minute, with or without an initial Non-depolarising muscle relaxants have no an aminosteroid muscle relaxant, Flaxedil® (Concord) ~ bolus by intravenous injection (of a solution con- tive or analgesic effects and are not considered to I~ intermediate duration of action. It does not Injection, gallamine triethiodide 40 mg/mL. Net taining 20-250micrograms/mL) over not less a triggering factor for malignant hyperthermia. : ..... produce histamine release and lacks car- price 2-mL amp = £4.97 than 30 seconds, 1 microgram/kg For patients receiving intensive care and who ffects. Note. If patient is to be intubated more than 8 minutes require tracheal intubation and mechanical ventil~ has vagolytiu and sympathumimetic after start of intravenous infusion, intial intravenous be iess Suitable for prescribing (see Ix:w~ : injection dose is unnecessary tion, a non-depolarising muscle relaxant is chos~ increases pulse rate and according to its onset of effect, duration Of action It is rarely used since the other Maintenance in ventilated patients, by intravenous infusion, 0.05-2 micrugrams/kg/minute according and side-effects. Rocuronium, with a rapid ons¢! 01 g drugs have a more predict- MIVACURIUM effect, may facilitate intubation. Atracurium or ¢ts~ to anaesthetic technique and adjusted according and it should be avoided in patients Indications: muscle relaxation for surgery (short tracurium may be suitable for long-term muscle to response; supplemental doses in light anaes- impairment. duration) thesia, by intravenous injection every 2-5 min- relaxation since their duration of actiun is_not Cautions: see notes above; low plasma cholin- dependent on elimination by the liver ur the kid- utes IUM BESIL~TE esterase activity neys. :: :: Maintenance in spontaneous respiration anaes- late) Side-effects: see notes above thesia, by intravenous infusion, initially Dose: by intravenous injection, 70- CAUTIONS. Allergic cross-reactivity beot~,~ muscle relaxation for surgery (short 250 micrograms/kg; maintenance 100 mic- 40nanograms/kg/minute adjusted according to neuromuscular blocking agents has been report . ~ntermediate duration) response, usual range 25-100 nanograms!kg/ caution is advised in cases of hypersensitivity t0 rograms/kg every 15 minutes; CHILD 2~ months notes above initially 150micrograms/kg, 7 months-12 years minute these drugs. Their activity is prolonged in patiea~ see notes above CHILD 1-12 years, maintenance. I~v intravenous with myasthenia gravis and in hypothermia, th initially 200 micrograms/kg; maintenance (CHILD infitsion, 0.05-1.3 micrograms/kg/minute (with or fore lower doses are required. Resistance ~..Y by introvet nts injection, ADULT and CHILD 2 months-12 years) 100micrograms/kg every 6- without an initial bolus by intravenous injection develop in patients v, ith burns who may req .u~.. 1 month initially 300-600micrograms/kg, 9 minutes over not less than 30 seconds, I micrugram/kg/ increased" ¯ "," doscs¯ :; low p’smala cholincstera se actiWty. 100-200 micrograms/kg as required Nou,. Doses up to 150 micrograms!kg may be glvcn over minute) according to anaesthetic technique and i~ intravenous infitsion. 5-10 micrograms/kg/ 5-15 seconds, higher doses should be given over 30 sec- in these pa en s requ res dose tnlmtion for rrllvaClP. onds. In patients with asthma card ovascular disease or adjusted according to response rium. Interactions: Appendix I (muscle rclaxant~I (300-600 micrugrams/kgihour) FAM001159-0006 604 15.1.3 Antimuscarinic drugs 1.5. 1.4 Sedative and analgesic per i-upe~ auvc u, ~ro* !~ ~versal of non-depolarising neuromuscular block, The use of a suitable local anaesthetic cream (sec- cholinergic syndrome (excitement, ataxia, hallucina. by intravenous injection, 200 micrograms per I mg tion 15.2) should be considered to avoid pain at Nitrous oxide tions, behavioural abnormalities, and drowsiness). ~, of neostigmine, or 10-15 micrograms./kg with neD- injection site. Glyeopyrronlum produces good drying of sali, Nitrous oxide is used for maintenance of anaes- vary secretions. When given intravenously it pr0- ¯ "~ sfigmine 50 micrograms&g; CHILD 10 micrograms/ thesia and, in sub-anaesthetic concentrations, for ANAESTHESIA AND DRIVING. See section 15.1. duces less tachycardia than atropine. It is widely analgesia. For anaesthesia it is commonly used in a ," kg with neostigmine 50 micrograms/kg used with neostigmine for reversal of non-depolar. con~cntration of 30 to 70Yo in oxygen as part of a iii islng muscle relaxants (section 15.1.5). balanced technique in association with other inhala- Rbblnul® (Anpharm) 15.1.4.1, Anxiolytics and Phenothiazines have too little drying activity to tional or intravenous agents. Nitrous oxide is unsat- :: fIniection, g ycopyrronium bromide be effective when used alone. ’;~ :’ : ~ neuroleptics isfactory as a sole anaesthetic owing to lack of i ~200m crograms/mL, net pnce I-mL amp = 60p; potency, but is useful as part of a combination of ! ’ tL3-mL amp = £1.01 Anxiolytic benzodiazepines are widely used ATROPINE SULPHATE Available as a generic from Antigen drugs since it allows a significant reduction in dos- whereas neuroleptics such as ehlorpromazine (sec- Indications: drying secretions, reversal of execs. age. tion 4.2.1) are rarely used in the UK for premedi- A mixture of nitrous oxide and oxygen containing sive bradycardia; with neostigmine for reversal of II With neostigmine metilsulphate cation although chlorpromazine was used to : ~ ~-ction 15.1.6 50% of each gas (Entonox~, Equanox~) is used to non-depolarising neuromuscular block; antispas. prevent shivering in induction of hypothermia. Lt. produce analgesia without loss of consciousness. modic (section 1.2); bradycardia (section 2.3.1); Alimemazine (trlmeprazlne) (section 3.4. l) is still Self-administration using a demand valve is popu- eye (section 11.5) H-YOSCINE HYDROBROMIDE occasionally used as a premedicant for children (but lar in obstetric practice, for changing painful dress- Cautions: cardiovascular disease; see also section i igcopolamine Hydrobromide) see section 15.1.4). ings, as an aid to postoperative physiotherapy, and 1.2; interactions: Appendix I (antimuscarinics) Indications: drying secretions, amnesia; other DURATION OF ACTION. Since atropine has a shorter in emergency ambulances. ’ ind cations (section 4.6) Nitrous oxide may have a deleterious effect if duration of action than neostigmine, late unopposed bradycardia may result; close monitoring of the patient Cautlons: see under Atropine Sulphate; avoid in Benzodiazepines used in patients with an air-containing closed space is necessary ~;~the elderly (see notes above) since nitrous oxide diffuses into such a space with a Benzodiazepines possess useful properties for pre- Side-effects: tachycardia; see also section 1.2 ~ontra-indications: