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PHRM 845 > depression > Flashcards

depression Flashcards

1
Q

types of depression

  • ___ (60%)
  • major depressive disorder (25%)
  • bipolar affective (15%)

common mental illness of general population
- 10%, underdiagnosed, untreated, suicidal

A
  • reactive
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2
Q

clinical features

physiological - decreased ___, appetite changes, fatigue, psychomotor dysfunctions
- ___ irregularities, palpitations, constipations headaches/non-specific body aches

psychological - dysphoric mood, worthlessness, excessive guilt, loss of interest/pleasure in all or most activities

cognitive - decreased ___ , suicidal ideation

diagnosis: not due to drugs, medical conditions, or bereavement

A
  • sleep, menstrual
  • concentration
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3
Q

drug induced depression

Antihypertensive and Cardiovascular:
- ___ , methyldopa, propranolol, metoprolol, prazosin, clonidine, digitalis

Sedative-Hypotics
- ___ , benzodiazepines, barbiturates, meprobamate

Anti-inflammatory and analgesics
- indomethacin, phenylbutazone, ___ , pentazocine

steroids
- ___ , oral contraceptives, ___ withdrawal

MSC
- antiparkinson, anti-neoplastic, neuroleptics

A
  • reserpine
  • alcohol
  • opiates
  • corticosteroids, estrogen
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4
Q

biogenic amine hypoothesis of depression

  • reserpine causes depression by depleting ___ and ___ from vesicles
  • genetic polymorphisms in ___ promoter
  • alterations in 5HT1A/2C and a2 receptors
A

NE, 5HT
SERT

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5
Q

neuroendocrine hypothesis of depression

changes in ___ axis
1) stress causes hypothalamus to release ___
2) promotes the release of ___ from pituitary
3) promotes release of ___ from adrenal

overactivity and elevated ___ found in almost all depressed patients
- may ___ feedback response in hypothalamus and pituitary
- causes insomnia, anxiety, and decreased appetite and libido
- antidepressants and ECT reduce these levels

A
  • HPA
  • CRF
  • ACTH
  • cortisol
  • CRF
  • desensitize
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6
Q

CRF1 receptor
- arousal
- ___ like behavior
- disruption of ___ behaviours
- disruption of ___

CRF2
- slow adaptive recovery
- ___ suppression

A
  • anxiety
  • sexual
  • sleep
  • appetite
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7
Q

Neurotrophic hypothesis of depression

  • brain derived neurotrophic factor (BDNF) - critical in neural ___ , resilience, neurogenesis
  • stress and pain ___ BDNF levels in animals
  • decreases volume of ___ (memory and regulation of HPA)
  • BDNF acts as an ___ in animals; antidepressants increase BDNF and can increase hippocampal ___

conflicting animal studies with opposing evidence tho

A
  • plasticity
  • decrease
  • hippocampus
  • antidepressant
  • volume
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8
Q

integration of hypotheses of depression

  • HPA and ___ abnormalities regulate BDNF levels
  • hippocampal glucocorticoid receptors are activated by ___ during stress (decreasing BDNF)
  • chronic activation of ___ receptors increases BDNF signaling ( >2 weeks), leads to ___ of HPA axis
A
  • steroid
  • cortisol
  • monoamine, downregulation
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9
Q

Why does therapy take 2-3 weeks?

antidepressants cause the amount of neurotransmitter in the intrasynaptic space to ___

is the delay in clinical effect due to:
- ___ of presynaptic receptors?
- presynaptic and postsynaptic ___?

no one really knows

A

increase
activation
adaptation

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10
Q

MOA: MAO-i

  • ___ and ___ are degraded by monoamine oxidase
  • by inhibiting, we increase the amount transmitted by vesicles into the synapse
A
  • NE, 5HT
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11
Q

MAO-i

non-selective:
- ___ (Nardil)
- ___ (Parnate)

MAO-B selective:
- ___ (Eldepryl/Ensam)
- ___ (Xadago)

MAO-A selective:
- ____ (Manerix)

A
  • phenelzine
  • tranylcypromine
  • selegiline
  • safinamide
  • moclobemide
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12
Q

MAO-i Structures

A

phenelzine

similar to amphetamine

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13
Q

MAO-i Structures

A

tranylcypromine

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14
Q

MAO-i

Severe SE:
- headache, drowsiness, drymouth, weight gain, orthostatic hypotension, sexual dysfunction

