IDT Exam 2 Flashcards by Ammon Kunz

8 subcategories of depression

Characterized as mild, moderate, or severe
Reactive
Agitated
Atypical
Dysthymia
PMS
Post-partum
Psychotic
SAD

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Treatments for depression

Talk
Light
Antidepressants
Exercise
Electroconvulsive

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What is the simple biogenic amine hypothesis

Antidepressants extend duration of biogenic amines (norepinephrine, serotonin, maybe dopamine) through blocking reuptake or metabolism (SSRIs vs. MAOIs)

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Serotonin associated symptoms

Agitation
Dysphagia
Dyssomnia
Anxiety
No libido

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Norepinephrine associated symptoms

Focus/alert
Memory
Energy

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Problem with biogenic amine hypothesis

Biogenic amines increase in 2-3 hours
Antidepressants take weeks to months to work

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Alternative antidepressant and ETC action hypothesis

Increase in biogenic amines increases neurotrophic agents (bdnf) and neuronal sprouting leading to structural changes

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TCAs block

Both NE and 5-HT transporters

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Examples of TCAs

Imipramine
Amitriptyline
Desipramine
Doxepin
Maprotiline

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TCAs SEs

Alpha-1 antagonist → vasoconstriction
Muscarinic cholinergic antagonist
NE activation of beta adrenergic receptors
Overall: increased HR
H1 antagonist → sedation
+ alpha1 antagonist → weight gain (worst in amitriptyline and doxepin)
Death if overdosed

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MAOIs block

NE and 5-HT breakdown

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Examples of MAOIs

Phenylzine
Tranylcipromine
Isocarboxazid

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MAOIs are used for

Treatment resistant or atypical depression

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MAOI SE

Insomnia/daytime sleepiness
Dry mouth
Liver toxicity in phenylzine
Prolongs T1/2 in oxidatively deaminated drugs

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What dray combos way cause serotonin syndrome

-triptans
SSRI
mepiridine
Dextromethorphan

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How to treat serotonin syndrome

Oxygen
Sedation
Serotonin antagonist → Cyproheptadine

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What foods can be toxic if eaten with MAOI

Tyramine rich foods
Fermented, aged, cured, and pickled foods

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What is a selective MAOI

Selegiline → Parkinson’s

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Why are SSRIs better than TCAs

They have no affinity for alpha adrenergic, muscarinic, histamine or dopamine receptors

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Fluoxetine characteristics

Most stimulating ssri
Hyponatremia

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How do SSRIs cause hyponatremia

They increase vasopressin
Mostly problematic in pts with electrolyte imbalance (bulimia)

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What is discontinuation syndrome and do how you treat it

When you quit SSRI use
Nightmares
Agitation
Brain zaps
Taper dose instead of cold turkey

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SNRI examples

Venlafaxine
Deafenlafaxine
Duloxetine
Levomilnacipran

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Vilazodone, vortioxetine, and trazadone MOA

Serotonin receptor antagonist (5HT:1A, 3, and 7)
and block SERT
Vortioxetine is partial 5HT1A/B agonist
Trazodone is also H1 and Alpha1 antagonist

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St Johns Wort characteristics

Hyperforin Similar efficacy and SEs to SSRIs Induces Cyp3A

Mirtazapine MOA

May potentiate NE and 5HT release by blocking autoreceptors H1 antagonism (sleepy)

Atypical antidepressants

Mirtazapine Bupropion Esketamine Dextromethorphan + bupropion Brexanolone

Mirtazapine MOA

Presynsptic autoreceptor antagonist

Bupropion MOA

Central nicotinic receptor antagonist

Esketamine MOA

NMDA receptor antagonist

Dextromethorphan + bupropion MOA

NMDA receptor antagonist

Brexanolone MOA

Progesterone metabolite and GABAa receptor positive allosteric modulator

TCA SAR

3-4 atoms between N an ring C3 Monohalogenation 3 amines block 5HT reuptake 2 amines block NE reuptake 3 amines can be converted to 2 amines

3 amines tend to be more

Sedating

TCAs are generally metabolized by

2D6 and 2C19

Imipramine metabolites and activity

Desipramine (desmethylimipramine) 2-hydroxydesipramine Both active

Common TCA ring systems

Dibenzazepine Dibenzocycloheptenes Dibenzoxepin

Amitriptyline facts Gets metabolized to

Highest antimuscarinic and sedative fx Metabolized to nortryptyline which has less above SE

Tetracyclic TCA

Maprotiline 500 fold more NET inhibition than SERT

Which MAOI is prodrug

Phenelzine

Phenelzine inhibits

2B6

Non selective MAOIs

Tranylcypromine Phenelzine Isocarboxazid

MAOBI

Selegiline

Which MAOI are irreversible

All

Fluoxetine and norfluoxetine inhibit

2D6 and 2C19

Sertraline inhibits

2D6 weak/moderate

Sertraline metabolite

N-desmethylsertraline (less active)

How is paroxetine metabolized

2D6 removes methylene creating an inactive catechol metabolite

Fluoxetine SERT fold

30-fold SERT over NET

Sertraline -fold SERT over NET

1400-fold SERT over NET

Paroxetine -fold SERT over NET

300-fold SERT over NET

Fluvoxamine -fold SERT over NET

600-fold SERT over NET

Citalopram -fold SERT over NET

3000-fold SERT over NET

How many enantioners does sertraline have?