porphyria (section 9.8.2) resulting increase in pressure. This effect may be medication including relief of anxiety, sedation, and Dose: premedication, by intravenous injection, : Side-effects: see under Atropine Sulphate; brady- dangerous in the presence ofa pneumothorax which amnesia; short-acting benzodiazepines taken by 300-600 micrograms immediately before induc- i, cardia may enlarge to compromise respiration. tion of anaesthesia, and in incremental doses of Dose: premedication, by subcutaneous or intra- mouth are the most common premedicants. They Exposure of patients to nitrous oxide for pro- have no analgesic effect so an opioid analgesic may 100 micrograms for the treatment of bradycardia muscular injection, 200-600 micrograms 30- longed periods, either by continuous or by intermit- sometimes be required for pain. By intramuscular injection, 300~00micrograms 60 minutes before induction of anaesthesia, usu- tent administration, may result in megaloblastic Benzodiazepines can alleviate anxiety at doses 30~0 minutes before induction; CHILO ally with papaveretum anaemia owing to interference with the action of that do not necessarily cause excessive sedation and 20 micrograms/kg vitamin B~2. For the same reason, exposure of thea- they are of particular value during short procedures For control of muscarinic side-effects of neo- Hyoscine (Non-proprietary) 115~] tre staff to nitrous oxide should be minimised. or during operations under local anaesthesia stigmine in reversal of competitive neuro- InJection, hyoscine hydrobromide Depression of white cell formation may also occur. (including dentistry). Amnesia reduces the likeli- muscular block, by intravenous injection, 0.6- 400 micrograms/mL, net price I-mL amp = 1.2 mg £2.70; 600 micrograms/mL, l-mL amp = £2.81 hood of any unpleasant memories of the procedure (although benzodiazepines, particul~ly when used NITROUS OXIDE Arrhythmias after myocardial infarction, see sec- for more profound sedation, can sometimes induce Indications: see notes above tion 2.3.1; see also cardiopulmonary resuscitation ¯ With papaveretum sexual fantasies). Benzodiazepines are also used in Cautions: see notes above; interactions: Appen- algorithm, inside back cover See under papaveretum (section 4.7.2) dix 1 (anaesthetics, general) nteasive care units for sedation, particularly in Side-effects: see notes above those receiving assisted ventilatiofi, i - !, " Atropine (Non-proprietary) Benzodiazepines may occasionally cause marked Dose: using a suitable anaesthetic apparatus, a Injection, atropine sulphate 600 micrograms,/mL, h5:i:~ ~ Sedative and analgesic respiratory depression and facilities for its treat- mixture with 25-30% oxygen for maintenance of net price l-mL amp = 47p peri-operative drugs ment are essential; flumazenil (section 15.1.7) is light anaesthesia Note. Other strengths also available used to antagonise the effects of benzodiazepines. Analgesic, as a mixture with 50% oxygen, Injection, prefilled disposable syringe, atropine Anxiolytics and neuroleptics 15.1.4.1 Diazepam is used to produce mild sedation with according to the patient’s needs sulphate 100 micrograms/mL, net price 5 mL = Non-opioid analgesics 15.1.4.2 amnesia. It is a long-acting drug with active metab- £4.16, 10mL =£4.66, 30mL= £8.52 15.1.4.3 Opioid analgesics Available from Celhech (Min-l-Jet~) olites and a second period of drowsiness can occur is.i.U- Antimuscarinic drugs several hours after its administration. Peri-operative Injection, prefilled disposable syringe, atropine These drugs are given to allay the apprehension of use of diazepam in children is not generally recom- Antimuscarinic drags are used (less commonly sulphate 200 micrograms/mL, net price 5 mL = the patient in the pre-operative period (including mended; its effect and timing of response are unreli- nowadays) as premedicants to dry bronchial and £4.24; 300 micrograms/mL, 10 mL = £4.32 the night before operation), to relieve pain and dis- able and paradoxical effects may occur. salivary secretions which are increased by intuba- Available from Aurum comfort when present, and to augment the action of Diazepam is relatively insoluble in water and tion, by surgery to the upper airways, and by some subsequent anaesthetic agents. A number of the ¯ With morphine preparations formulated in organic solvents are inhalational anaesthetics. They are also used before drugs used also provide some degree of pre-opera- painful on intravenous injection and give rise to a or with neostigmine (section 15.1.6) to prevent See under Morphine Salts (section 4.7.2) tive amnesia. The choice will vary with the individ- high incidence of venous thrombosis (which may bradycardia, excessive salivation, and other mus- ual patient, the nature of the operative procedure, not be noticed for several days after the injection). carinic actions of neostigmine. They are also used GLYCOPYRRONIUH BROMIDE the anaesthetic to be used and other prevailing cir- Intramuscular injection of diazepam is painful and to prevent bradycardia and hypotension associated Indications: see under Atropine Sulphate cumstances such as outpatients, obstetrics, recovery absorption is erratic. An emulsion preparation for with agents such as halothane, propoful, and suxa- Cautions: cardiovascular disease; see also Atro- facilities etc. The choice would also vary in elective intravenous injection is less irritant and is followed methonium. pine sulphate (section 1.2); interactions: Appen- and emergency operations. by a negligible incidence of venous thrombosis; it is Atropine is now rarely used for premedication dix I (antimuscarinics) not suitable for intramuscular injection. Diazepam but still has an emergency role in the treatment of Side-effects: see under Atropine Sulphate PREMEDICATION IN CHILDREN. Oral adminis- is also available as a rectal solution. vagotonic side-effects. For its role in acute arrhyth- Dose: premedication, by intramusctdar or intra- tration is preferred to injections where possible but Temazepam is given by mouth and has a shorter mias after myocardial infarction, see section 2.3.1; venous injection, 200-400micrograms, or 4- is not altogether satisfactory; the rectal route should duration of action and a more rapid onset than see also cardiopulmonary resuscitation algorithm, 5micrograms/kg to a max. of 400micrograms; only be used in exceptional circumstances. Oral diazcpam given by mouth. It has been used as a pre- section 2.7.3¯ CHILD by intramuscular or preferably /~v intra- alimcmazine (trimcprazine) is still used but when mcdicant in inpatient and day-case surgery; anxio- Ilyoseine effectively reduces sccretions and also venous injection, 4-8 microgramsJkg to a max. of given alone it may cause postoperative restlessness lyric and sedative effects last about 90 minutes