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Antidepressants

(FLUOXETINE)
Presented by:
Arni Grace Gabriel

Depression
An illness that involves the body, mood,

and thoughts and that affects the way a


person eats, sleeps, feels about himself
or herself, and thinks about things.
It is a mood disorder that causes a

persistent feeling of sadness and loss of


interest.

Principal types of Depression


Major Depression

- also called clinical depression


- more severe than depression
Dysthemia
- also called Persistent Depressive Disorder
- If person has depressed mood for most the
time almost every day for at least two years.
- less severe than major depression.
Bipolar disorder
- also caleed manic depression
- entails periods associated with elevated or even
irritable feeling (mania), alternating along with
periods associated with depression.

Pathophysiology
Neurotrophic hypothesis

-Postulates that a loss of BDNF is directly

involved in the pathophysiology of depression,


and that its restoration may underlie the
therapeutic efficacy of antidepressant treatment.
Monoamine Hypothesis

Thetheorythatdefectsinthephysiologyand
metabolismof amines,
especiallycatecholamines(noradrenaline/norepi
nephrineanddopamine)andanindoleamine(ser
otonin).

Neuroendocrine Factors

- depression is known to be associated


with a number of hormonal activities.
- Abnormalities of the HPA axis
(hypothalamic- pituitary-adrenal axis)
- increased cortisol, increased ACTH

MOA of Fluoxetine

Pharmacokinetics
Absorption
Well absorbed from the GI tract after oral

administration.The oral bioavailability of


fluoxetine is estimated to be about 60
80%.
Food may delay its absorption by
approximately 12 hrs but generally does
not affect the amount of drug that reaches
the circulation.
Peak fluoxetine plasma concentrations of
1555 ng/mL are achieved within 68 hrs
after oral administration of a 40-mg dose.

Distribution
High affinity for plasma proteins which is
independent of plasma concentration and
is approximately 94.5% protein-bound at
plasma concentrations of 2001000 ng/mL.
The apparent Vd of fluoxetine and
norfluoxetine (active metabolite) in healthy
adults is an average of 2045 L/kg.

Metabolism
Fluoxetine and norfluoxetine are

slowly cleared from the circulation.


The elimination t1/2of fluoxetine is
approximately an average of 23
days, and may range from 19 days.
For norfluoxetine, the average
elimination t1/2is about 79 days,
with a range of 315 days.
Fluoxetines elimination t1/2has been
reported to be longer after multiple
dosing(about 45 days) compared to

Elimination
Owing to the relatively slow elimination of

fluoxetine and norfluoxetine, significant


accumulation of these pharmacologically
active agents may occur.
It is expected that even after
discontinuation of fluoxetine therapy, the
parent drug and its metabolites will remain
in the circulation for several weeks,
depending on patient characteristics,
previous dosage regimen and duration of
therapy.
This may be clinically significant especially

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