Depressive Disorders (2) (Behavior)

What does neurotransmission depend on

Neurotransmitters

Receptors

Reuptake Mechanism

How many neurons are in the brain

100 billion

How many neurons are in the cerebrum

10-20 billion

How many neurons are in the cerebellum

55-70 billion

How do neurons communicate with each other

They release neurotransmitters from an axon, across the synaptic cleft, to the dendritic receptor

What does a neurotransmitter do once it binds to the receptor

Opens ion channels to fire an action potential

What are the groups of neurotransmitters in relation to action potential

Excitatory

Inhibitory

Both

Excitatory neurotransmitters

Increase likelihood a neuron will fire

Inhibitory neurotransmitters

Decrease the likelihood a neuron will fire

What type of neurotransmitter is gluamate

Excitatory

What type of neurotransmitter is Histamine

Excitatory

What type of neurotransmitter is Dopamine

Both excitatory and inhibitory

What type of neurotransmitter is Acetylcholine

Excitoary

What type of neurotransmitter is Norepinephrine

Excite

What type of neurotransmitter is Epinephrine

Excite

What is the process of an excitatory neurotransmitter

Binds to postsynaptic receptors

Opens Na+ channels

Na enters = Depolarization

More Na enters = Threshold is met = Action potential

What type of neurotransmitter is Serotonin

Inhibt

What type of neurotransmitter is GABA

Inhibit

What type of neurotransmitter is Glycine

Inhibit

What is the process of an inhibitory neurotransmitter

Binds to receptor

K and Cl channels are opened

Cl enters and K leaves = Hyperpolarization

Moves further from threshold

What neurotransmitters are important in depressive disorders

Monoamines

Gluamate

What neurotransmitters are monoamides

Serotonin

Norepinephrine

Dopamine

What is the makeup of serotonin

5-hydroxytrptamine (5-ht)

Tryptophan + Tryptophan + Hydroxlase

Where is serotonin found in the body

GI tract - 90%

Brain - 10%

Raphe nuclei

A structure of the brainstem that releases serotonin

Where is most serotonin found

In the GI tract

Enterochromaffin cells

GI cells that contain serotonin

What is the effect of serotonin in the GI tract

Bowel function

Can serotonin cross BBB

no

What does serotonin effect

Mood

Social behavior

Appetite

Sexual desire and sexual function

Memory and learning

Sleep

Temperature regulation

How is serotonin removed from synapse

Reuptake channels

MAO-A

Monoamine Oxidase (MAO)

An enzyme that breaks down serotonin, norepinephrine, and dopamine

What neurotransmitters are catecholamines

Epinephrine

Norepinephrine

Dopamine

What is dopamine derived from

Tyrosine

What is norepinephrine dervied from

Tyrosine

Where is tyrosine absorbed

GI tract

Where does tyrosine concentrate in the body

Brain

Dopaminergic Neurons / Substantia Nigra

Neurons in the brains that convert tyrosine into dopamine

What are the steps of makes epinephrine

STEP 1: Tyrosine + Tyrosine Hydroxylase = L-DOPA

STEP 2: L-DOPA + L-amino acid decarboxylase = Dopamine

STEP 3: Dopamine + Dopamine beta-hydroxylase = Norepinephrine

STEP 4: Norepinephrine + (PNMT) = Epinephrine

Tyrosine Hydroxylase

Converts tyrosine into L-dopa

L-dopa

A precursor to dopamine

L-amino acid decarboxylase

Converts L-dopa into Dopamine

Dopamine Beta-Hydroxylase

Converts dopamine into norepinephrine

Phenylethanolamine N-methyltransferase (PNMT)

Converts norepinephrine to epinephrine

What are the effects of norepinephrine

Attention

Responding reactions

Arousal/Alertness

Memory

“Fight or Flight”

Where is norepinephrine found in the body

Adrenal Medulla

Locus Coeruleus

Postganglionic Neurons of Sympathetic

Locus Coeruleus

A structure in the brainstem that holds norepinephrine

What removes norepinephrine from the synapse

MAO-A and MAO-B

Vanillylmandelic Acid

The metabolite of norepinephrine by MAO-A/B

D1 Receptor

The excitatory receptor of dopamine

D2 Receptor

Inhibitory receptor of dopamine

Effect of dopamine on the body

Pleasure

Motivation (planning and problem solving)

Reward

Memory

Attention

Motor contro

Where is dopamine found in the body

Basal Ganglia (Substania Nigra)