provides a degree of amnesia, sedation and anti- 200 micrograms when pain is present. although there may be residual drowsiness. emesis. Unlike atropine it may produce bradycardia Intra-operative use. 10’ intravenous iniection, as for Atrupine or hyuscine is often givcn orally to chil- I,orazepam produces more prolonged sedation rather than tachycardia. In some patients, especially premeditation, repeated i f necessary dren, but may be given intravenously immediately than ternazepam and it has marked amnesic effects. the elderly, hyoscine may cause the central anti- Control of muscarinic side-effects of neostigraine in bctbre induction. FAM001159-0007 16 Prescribing in palliative care Prescribing for the elderly 17 NAUSEA AND VOMITING. Haloperidol is given in MIXING AND COMPATIBILITY. The general prin- a subcutaneous infusion dose of 2.5-10mg/24 ciple that injections should be given into separate hours. Equivalent doses of morphine sulphate by mouth (as oral solution orstandard tablets oras modified-release tablets) sites (and should not be mixed) does not apply to orof diamorphine hydrochloride by intramuscular injection or by subcutaneous infusion Levomepromazine (methotrimeprazine) causes the use of syringe drivers in palliative care. Pro- sedation in about 50% of patients; it is given in a vided that there is evidence of compatibility, These equivalences are approximate only and may need to be adjusted according to response subcutaneous infusion dose of 25-200 mg/24 hours, selected injections can be mixed in syringe drivers. although lower doses of 5-25 mg/24 hours may be Not all types of medication can be used in a subcu- ORAL MORPHINE PARENTERAL DIAMORPHINE effective with less sedation.¯ taneous infusion. In particular, chlorpromazme, Morphine Morphine Diamorphine Diamorphine sulphate Cyclizine is particularly liable to precipitate if prochlorperazine and diazepam are contra-indi- sulphate hydrochloHde by hydrochloHde by mixed with diamorphine or other drugs (see under cated as they cause skin reactions at the injection oral solution or modified-release intramuscular subcutaneous standard tablets Mixing and Compatibility, below); it is given in a site; to a lesser extent cyclizine and levomepro- tablets injection infusion subcutaneous infusion dose of 150 rag/24 hours. mazine (methotrimeprazine) may also sometimes : 1every 4 hours every 12 hours every 4 hours every 24 hours Metoclopramide may cause skin reactions; it is cause local irritation. given .in a subcutaneous infusion dose of_ 30- -_; " ~ ~-Smg.,~: -~ .::20mg~ ..... ~ ,~;- ._,~2.Smg ~ ’~,-,: :..% In theory injections dissolved in water for injec- . ~- " 15 mg,.? -~ 10 mg 100 mg/24 hours. tions are more likely to be associated with pain 30 mg 5 mg 20 mg "-,-’L - 15mg .-, 50rag .... Octreotide (section 8.3.4.3), which stimulates (possibly owing to their hypotonicity). The use of ~’~.’ 5rag. ’ ::* -:?- "30mg.:, ": : water and electrolyte absorption and inhibits water physiological saline (sodium chloride 0.9%) how- 20 mg 60 mg 7.5 mg 45 mg secretion in the small bowel, can be used by subcu- ever increases the likelihood of precipitation when ...... 30.rag , . " :" ,.-:"...... ::-,~S1o¯i~- ...... /"i?.? . ¯~nig:i. ": ? taneous infusion, in a dose of 300-600 micrograms! 9Om~ more than one drug is used; moreover subcutaneous 40 mg 120 mg 15 mg 90 mg 24 hours to reduce intestinal secretions and vomi- infusion rates are so slow (0.1-0.3mL/hour) that "_~i,i~.~.. ’rO~g ’~ ...... , ...... " 180rag " i:~’/,, _’~": %.. 20rag "": ...... ting. -"~".~’,.: . 120 rag; ..... ~ pain is not usually a problem when water is used as 80 mg 240 mg 30 mg 180 mg a diluent. := ...... loo~mg " . . -: 300mg ." ~...-~,~:~,40mg-~.=-:-.;~,. ..=~,~=--240-mg-.,~ -~,~ BOWEL COLIC AND EXCESSIVE RESPIRATORY Diamorphine can be given by subcutaneous infu- <,.~ . 130 mg 400 mg 50 mg 300 mg SECRETIONS. Hyoscine hydrobromide effectively sion in a strength of up to 250mg/mL; up to a !ii,,.’=:~ 160mg .. ¯. 500rag..:. =..: - .:.!:60rag~ ¯i ¯,...... -," :360rag -,:;, reduces respiratory secretions and is sedative (but strength of 40 mg/mL either water for injections or :..- 200 mg 600 mg 70 mg " 400 mg occasionally causes paradoxical agitation); it is physiological saline (sodium chloride 0.9%) is a given in a subcutaneous infusion dose of 0.6- suitable diluent--above that strength only water for 2.4 rag/’24 hours. injections is used (to avoid precipitation). ff[~’r~kthrough pain occurs give a subcutaneous (preferfible) or intramuscular injection of diamorphine equivalent to Hyoscine butylbromide is effective in bowel The following can be mixed with diamorphine: one-sixth of the total 24-hour subcutaneous infusion dose. It is kinder to give an intermittent bolus injection subcuaa. colic, is less sedative than hyoscine hydrobromide, neously.--absorption is smoother so that the risk of adverse effects at peak absorption is avoided (an even better but is hot always adequate for the control of respir- method is to use a subcutaneous butterfly needle). atory Secretions; it is given in a Subcutaneous infu- CYclizinea Hyoscine l~ydrobmmide To minimlse the risk of infection no individual subcutaneous infusion solution should be used for longer than 24 hours. sion dose of 20-60mg/24 hours (important: this Dexamethasone2 Levomepromazme HaloperidoP Metoclopramide4 dose of hyoscine butylbromMe must not be con- Hyoscine butylbromide Midazolam fused with the much lower dose Ofhyoscine hydro- bromide, above). ¯ Subcutaneous infusion solution should be moni- Glyeopyrronium 0.6-1.2mg/24 hours may also Prescribing for the elderly tored regularly both to check for pre¢:ipitation (and be used. discoloration) and to ensure that the infusion is run- OId:~cx:ople, especially the very old, require spec al FORM OF MEDICIN E, Frail elderly patients may ning at the correct rate. dam-and consideration from prescribers. Medicines RESTLESSNESS AND ’CONFUSION.