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OUTLINE
Antidepressants
Mechanisms of Antidepressants
SSRIs
SNRIs
DEPRESSION
Early detection of psychosis and depression can
minimize the of these disorders
SYMPTOMS
Sadness intense
Hopelessness
Despair
No pleasure in usual activities
Sleep pattern & appetite changes
Loss of energy
Suicidal thoughts
Mania is characterize by the opposite behaviour
that there is over enthusiasm, rapid thinking and
speech patterns, extreme self-confidence and
impaired judgement
Mania and depression are different from
schizophrenia. Schizophrenic has disturbances in
thought (delusion, hallucination)
ANTIDEPRESSANTS
SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paraxetine
Sertraline
SEROTONIN/NOREPINEPHRINE RE-UPTAKE
INHIBITORS
Duloxetine
Venlafaxine
ATYPICAL ANTIDEPRESSANTS
Bupropion (very important)
Mirtazapine
Nefazodone
Trazodone (very important)
TRICYCLIC ANTIDEPRESSANTS (POLYCYCLIC
ANTIDEPRESSANTS)
Amitriptyline
Amoxapine
Clomipramine
Desipramine
Doxepine
Imipramine
Transcriber/s: Team HRH
Formatting: Jan Cynric Cacao
Editor/s: Jan Monzon
Atypical Antidepressants
Tricyclic Antidepressants
MAO Inhibitors
Mania and Bipolar Disorders
Other Mood Stabilizers
Maprotiline
Nortriptyline
Protriptyline
Trimipramine
MONOAMINE OXIDASE INHIBITORS
Phenelzine
Selegiline
Trancyclopramine
MANIA & BIPOLAR DRUGS
Carbamazipine (important)
Lithium salts(older drug)
Valproic acid
*Most effective antidepressants will potentiate either
directly or indirectly the actions of neurotransmitter
NOREPINEPHRINE or SEROTONIN. In some of the
drugs both of the neurotransmitters are affected. This
leads to Biogenic amine theory.
MECHANISMS
BIOGENIC AMINE THEORY
Depression is associated with deficiency of
monoamines, especially Norepinephrine and
Serotonin, at functionally important receptor sites
in the brain and that elation(opposite of
depression) is associated with excess of such
amines
Conversely, the theory states that mania is caused
by overproduction of NE and 5HT. However this
theory does not explain why the pharmacological
effects of any antidepressants and anti-mania
drugs on neurotransmission occurs immediately
whereas the time course of therapeutic response
occurs over several days.
We have to modify the biogenic amines here. The
potency of antidepressant drugs in blocking our
neurotransmitters does not correlate with
clinically anti-depressant effects; its not all about
the binding but the modification of effect
Some of them may be mild or attenuated others
would not be attenuated at all. So this suggests
that there is decreased uptake of
neurotransmitters NE or 5HT as the only initial
effect of the drugs
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Panic
Generalized Anxiety
Post-traumatic Stress
Social anxiety disorder
Premenstrual dysphoric disorder
Bulimia nervosa - Fluoxetine (only approved
drug)
PHARMACOKINETICS
ORAL: ALL well absorbed
Peak levels: 2 8 hours
Food: little effect on absorption
SERTRALINE food increases absorption;
significant First-pass metabolism
Well distributed; large volumes of
distribution(excess of our body weight 15-30kg)
Plasma half-lives: 16 -36 hours
Metabolism = Hepatic: P450 enzymes
Extensive glucoronide or sulfate conjugation
(metabolites does not contribute to the activity of
the parent drug)
FLUOXETINE:
Much longer half-life: 50 hours
(sustained release preparations which
will allow the doctors to dose a patient
only once a week)
S-norfluoxetine (S-enantiomer): potent
(half-life: parent drug: 50 hours,
metabolite: average is 10 days and as
potent as the parent compound)
Along with Paroxetine very potent
inhibitors of CYP2D6 (elimination of
TCA drugs, neuroleptic drugs, some
anti-arrhythmic, adrenergic as well as
adrenergic antagonist drugs. SO if you
inhibit CYP2D6, this will cause toxicity.
It also notable that Caucasians
metabolize Paroxetine and Fluoxetin.
There also isoenzymes that are involve
in metabolism of SSRIs, this will affect
multiple medications.
