Skeletal muscle relaxants
The drugs described are used for the relief of chronic muscle
spasm or spasticity associated with neurological damage;
they are not indicated for spasm associated with minor
injuries. They act principally on the central nervous system
with the exception of dantrolene, which has a peripheral site
of action. They differ in action from the muscle relaxants
used in anaesthesia, which block transmission at the
neuromuscular junction.
The underlying cause of spasticity should be treated and
any aggravating factors (e.g. pressure sores, infection)
remedied. Skeletal muscle relaxants are effective in most
forms of spasticity except the rare alpha variety. The major
disadvantage of treatment with these drugs is that reduction
in muscle tone can cause a loss of splinting action of the
spastic leg and trunk muscles and sometimes lead to an
increase in disability.
Dantrolene sodium p. 821 acts directly on skeletal muscle
and produces fewer central adverse effects. It is generally
used in resistant cases. The dose should be increased slowly.
Baclofen p. 649 inhibits transmission at spinal level and
also depresses the central nervous system. The dose should
be increased slowly to avoid the major side-effects of
sedation and muscular hypotonia (other adverse events are
uncommon).
Diazepam p. 220 has undoubted efficacy in some children.
Sedation and occasionally extensor hypotonus are
disadvantages. Other benzodiazepines also have muscle-
relaxant properties.
2.1 Muscular dystrophy
DRUGS FOR NEUROMUSCULAR DISORDERS
Ataluren 24-May-2017
lDRUG ACTIONAtaluren restores the synthesis of
dystrophin by allowing ribosomes to read through
premature stop codons that cause incomplete dystrophin
synthesis in nonsense mutation Duchenne muscular
dystrophy.
lINDICATIONS AND DOSE
Duchenne muscular dystrophy resulting from a nonsense
mutation in the dystrophin gene, in ambulatory patients
(initiated by a specialist)
▶BY MOUTH
▶Child 5–17 years:(consult product literature)lINTERACTIONS→Appendix 1 : ataluren
lSIDE-EFFECTS
▶Common or very commonAppetite decreased.constipation
.cough.enuresis.fever.flatulence.gastrointestinal
discomfort.haemorrhage.headache.hypertension.
hypertriglyceridaemia.nausea.pain.rash erythematous.
vomiting.weight decreased
lPREGNANCYManufacturer advises avoid—toxicity in
animalstudies.
lBREAST FEEDINGManufacturer advises discontinue
breastfeeding—present in milk inanimalstudies.
lHEPATIC IMPAIRMENTManufacturer advises close
monitoring—safety and efficacy not established.
lRENAL IMPAIRMENTManufacturer advises close
monitoring—safety and efficacy not established.
lMONITORING REQUIREMENTSManufacturer advises
monitor renal function at least every 6 – 12 months, and
cholesterol and triglyceride concentrations at least
annually.
lDIRECTIONS FOR ADMINISTRATIONManufacturer advises
the contents of each sachet should be mixed with at least
30 mL of liquid (water, milk, fruit juice), or 3 tablespoons
of semi-solid food (yoghurt or apple sauce).
lPATIENT AND CARER ADVICEManufacturer advises
patients should maintain adequate hydration during
treatment.
Missed dosesManufacturer advises if a morning or midday
dose is more than 3 hours late, or an evening dose is more
than 6 hours late, the missed dose should not be taken and
the next dose should be taken at the normal time.
lNATIONAL FUNDING/ACCESS DECISIONS
NICE decisions
▶Ataluren for treating Duchenne muscular dystrophy with a
nonsense mutation in the dystrophin gene (July 2016 )
NICE HST3
Ataluren, within its marketing authorisation, is
recommended for treating Duchenne muscular dystrophy
resulting from a nonsense mutation in the dystrophin
gene in people aged 5 years and older who can walk, only
when:
.the manufacturer provides ataluren with the discount
agreed in the patient access scheme,and
.the conditions under which ataluren is made available
are set out in the managed access agreement between
the manufacturer and NHS England, which should
include the conditions set out in sections 5. 12 – 5. 15 and
5. 23 of the guidance.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
it appropriate to stop.
http://www.nice.org.uk/guidance/HST3
Scottish Medicines Consortium (SMC) Decisions
TheScottish Medicines Consortiumhas advised (April 2016 )
that ataluren (Translarna®)isnotrecommended for use
within NHS Scotland for the treatment of Duchenne
muscular dystrophy resulting from a nonsense mutation in
the dystrophin gene, in ambulatory patients aged 5 years
and older as the economic case was not demonstrated.
All Wales Medicines Strategy Group (AWMSG) Decisions
TheAll Wales Medicines Strategy Grouphas advised
(August 2016 ) that the NICE HST advice for ataluren
(Translarna®) should be implemented within NHS Wales.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Granules
▶Translarna(PTC Therapeutics Ltd)A
Ataluren 125 mgTranslarna 125 mg granules for oral suspension
sachets| 30 sachetP£ 2 , 532. 00
Ataluren 250 mgTranslarna 250 mg granules for oral suspension
sachets| 30 sachetP£ 5 , 064. 00
Ataluren 1 gramTranslarna 1 , 000 mg granules for oral suspension
sachets| 30 sachetP£ 20 , 256. 00Nusinersen 18-May-2018
lDRUG ACTIONNusinersen is an antisense oligonucleotide
that increases the production of survival motor neurone
(SMN) protein, thereby helping to compensate for the
defect in the SMN 1 gene found in 5 q spinal muscular
atrophy.lINDICATIONS AND DOSE
5 q spinal muscular atrophy (initiated by a specialist)
▶BY INTRATHECAL INJECTION
▶Neonate:Initially 12 mg for 4 doses on days 0 , 14 , 28 and
63 , then 12 mg every 4 months, for advice on missed
doses—consult product literature.
continued→BNFC 2018 – 2019 Muscular dystrophy 647
Musculoskeletal system10