Transcript Antipsychotic Agents (Neuroleptic Drugs)

Trazodone
Trazodone is a second line agent for treatment of 
depression. Antidepressant effects take several weeks
to develop.Trazodone produces selective blockade of
serotonin reuptake and may also stimulate serotonin
receptor directly.
Common side effects are sedation, orthostatic 
hypotension, dry mouth, and nausea. In contrast to the
tricyclic agents, trazodone has minimal anticholinergic
actions and is not cardiotoxic. Accordingly, trazodone
may be useful for elderly patients and other individuals
for whom the cardiac and anticholinergic effects of the
tricyclics may be intolerable.
Amoxapine is chemicly related to the antipsychotic agent
loxapine, and has both antidepressant and neuroleptic
properties. Anidepressant effects are equivalent to those
of the tricyclics. Because it can cause serious side
effects, amoxapine should be reserved for patients with
psychotic depression.
Anticholinergic, sedative effects. 
Following overdose, the risk of seizures is greater than 
with tricyclics. Caution should be exercised in patients
with epilepsy. It can block receptors for dopamine. As a
result the drug can cause extrapyramidal side effect
Bipolar disorder is a cyclic disorder characterized by 
recurrent fluctuation in mood. Typically, patients
experience alternating episodes of mania and depression
separated by periods in which mood is normal.
Lithium 
Lithium is a simple inorganic ion that carries a single positive
charge.
In the periodic table of elements, lithium fall within the same 
group as potassium and sodium. Accordingly, lithium has
properties in common with these 2 elements.
The mainstay of therapy is lithium. Lithium can provide 
symptomatic control during both the manic phase and the depress
phase. In addition, when taken prophylactically, lithium can
reduce the frequency and severity of recurrent mania and
depressive episodes.

When used for initial control of acute mania, lithium is
usually combined with abenzodiazepine or an
antipsychotic agent. These drugs help suppress
symptoms until lithium takes effect. Once lithium has
taken effect in about 2 weeks, the benzodiazepine or
antipsychotic should be gradually withdrawn.

When used during the depressive phase, lithium can be
combined with an antidepressant. Options include a
tricyclic antidepressant.
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The mode of action is unknown.
Note: Lithium is believed to attenuate
signaling via receptors coupled to the
phosphatidylinositol bisphosphate (PIP2)
second-messenger system.
Lithium interferes with the resynthesis (recycling)
of PIP2, leading to its relative depletion in
neuronal membranes of the
CNS.
Lithium is well absorbed following oral administration.
The drug distributes evenly to all tissues and body
fluids. Lithium has a half life (15-30 h). The drug is
administered in divided daily doses. Lithium is
available in lithium carbonate, as capsules, standard
tablets, slow release tablets, contains 300 mg lithium
carbonate, dose 3 to 4 times daily.
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Sodium depletion will decrease renal excretion of 
lithium, thereby causing the drug to accumulate.
Toxicity may result. Accordingly, it is important that
sodium levels remain normal. Since diuretics promote
sodium loss, these agents must be employed with
caution. Sodium loss secondary to diarrhea can be
sufficient to cause lithium accumulation.
Lithium has a low therapeutic index (0.8-1.4 mEq/L), 
greater than 1.5 mEq /L is toxic. Measurement of
plasma lithium levels is an essential component of
treatment. Lithium levels must be kept below 1.5 mEq/
L, levels greater than this can produce significant
toxicity.
Lithium is the drug of choice for patient with bipolar 
disorder. It control the manic episodes in these patients
and it is used for long term prophylaxis against
recurrent mania and depression in these patients.
The effect of lithium is start after 2 to 3 weeks, for this
reason antipsychotic durg is initially administered with
lithium, when lithium start to act the antipsychotic
agent is then gradually withdrawn
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Adverse effects of lithium can be divided into 2 types:
Effects that occur at therapeutic drug levels. 
Below 1.5 mEq/ L : nausea, vomiting, diarrhea, thirst,
polyuria, muscle weakness, fine hand tremor.
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
Adverse effects that occur when lithium levels are 
excessive:
Certain toxicities are closely correlated with the 
concentration of lithium in plasma:
Plasma levels exceed 1.5 mEq/ L: more serious toxicities 
appear.
1.5-2.0 mEq/L: Coarse hand tremor, confusion, sedation. 
2.0-2.5 mEq/L: Ataxia, tinnitus, blurred vision and 
seizures.
Greater than 2.5 mEq/L symptoms may progress rapidly 
to generalized convulsions, oliguria and death.
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The most common cause of lithium accumulation is
sodium depletion.
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To keep lithium levels within the therapeutic rage,
plasma drug levels should be monitored routinely.
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Levels should be measured every 2 to 3 days at the
beginning of treatment and every 1 to 3 months during
maintenance therapy.
Polyuria occurs in 50% t0 70% 0f patients taking lithium
chronically.
Lithium promotes polyuria by antagonizing the effects of
antidiuretic hormone.
To maintain adequate hydration, patients should be
instructed to drink 8 to 12 glasses of fluids daily.
Chronic administration of lithium has occasionally been
associated with degenerative changes in the kidney.
Kidney function should be assessed prior to treatment and
once a year thereafter
Long term use of lithium can cause enlargement of the
thyroid gland (goiter).
Treatment with thyroid hormone or withdrawal of lithium
will reverse thyroid hypertrophy.
Measurement of thyroid hormones T3 and T4 and TSH
should be obtained prior to treatment and annually
thereafter.
Use of lithium during the first trimester of pregnancy is
associated with an 11% incidence of birth defects(
usually malformations of the heart).
Accordingly lithium is contraindicated during the first
trimester of pregnancy.
Lithium readily enters breast milk and can achieve
concentrations that are potentially harmful to the
nursing infant.
Consequently breast feeding during lithium therapy
should be discouraged.
Diuretics promote sodium loss and can thereby increase
the risk of lithium toxicity by increasing lithium
reabsorption from the renal tubules.
Thank you