4 but only the 1S, 4S is used

Sertraline EWG Amine

Dichloro on benzene Secondary

Fluoxetine EWG Amine

Triflouromethyl Secondary

Paroxetine EWG Amine

Fluorine Secondary (part of ring)

Fluvoxamine EWG Amine

Triflouromethyl Primary

Citalopram EWG Amine

Fluorine and Cyano group Tertiary

Paroxetine inhibits

2D6 irreversibly

Fluvoxamine inhibits

1A2 2C19

WhichSSRI is UV light sensitive

Fluvoxamine can be changed from E to Z isomer (inactive)

How does trazodone work

N-dealkylation by 3A4 creates mCPP which is a 5HT2a partial agonist

How does nefazodone work

3A4 metabolizes it to mCPP and alpha-hydroxynefazodone Both are active

Nefanodone inhibits

3A4 Nefazodone and alpha-hydroxynefazodone

Which antidepressant may cause hepatotoxicicity

Nefazodone

How is vilazodone different from trazodone and nefazodone

No mCPP metabolite And no active metabolites

Vortioxetine metabolism

2D6 inactivates it *reduce dose if used with strong 2D6 inhibitors

Venlafaxine metabolism

2D6 → O-desmethylvenlafaxine AKA desvenlafaxine 3A4 → N-desmethylvenlafaxine Minimal activity Lastly glucuronidation

SNRIs do not have

EWGs

Duloxetine is a moderate

2D6 inhibitor

Levomilnacipran inhibits

Nothing

Vortioxetine inhibits

Nothing

Bupropion resembles

Amphetamine

Bupropion metabolism

2B6 → hydroxybupropion Reduction → hydrobupropion Both active

Bupropion inhibits

2D6 So does hydroxybupropion

Mirtazepine inhibits

Nothing

What causes the decrease in antimuscarinic SEs in Mirtazapine compared to TCAs

The basic nitrogen is closer to the ring system

How is esketamine metabolized

2B6 and 3A4 N-demethylation

Esketamine is similar to

Phencyclidine/PCP/angel dust Both are Nmda receptor antagonists

What is DSM 5

Screening tools for depression

PHQ-9 self GDS geriatric HAM-D clinician MADRS both

Diagnostic criteria for major depressive disorder

Depression Energy Sleep Interest Guilt Concentration Appetite Psychomotor changes Suicidality

What lowers MDD recovery rates

Crisis/trauma R Anxiety Personality disorders Physical illness Young

What medicines or conditions increase risk of MDD

Hypothyroidism Low T (can be drug induced) Diabetes Anemia

Sedatives vs. hypnotics

Induce sedation and decrease activity Induce onset and maintain sleep

What brain region is Central in the lambic system

Amygdala

What does the striatum do in fear response

Expression: Fight/flight

What does the brainstem do in fear response

Regulate autonomic responses

What does the hypothalamus do in fear response

Hormonal stress response

Melatonin comes from

Serotonin converted in pineal gland

The master clock is located in

The suprachiasmatic nucleus in the hypothalamus

Why is the ascending arousal system

Sleep-wakefulness-excitement-panic

Berzodiazopine cons

Tolerance Depressant/sedative Impaired reasoning and memory Bad with opioids and alcohol

Benzodiazepine pros

Quick acting High therapeutic index Very effective for anxiety

How do gabapentin and pregabalin work

Inhibit neurotransmitter release by binding to alpha2delta subunit of presynaptic calcium channel

Pregabalin and gabapentin cons

Severe/fatal breathing problems esp when used with opioids and in pts with decreased lung function

Symptoms of cheese reaction

Elevated tyramine (a sympathomimetic) increases NE release which increases blood pressure and can evoke hypertensive crisis

Betablockers treat

Acute physiological symptoms: Palpitations Tremor GI upset

Buspirone acts as a

5-HT1A partial agonist

What is 1-PP

It is the active metabolite of buspirone and alpha2 antagonist which may increase panic attack

Barbiturates increase

- GABA efficacy - Duration of channel opening

Benzodiazepines increase

- GABA affinity - Frequency of channel opening

Preferred GABAa pentameric combo

2 alpha 1 beta 1 gamma 1 beta or gamma

Benzodiazepines bind between

Alpha and gamma subunits

GABA binds between

Alpha and beta subunits

What is flumazenil

Competitive benzodiazepine antagonist

Buspirone is metabolized by

3A4

Buspirone has how many metabolites

6 hydroxybuspirone 5HT1A 1PP an alpha2 antagonist

Benzodiazepine SAR

Must have 7 member ring C7 EWG Can have Groups on 1, 3, and2’

Which benzodiazepine has no active metabolites

Lorazepam