C H A P T E R 2 5
Muscle relaxants
391
not used for the treatment of muscle spasms associated
with musculoskeletal injury or rheumatic disorders.
Table 25.2 presents additional information about these
agents, including usual indications.
Nutritional:
Calcium in muscles
Pharmacokinetics
Dantrolene is used in oral or parenteral forms. Dantro-
lene is slowly absorbed from the GI tract and metabolised
in the liver with a half-life of 4 to 8 hours. Excretion
is through the urine. Dantrolene crosses the placenta
and was found to be embryotoxic in animal studies.
Use should be reserved for those situations in which
the benefit to the mother clearly outweighs the risk to
the fetus. Dantrolene enters breast milk and is contra
indicated for use during breastfeeding. Safety for use in
children younger than 5 years of age has not been estab-
lished; because the long-term effects are not known,
careful consideration should be given to use of the drug
in children.
The botulinum toxins are not generally absorbed
systemically, and there is no pharmacokinetic informa-
tion available.
Contraindications and cautions
Dantrolene is contraindicated in the presence of any
known allergy to the drug. It is also contraindicated
in the following conditions: spasticity that contributes
to locomotion, upright position or increased function,
which would be lost if that spasticity were blocked
;
active hepatic disease,
which might interfere with metab-
olism of the drug and because of known liver toxicity
;
and breastfeeding
because the drug may cross into
breast milk and cause adverse effects in the infant.
The
botulinum toxins are contraindicated in the presence
of allergy to any component of the drug or with active
infection at the site of the injection
because injecting the
drug could aggravate the infection.
Caution should be used with dantrolene in the fol-
lowing circumstances: in women and in all people
older than 35 years
because of increased risk of poten-
tially fatal hepatocellular disease
(Box 25.2); in people
with a history of liver disease or previous dysfunction,
which could make the liver more susceptible to cellular
toxicity;
in people with respiratory depression,
which
could be exacerbated by muscular weakness;
in people
with cardiac disease
because cardiac muscle depres-
sion may be a risk;
and during pregnancy
because of
the potential for adverse effects on the fetus.
Caution
should be used with the botulinum toxins with any
peripheral neuropathic disease; with neuromuscular dis-
orders,
which could be exacerbated by the effects of the
drug
; with pregnancy and breastfeeding; and with any
known cardiovascular disease.
Adverse effects
The most frequently seen adverse effects associated
with dantrolene relate to drug-caused CNS depression:
drowsiness, fatigue, weakness, confusion, headache and
insomnia, and visual disturbances. GI disturbances may
be linked to direct irritation or to alterations in smooth
muscle function caused by the drug-induced calcium
TABLE 25.2
DRUGS IN FOCUS Direct-acting skeletal muscle relaxants
Drug name
Dosage/route
Usual indications
botulinum toxin type A
(Botox, Dysport)
Adult: 20 units (0.5 mL solution) injected as
divided doses of 0.1 mL (four units) into each
of five sites (two in each corrugator muscle
and one in the procerus muscle) repeated
every 3–4 months; local injection associated
with particular disorder—see manufacturer’s
guidelines
Improvement of appearance in glabellar
(frown) lines associated with corrugator
or procerus muscle activity in adults;
treatment of cervical dystonia; approved
in 2004 for treatment of strabismus and
blepharospasm associated with dystonia
in people ≥12 years of age; treatment
of severe primary axillary hyperhidrosis
(sweating) when injected into the axillary
area
dantrolene (Dantrium)
Adult: initially 25 mg PO; increase based
on spinal cord injuries; prevention and
management of response to a maximum
400 mg/day for spasticity
Paediatric: initially 0.5 mg/kg per day PO b.d.,
titrate to a maximum 100 mg PO q.i.d. for
spasticity
Management of upper motor neuron–
associated muscle spasticity such as
spinal cord injury, myasthenia gravis,
cerebral palsy, multiple sclerosis,
muscular dystrophy, polio, tetanus,
quadriplegia and amyotrophic lateral
sclerosis (ALS); prevention or treatment
of malignant hyperthermia—a state of
intense muscle contraction prophylaxis
in susceptible people who must undergo
anaesthesia and after acute episodes to
prevent recurrence
