CNS DEPRESSION

Females

_________ are more at risk of developing depression than males.

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.

○ SSRI

○ SNRI

○ TCA

○ MAOi’s

Drugs That Increases Levels of Monoamines

NEUROTROPHIC HYPOTHESIS

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

decreased BDNF

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

NEUROENDOCRINE FACTORS

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

CRF (cortisol releasing factors)

When you feel stress hypothalamus will release_________________.

ACTH (Adrenocorticotropic hormone)

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

○ Pituitary gland will send____________to activate adrenal cortex

glucocorticoids,

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

decrease PCA

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

DEPRESSION

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

hypothyroidism

Patients with__________ presents with depression as initial symptom

Hyperadrenalism

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

Major depressive disorder (MDD)

Most commonly diagnosed type of depression

○ Clonazepam is given

Persistent depressive disorder

○ Always depressed even if you communicate with others

Premenstrual depressive disorder

○ Menstruation is nearing, hormonal imbalance

post-partum depression

Depressive disorder due to another medical condition

○ Depressants induce depression

Substance/medication-induced depressive disorder

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.

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

Selective Serotonin Reuptake Inhibitors (SSRI)

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

Serotonin-norepinephrine Reuptake Inhibitors (SNRI)

inhibits the reuptake of both serotonin and norepinephrine

Tricyclic Antidepressants

has 3 benzene rings in the structure, thus tricyclic.

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.

Lithium

for bipolar disorder

serotonin transporter (SERT) , norepinephrine transporter (NET)

MOA OF SSRI:

● Highly-selective blockade of__________.

● Little effect on____________.

1. CItalopram

2. Escitalopram

3. Fluoxetine

4. Fluvoxamine

5. Paroxetine

6. Sertraline

EXAMPLES OF SSRI?

Citalopram

CELEXA

ESCILATALOPRAM

LEXAPRO

FLUOXETINE

PROZAC

FLUVOXAMINE

LUVOX

PAROXETINE

PAXIL

SERTRALINE

ZOLOFT

ADE OF SSRI

1. Sedation

2. Insomnia

3. Headache, drowsiness, diarrhea

4. Sexual dysfunction

5. Anxiety and suicidal thinking

6. Discontinuation syndrome

1. NSAIDS

2. Anticoagulants, antiplatelets

3. Serotonergic agents

SSRI can have interactions with?

1. Duloxetine

2. Venlafaxine

3. Sibutramine

4. Desvenlafaxine

5. Levomilnacipran

DRUG EXAMPLES OF SNRI?

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

DULOXETINE

CYMBALTA

VENLAFAXINE

EFFEXOR

SIBUTRAMINE

MERIDIA

DESVENLAFAZINE

PRISTIQ

THERAPEUTIC USE OF SNRI

1. Major Depression

2. Chronic Pain Disorders

3. Fibromyalgia

4. Perimenopausal Symptoms

ADE OF SNRI

1. Anticholinergic

2. Sedation

3. Hypertension

4. Sexual dysfunction

Uncontrolled Angle-Closure Glaucoma

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

TRICYCLIC ANTIDEPRESSANTS (TCAs)

- They are not commonly used today because of their

side effects.

- They cause significant cardiac arrhythmia.

1. Imipramine

2. Desipramine

3. Clomipramine

4. Trimipramine

5. Amitriptyline

6. Nortriptyline

7. Doxepin

8. Protriptyline

DRUG EXAMPLES OF TCA’S

Amitriptyline

Elavil

Clomipramine

Anafranil

Trimipramine

Tofranil

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.

ADE OF TCA’s

Manic depressive patients

TCA should be used with caution in _____________patients.

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.

1. Phenelzine

2. Isocarboxazid

3. Tranylcypromine

4. Moclobemide

5. Selegiline

DRUG EXAMPLES OF MAOI’s

Phenelzine

act on MAO-A and MAO-B

Selegiline

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

MOA OF MAOI’s

1. Blockade of MAO-A and MAO-B

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

MAO-A

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

MAO-B

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

ADE OF MAOI’s

hypertensive crisis

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

• Tyramine containing foods

• MAO + SSRI

MAOI’S can interact with

1. Bupropion

2. Mirtazapine

3. Amoxapine

4. Maprotiline

5. VIlazodone

6. Buspirone

7. Nefazodone

8. Trazodone

TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS

MOA OF BUPROPION

A dopamine and norepinephrine reuptake inhibitor (DNRI)

ADE OF BUPROPION

Smoking cessation

OTHER THREAPEUTIC USE OF BUPROPION?

AMOXAPINE

● Acts as a strong Norepinephrine reuptake inhibitor

● Weak 5HT reuptake inhibitor

● Inhibits D2 receptor

ADE OF AMOXAPINE

Parkinsonism

because of depletion of dopamine

Cardiotoxicity

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

MOA OF MIRTAZAPINE

Blocks ɑ2 receptor therefore enhancing NE-5HT transmission

ADE OF MIRTAZAPINE

APPETITE STIMULANT

OTHER THERAPEUTIC USE OF MIRTAZAPINE

NEFAZODONE and TRAZODONE (Desyrel)

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

ADE OF NEFAZODONE AND TRAZODONE

LITHIUM SALTS

Most likely used for bipolar disorders

BRAND NAME: ESKALITH

MOA OF LITHIUM SALTS

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

magnesium

Lithium inhibits some enzymes that displaces the cofactor__________via transduction

1. MOOD STABILIZER

2. OLD DOC FOR BIPOLAR DISORDER AND MANIA

THERAPEUTIC USE OF LITHIUM SALTS

ADE OF LITHIUM SALTS

1. Aripiprazole (Abilify)

2. Olanzapine (Zyprexa)

3. Risperidone (Risperdal)

4. Quetiapine (Seroquel)

5. Ziprasidone

6. Chlorpromazine (Thorazine)

Antipsychotics EXAMPLES

OTHER DRUGS FOR BIPOLAR DISORDER

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

2. Carbamazepine (Tegretol) - anticonvulsant

3. Antipsychotics