Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

HNNS > HNS50 Anti-depressants > Flashcards

HNS50 Anti-depressants Flashcards

1
Q

Depression symptoms

A
  1. Sadness, emptiness, hopelessness
  2. Changes in sleep pattern (insomnia / oversleeping)
  3. Diminished pleasure / apathy towards life activities
  4. Increased anger / irritability
  5. Significant changes in appetite / body weight
  6. Fatigue / loss of energy
  7. Feeling of self-loathing / suicidal thoughts

For a period of weeks / months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Differences in men vs women symptoms

A

Difference in hormone (testosterone)

Men:

  • Anger
  • Compulsiveness
  • Insomnia

Women (more likely to get depression):

  • Sadness / Worthlessness
  • Procrastination
  • Oversleeping
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Classifications of depression

A
  1. Minor depression disorder
    - less severe
    - >=2 symptoms
    - duration ~2 weeks (short)
  2. Major depression disorder
    - severe
    - >=5 symptoms that interfere with patient’s ability to function
    - duration >2 weeks (relatively short)
  3. Dysthymic disorder (dysthymia) —> persistent mild depression
    - less severe
    - >=2 symptoms
    - duration >2 years (long)

Diagnosis: Based on clinical interview (Diagnostic and Statistical Manual of Mental Disorders)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Depression causes

A

Multifactorial, combination of factors

  • Genes (Slc6a15 gene: neutral a.a. transporter)
  • Environmental
  • Personality
  • Brain chemistry
  • Brain hormones
  • Stress (traumatic events)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

2 hypothesis for cause of depression

A
  1. Monoamine hypothesis
  2. Neurotrophic (neurogenesis) hypothesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Monoamine hypothesis

A

Depression is caused by Low levels / Deficit in function of neurotransmitters:

  1. Serotonin (from Tryptophan, mostly Inhibitory)
  2. Norepinephrine (Catecholamine, from Tyrosine, Excitatory)
  3. Dopamine (Catecholamine, from Tyrosine, Excitatory + Inhibitory)

ALL antidepressants enhance ***Synaptic availability of these neurotransmitter

Not a perfect hypothesis:

  • Many do NOT have alterations in function / levels of monoamine
  • Monoamines ↑ immediately with antidepressant use, but maximum benefits are not seen until many weeks later
  • Common for patient to feel worse for the 1st week of treatment
  • Removal of serotonin precursor (Tryptophan) in human did NOT lead to depressive response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Neurotrophic (neurogenesis) hypothesis

A
  1. Impaired growth of neurons —> associated with depression
    —> Anti-depressants promote growth of neurons + synaptic connectivity
  2. Depression associated with 5-10% volume loss in hippocampus
  3. Depressed, stressed / in pain —> ↓ BDNF (Brain-derived neurotrophic factor) levels
    —> ↑ BDNF associated with ↑ neurogenesis
    —> Infusion of BDNF into brain —> anti-depressant effects
    —> Anti-depressants ↑ BDNF levels (in animals models with chronic administration but not with acute treatment)

BDNF regulate:

  1. **Neural plasticity (differentiation) + **Neurogenesis (growth)
  2. ***Emotions

Not a perfect hypothesis:

  • BDNF knockout mice do NOT have depressive / anxious behaviour
  • Social-stressed animals showed ↑ BDNF rather than ↓
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Medications

A
  • Takes several weeks to work
  • NT only have short time to relay message to postsynpatic cells before reuptake / destroyed
    —> Anti-depressant work by ↑ amount of NT in brain by
    1. Prevent break down
    2. Prevent reuptake into cell

NA:

  • Alertness
  • Energy

Dopamine:

  • Attention
  • Motivation
  • Pleasure
  • Reward

Serotonin:
- Obsession and compulsion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

8 types of Anti-depressants

A
  1. Selective serotonin reuptake inhibitor (SSRI)
  2. Noradrenaline reuptake inhibitor (NARI)
  3. Serotonin-Norepinephrine reuptake inhibitor (SNRI)
  4. Tricyclic antidepressant (TCA)
  5. Serotonin antagonist-reuptake inhibitor (SARI)
  6. α2 adrenoceptor antagonist
  7. Monoamine oxidase inhibitor (MAOI)
  8. Melatonin receptor agonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q
  1. Selective serotonin reuptake inhibitor (SSRI)
A

Drugs:

  1. Fluoxetine (Prozac)
  2. Paroxetine (relative severe weight gain / sexual dysfunction)
  3. Citalopram
  4. Escitalopram
  5. Sertraline
  6. Fluvoxamine

1st line pharmacological treatment

  • Fewest SE
  • Mild to moderate, transitory SE
  • Safety in overdose
  • Low cost

MOA:
- Selectively blocks reuptake of Serotonin by binding to ***serotonin transporter (normally take up excessive serotonin into presynpatic cell) on presynaptic neuron
—> ↑ 5-HT concentration in synaptic cleft