Hypertensive crisis: avoid certain foods (containing ___ ) and drugs

Interactions with OTCs: colds preparations, diet pills, and ___

Interactions with Rx: ___ , ___ , and ___

A
  • tyramine
  • St. John’s Wort
  • TCAs, SSRIs, L-DOPA
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15
Q

Tricyclic antidepressants

indications: depression, panic disorder, chronic pain, and enuresis

overdose/toxicity: extremely dangerous, depressed patients have an ___ in suicidality
- patients are more likely to commit self-harm or suicide ___ weeks into treatment

A

increase
- 2

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16
Q

tertiary amines

inhibit both NE and 5HT ___ via NET and SERT

also act as receptor antagonists
- antihistamine (H1)
- antimuscarinic
- antiadrenergic (a1)

major side effects: these agents cause the most ___ , autonomic side effects, and weight gain

Other Side Effects: conduction disturbances of ___

A

reuptake
- sedation
- heart

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17
Q

tertiary amines

___ (Tofranil)
- metabolized to desipramine
- enuresis and ADHD

___ (Elavil)
- metabolized to nortiptyline

A

imipramine
amitriptyline

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18
Q

tertiary amines

trimipramine (Surmontil)

clomipramine (Anafranil)
- used for ___

____ (Adapin, Sinequan)

A

OCD
doxepin

clomipramine - causes orgasm when yawning

19
Q

secondary amines

Drug
- ___ (Norpramin)
- ___ (Pamelor)
- ___ (Vivactil)
- ___ (Lumdiomil) - ___ inhibitor (tetracycline reduced side effects)

SE: ___ sedation, ___ anticholinergic, ___ autonomic, ___ weight gain, ___ cardiovascular than tertiary amines

in general, side effects of all TCAs
- anticholinergic, ___ (elderly), neurological, weight ___
- ___ suicidality

A
  • desipramine
  • nortriptyline
  • protriptyline
  • maprotiline, NET
  • less, less, less, less, less
  • CV, gain
  • increased
20
Q

SSRI

Drug
- ___ (Prozac): little autonomic SE, no ___
- ___ (Luvox)
- ___ (Paxil)
- ___ (Zoloft)
- ___ (Celexa)
- ___ (Lexapro): isomer of citalopram

A
  • fluoxetine, sedation
  • fluvoxamine
  • paroxetine
  • sertraline
  • citalopram
  • escitalopram
21
Q

SSRI

T or F: there is a structural pattern to SSRIs

A

False: all over the place

22
Q

SSRI

Uses: depression, alcoholism, OCD, enuresis, PTSD, eating disorders, social phobias, panic anxiety, PMDD, GAD

SE: N/V, headache, sexual dysfunction, ___ , insomnia, tremor

D/C syndrome: brain ___ , dizziness, ___ , nausea, insomnia, tremor, confusion, vertigo

Serotonin Syndrome: when given with ___ , TCAs, metoclopramide, triptans, ___ , St. John’s wort
- symptoms: hyperthermia, muscle rigidity, restlessness, myoclonus, hyperreflexia, sweating, shivering, seizures, and coma
- treatment: d/c of medication and management of symptoms, administration of serotonin antagonists ( ___ or methysergide); ___ to control myoclonus

A
  • anxiety
  • zaps, sweating
  • MAOIs, tramadol
  • cyproheptadine, benzodiazepines
23
Q

SSRI + 5HT1A partial agonists

___ (Viibryd)
- IC50 for SERT and 5HT1A ___ (0.5 nM)
- 60-70% intrinsic activity
- reduced ___ SE vs pure SSRIs
- similar 5HT1A actions to: aripiprazole and buspirone