- Haloperidol have difficulty swallowing tablets; if left in the has little sedative effect; it is given in a subcutane- fo~" Older People, a component document offthe mouth, ulceration may develop. They should ous infusion dose of 5-15 mg/24 hours. PROBLEMS ENCOUNTERED WITH SYRINGE National Service Framework for Older People,j always be encouraged to take their tablets or cap- describes how to maximise the benefits of medi- Levomepromazine (methotrimeprazine) has a DRIVERS. The following are problems that may be sales with enough fluid, and in some cases it may sedative effect; it is given in a subcutaneous infu- encountered with syringe drivers and the action that cmes and how to avoid excessive, inappropriate, or be helpful to discuss with the patient the possibility sion dose of 50-200 mg/24 hours. should be taken: in.adequate consumpt on ofmed cines by older pea- of prescribing the drug as a liquid if available. Midazolam is a sedative’and an antiepileptic, and P)~:~, _ MANIFESTATIONS OF AGEING. In very old sub- is therefore suitable for a very restless patient; it is ¯ if the subcutaneous infusion runs too quickly check jects, manifestations of normal ageing may be mis- given in a subcutaneous infusion dose of 20- the rate setting and the calculation; P,OLYPHARMACY. Elderly patients often receive taken for disease and lead to inappropriate 100 rag/24 hours. ¯ if the subcutaneous infusion runs too slowly check the start button, the battery, the syringe driver, the multiple: drugs for their multiple diseases. This prescribing. For example, drugs such as prochlor- cannula, and make sure that the injection site is not greatly increases the risk of drug interactions as perazine are commonly misprescribed for giddiness CONVULSIONS. If a patient has previously been inflamed; well.as adverse reactions, and may affect compli- due to age-related loss of pastural stability. Not receiving an antiepileptie or has a primary or sec- ¯ ante (see Taking medicines to best effect under only is such treatment ineffective but the patient ondary cerebral tumour or is at risk of convulsion ifthereisaninjectionsitereoctionmakesurethatthe site does not need to be changed--firmness or swell- General guidance). Moreover. symptoms such as may experience serious side-effects such as (e.g. owing to Uraemia) antiepileptic medication ing at the site of injection is not in itself an indication ,i headache sleeplessness and lightheadedness which parkinsonism, pastural hypotension, and confusion. should not be stopped. Midazolam is the benzodi- for change, but pain or obvious inflammation is. may be associated with social stress, as in widow- azepine antiepileptic of choice for continuous sub- hoiSd~’ oneliness, and family dispersal can lead to SELF-MEDICATION. Self-medication with over- cutaneous infusion, and is given in a dose of 20- i the-counter products or with drugs prescribed for a 40 rag/24 hours. ~i"th(:i" prescribing, especially of psychotropics, previous illness/or even for another person) may be I. Cyclizine may precipitate at concentrations above Thd’h~e of drugs in such cases can at best be a poor I 0 mg/mL or in the presence of physiological saline or i an added complication. Discussion with both the ,I substitute for effective social measures and at worst PAIN CONTROL. Diamorphine is the preferred .as the concentration of diamorphinc relative to eyclizine patient and relatives as well as a home visit may be ~;~,,se a ser ous threat from adverse reactions. Whilst opioid since its high solubility permits a large dose increases: mixlurcs ofdiamorphine and cyclizine are i~ needed to establish exactly what is being taken¯ ,~ Unnecessary medication should bc avo ded, elderly to be given in a small volume (see under Mixing also liable to prcelpilale after 24 hours. 2. Special care is nccdcd to av’old prcclpitation of patients should not be denied effective treatments SENSITIVITY. The ageing nervous system shows and Compatibility, below). The table below gives such as those for stroke prophyhlxis in atrial libril- the approximate doses of morphine by mouth (as dexamcthasone when preparing. i increased susceptibility to many commonly used oral solution or standard formulation tablets or as 3. Mixtures of hal,.)pcridol and diamorphine are liable Io lation or for osteoporosis, drugs, such as opioid analgesics, benzodiazcpincs, prccipilalc atler 24 hours if halopcridol eonccntralion is ~" antipsychotics, and anliparkinsonian drugs, all of modified-release tablets) equivalent to diamorphim, above 2 mg/mL. by injection (intramuscularly or by subcutaneous ~nt ofllcahh. National Service Framework Ibr which must be used with caution. Similarly, other 4. Under some eondilions metoclopran’fide nlay become " Older People¯ London: l)cpartmcnt of Ilcahh. March organs may also be more susceptible to the effects infusion). 2001 discoloured; such solutions shoukl bc discarded. of drugs such as untihypertcnsives and NSAIDs. FAM001159-0008 vrescno~ng In palliative care ¯ I.$ icines to the infant’s feed, since the drug may inter- Where the dose for children is not stated, pre- act with the milk or other liquid in it; moreover the scribers should seek advlee fr0m a drug information Prescribing in palliative: care ¯ : ingested dosage may be reduced if the child does eefitre or’refer to a current edition of a spechlist , ¯ ,. not drink all the contents. text on the use of medicines in ~:hildren. , , . , .,.,. Parents must be warned to keep all medicines out Palliative care is the active iotal care of patients Equivalent si’ngle dosesofstrong’ahalgesicsl of the reach of children, see Safety in the Home, DOSe: FREQUEI~ICY~ Antibacteriaisaie"generaliy whose disease is not responsive to curative treat- These equivalences are intended only as an approxi- p. 2. given at regular interval~ throughout the day. :Some meat. Control of pain. of other symptoms, and o’f maie guide; patients should be carefully’monit0red flexibility should be allowed-in children to avoid psychological, social and Spiritual problems, is par- after any, change in med cation and dose t !rat on waking them during the night. For example;, .the amount to pi’ovide the best’quality Of life foi" may be required .. night-time dose may be given at the parent’s bed- p~tients and their f’amilies.’ C,’ireful assessment Of ...... ’ ’ :: : Rare paedlatHc conditions ~ .... time .... . : ...=,.,- :. -, ...4 _,.: symptoms and needs of the patient shOuld.be under- Information on substances such as biotin and sod- Where new or potentially toxic drugs are used, 9k.en bya mul!idisciplinary team’...... Analgesic::. i. i ’ " .....Dose ium benzoate used in rare metabolic conditions can the manufacturers’, recommended doses should be Specialist ’palliative’care is availai~le ~n’m0si’areas rph!fie sa!ts (oral) " ’ ..... ~ r " : ~ :’ ’: [~’ ~" ’ 10’rag -" be obtained from: carefully followed. -. - - _- - as day hospice care, home care teams (often known ~0 Drug Information Centre, Alder Hey Children’s Hospital, iamorphine hydrochloride (intramu~lar) .;:.. ,3 mg, . as Macmillan teams), in:patienLhospiee.care, and Hydromorph6rmhydrochloride , : .:~. " 1.3mg:~ ¯ Liverpool L 12 2AP. Telephone (015 I) 252 5381; hosi0i~i t~ams~ l’viagY’acuie~fiospfta s and ieach ng Ox~odo0e ..... ,::::,.:: c~ . :..: .-. -. 5rag.-.,’, Pharmacy, Great Ormond Street Hospital for Children, centres now have i:onsultative, hospital-based Great Ormond St, London, WCI N 3JH. Telephone (020) 7405 9200 teams. . _ ORALROUTE>.Mo~hfn6 iff g yen:b), mouth as an Hospice care~0f terrfiinally ill: patients" fia’g’sh6~ Oral :s01utlon’or as standard" (’immediate release’) the importance of symptom control and-psychoso-- table~(regularlyevery ~4 :hours, the initial d0’se Dosage in Children cial support of the patient and family. Families d~p~i~difig I~el~’ 6fi~the patient’s previous treat- should be included in the care of the patient if they ment. A dose of’5:-q0h~g is enough to replace a Children’s doses in the BNF are stated in the indi- ¯ . ¯ -¯.: ~ ~¯.