What removes dopamine from the synapse

MAO-A/B

COMT

Catechol O-methyltransferase

Removes dopamine from the synapse

Effects of glutamate on the body

Learning and memory formation

Cognition

Concentration

Interest

Increased sensitivity to pain

Mood regulation

What is the most abundant excitatory neurotransmitter

Glutamate

What are the receptors for glutmate

NMDA

AMPA

Kainate

How is glutamate removed from the synapse

Glutamate transporters

Glutamine Synthetase

Glutamine Synthetase

Enzyme in glial cells that converts glutamate into glutamine

Biogenic Amine Hypothesis

Depression is due to decreased activity of norepinephrine, serotonin, dopamine

Mania is caused by increased activity of norepinephrine, serotonin, dopamine

What are the benefits of using SSRIs

Effective

Well tolerated

Ease of dosing

Low cost

Generally safe in overdose

What agent is used as first line antidepressant

SSRIs

FDA Indications for SSRIs

Major depressive disorder

Premenstrual dysphoric disorder

Panic disorder

Obsessive-compulsive disorder

Generalized anxiety disorder

Social anxiety disorder

Post-traumatic stress disorder

Bulimia nervosa

Premature ejaculation

Off Label uses of SSRIs

Postpartum depression

Body dysmorphic disorder

Premature ejaculation

Vasomotor symptoms associated with menopause

Irritable bowel syndrome

Where is SSRIs absorbed

GI tract

What SSRI is not given daily

Fluvoxamine (Luvox)

Where is SSRIs generally metabolized

Liver

What SSRIs use CYP450 to activate

Citalopram (Celexa)

Escitalopram (Lexapro)

MOA of SSRIs

Selectively blocks 5-HT receptors

Inhibits presynaptic reuptake by 80%

Prolongs serotonin in synapse

How long until therapuetic effects are seen with SSRIs

3-8 weeks

What should be considered for choosing SSRIs

Side Effects

Patients Symptoms / Goals

Response to Prior Antidepressants

Comorbidities

FHx response to antidepressants

Dosing

Cost

Indications for Fluvoxamine (Luvox)

OCD

Social Anxiety Disorder

What are the general side effects of SSRIs

GI Dysfunction (Dry mouth, constipation, nausea, diarrha)

Sexual Dysfunction (Decreased libido, ED, vaginal dryness, orgasmic dysfunction)

Sleep Distrubance

Weight Gain / Appetite Irregularity

Increased bleeding risk

QT prolongation

Orthostatic Hypotension

Hyponatremia

Sleep Irregularity

Headaches

Tremors

Agitation

Dizziness

Sweating

Mood Irregularity

BLACK BOX: Suicide Risk in Children and Young Adults

How does SSRIs and SNRIs increase bleed risk

Platelet serotonin depletion

Increases gastric acid = Upper GI bleed

CYP450 Drug interactions

What anticoagulant/antiplatelets have interactions with SSRIs and SNRIs

Warfarin (Coumadin)

Aspirin

P2Y12 Receptor Antagonist (Plavix)

What SSRIs have high risk of QT prolongation

Citalopram

Escitalopram

What is the most common electrolyte abnormality with SSRIs

Hyponatrmia

Who is more at risk from hyponatremia with SSRIs

Elderly

What SSRI has risk of anticholinergic effects

Paroxetine

What SSRIs has highest risk of causing drowsy

Paroxetine

What SSRIs does not have risk of drowsy

Fluoxetine

What SSRIs are highest risk of causing insomina and agitation

Fluoxetine

Sertraline

What SSRI has the highest risk of causing orthostatic hypotension?

Paroxetine

What SSRI has the highest risk of ED

Paroxetine

What SSRI is highest risk for GI toxicity

Sertraline

What SSRI does not have weight gain risk

Fluxetine

What SSRI has highest risk of weight gain

PAroxetine

What was the first approved SSRI

Fluoxetine (Prozac)

What are the benefits of using Fluoxetine

Longest half-life

Lowest withdrawl potential

Weight neutral or Weight Loss

What SSRI is ideal for use of eating disorders

Fluoxetine (Prozac)

How old do you need to use Fluoxetine (Prozac)

8 year (MDD)

What SSRI is safest in cardiac symptoms

Sertraline (Zoloft)

What is different about absorption of Sertraline than other SSRIs

Increases with food

When is Sertraline (Zoloft) favored

Breastfeeding / Pregnant

Cardiac Disease

Elderly

What are the cons to using Paroxetine (Paxil)

High risk of withdrawl

Sedation (Anticholinergic)

Weight Gain

Sexual Dysfunction

Birth Defects

Paroxetine has been linked to what birth defect when taken in the first trimester

ASD and VSD

What SSRI has the least effect on CYP450

Citalopram / Escitalopram

How old can you use Citalopram / Escitalopram

12 years

What is favored use of Citalopram / Escitalopram

Agitation

Anxiety Symptoms