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P A R T 4
Drugs acting on the central and peripheral nervous systems
ANTIMANIC DRUGS
Mania, at the opposite pole from depression, occurs
in individuals with bipolar disorder, who experience a
period of depression followed by a period of mania. The
cause of mania is not understood, but it is thought to
be an overstimulation of certain neurons in the brain.
The mainstay for treatment of mania has always been
lithium (
Lithicarb
,
Quilonum
). Today, many other
drugs are used successfully in treating bipolar disorders,
including aripiprazole (
Abilify
), olanzapine (
Zyprexa
,
Zyprexa Zydis
), quetiapine (
Seroquel
) and ziprasidone
(
Zeldox
), which are atypical antipsychotics; and lam-
otrigine (
Lamictal
), an antiepileptic agent discussed in
greater detail in Chapter 23. These new approvals were
the first advances since the 1970s in the treatment of
bipolar disorder (see Table 22.2).
Lithium salts (
Lithicarb
,
Quilonum
) are taken orally
for the management of manic episodes and prevention of
future episodes. These very toxic drugs can cause severe
CNS, renal and pulmonary problems that may lead to
death. Despite the potential for serious adverse effects,
lithium is used with caution because it is consistently
effective in the treatment of mania. The therapeutically
effective serum level is 0.6 to 1.2 mEq/L.
Therapeutic actions and indications
Lithium functions in several ways. It alters sodium
transport in nerve and muscle cells; inhibits the release
of noradrenaline and dopamine, but not serotonin, from
stimulated neurons; increases the intraneuronal stores
of noradrenaline and dopamine slightly; and decreases
intraneuronal content of second messengers. This last
mode of action may allow it to selectively modulate the
responsiveness of hyperactive neurons that might con-
tribute to the manic state. Although the biochemical
actions of lithium are known, the exact mechanism of
action in decreasing the manifestations of mania are not
understood.
Pharmacokinetics
Lithium is readily absorbed from the GI tract, reaching
peak levels in 30 minutes to 3 hours. It follows the
same distribution pattern in the body as water. It slowly
crosses the blood–brain barrier. Lithium is excreted from
the kidney, although about 80% is reabsorbed. During
periods of sodium depletion or dehydration, the kidney
reabsorbs more lithium into the serum, often leading
to toxic levels. Therefore, people must be encouraged
to maintain hydration while taking this drug. Lithium
crosses the placenta and enters breast milk, and has been
associated with congenital abnormalities (see Contra
indications and cautions).
Contraindications and cautions
Lithium is contraindicated in the presence of hyper
sensitivity to lithium. In addition, it is contraindicated
in the following conditions: significant renal or cardiac
disease
that could be exacerbated by the toxic effects of
the drug
; a history of leukaemia; metabolic disorders,
including sodium depletion; dehydration; and diuretic
use
because lithium depletes sodium reabsorption and
• Drugs in this group should be taken exactly as prescribed.
Because these drugs affect many body systems, it is
important that you have medical checkups regularly.
• Common effects of these drugs include:
•
Dizziness, drowsiness and fainting:
Avoid driving or
performing hazardous or delicate tasks that require
concentration if these occur. Change position slowly. The
dizziness usually passes after 1 to 2 weeks of drug use.
•
Pink or reddish urine (with phenothiazines):
These drugs
sometimes cause urine to change colour. Do not be
alarmed by this change; it does not mean that your
urine contains blood.
•
Sensitivity to light:
Bright light might hurt your eyes
and sunlight might burn your skin more easily. Wear
sunglasses and protective clothing when you must be
out in the sun.
•
Constipation:
Consult with your healthcare provider if
this becomes a problem.
• Report any of the following conditions to your
healthcare provider:
sore throat, fever, rash, tremors,
weakness and vision changes.
• Tell any doctor, nurse, midwife or other healthcare
provider that you are taking this drug.
• Keep this drug and all medications out of the reach of
children.
• Avoid the use of alcohol or other depressants while you
are taking this drug. You also may want to limit your use of
caffeine if you feel very tense or cannot sleep.
• Avoid the use of over-the-counter drugs while you are on
this drug. Many of them contain ingredients that could
interfere with the effectiveness of your drug. If you feel
that you need one of these preparations, consult with
your healthcare provider about the most appropriate
choice.
• Take this drug exactly as prescribed. If you run out of
medicine or find that you cannot take your drug for any
reason, consult your healthcare provider. After this drug
has been used for a period of time, additional adverse
effects may occur if it is suddenly stopped. This drug
dosage will need to be tapered over time.
