CNS DEPRESSION

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Females

_________ are more at risk of developing depression than males.

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Monoamine hypothesis

a hypothesis of depression that is connected to catecholamines and says that there is depletion of monoamines like NE, 5HT and Dopamine that can cause depression.

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○ SSRI

○ SNRI

○ TCA

○ MAOi’s

Drugs That Increases Levels of Monoamines

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NEUROTROPHIC HYPOTHESIS

This theory hypothesizes that depression is due to deficiency of BDNF (Brain Derived Neurotrophic Factor).

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decreased BDNF

Increased cortisol leads to_________, and then leading to decreased PCA (Prefrontal cortex Activity) which promotes higher order cognitive processing.

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NEUROENDOCRINE FACTORS

● hypothesizes that stress is associated with hypothalamic pituitary axis (HPA)

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CRF (cortisol releasing factors)

When you feel stress hypothalamus will release_________________.

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ACTH (Adrenocorticotropic hormone)

Pituitary gland will then be activated upon the release of CRF.

○ Pituitary gland will send____________to activate adrenal cortex

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glucocorticoids,

Upon activation, the adrenal cortex then releases____________ in which one of them is cortisol

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decrease PCA

In neuroendocrine factors, production of cortisol will send a negative feedback to our brain to___________, which leads to decreased higher cognitive learning.

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DEPRESSION

is a common and serious medical illness that negatively affects how you feel, the way you think and how you act

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hypothyroidism

Patients with__________ presents with depression as initial symptom

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Hyperadrenalism

_____________or Enlarged adrenal cortex, causing increased release of cortisol may also cause depression

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Major depressive disorder (MDD)

Most commonly diagnosed type of depression

○ Clonazepam is given

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Persistent depressive disorder

○ Always depressed even if you communicate with others

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Premenstrual depressive disorder

○ Menstruation is nearing, hormonal imbalance

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post-partum depression

Depressive disorder due to another medical condition

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○ Depressants induce depression

Substance/medication-induced depressive disorder

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Psychotherapy Cognitive Behavioral Therapy (CBT)

● is an example of one type of psychotherapy that can help people with anxiety and depressive disorders.

● It teaches people different ways of thinking, behaving, and reacting to anxiety-producing and fearful objects and situations.

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ELECTROCONVULSIVE THERAPY (ECT)

● It is a medical treatment most used for patients with severe major depression or bipolar disorder who have not responded to other treatments.

● It involves a brief electrical stimulation of the brain while the patient is under anesthesia to stimulate presynapse to have release of catecholamines

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Selective Serotonin Reuptake Inhibitors (SSRI)

inhibits the reuptake of serotonin (regulation of neurotransmitters in the synaptic cleft).

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Serotonin-norepinephrine Reuptake Inhibitors (SNRI)

inhibits the reuptake of both serotonin and norepinephrine

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Tricyclic Antidepressants

has 3 benzene rings in the structure, thus tricyclic.

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Monoamine Oxidase Inhibitors (MAOI)

MAO metabolizes the catecholamines (most especially serotonin and norepinephrine in the synapse). Hence, MAO needs to be inhibited by___________in order for to not metabolize the neurotransmitters in the synapse and bind to the post-synapse.

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Lithium

for bipolar disorder

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serotonin transporter (SERT) , norepinephrine transporter (NET)

MOA OF SSRI:

● Highly-selective blockade of__________.

● Little effect on____________.

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1. CItalopram

2. Escitalopram

3. Fluoxetine

4. Fluvoxamine

5. Paroxetine

6. Sertraline

EXAMPLES OF SSRI?

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Citalopram

CELEXA

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ESCILATALOPRAM

LEXAPRO

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FLUOXETINE

PROZAC

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FLUVOXAMINE

LUVOX

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PAROXETINE

PAXIL

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SERTRALINE

ZOLOFT

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ADE OF SSRI

1. Sedation

2. Insomnia

3. Headache, drowsiness, diarrhea

4. Sexual dysfunction

5. Anxiety and suicidal thinking

6. Discontinuation syndrome

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1. NSAIDS

2. Anticoagulants, antiplatelets

3. Serotonergic agents

SSRI can have interactions with?

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  1. Duloxetine

  2. Venlafaxine

  3. Sibutramine

  4. Desvenlafaxine

  5. Levomilnacipran

DRUG EXAMPLES OF SNRI?

