320
P A R T 4
Drugs acting on the central and peripheral nervous systems
accumulation of these neurotransmitters in the synaptic
cleft and increased stimulation of the postsynaptic
receptors. The exact mechanism of action in decreasing
depression is not known but is thought to be related to
the accumulation of noradrenaline and 5HT in certain
areas of the brain.
TCAs are indicated for the relief of symptoms of
depression. The sedative effects of these drugs may
make them more effective in people whose depression
is characterised by anxiety and sleep disturbances. They
are effective for treating enuresis in children older than
6 years (see Box 21.1). Some of these drugs are being
investigated for the treatment of chronic, intractable
pain. In addition, the TCAs are anticholinergic. Clomi
pramine is now also approved for use in the treatment of
obsessive–compulsive disorders (OCDs).
Pharmacokinetics
The TCAs are well absorbed from the gastrointestinal
(GI) tract, reaching peak levels in 2 to 4 hours. They are
highly bound to plasma proteins and are lipid soluble;
this allows them to be distributed widely in the tissues,
including the brain. TCAs are metabolised in the liver
and excreted in the urine, with relatively long half-
lives, ranging from 8 to 46 hours. The TCAs cross the
placenta and enter breast milk (see Contraindications
and cautions).
Contraindications and cautions
One contraindication to the use of TCAs is the presence
of allergy to any of the drugs in this class
because of
the risk of hypersensitivity reactions
. Other contrain
dications include recent myocardial infarction
because
of the potential occurrence of reinfarction or extension
of the infarct with the cardiac effects of the drug
; mye
lography within the previous 24 hours or in the next
48 hours
because of a possible drug–drug interaction
with the dyes used in these studies
; and concurrent use
of an MAO inhibitor
because of the potential for serious
adverse effects or toxic reactions.
In addition, pregnancy
and breastfeeding are contraindications
because of the
potential for adverse effects in the fetus and neonate
;
TCAs should not be used unless the benefit to the mother
clearly outweighs the potential risk to the neonate.
TABLE 21.1
DRUGS IN FOCUS Tricyclic antidepressants (continued)
Drug name
Common side effects
Usual dosage
Sedation
Anticholinergic Hypotension Cardiovascular
Amines (continued)
doxepin (Deptran,
Sinequan)
+++
+++
++
++
10–100 mg PO
b.d.
imipramine
(Tofranil)
++
++
+++
++
Adult:
50–200 mg/day
PO
Paediatric
(5–8 years):
20–30 mg/day
Paediatric
(>12 years):
25–75 mg/day
Maximum
2.5 mg/kg/day
trimipramine
(Surmontil)
+++
++
++
++
Adult:
75–150 mg/day
PO
Paediatric:
50 mg/day PO
Geriatric:
50–100 mg/day
PO
Secondary amines
nortriptyline
(Allegron)
+
+
+
+
Adult: 25–50 mg
PO t.d.s.
(Allegron) to q.i.d.
Geriatric:
30–50 mg/day PO
in divided doses
+ + + +, marked effects; + + +, moderate effects; + +, mild effects; +, negligible effects.
