C H A P T E R 5 2
Drugs affecting the urinary tract and the bladder
825
Contraindications and cautions
These drugs are contraindicated in the presence of
known allergy to the drugs
to avoid hypersensitiv-
ity reactions
; with pyloric or duodenal obstruction or
recent surgery
because the anticholinergic effects can
cause serious complications
; with obstructive urinary
tract problems,
which could be further aggravated by
the blocking of muscle activity
; and with glaucoma,
myasthenia gravis or acute haemorrhage,
which could
all be exacerbated by the anticholinergic effects of these
drugs.
Caution should be used in people with renal or
hepatic dysfunction,
which could alter the metabolism
and excretion of the drugs
, and in pregnant and breast-
feeding women
because of potential adverse effects on
the fetus or neonate secondary to the anticholinergic
effects of the drugs.
Adverse effects
Adverse effects of urinary tract antispasmodics are
related to the blocking of the parasympathetic system
and include nausea, vomiting, dry mouth, nervousness,
tachycardia and vision changes.
Oxybutynin has numerous anticholinergic effects,
making it undesirable in certain conditions or situations
that might be aggravated by decreased sweating, urinary
retention, tachycardia and changes in GI activity.
Clinically important drug–drug interactions
Decreased effectiveness of phenothiazines and haloper-
idol has been associated with the combination of these
drugs with oxybutynin. If any such combinations must
be used, the person should be monitored closely and
appropriate dose adjustments made. There is a risk of
increased QT interval and serious cardiac arrhythmias
if solifenacin is combined with other drugs that prolong
the QT interval (antihistamines, antipsychotics); the
person must be monitored closely if this combination is
used. There is also a risk of increased serum levels and
toxic effects if solifenacin is combined with ketocona-
zole or other cytochrome P450 (CYP) 3A4 inhibitors;
the dose of solifenacin must be reduced and the person
monitored closely. Tolterodine levels and toxicity can
increase if it is taken with CYP 2D6 inhibitors (fluox-
etine); the dose of tolterodine must be reduced if this
combination is used.
TABLE 52.3
DRUGS IN FOCUS Urinary tract antispasmodics
Drug name
Dosage/route
Usual indications
darifenacin (Enablex)
7.5 mg/day PO; may be increased to 15 mg/day
Treatment of overactive bladder in people
with urinary urgency, incontinence or
frequency
oxybutynin (Ditropan,
Oxytrol)
5 mg PO t.d.s. to q.i.d.; ER tablets—5 mg/day
PO up to a maximum 30 mg/day
Transdermal patch: apply to dry, intact skin q
3–4 days
Paediatric (>5 yr): 5 mg PO b.d., up to a
maximum 5 mg PO t.d.s.
Symptomatic relief of urinary bladder
spasm; treatment of overactive bladder
solifenacin (Vesicare)
5–10 mg/day PO
Treatment of overactive bladder in people
with urinary urgency, incontinence or
frequency
tolterodine (Detrusitol)
1–2 mg PO b.d.; ER capsules—4 mg/day;
reduce dose in people with hepatic
impairment to 1 mg PO b.d.
Treatment of overactive bladder in people
with urinary urgency, frequency or
incontinence
Prototype summary: Oxybutynin
Indications:
Relief of symptoms of bladder instability
associated with uninhibited neurogenic and
reflex neurogenic bladder; treatment of signs and
symptoms of overactive bladder.
Actions:
Acts directly to relax smooth muscle in
the bladder; inhibits the effects of acetylcholine at
muscarinic receptors.
Pharmacokinetics:
Route
Onset
Peak
Duration
Oral
30–60 mins 3–6 hours 6–10 hours
Transdermal
system Varies
6–8 hours 96 hours
T
1/2
:
Unknown; metabolised in the liver and excreted
in urine.
Adverse effects:
Drowsiness, dizziness, blurred
vision, tachycardia, dry mouth, nausea, urinary
hesitancy, decreased sweating.