Therapeutic dose: 80% activity of transporter is inhibited

Pharmacokinetics:
- Fluoxetine, Paroxetine: CYP2D6 inhibitors
—> Tricyclic antidepressant (2D6 substrate) (elevation of TCA conc)
—> NOT used in combination

  • Fluvoxamine: CYP3A4 inhibitors
    —> Diltiazem (Ca channel blocker, 3A4 substrate)
    —> Bradycardia / Hypotension
  • Citalopram, Escitalopram, Sertraline: more modest CYP interactions

SE (enhanced serotonergic tone):

  1. Nausea, GI disturbance, Diarrhoea
    - ↑ serotonergic activity in gut
  2. Diminished sexual function and interest
    - ↑ serotonergic activity in spinal cord / above —> effect persist as long as on the drug
  3. Reduced coagulation / ↑ Bleeding risk
    - inhibit serotonin reuptake into platelets, reduce serotonin-mediated platelet activation
  4. Vasoconstriction
    - inhibits nitric oxide synthase —> CI in pregnant women with hypertension / pre-eclampsia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q
  1. Noradrenaline reuptake inhibitor (NARI)
A

Drugs:

  1. Atomoxetine
  2. Maprotiline
  3. Reboxetine

MOA:
- Selectively blocks reuptake of NA by binding to NA transporter on presynaptic neuron
—> ↑ NA concentration in synaptic cleft

SE (NA effects):

  1. ↑ BP
  2. Changes HR
  3. CNS activation (e.g. insomnia, anxiety, agitation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q
  1. Serotonin-Noradrenaline reuptake inhibitors (SNRI)
A

Drugs:

  1. Venlafaxine
  2. Desvenlafaxine
  3. Duloxetine
    (4. Bupropion: NDRI)

MOA:
- Blocks reuptake of Serotonin + NA by binding to BOTH Serotonin + NA transporter on presynaptic neuron
—> ↑ Serotonin + NA concentration in synaptic cleft

SNRI: do NOT have much affinity for other receptors (unlike TCA) —> less SE

SE:
- same as SSRI, NARI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q
  1. Tricyclic Antidepressants (TCA)
A

Drugs:

  1. Amitriptyline
  2. Nortriptyline
  3. Clomipramine
  4. Imipramine
  5. Dosulepin

MOA:
- Blocks reuptake of Serotonin + NA + Dopamine
—> more SE

Usage:
- declined after SSRI introduction
—> poor tolerability
—> difficulty to use
—> lethality in overdose
—> serious drug interactions
- ***ONLY used when patients NOT respond to SSRI
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q
  1. Serotonin antagonist-reuptake inhibitor (SARI)
A

Drug:
Trazodone

MOA:
3 properties:

  1. 5-HT2a antagonism (most potent binding property)
    —> 5-HT2a receptors increased in depressive patients
    —> inhibit activation of 5-HT2a —> ↑ NT release
  2. Block serotonin reuptake transporter (SERT) (100 fold less potent)
  3. 5-HT1a agonist
    —> Trazadone converted to active metabolite mCPP (meta-chloro-phenylpiperazine)
    —> agonist at 5-HT1a (very weak agonist at 5-HT2a)
    —> specifically Antidepressant effect

SE:

  • Agonist actions at other subtypes of serotonin receptors —> SE
  • ***Desensitisation from activation of serotonin receptors over time
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q
  1. α2 adrenoceptor antagonist
A

Drug:

  1. Mianserin
    (2. Mirtazapine: NaSSA)

MOA:
Block α2 presynaptic autoreceptor (NOT transporter!!!) on presynpatic neuron
—> Suppress -ve feedback
—> ↑ NA release

SE:

  1. Sedation
  2. Dry mouth
  3. Dizziness
  4. Vertigo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  1. Monoamine oxidase inhibitors (MAOI)
A

Drugs:

  1. Non-selective MAOI: Phenelzine, Tranylcypromine
  2. Selective MAOI (MAOa): Moclobemide

MOA:
Inhibit monoamine oxidase in presynaptic cell
—> Inhibit degradation of NT
—> ↑ ALL 3 NT levels

2 isoforms of monoamine oxidase:
MAOa: 5HT, NA, Adrenaline, Dopamine, Tyramine
MAOb: Dopamine, Phenylethylamine, Tyramine

Usage:
- Rare (∵ toxicity, potential lethal food / drug interactions esp. Tyramine-rich food)
—> **Tyramine cause release of stored monoamines (dopamine, NA, adrenaline)
—> MAOI also block breakdown Tyramine (also ↑ NA, adrenaline, dopamine)
—> ↑ BP, HR
—> **Hypertensive crisis (stroke, heart attack, death)
—> ∴ must stick to low-tyramine diet
—> High-tyramine food: avocados, bananas, pineapple, eggplants

  • Treatment of depression unresponsive to other antidepressant

SE:
**1. Hypertensive crisis with tyramine-rich food
2. Orthostatic hypotension
3. Weight gain
4. Insomnia
5. Restlessness
6. Confusion
**7. Serotonin syndrome: combination of MAOI with serotonergic agent (SSRI, SNRI, TCA)
—> over-stimulation 5HT receptor in brain
—> coma, confusion, chills, tremors, fever, hyperhidrosis
—> life-threatening

