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P A R T 4
Drugs acting on the central and peripheral nervous systems
effects. Such adverse GI effects may include GI irritation,
diarrhoea, constipation and abdominal cramps. Dantro-
lene may also cause direct hepatocellular damage and
hepatitis that can be fatal. Urinary frequency, enuresis
and feelings of urinary urgency reportedly occur, and
crystalline urine with pain or burning on urination may
result. In addition, several unusual adverse effects may
occur, including acne, abnormal hair growth, rashes,
photosensitivity, abnormal sweating, chills and myalgia.
The botulinum toxins have been associated with
anaphylactic reactions; with headache, dizziness, muscle
pain and paralysis; and with redness and oedema at
the injection site. Adverse effects associated with use of
botulinum toxin type A for cosmetic purposes include
headache, respiratory infections, flulike syndrome and
droopy eyelids in severe cases. Pain, redness and muscle
weakness have also been reported. The reactions tend to
be temporary, but there have been reports of reactions
that lasted several months.
Clinically important drug–drug interactions
If dantrolene is combined with oestrogens, the inci-
dence of hepatocellular toxicity is apparently increased.
If possible, this combination should be avoided. If the
botulinum toxins are used with other drugs that inter-
fere with neuromuscular transmission—neuromuscular
junction (NMJ) blockers, lincosamides, quinidine, mag-
nesium sulphate, anticholinesterases, succinylcholine or
polymyxin—or with aminoglycosides, there is a risk of
additive effects. If any of these must be given in combi-
nation, extreme caution should be used.
Understanding the risks of liver damage with
dantrolene
Dantrolene (Dantrium) is associated with potentially
fatal hepatocellular injury. When liver damage begins to
occur, people often experience a prodrome, or warning
syndrome, which includes anorexia, nausea and fatigue.
The incidence of such hepatic injury is greater in women
and in individuals older than 35 years of age.
In women, a combination of dantrolene and oestrogen
seems to affect the liver, thus posing a greater risk.
Women of all ages may be at increased risk, because
those entering menopause may be taking hormone
replacement therapy. People older than 35 years of
age are at increasing risk of liver injury because of the
changing integrity of the liver cells that comes with age
and exposure to toxins over time.
If a particular woman needs dantrolene for relief
of spasticity, she should not be taking any oestrogens
(e.g. birth control pills, hormone replacement therapy)
and she should be monitored closely for any sign of liver
dysfunction. For safer relief of spasticity in these women,
baclofen may be helpful.
Gender considerations
BOX 25.2
Prototype summary: Dantrolene
Indications:
Control of clinical spasticity resulting
from upper motor neuron disorders; preoperatively
to prevent or attenuate the development of
malignant hyperthermia in susceptible people;
IV for management of fulminant malignant
hyperthermia.
Actions:
Interferes with the release of calcium from
the sarcoplasmic reticulum within skeletal muscles,
preventing muscle contraction; does not interfere
with neuromuscular transmission.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Slow
4–6 hours
8–10 hours
IV Rapid
5 hours
6–8 hours
T
1/2
:
9 hours (oral), 4 to 8 hours (IV); excreted in the
urine.
Adverse effects:
Drowsiness, dizziness, weakness,
fatigue, diarrhoea, hepatitis, myalgia, tachycardia,
transient blood pressure changes, rash, urinary
frequency.
Care considerations for people receiving a
direct-acting skeletal muscle relaxant
Assessment: History and examination
■
■
Assess for contraindications or cautions for the
use of the drug
including any known allergies
to prevent hypersensitivity reactions
; cardiac
depression; epilepsy; muscle weakness; respiratory
depression,
which could be exacerbated by the
effects of these drugs
; pregnancy and breastfeeding,
which require cautious use
; renal or hepatic
dysfunction,
which could alter the metabolism and
excretion of the drug
; and local infections (if using
botulinum toxins)
to prevent exacerbation of the
infections
.
■
■
Assess temperature; skin colour and lesions; CNS
orientation, affect, reflexes, bilateral grip strength
and spasticity; respiration and adventitious sounds;
pulse, electrocardiogram (ECG) and cardiac
output; bowel sounds and reported output; and
liver and renal function tests
to determine baseline
status before beginning therapy and for any
potential adverse effects.
■
■
Refer to the Critical thinking scenario for a full
discussion of care for a person who is receiving a
direct-acting skeletal muscle relaxant.
