Transcript 14 - CNS 7

ANTI DEPRESSANT
DRUGS
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DEPRESSION
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INTENSE FEELINGS OF SADNESS
HOPELESSNESS
DESPAIR
INABILITY TO EXPERIENCE
PLEASURE IN USUAL ACTIVITIES..
Weight loss/weight gain
Changes in sleep pattern
Recurrent thoughts of death
Suicidal tendencies
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MANIA
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OPPOSITE BEHAVIOR
ENTHUSIASM
RAPID THOUGHT AND SPEECH .
IMPAIRED JUDGEMENT.
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Causes of depression
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Heredity – upto 40%
Psychological-low self esteem
Life experiences-poverty, unemployment,
death of parent
Medical conditions- hepatitis,
hypothyroidism, parkinsons
In women –ante/post natal, post
menopausal
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Antidepressant Drugs
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BLOCKADE OF
NEUROTRANSMITTER REUPTAKE
DOPAMINE
SEROTONIN
NOREPINEPHRINE
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What does the biogenic amine
theory of depression propose?
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That depression is due to a deficiency of
norepinephrine, serotonin and dopamine
in the synapses of the CNS.
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Tricyclic antidepressants
(TCAs)
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Amitriptyline
Imipramine - NOREPINEPHRINE
Desipramine
Doxepin
Clomipramine - SEROTONIN
Nortriptyline
Protriptyline
Maprotiline – Second generation
Amoxapine -- Second generation
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MODE OF ACTION
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These drugs are thought to increase
levels of norepinephrine and
serotonin in the synaptic cleft by
blocking neuronal reuptake.
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They also block histamine, cholinergic and
alpha-adrenergic receptors. Which
accounts for a large proportion of their
side effects
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Actions
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Elevate mood
Improve mental alertness
↑ physical activity
More than 2 weeks need..
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Clinical indications for tricyclics
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Mood disorders
Panic disorder
Generalized anxiety disorder
Posttraumatic stress
disorder(clomipramine)
Pain disorders
Enuresis in children(imipramine)
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Tricyclic Antidepressants
Most Common Adverse Effects
 Urinary retention
 Constipation
 Weight Gain
 Sexual Dysfunction
 Confusion/Delirium
 Orthostatic Hypotension
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Over dosage
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restlessness/excitement
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tonic-clonic seizures or dystonia
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Hypoxia, hypotension
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coma
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Amitriptyline
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anticholinergic properties greater than
Imipramine
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sedation: > Imipramine
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antihistaminic properties
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orthostatic hypotension ???
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mild analgesic
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Clinical uses
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endogenous depression
prophylaxis for migraine
eating disorder associated with
depression
sedative for non-depressed patients
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Imipramine - Clinical uses
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endogenous depression
reactive depression
enuresis
alcoholism
cocaine withdrawal
attention deficit disorders
with amphetamine or methyphenidate for
narcolepsy
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Clomipramine - Clinical Uses:
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Obsessive-compulsive disorder
panic disorder
agoraphobia
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Monoamine oxidase inhibitors
(MAO-I’s)
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Phenelzine
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Tranylcypromine
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Clorgyline (specific for MAO type A )
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Isocarboxazid
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What is Monoamine oxidase?
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MAO is a mitochondrial enzyme that is involved
in the metabolism of catecholamine
neurotransmitters.
2 types: MAO-A and MAO-B
Within the neurons MAO-A is responsible for
the inactivation of any serotonin or
NONEPINEPHRINE that may leak out of
presynaptic storage vesicles
MAO-B is responsible for the metabolism of
dopamine and works in a similar manner
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Clinical Uses
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Most useful in patients with significant
anxiety, phobic features and
hypochondriasis
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depressive phase of bipolar disorder
severe reactive depression not
responsive to other drugs
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Most Common Adverse Effects
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Sleep disturbances
Orthostatic Hypotension
Weight Gain
Sexual Dysfunction
Drug/Food Interactions **
Food – Tyramine (cheese, chicken liver, beer,
red wine)
With SSRIS : SEROTONIN SYNDROME.
TOXICITY : SUPPORTIVE THERAPY
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Drug-Drug Interactions
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TCAS
SSRIS
BUSPIRONE
SYMPATHOMIMETICS
CNS DEPRESSANTS
OPIOD ANALGESICS
GENERAL ANAESTHESIA
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Selective Serotonin - Reuptake
Inhibitors - (SSRIs)
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Fluoxetine
Sertraline
Paroxetine
Nefazodone
Trazodone
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Serotonin- specific reuptake
inhibitors (SSRIS)
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FLUOXETINE (PROZAC)
SERTRALINE (ZOLOFT)
PAROXETINE( PAXIL)
FLUVOXAMINE (LUVOX)
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Action
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New group
Selectively inhibit serotonin reuptake.
With affecting reuptake of norepinephrine
or dopamine.
Fewer anticholinergic and lower cardiac
toxicity.
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Clinical Uses:
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endogenous depression
obsessive-compulsive disorder
obesity
bulimia nervosa – (Fluoxetine)
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Most Common Adverse Effects:
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Nausea
Headache
Insomnia
Nervousness
Fatigue
Sexual Dysfunction
Inappropriate ADH secretion
Extrapyramidal effects
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Drug-Drug Interactions
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Tryptophan
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TCAS
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MAO – I ‘s
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ANTIMANIC AGENTS
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What is mania?
Elevated mood with grandiose ideas,
expansiveness, pressured speech, flight of
ideas, decreased sleep and increased
activity
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Lithium Pharmacology
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Absorption : oral
Excretion : urine
Very toxic
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Mech ????
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Neurotransmitter release modulation
Li – Na exchange
Second messenger effect
PIP2 (Phoshphadityl Inositol
biphosphate) ↓
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Rx
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Manic depressive patients
Acute manic episodes
Prevent recurrence of mania
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Adverse Effects
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Tremor-- common side effect
choreoathetosis
motor hyperactivity
ataxia
dysarthria
aphasia
Psychiatric manifestations
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Others
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Thyroid function effects
Renal Effects:
Polydipsia; polyuria
Edema
Cardiac Effects - arrhythmias
Contraindicated in pregnancy
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Lithium Overdosage
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peritoneal dialysis -- effective
hemodialysis -- effective; preferred
Other mood stabilizers:
 Carbamazepine
 Valproic acid
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PSYCHIATRIC COUNSELLING
MEDITATION
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Don’t worry
be
Happy
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