Guideline:

  • Serotonergic antidepressant discontinued for >=2 weeks before starting MAOI (Fluoxetine 4-5 weeks ∵ long t1/2)
  • MAOI discontinued for >=2 weeks before starting serotonergic antidepressant
17
Q
  1. Melatonin receptor agonist
A

Drug:
Agomelatine (NOT approved by FDA as a drug yet: Supplement now)

Link between sleep problems and depressed mood
—> New target to combat depression: Body’s internal clock
—> Agomelatine as effect as widely prescribed antidepressant

MOA:
Synthetic version of melatonin
—> act on Melatonin receptor (+ 5-HT2c receptor —> NOT ↑ serotonin level BUT ↑ dopamine + NA level in brain)

Melatonin:
- Important for regulation of sleep
- Released in response to darkness by ***pineal gland
—> levels vary according to circadian rhythm
—> in tune: helps sleep and wake
—> out of tune: disrupt energy, alertness and mood

SE:
- Derangement in ***liver function —> Regular liver function monitoring

18
Q

Common and Key SE of antidepressant

A

Common:
1. Dry mouth
2. Nausea
Etc.

Key SE:
***↑ Suicidal risk under 25, >65 no associated suicidal risk
—> FDA Black box warning MUST be added to ALL antidepressant

19
Q

Antidepressant discontinuation symptoms

A 
ABCDEF:
A: agitation, anxiety
B: balance problems, bad dreams
C: concentration problems
D: dizziness, diarrhoea
E: electric shock-like sensations
F: flu-like symptoms

—> Severe: Psychosis, Confusion, Excitement

***Doses should be gradually reduced over >=4 week period

20
Q

Other applications of antidepressant

A
  1. Panic disorder
  2. GAD
  3. PTSD
  4. OCD
  5. Pain disorder
  6. Premenstrual dysphoric disorder
  7. Smoking cessation (Bupropion)
  8. Bulimia
21
Q

Non-responders

A

25% of patients
—> were worse on antidepressant
—> could be due to cause of depression (NOT altered level of NT)

Even though antidepressant changed level of NT
—> do not help

22
Q

Antidepressant effect and placebo

A

People’s belief in the power of antidepressant may explain why they do well on placebo

  • Mild / Moderate depression: difference is nonexistent to negligible
  • Severe cases (13%): significantly more effective
23
Q

Alternative therapy

A

Antidepressant use only when risk of untreated depression&raquo_space;> risk of antidepressant

Psychotherapy / Talk therapies
1. Cognitive-behavioural therapy
2. Interpersonal therapy
—> teaching new ways of thinking / behaving
—> changing habits that contribute to depression

Indication:
- Mild / Moderate depression —> Psychotherapy relieves symptoms at the same rate as drugs / placebos

Barriers:
1. Many doctors prescribing antidepressant are primary care doctor (NOT psychiatrist)
—> cannot offer talk therapy
2. Insurance companies resist paying session of talk therapy (high cost)
3. Time consuming

24
Q

Summary

A

8 drugs

  1. SSRI:
    - Fluoxetine (2D6 inhibitor)
    - Citalopram
    - Sertraline
    MOA: Selectively blocks reuptake of Serotonin by binding to ***serotonin transporter (normally take up excessive serotonin into presynpatic cell) on presynaptic neuron
  2. NARI:
    - Atomoxetine
    - Maprotiline
    - Reboxetine
    MOA: Selectively blocks reuptake of NA by binding to NA transporter on presynaptic neuron
  3. SNRI:
    - Venlafaxine
    - Duloxetine
    (- Bupropion: NDRI)
    MOA: Blocks reuptake of Serotonin + NA by binding to BOTH Serotonin + NA transporter on presynaptic neuron
  4. TCA:
    - Amitriptyline
    - Clomipramine
    - Dosulepin
    MOA: Blocks reuptake of Serotonin + NA + Dopamine
  5. SARI:
    - Trazodone
  6. 5-HT2a antagonism (most potent binding property) —> inhibit activation —> ↑ NT
  7. Block serotonin reuptake transporter (SERT)
  8. 5-HT1a agonist
  9. α2 adrenoceptor antagonist:
    - Mianserin
    (- Mirtazapine: NaSSA)
    MOA: Block α2 presynaptic autoreceptor on presynpatic neuron —> Suppress -ve feedback
  10. MAOI
    - Phenelzine, Tranylcypromine (Non-selective MAOI)
    - Moclobemide (Selective MAOI (MAOa))
    MOA: Inhibit monoamine oxidase in presynaptic cell —> Inhibit degradation of NT
  11. Melatonin receptor agonist
    - Agomelatine
    MOA: Synthetic version of melatonin —> act on Melatonin receptor —> Regulation of sleep

HNNS (58 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions