BNF for Children 2011-2012

512 10.2 Drugs used in neuromuscular disorders BNFC 2011–201210 Musculoskeletal and joint diseases10.1.5 Other drugs for rheumaticdiseasesClassification not used in BNF for Children.10.2 Drugs used inneuromuscular disorders10.2.1 Drugs that enhance neuromusculartransmission10.2.2 Skeletal muscle relaxants10.2.1 Drugs that enhanceneuromusculartransmissionAnticholinesterases are used as first-line treatment inocular myasthenia gravis and as an adjunct to immunosuppressanttherapy for generalised myastheniagravis.Corticosteroids are used when anticholinesterases donot control symptoms completely. A second-line immunosuppressantsuch as azathioprine is frequently used toreduce the dose of corticosteroid.Plasmapheresis or infusion of intravenous immunoglobulin[unlicensed indication] may induce temporaryremission in severe relapses, particularly where bulbaror respiratory function is compromised or before thymectomy.AnticholinesterasesAnticholinesterase drugs enhance neuromuscular transmissionin voluntary and involuntary muscle in myastheniagravis. They prolong the action of acetylcholineby inhibiting the action of the enzyme acetylcholinesterase.Excessive dosage of these drugs can impairneuromuscular transmission and precipitate cholinergiccrises by causing a depolarising block. This may bedifficult to distinguish from a worsening myasthenicstate.Muscarinic side-effects of anticholinesterases includeincreased sweating, increased salivary and gastric secretions,increased gastro-intestinal and uterine motility,and bradycardia. These parasympathomimetic effectsare antagonised by atropine.Edrophonium has a very brief action and it is thereforeused mainly for the diagnosis of myasthenia gravis.However, such testing should be performed only bythose experienced in its use; other means of establishingthe diagnosis are available. A single test-dose usuallycauses substantial improvement in muscle power (lastingabout 5 minutes) in patients with the disease (ifrespiration already impaired, only in conjunction withsomeone skilled at intubation).Edrophonium can also be used to determine whether apatient with myasthenia is receiving inadequate orexcessive treatment with cholinergic drugs. If treatmentis excessive an injection of edrophonium will either haveno effect or will intensify symptoms (if respirationalready impaired, give only in conjunction with someoneskilled at intubation). Conversely, transientimprovement may be seen if the patient is being inadequatelytreated. The test is best performed just beforethe next dose of anticholinesterase.Neostigmine produces a therapeutic effect for up to 4hours. Its pronounced muscarinic action is a disadvantage,and simultaneous administration of an antimuscarinicdrug such as atropine or propanthelinemay be required to prevent colic, excessive salivation,or diarrhoea. In severe disease neostigmine can begiven every 2 hours. In infants, neostigmine by eithersubcutaneous or intramuscular injection is preferred forthe short-term management of myasthenia.Pyridostigmine is less powerful and slower in actionthan neostigmine but it has a longer duration of action.It is preferable to neostigmine because of its smootheraction and the need for less frequent dosage. It isparticularly preferred in patients whose muscles areweak on waking. It has a comparatively mild gastrointestinaleffect but an antimuscarinic drug may still berequired. It is inadvisable to use excessive dosesbecause acetylcholine receptor down regulation mayoccur. Immunosuppressant therapy may be consideredif high doses of pyridostigmine are needed. Neostigmineand pyridostigmine should be given to neonates 30minutes before feeds to improve suckling.Neostigmine and edrophonium are also used to reversethe actions of the non-depolarising neuromuscularblocking drugs (section 15.1.6).NEOSTIGMINECautions asthma (extreme caution), bradycardia,arrhythmias, recent myocardial infarction, epilepsy,hypotension, parkinsonism, vagotonia, peptic ulceration,hyperthyroidism; atropine or other antidote tomuscarinic effects may be necessary (particularlywhen neostigmine is given by injection), but not givenroutinely because it may mask signs of overdosage;interactions: Appendix 1 (parasympathomimetics)Contra-indications intestinal or urinary obstructionRenal impairment may need dose reductionPregnancy manufacturer advises use only if potentialbenefit outweighs riskBreast-feeding amount probably too small to beharmfulSide-effects nausea, vomiting, increased salivation,diarrhoea, abdominal cramps (more marked withhigher doses); signs of overdosage include bronchoconstriction,increased bronchial secretions, lacrimation,excessive sweating, involuntary defaecation andmicturition, miosis, nystagmus, bradycardia, heartblock, arrhythmias, hypotension, agitation, excessivedreaming, and weakness eventually leading to fasciculationand paralysisIndication and doseTreatment of myasthenia gravis. By mouth (as neostigmine bromide)Neonate initially 1–2 mg, then 1–5 mg every 4hours, give 30 minutes before feeds