¯,....-. wish. ~e~e~’:.a~algesi~"(s’dch’as paraeetamol or c0-~rox- vidual dru.g entries as far as possible, except where ,::Many patients wish to remain at.home with tl]eir dmol),’but 10-20mg or more is ’required to replace paediatric use is not recommended, information is .. ’ ~.", Z ::> ¯ _ families. Although some families maY at first be a "strong-6ffe:(cbfi~arahle to filorphine itself). If the- not available, or there are special hazards. afraiylofcaring for the patient at home, support can firsi dose’of mowhine :is.ia~ more: effective thali ibe Doses are generally based on body-weight (in kil- provided by community.nursing seryices, soc!al previous analgesic," ’th’~"next ’dose’sh0ialdZ’be ograms) or the following age ranges: seryices, voluntary.agencies and hospices together increased by 50"/o, the aim being to choose the low- . -. with the general practitioner. :The family may:be est.dose.which preyents palm Thedose should be fast month (neonate) reassured by the knowledge that the patient will be adjusted wlthc~e ful.assessme~i 0f ~e pain and)he up to i year (infant) admitted to a hospital or hospice if the family can- use of adjuvant analgesics: (such as NSAIDs) 1-5 years fibt’cbpe .... ° " .’- ’ ~ ~" . slaould also be 0nkider¢~ Alihough fiadrpfiine.in a 6.-12 years_ - , " " oseof5-20mgisusual y adequate there should be no hesitation..., in .increasing.. it. stepw, se. according ...t° Unless the age is specified, the term ’child" in’ih~"~ ~": : ~-’!-.~ -’ ’-- :- :~ ~ ~ ~, .:; " ~: ):~ "~ -~ DRUG TREATMENT. The number of drugs should be as.few as possible, for even the taking of medi: response to 100 mg or occasionally up to 500rag m" BNF includes persons aged 12 years and younger. " ’ J higher if necessary. It may I~ possible to Omh the .. . , cine may be an effort. Oral medication is usually satisfactory unless there is severe nausea and vomi- overnight dose if double the usual, dose is given’at DOSE- CALCULATION. Children’s doses:may :be ting, dysphagia, weakness, el" coma, in wh ch case bedtime: ; .,.~, .:..! =..- :./.’:.,’!~:~.-:.i~ ~l,3ulat&l fr6fff-adult doses b~, usifig:age:,¯ body- .... : . . parenteral medication may be necessary, i :. ::. : :: If, pain occurs, between: regular doses (’break- weight, or body-surface area, or by a combination ¯ :. 7 :. ’ .) through pain’), aa additional dose (’rescue dose’) 6f’th~¢’fadfOt~.’.Tbe-most reliablemethods ~tre ¯ ;. ¯ . ~..., should be given. An additional’dose should also be thosd; based on’ b6i:ly-surface area¯ " ¯ ...... 4, . .o given 30 minutes before an activity that causes pain ,¯. . .¯.,, _- Body-weight,...... may. be ~ed. to calcu: " " ate: doses . Pain -:’i- :"~- ~ " ’ -: ’ (e.g. wound dressing). Fentanyl lozenges are also expressed, in.mg/kg~. .Young children may require a licensed.for breakthr0hgh pain;. ~:’.~ :" ’ Analgesics are more effective in preventing pain higher dose per kilogram than adults because of , . When’ the pain is e0nta:olled and ih’e patient’s 24-- than. in the relief of established pain; it is important their higher metabolic rates. Other problems need to hour moiphine requiremeni.is established, the daily that they are given regularly. be considered. For example,¯ calculation by body- dose can be given as a single dose or in 2 divided "-~The non-opioid analgesics aspirin or paraceta- weight.in the~obese child may result in much higher doses as a modified-release preparation.. ,. doses being administered than necessary; in such tool given regularly will often make the use of opi" Preparations suitable for twice daily administra- cases, dose should be calculated from an ideal oids unnecessary. Aspirin (or other NSAIDs if tion include MST Continus® tablets or suspension, Weight, related to lidghtlimd age preferred) may also control the pain of bone sec- and Zomorph® capsules. Preparations that allow ondaries; naprexen, flurbiprufen, and indometacin .Body-iurface area (BSA),estimates are more administration of th~ total daily indrphine require- accurate .for calculation of paediatrie doses than (section I 0.1. I) are valuable and if necessary can be mem as a single dose include MXL® capsules. Mor- body~-we!ght since" many’ physilological phenomena given rectally. Radiotherapy, bisphosphonates (sec- cap SR~ capsules may be given either twice daily or correlate better to body-surface area. The average tion 6.6.2) and radioactive isotopes of strontium as a single’daily dose. :: ¯ " " : body-sfiffacearea of a 70-kilogram human is about (Metastron® available from Amersham) may also The startlng dose of modified-release prepara- be useful for pain due to bone metastases... - 1.8m2. Thus, to calculate the dose for a child the tions designed for twice daily administration is ush- following formula may be used: An opioid such as codeine or dextropropoxy- ally 10-20mg evet:y 12 hours if n0 other analgesic Approximate dose for patient = phene, alone or in combination with a non-opioid (or only paraeetamol) has been;’taken previously~ analgesic at adequate dosage, may be helpful in the but to replace a weaker opioid analgesic (such as control of moderate pain if non-opinids alone are , ~urface area 9f patient (m~) X adult dose co-proxamol) the starting dose is Usually 20-30 mg not sufficient. If these preparations are not control- 1.8 every 12 hours. Increments should be made to the ling the pain, morphine is the most useful opioid dose, not to the frequency of administration, which analgesic. Alternatives to morphine are hydromor- More precise body-surface values may be calcu- should remain at every 12 hours. phone, oxycodone (section 4.7.2) and transdcrmal lated from height and weight by means ofa nomo- The effective dose of modified-release prepara- fentanyl (see below and section 4.7.2). Initiation of gram (e.g.J. lnsley, A Paediatric Vade-Mecum, tions can alternatively be determined by giving the an opioid analgesic should not be delayed by con- 13th Edition, London, Arnold, 1996); see also BNF oral solution of morphine every 4 hours in increas- eern over a theoretical likelihood of psychological Inside back covers. ing doses until the pain has been controlled, and dependence (addiction). then transferring the patient to the same total 24- FAMO01159-0009 I I u:i’..I I~lll~ III pd, llldUV~ u~.rl~,.~’1 |~: ~Jllj/’or children . 12 p~lcr, .... II’ feed since the drull:~Yv~?t:hre .Where the dose.for children is not stated, pre- ...... Prescribing in palliative care : ’ ...... " + ~ +’, :11’ , ’’’ ,.:,.,::’’~ + : ~, icines to the It!,/~’ l,r other liquid inili ]luc~d does cefitre’scribers or’refer should s’Oekto h’curi’ent advk:efi-om edition a drug of informationa specialist act with the It!!~"/i)ay be reduced u ,, - tekt off’the uSe"ofmedicin~s ih :hildren:’ " ; ngested do~alt~ l)ntents " Pallhtive care is the active total care of patients Equivalen’t si’ngle dosesof strong:a’nalgesicsi’[= ." ii ...... --’-k all Ih#i:hl w.- ...... :’~, .^ t.ee. all medicines e Home out 1~OSi:]~REQUE~NCY...Ahii:bacierlafs.~fie"geneml/y whose disease is not i:esp0nsive to curaiive treat- These equivalences are intended only as an approxi- Parents mU~l~’,’,hlldren see Safety Ill ’" " given at.’regular iniervais .thmugh0tlt tl~e day. ¯Some meat. Control of pain, of other symptoms+ and o’f maie guide; patients should be catefullymohit0i:ed of the r~aeh ot .. , flexibility, should be allowed.:in: children, to avoid ps~ichrlogical, social and spiritual problems, is par- after any, change in medication and dose titration p. 2. waking them during thenighL.For example;, .the amount to pi’ovide the besi ’qualityol’. life foi. maybe required " ...... night-!tree dqse, Inay be giyga~at3he parent’s bed- p~itients and their families. careful assessment Of ’ ~’:’" ...... ’ :: ;’+’ time.: -, .., ~..~ :: .;,~,._:: ,:. , ::.....-. _,u symptoms and needs of the pat[eiR Should be under- , , . Where new.or potentia!ly.toxic drugs are used, taken bya multidisciplinhry teaifi’...... " "’ . Analgesic :[ . "= = :: ~:’ md‘,, ~D~sr~;.~ I~stances such as blot#!l;of|thtlOasandsod-can in the manufacturers’, recommended doses should be Specialist palliative care is av.aila.ble in most areas InformatiOn ollo~ In rare metabohc I Morphifie sa!t* (oral) " ..... ~ .... -:, :;;:: >i :.,’ldffig-;;r,. carefully followed.: ..... : ~:: .’:--. ,’, .-;.-_ . [ as day hospice care, home care teams (often known Diamorphine hydrochloride (int~tmu~ular) :; i b,:,3 rng I ;o k=ium ^k,~ ber~OaW ned ~|ltlll tl~ ...... ChihhVl¢* " ’ ’ Hospital, _,.%Macmillan 3earns),. in:patienLJaospige+car¢, and Hydromorphonehydrochloffde ,;: ’: ,~ .’; ::..I..3mg:~ h’o’spiiai ieams. Many a~ufe,’fiosp~tal~-and te~ichin~ Oxy~;odone ..... ; ¯ .:: .’-, 5mg~ t/: Drug [nrof~lll.’~’ Ii1~ ~. Telephone (0151)2’ ~l:q/.~hll~h..en centres now have i:onsultative, hospital-based Liverpool L I ~I i nond Street Ilospital fl r:’hone m’~m l Pharmacy. O re~Imt,’7~ndom, wcIN 3Jtl. teal ...... teams. ORAL ffOUTE!Morphi’n~: is given:by mouth ~s an Great OI.monU ~ Hospice cam%f terrriinally ill:phtienfffia~s’stir~. 0ral :~61ution’or as "standard’ (’immediate relea.se.) 7405 9200 ,’ ;5% "+ .:, ¯ ± the importance of symptom control, and psychoso- tablets" t:egt~larly-’e~’ei’y ;,~ hours. the initial d6’se cial support of the:patient’and family:Families " " L+ -+ d~p~h’ding lai-gel~; off: the’ patient’s previous’ire~f- "=-"’Y~_=~ Children ..... + .... ":’:",- ,.., .’ +:- --,:-;-, ...... -. sh0uld be included in the care of the patient if they meat. A dose of5-l0ing is enough tor~plaee’~i wish ~eakff afiiilgeffi~’ (s’uch’as p~racetamol or c0-p.r0x: Ch Idren’S d°sPm1" I~’~s~;aTNFp~iOOSagO~lel?dsl;tetp~elhd:e""" .... :": "~ +,’~.i + :~:’ "+.i- :,Manypatients wish to remain at. home with their a’hiol),~bui~ 10-20 mg or more is required to replace fanailies~ Although some families may .at" firs(be a ~0ng 6n’e (cb~pargble t° i~orphine itsel0. It’ihe. vidual drug fl1,12~1ot recommended, hll’flmatmn Is afraid, of caring for the patient at home, support can first dose Of morphine ’is’ h0 mord eft&live thali:ili~ + :-,+ :..+ -++" ::+’+ ,, ’+,.~+ ¯ :,: ,:’,:+ paediatric use ’" iete are special hazarU,~, _.’’ .., provided by community nursing services, social previous analgesic,: the "nex( ’dose ’ sh~fild ="l~e not available, or, "- bas^" ^- bodv.\V¢lglal tm Kn- services, voluntary agencies and hospices, together increased by 50%, the aim being to choose the low- with the’ general practitioner.13;he fam!ly may!be es! fl0Se.:~hichpreyenis pairL ..Thedose.should be ograms) or Ilia o reassured by the knowledge that the patient will be adjusted ~’ith careful assessment of the pain a~d’tbe admitted to a hospital or hospice if the family can- use Of adjuvant analgesic~; ’(such as NSAIDs) fu~t month (u~’11#0 hotcope. =. ’ ’ . " f-. " " " : ~ should also be omidered. Al~ough ~m0r:pfiind jna up to I year (I"I~!~0 .~ii’."i.,+:’ii ~ . :’ . i ~i ’;, ’.i’ i".~ :i ~ ’ ’’+ ddse of 5-220 mg is usualiy a~deqfiate ifiere sl~dtijd 1~ I-5 yean DRuG TREATMENT The numb’er’0f~gs :sh’ouid no hesitation in increasing it stepwise according to response to I00 mg or occasionally up to 500nag o~ ,,hi!: ...... , ..... -+ ...... :IV-°+: be as.few as possible, for even the taking of medi: +-!+ ’7+ g, ,+, E, cI. higher if necessary. It may be possible to 0m~t the UnlesS .... cine may be an effort. Oral medication, is usually r=Ons aged 12 y overnight dose if double the usual dose is given’at BNF includ¢~ I" satisfactory unless there is severe nausea and vomi- ’TON Ch Idren’s lieges maybe .... _ .," .= ..... u ..... :, +:,:, :.:~; ~.. . . ting, dysphagia,.weakness, of_ qom~, in which,case bedtime: " ; .+ .~. ¯ . ’ :: - :: ; , ..~ !o :-:::.i.~ : If, pain occurs, between, regular doses (’break- DO:~I= parenteral medication may be necessary, i !- .::, ; .. CALCU.!/~dUl, doses’bY usinll "ge:ina~iffn . . through pain’), art additional dose (,rescue dose’) . . : , ,:., .: . , ,., - ;:. . e’alcidat~l IPOt~’ i~t rface area or by a t’°l~°’~s are ...... " " should be given. An additional’dose should .also be weight, or btat~- The molt tellable nl¢inu~. ¯ + . : :-...+ given 30 minutes before an activity that causes pain thos+’b.,isedt)flt’~.1,~’6f’th~s¢ ; fa¢10t~,’~ly.surfai:b urea. "’ ’ ’ - doses -’ ..... +- " Pain’ : : ’ ’, :’, + .... + ::. (e.g. wound dressing). Fentanyl lozenges are also be used tO cnleulat~.. " ’ " ...... "" " "-’ "" "+ "" , ,: licensed for breakthrohgh pain:u ’+. ’+" " " " ’ :: ,..,. Analgesics are more effective in preventing pain When the pain is controlled’and ~h;e patient’s 24- than in the relief of established pain; it is important expressed m .~, tilogram than a+uu+ +. hour morphine requirement.is establisbed, the d aiiy " " that they are given regularly...... higher dose I~l h~dle rates, other prO!d°ll~.n=l~ " .... dose can be given as a single dose or in 2 divided their higher 1~t’~’,,~¢r examp e, calculallt’n I~ hi-h~r ’..The non-opioid analgesics aspirin or paraceta- doses as a modified-release pmparation. . :- ,, ...... _ be considct~,l,.’.~¢ eh Id may result in 111uc.. g . real given regularly will often make the use of opt: ~.= 0|We . ’ If~’ In SUCh Preparations suitable for twice daily adminisffa- weight m tin," ,.., it stered than neceSSl ;, .. ida.= aids unnecessary. Aspirin (or, other NSAIDs if tion include MST Continus® tablets or suspension, doses bring ~}u~,ld be calculated ffonl ..... preferred) may also control the pain of’ bone sec- and Zomorph® capsules. Preparations that allow gases, dose spSi’h¢lght+imd age: . ondaries; naproxen, flurbiprofen, and indometacin ,~ +ire more administration of the total daily morphine rg~lu:ii’e- weight, relate1 u (section l 0.1. l ) are valuable and if necessary can be ment as a single dose include MXL® capsules. Mar: Bodw.~urfll¢ Ill’Ca (BSA) estlmatt dimes than given rectally. Radiotherapy, bisphosphonates (sec- cap SR® capsules may be given either twice dail), Or ... a-=- ¯ ~lolhttion of l~aediatrl¢ phenomena accurate tar ~{ .. many ,4hvslblogical tion 6.6.2) and radioactive isotopes, of strontium asingledailyd0se.~ .... + : " ~ :’ body-weq;m "’] ’0 body-surface area, ’l’h¢ ave,rage...... (Metastron® available from Amersham) may also The Starting dose of modified-release" prepara- , be useful for pain due to bone metastases... ¯ c0?reiate .b¢lt,,’r zi\,t ~ at~f a 70-kilogn70-1diagram hunllul IS.l~°°ut tions designed for twice daily administration is Us’u’ the dose fill’ It oh1 d the I ¯ An opioid such as codeine.or dextropropoxy- al.ly 10-20mg evet:y 12 hours if no other analgesic Wm’+7 3; h the ,,, phone, alone or in combination with a non--opioid (or only paracetamol) has been:iaken previousl~ followi+ l Or’ nl’:~::;’ ;oY);afi:~l - analgesic at adequate dosage, may be helpful in the but to replace a weaker opioid analgesic (such as AppmxinulN control of moderate pain if non-opioids alone are co-proxamol) the starting dose is usually 20-30 mg not sufficient. If these preparations are not control- every 12 hours. Increments should be made to the ,mar.fa,~l~,x¢ ~ ~tient (m:) x adult dtl~ ling the pain, morphine is the most.useful opioid dose, not to the frequency of administration, which analgesic. Alternatives to morphine are hydromor- should remain at every 12 hours. phone, oxycodone (section 4.7.2) and transdermal ~,b.-surface vM c.~ Illlly ,IC ca cu- i The effective dose of modified-release prepara- More I’,n: Controlled drugs and drug dependence 9 PRESCRIBING_. DRUGS LIKELY TO CAUSE There is no standard application form but applica- Schedule 2 includes drugs such as diamorphine DEPENDENCE-OR HISUSE. The prescriber has tions must be supported by a letiel: from a doctor Northern and Yorka’hire . (heroin), morphine, pethidine, secobarbital, gluteth- three main responsibilities: Telephone (0113) 295 1337; fax (0113 ) 295 1310 giving details of: imide, amfetamine, and cocaine and are subject to South East (WesO and Eastern I. To avoid creating dependence by introducing drugs ::: :" the full controlled drug requirements relating to pie- Telephone (01865) 226734; fax (01865) 226652 to patients without sul]icient reason. In this context, ¯ the patient’s name and current address; - :. scriptions, safe custody (except for secobarbital), the Sonth West the proper use of the morphine-like drugs is well ¯ the quantities of drugs to be carried; ./.. need to keep registers, etc. (unless exempted in Telephone (0117) 918 6880; tax (OI 17) 918 6883 under,toad. The dangers of other controlled drugs o the strength and form in which the drugs will be dis- :! schedule 5). . are less clear because recognition of dependence is pensed; Schedule 3 includes the barbiturates (except secobarbi- Tkames and South East (Eas0 . not easy and its effects, and those of withdrawal, are - ¯ the dates of travel to and from the United Kingdom. ¯ tal, now schedule 2) boprenorphine, diethylpropion, Telephone (020) 7594 0811 ; fax (020) 7594 0866 . le~s obvious. Perhaps the most notable result of unln- flunitrazepam, mazindo], meprohamate, pentazocine, Trent ’ " h~ited prescribing is that a very large number of Ten. days should be allowed for processing the ~ ~ phentermine, and temazepam. They are subject to the Telephone (0116) 225 6360;fax (0116) 225 6370 patients in thecountry take tablets which dothem application. ¯ ~:~" special prescription requirements (except for pheno- West Midlandv neither much good nor much harm, but are commit- ~-’i barbital and temazepam, see p. 7) but not to the safe Individual doctors who wish to take Controlled Telephone (0121) 580 433 I; fax (012 I) 525 7980 ted to them indefinitely because they cannot readily ,:;~.~custudy requirements (except for buprenorphine, Drugs abroad while accompanying patients, may be stopped. ic::~ diethylpropion flunitrazepam, and temazepam) nor similarly be issued with lieences. Licences are not SCOTLAND 2. To sec that the patient dons not gradually increase the z~, ,:to the need to keep registers (although there are normally issued to doctors who wish to take Con- Telephone (0131)551 8715; faxi0131) 551 i392 dose of a drug, given for good medical reasons, to the % requirements for the retention of invoices for 2 trolled Drugs abroad solely in casea family emer- point where dependence becomes more likely. This :i:-:" years). WALES tendency is seen especially with hypnotics and gency should arise. i~ Schedule 4 includes in Part 1 bcnzodiazepines (except Telephone (029) 2082 6260; fax (029) 2082 5473 anxiolytics (for CSM advice see section 4.1). The These import/export lieences for named individu- : :, flunitrazepam and temazcpam which are in schedule prescriber should keep a close eye on the amount 3) that are subject to m n ma control¯ Part It includes als do not have any legal status outside the UK and In Northern Ireland, the Misuse of Drugs (Notifi- :. prescribed to prevent patients from accumulating are only issued to comply with the Misuse of Drugs androgenic and anabolic steroids, clenbuterol, chorionic gonadotrophin (HCG), non-human chorio- cation of and Supply to Addicts) (Northernlreland) . stocks that would enable them to arrange their own Act and facilitate passage through UK Customs and dosage or even that of their families and friends. A :! nie gonadotrophin, somatotropin, somatrem, and Regulations 1973 require doctors to send particu- minimal amount should be prescribed in the first Excise control. For clearance in the country to be , somatropin. Controlled drug prescription require- lars of persons whom they consider to be addicted visited it would be necessary to approach that coun- .instance, or when seeing a new patient for the first .:. ments do not apply and Schedule 4 Controlled Drugs to certain controlled drugs to Chief Medical Officer try’s izonsulate in the UK. are not subject to sate custody requirements. rime. of the Department of Health and Social Services. 