___ (Trintellex)
- SERT (2 nM), 5HT1A partial agonist (15 nM) (70-80% intrinsic activity), and 5HT3 (4 nM)

A

vilazodone
- similar
- sexual

vortioxetine

24
Q

Tetracyclic and Unicyclic

___ (Ludiomil)
- ___ inhibitor

___ (Ascendin)
- ___ inhibitor
- ___ antagonists

A

maprotiline
- NET

amoxapine
- NET
- D2

25
Q

Tetracyclic and Unicyclic

___ (Remeron)
- a2, __ , 5HT__ , 5HT __ antagonists

A

mirtazapine
- H1
- 5HT2 , 5HT3

26
Q

Tetracyclic and Unicyclic

___ (Wellbutrin)
- ___ inhibitor
- ___ and ___ inhibitor
- also treat GAD
- “ ___ “ for smoking cessation

A

bupropion
- DAT
- NET, SERT
- Zyban

27
Q

5-HT2 antagonists/SERT inhibitors

___ (Dyserel)
- ___ antagonist
- weak ___ inhibitor
- off label ___ (a1, H1, with 5HT2)

A

trazodone
- 5HT 2A
- SERT
- hypnotic

Have to take huge doses as antidepressant, super sedating

28
Q

SNRIs

___ (Effexor)
- ___ and __ inhibitor
- treats GAD and panic disorder
- might be useful for diabetic ___ and ___ prophylaxis (?)

A

venlafaxine
- NET, SERT
- neuropathy, migraine

29
Q

SNRIs

___ (Pristiq)
- ___ and ___ inhibitor
- useful for vasomotor symptoms associated with ___ (?)

A

desvenlafaxine
- NET, SERT
- menopause

30
Q

SNRIs

___ (Cymbalta)
- ___ and ___ inhibitor
- treats GAD
- treats peripheral ___

A

duloxetine
- NET, SERT
- neuropathy

31
Q

SNRIs

___ (Ixel)
- ___ and ___ inhibitor
- approved for ___

A

milnacipran
- NET, SERT
- fibromyalgia

32
Q

SNRIs

___ (Fetzima)
- active enantiomer or ___
- ___ and ___ inhibitor

A

levomilnacipran
- milnacipran
- NET, SERT

33
Q

NSRIs

___ (Vestra, Edronax)
- possible less side effects than ___
- not available in US

A

reboxetine
- Prozac

34
Q

NSRIs

___ (Straterra)
- originally intended to be an antidepressant (not approved)
- used for ___

A

atomoxetine
- ADHD

35
Q

Selectivity Profiles

___ number = more selective
- amitriptyline more selective for ___
- nortriptyline more selective for ___
- escitalopram is super selective for ___

A

smaller
- 5HT
- NE
- 5HT

36
Q

SNDRIs

“triple blockers” / “triple reuptake inhibitors”
- ___ and ___
- early research as Parkinson’s therapies
- ___ currently being researched as an appetite suppressant
- new drugs coming out for treatment of depression

A
  • tesofensine, brasofensine
  • tesofensine
37
Q

rapidly acting antidepressants: NDMA antagonists

  • ___ subanesthetic doses
  • ___ (muscarinic and NMDA antagonists)
  • Lanicemine “low trapping”
  • GLYX-13 partial NMDA antagonists
A
  • ketamine
  • scopolamine
38
Q

clinical used NMDA antagonists

___ - subanesthetic doses

___ (Spravato) - in conjunction with oral antidepressant
- CNS effects: ___ , drug interactions
- intranasal, phased dosing
- available only through ___ program

A

ketamine
esketamine
- depression
- REMS

39
Q

Postpartum Depression

PPD occurs within 4 weeks and can last for over a year. 10-15% of moms

SSRIs ( ___ and ___ ) and ___

___ (Zulresso) - new MOA involving ___ receptors

A
  • fluoxetine, paroxetine, venlafaxine
  • brexanolone, GABA A
40
Q

Brexanolone (Zulresso)

  • ___ levels increase during pregnancy
  • ___ receptors desensitize (?)
  • levels return to normal postpartum
  • brexanolone resensitizes receptors
  • ___ program
  • ___ hr infusion ($20,000-30,000)
A
  • allopregnanolone
  • GABA-A
  • REMS
  • 60 hr
41
Q

new agents in development

psychedelics: MDMA, psilocybin, LSD

5HT ___ receptor antagonists

metabotropic ___ receptor agonosts

reversible inhibitors of ___ A (RIMAs)
- moclobemide and brofaromine
- are as efective as ___ and better tolerated

A
  • 5HT2C
  • glutamate
  • monoamine oxidase
  • TCAs
42
Q

T or F: antidepressants can treat various pain states via interfering with transmission

A

T

43
Q

PCOL of ___ (Addyi)

  • hypoactive ___ desire disorder
  • developed as an antidepressant
  • polypharmacology: agonist at 5HT ___ and antagonist at 5HT ___ / ___
  • regional selectivity: prefrontal cortex
  • controversial
A
  • sexual
  • 1A, 2A/C

PHRM 845 (62 decks)

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