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MOA OF SNRI

Moderately selective blockade of NET and SERT - causes increased level of serotonin and norepinephrine in the synapse; hence, higher chance of binding in post-synapse and cause response

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DULOXETINE

CYMBALTA

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VENLAFAXINE

EFFEXOR

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SIBUTRAMINE

MERIDIA

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DESVENLAFAZINE

PRISTIQ

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THERAPEUTIC USE OF SNRI

1. Major Depression

2. Chronic Pain Disorders

3. Fibromyalgia

4. Perimenopausal Symptoms

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ADE OF SNRI

1. Anticholinergic

2. Sedation

3. Hypertension

4. Sexual dysfunction

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Uncontrolled Angle-Closure Glaucoma

SNRI can have a contraindication for patients with_________ since norepinephrine increases intraocular pressure; hence, it increases the risk for UACG.

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TRICYCLIC ANTIDEPRESSANTS (TCAs)

- They are not commonly used today because of their

side effects.

- They cause significant cardiac arrhythmia.

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  1. Imipramine

  2. Desipramine

  3. Clomipramine

  4. Trimipramine

  5. Amitriptyline

  6. Nortriptyline

  7. Doxepin

  8. Protriptyline

DRUG EXAMPLES OF TCA’S

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Amitriptyline

Elavil

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Clomipramine

Anafranil

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Trimipramine

Tofranil

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MOA OF TCA’s

1. Inhibits neurotransmitter reuptake - SERT and NET

2. Blockade of serotonergic, alpha-adrenergic,

histamine, and muscarinic receptors - also blocks the

receptors where the serotonin and norepinephrine will

bind.

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ADE OF TCA’s

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Manic depressive patients

TCA should be used with caution in _____________patients.

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MONOAMINE OXIDASE INHIBITORS (MAOIs)

Does not block the reuptake transporters but blocks the enzymes in order to increase the levels of catecholamines in the synapse.

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  1. Phenelzine

  2. Isocarboxazid

  3. Tranylcypromine

  4. Moclobemide

  5. Selegiline

DRUG EXAMPLES OF MAOI’s

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Phenelzine

act on MAO-A and MAO-B

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Selegiline

act on MAO-B only; Used for Parkinson’s Disease; Used to increase dopamine levels

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MOA OF MAOI’s

1. Blockade of MAO-A and MAO-B

2. MAO-B irreversible selective; MAO-B inhibition

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MAO-A

shows greater affinity for hydroxylated amines, such as noradrenaline or norepinephrine and serotonin.

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MAO-B

higher affinity for non-hydroxylated amines, such as dopamine and tyramine (amino acid).

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ADE OF MAOI’s

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hypertensive crisis

MAOI’s can also cause _________if taken with tyrosine-rich foods (ex. nuts, cheese) (Advise patients not to eat nuts or cheese

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  • Tyramine containing foods

  • MAO + SSRI

MAOI’S can interact with

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  1. Bupropion

  2. Mirtazapine

  3. Amoxapine

  4. Maprotiline

  5. VIlazodone

  6. Buspirone

  7. Nefazodone

  8. Trazodone

TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS

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MOA OF BUPROPION

A dopamine and norepinephrine reuptake inhibitor (DNRI)

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ADE OF BUPROPION

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Smoking cessation

OTHER THREAPEUTIC USE OF BUPROPION?

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AMOXAPINE

● Acts as a strong Norepinephrine reuptake inhibitor

● Weak 5HT reuptake inhibitor

● Inhibits D2 receptor

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ADE OF AMOXAPINE

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Parkinsonism

because of depletion of dopamine

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Cardiotoxicity

- because of increase level of norepinephrine in the synapse (sympathetic responses)

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MOA OF MIRTAZAPINE

Blocks ɑ2 receptor therefore enhancing NE-5HT transmission

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ADE OF MIRTAZAPINE

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APPETITE STIMULANT

OTHER THERAPEUTIC USE OF MIRTAZAPINE

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NEFAZODONE and TRAZODONE (Desyrel)

Weak 5HT reuptake inhibitor and with chronic use may increase 5HT release

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ADE OF NEFAZODONE AND TRAZODONE

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LITHIUM SALTS

Most likely used for bipolar disorders

BRAND NAME: ESKALITH

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MOA OF LITHIUM SALTS

Blocks recycling of phosphoinositides leading to decrease in the release of IP3 and DAG

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magnesium

Lithium inhibits some enzymes that displaces the cofactor__________via transduction

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  1. MOOD STABILIZER

  2. OLD DOC FOR BIPOLAR DISORDER AND MANIA

THERAPEUTIC USE OF LITHIUM SALTS

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ADE OF LITHIUM SALTS

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  1. Aripiprazole (Abilify)

  2. Olanzapine (Zyprexa)

  3. Risperidone (Risperdal)

  4. Quetiapine (Seroquel)

  5. Ziprasidone

  6. Chlorpromazine (Thorazine)

Antipsychotics EXAMPLES

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OTHER DRUGS FOR BIPOLAR DISORDER

1. Valproic acid (Depakote) - also used for seizure

2. Carbamazepine (Tegretol) - anticonvulsant

3. Antipsychotics

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