494
P A R T 5
Drugs acting on the autonomic nervous system
and parasympathetic crisis—and to reverse the effects of
non-depolarising neuromuscular junction blockers used
to cause paralysis in surgery. See Table 32.2 for usual
indications for each drug.
Pharmacokinetics
Anticholinesterase inhibitors are well absorbed after
oral administration and distributed throughout the
body. The sites of metabolism and excretion for all of
these drugs are not known. It is thought that they are
metabolised at the nerve synapse or in the tissues.
TABLE 32.2
DRUGS IN FOCUS Indirect-acting cholinergic agonists
Drug name
Dosage/route
Usual indications
Agents for myasthenia gravis
edrophonium (generic)
Diagnosis: 2 mg IV over 15–30 seconds, then
8 mg IV if response was seen or 10 mg IM,
repeat with 2 mg IM in 12 hours to rule out
false-negative results
Paediatric (diagnosis only): 0.5–2 mg IV based
on weight, or 2–5 mg IM
Diagnosis of myasthenia gravis; reversal
of toxicity from non-depolarising
neuromuscular junction–blocking drugs,
which are used to paralyse muscles
during surgery (see Chapter 28)
neostigmine (generic)
Adult: 0.5 mg SC or IM for control;
0.022 mg/kg IM for diagnosis; 0.5–2 mg IV
as antidote, maximum dose 5 mg
Paediatric: 0.01–0.04 mg/kg/dose IM, IV or SC
for control q 2– 3 hours; 0.04 mg/kg IM for
diagnosis; 0.07–0.08 mg/kg IV, slowly, for
antidote
Diagnosis and management of
myasthenia gravis; reversal of toxicity
from non-depolarising neuromuscular
junction–blocking drugs, which are used
to paralyse muscles during surgery (see
Chapter 28)
pyridostigmine
(Mestinon)
Adult: 60–180 mg PO b.d. to q.i.d
Paediatric: 7 mg/day PO in five or six divided
doses for myasthenia gravis
Management of myasthenia gravis;
antidote to neuromuscular junction
blockers; increases survival after
exposure to nerve gas
Agents for Alzheimer’s disease
donepezil (Aricept)
5–10 mg PO daily at bedtime
Management of Alzheimer’s dementia,
including severe dementia
galantamine (Galantyl,
Reminyl)
4–12 mg PO b.d.; reduce dose to 16 mg/day
maximum with renal or hepatic impairment;
available as an oral solution 4 mg/mL; range
16–32 mg/day; extended release tablets,
range 16–24 mg/day taken as a single dose
Management of mild to moderate
Alzheimer’s dementia delays progression
of disease
rivastigmine (Exelon)
1.5–6 mg PO b.d., based on response
and tolerance; transdermal system, one
4.6 mg/24 hours patch placed once a day,
maximum 9.5 mg/24 hours
Management of mild to moderate
Alzheimer’s dementia; treatment of
dementia related to Parkinson’s disease
In 2003, the Therapeutic Goods Administration
approved a new drug for treating Alzheimer’s disease.
The drug, memantine hydrochloride (
Ebixa, Memanxa
),
has been used in Europe for several years and has
been reported to slow the memory loss of people with
moderate to severe dementia associated with Alzheimer’s
disease. Memantine has a low to moderate affinity for
N
-methyl-
d
-aspartate (NMDA) receptors with no effects
on dopamine, gamma-aminobutyric acid, histamine,
glycine or adrenergic receptor sites. It is thought that
persistent activation of the CNS NMDA receptors
contributes to the symptoms of Alzheimer’s disease.
By blocking these sites, it is thought that the symptoms
are reduced or delayed.
The drug is available in a tablet form, and an oral
solution and is started at 5 mg/day PO, increasing by
5 mg/day at weekly intervals. The target dose is 20 mg/day
given as 10 mg twice daily. Dose reduction should be
considered in individuals with renal impairment. Headache,
dizziness, fatigue, confusion and constipation are common
adverse effects. The drug should not be taken with anything
that alkalinises the urine. Sufferers and family members
need to understand that this drug is not a cure but may
offer some extended time with mild symptoms.
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BOX 32.5
A new drug for treating Alzheimer’s disease