3. To avoid being used as an unwitting source of supply Schedule 5 includes those preparations which, because The Northern Ireland contacts are: of their strength, are exempt from virtually all Con- for addicts. Methods include visiting more than one Medical contact: doctor, fabricating stories, and forging prescriptions. trolled Drug requirements other than retention of Misuse of Drugs Act. ; ¯ invoices for two years. Dr lan McMaster C3 Castle Buildings¯ The Misuse of Drugs Act, 1971 prohibits certain Patients under temporary care should be given Belfast BT4 3PP activities in relation to ’Controlled Drugs’~ in par- only small supplies of drugs unless they present an Telephone (028) 9052 2421 ticular their manufacture, supply, and possession. unequivocal letter from their own doctors. Doctors Notification of drug misusers Fax (028) 9052 0781 should also remember that their own patients may The penalties applicable to offences involving the different drugs are graded broadly according to the Doctors are expected to report on a standard form be doing a collecting round with other doctors, cases of drug misuse to their regional or national Administrative contact: -: . especially in hospitals. It is sensible to decrease harmfulness attributable to a drug when it is mis- Health Promotion Branch used and for this purpose the drugs are defined in drug misuse database or i:entr~---see below for con- dosages steadily or to issue weekly or even daily tact ti~lephone numbers The National Drtigs Treat- (24.22 Castle Buildings the following three classes: ’ . : - Belfast BT4 3PP prescriptions for small amounts if it is apparent that filent~Moni’toririg System was introduced in Telephone (028) 9052 0532- ’ dependence is occurring. "Erigl~ind in April 2001; regional centres replace the Class A includes: alfentanil, cocaine, dextromoramide, The stealing and misuse of prescription forms diamorphine (heroin), dipipanone, lysergide (LSD), Regional Drug Misuse Databases. A similar system Prescribing of diamorphlne (heroin), could be minlmised by the following precautions: methadone, methylenedioxymetham fetamine h’as been introduced in Wales. . dipipanone, and cocaine for addicts (MDMA, ’ecstasy’), morphine, opium, pethidine, A report (notification) to their regional or national phencyclidine, and class B substances when prepared The Misuse of Drugs (Supply to Addicts) Regula- : (a) do not leave unattended if called away from the con- drug ¯misuse database or centre should be made for injection tions 1997 require that only medical practitioners suhing room or at reception desks; do not leave in a when a patient starts treatment for drug misuse. In Class B includes: oral amphetamines, barbiturates, who hold a special lieence issued by the Home Sec- car where they may be visible; when not in use, keep cannabis, cannabis resin, codeine, ethylmorphine, England and Wales further information is collected in a locked drawer within the surgery and at home; ¯ glutethimide, pentazocine, phenmetrazine, and phol- in Spring, including whether or not patients are con- retary may prescribe, administer or supply diamor- codine phine, dipipanoneI (DieonaP) or cocaine in the (b) draw a diagonal line across the blank part of the form tinuing to receive treatment. All types of problem under the prescription; Class C includes: certain drugs related to the amphet- drug misuse should be reported including opioid, treatment Of drug addiction; other practitioners amines such as benzfetamine and chlorphentermine, benzodiazepine, and CNS stimulant. must refer any addict who requires these drugs to a (c) write the quantity in words and figures when pre- buprenorphine, dicthylproplon, mazindol, mepro- treatment centre. Whenever possible the addict will The regional or national drug misuse database or scribing drugs prone to abuse; this is obligatory for bamate, pemofine, pipradrol, most benzodiazepines, be introduced by a member 6f staff from the treat- eonU-olled drugs (see Prescriptions, above); centres are now the only national and local source androgenic and anabolic steroids, clenbuterol, ment centre to a pharmacist whose agreement has chorionic gonadotrophin (HCG), non-human chorio- of epidemiological data on people presenting with (d) alterations are best avoided but if any are made they been obtained and whose pharmacy is conveniently nic gonadotrophin, somatotropin, somatrem, and problem drug misuse; they provide valuable infor- should be clear and unambiguous; add initials against sited for the patient. Prescriptions for weekly sup- altered items; somatropin mation to those working with drag misusers and plies will be sent to the pharmacy by post and will those planning services for them. The databases (e) if prescriptions are left for collection they should be be dispensed on a daily basis as indicated by the The Misuse of Drugs Regulations 2001 define the cannot, however, be used as a check on multiple left in a safe place in a scaled envelope. doctor. If any alterations of the arrangements are classes of person who are authorised to supply and prescribing for drug addicts because the data are requested by the addict, the portion of the prescrip- possess controlled drugs while acting in their pro- anonymised. fessional capacities and lay down the conditions tion affected must be represcribed and not merely TRAVELLING ABROAD. Prescribed drags listed in Enquiries about the regional or national drug mis- under which these activities may be carried out. In altered. General practitioners and other doctors schedules 4 and 5 to the Misuse of Drugs Regula- use database or centres (including requests for sup- the regulations drugs are divided into five schedules may still prescribe diamorphine, dipipanone, and tions 1985 are not subject to import or export plies of notification forms) can be made by each specifying the requirements governing such cocaine for pat&ms (including addicts) for relief of licensing but doctors are advised that patients Contacting one of the centres listed below: activities as import, export, production, supply, pos- pain due to organic diseuse or injury without a ,we- intending to carry Schedule 2 and 3 drugs abroad session, prescribing, and record keeping which cial licence. may require an export licence. This is dependent apply to them. ENGLAND For guidance on prescription writing, see p. 7. upon the amount of drug to be exported and further details may be obtained from the ttome Office by North West Schedule I includes drugs such as cannabis and lyser- telephoning (020) 7273 3806. Applications fiw Merseyside and Cheshire: telephone (0151) 231 4319; gide which are not used medicinally. Possession and I. Dipipanone in Diconal’ tablets has been much mis- licences should be sent to the ttome Office, Drugs fax (01511 231 4320 supply are prohibited except in accordance "¢,’ilh used by opioid addicts in recent years. Doctors and North Western: telephone (0161) 772 3782: fax (01611 Branch, Queen Anne’s Gate, London SW I I I 9AT. I lame Office aulhorily. others should be suspicious of people who ask for the 772 3445 tablets, cspecially iftemlxwary residents.