Excretion of SSRIs is primarily
through the kidneys except for
Sertraline and Paroxetine (fecal
excretion,50% for Sertraline). Dosages
of these drugs should be adjusted
downward if with liver impairment
ADVERSE EFFECTS
SSRIs have less severe adverse effects compared
to TCAs and MAO inhibitors
Headaches
Sweating
Anxiety & agitation
GIT effects: nausea, vomiting, diarrhea
Weakness & fatigue
Sleep disturbances (insomnia, somnolence)
Sexual dysfunction
Weight changes (gain weight most often)
Drug-drug interactions
CAUTIONS & CONTRAINDICATIONS
Sleep disturbances
Paroxetine and Fluvoxamine are more
sedating than activating drugs, useful in
depressed and patients with difficulty in
sleeping. Conversely patients who are
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ATYPICAL ANTIDEPRESSANTS
Mixed group of drugs that have actions on several
different sites
Not more efficacious than TCAs or SSRIs but
differ in their side effect profiles
BUPROPION
Weak dopamine & Norepinephrine re-uptake
inhibitor
Short half-life dosing frequency; extendedrelease formulation
Assists in decreasing craving & attenuates
nicotine withdrawal symptoms in patient who are
trying to quit smoking
Metabolism: CYP2D6 pathway
Low risk of drug to drug interactions
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SIDE-EFFECTS
Dry mouth (xerostomia), sweating, nervousness
Tremors
Low sexual dysfunction incidence
INCREASED Seizure risk when given at high
doses
MERTAZAPINE
ENHANCES Serotonin and Norepinephrine
neurotransmission
Blocks 5-HT2 receptors
Sedative due to anti-histaminic activity
(markedly seen)
Does not occupy muscarinic receptors
Does not have anti-muscarinic side effects or
interferes with sexual functioning which are
seen in SNRIs
Advantage on patients who are depressed
and have difficulty in sleeping
INCREASES appetite and weight gain
NEFAZODONE & TRAZODONE
Weak inhibitors of Serotonin re-uptake
Ability to block POSTSYNAPTIC 5-HT2A
receptors
Chronic use: DESENSITIZE 5-HT2A
PRESYNAPTIC receptors increased
SEROTONIN release
Both drugs are sedating due to potent antihistaminic activity
SIDE-EFFECTS:
Priapism Trazodone
Hepatotoxicity Nefazodone
TRICYCLIC ANTIDEPRESSANTS
Blocks norepinephrine and serotonin reuptake
into the neuron
If discovered today, may be classified under SNRIs
except for their difference in adverse effects
Tertiary amines
Imipramine prototype
Amytriptyline
Clomipramine
Doxepine
Trimipramine
Secondary amines
Desipramine
Nortriptyline
Protryptyline
Marprotiline and Amoxapine related tetracyclic
antidepressants; also known as polycyclics
all have similar therapeutic effects and choice of
the drug depends on how the patient will tolerate
the side effects or any pre-existing medical
conditions or the duration of action of the drug
MECHANISM OF ACTION
Inhibition of neurotransmitter re-uptake
Potent inhibitors of NE & Serotonin into
presynaptic neurons
Therapeutic doses: DOES NOT block
Dopamine transporters
Increases Monoamine concentrations in
synaptic cleft results in antidepressant
effects
Transcriber/s: Team HRH
Formatting: Jan Cynric Cacao
Editor/s: Jan Monzon
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PHARMACOKINETICS
ORAL: well-absorbed
EFFECTS ONSET require 2-4 weeks treatment
Enzyme regeneration weeks after drug
termination
SWITCHING Antidepressant drug : allow for 2
weeks delay
METABOLISM: Hepatic
EXCRETION: Urinary
ADVERSE EFFECTS
Drug-Drug interactions:
TYRAMINE (from diet) NOT degraded =
release of large amounts of stored
CATECHOLEAMINES = occipital headache,
stiff neck, tachycardia, nausea,
hypertension, cardiac arrhythmias, seizures,
even stroke
Tyramine-induced HPN: Treat with
PHENTOLAMINE or PRAZOSIN
Drowsiness, orthostatic hypertension,
blurring of vision, xerostomia, dysuria &
constipation
SEROTONIN Syndrome:
MAO INHIBITOR + SSRIs (Should not
be co-administered)
Washout period: 2 weeks
FLOUXETINE: 6 weeks
MAO Inhibitors + BUPROPION = SEIZURES
ADVERSE EFFECTS:
Headache, xerostomia, polydipsia, polyuria,
polyphagia, GIT distress (nausea and vomiting),
tremors, dizziness, fatigue, skin reaction &
sedation
HIGH LEVELS: Ataxia, slurred speech, coarse
tremors, confusion, seizures
SIDE EFFECTS
SEDATION
TRICYCLIC/POLYCYCLIC
ANTIDEPRESSANTS
MIRTAZAPINE
NEFAZODONE
TRAZODONE
AMITRIPTYLINE
AMOXAPINE
CLOMIPRAMINE
DOXEPIN
IMIPRAMINE
MAPROTILINE
NORTRIPTYLINE
TRIMIPRMINE
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TRICYCLIC/POLYCYCLIC
ANTIDEPRESSANTS
ORTHOSTATIC HYPOTENSION
MAO INHIBITORS
TRICYCLIC/POLYCYCLIC
ANTIDEPRESSANTS
WEIGHT GAIN
ATYPICAL ANTIDEPRESSANTS
SSRIs
GIT DISTRESS
SEROTONIN/NE
RE-UPTAKE INHIBITORS
ATYPICAL ANTIDEPRESSANTS
TRICYCLIC/POLYCYCLIC
AMITRIPTYLINE
DOXEPIN
IMIPRAMINE
PHENELZINE
TRANCYCLOPROMINE
AMITRIPTYLINE
CLOMIPRAMINE
IMIPRAMINE
DOXEPINE
TRIMIPRAMINE
MIRTAZAPINE
CITALOPRAM
ESCITALOPRAM
FLUOXETINE
FLUVOXAMINE
PAROXETINE
SERTRALINE
DULOXETINE
VENLAFAXINE
NEFADOZONE
CLOMIPRAMINE
-ENDTRANSCRIPTION DETAILS
Latest
PPT
BASIS
REMARKS
RECORDINGS
NOTES
DEVIATIONS
810%
CREDITS
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