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Pharmaco > Class 4- depressive disorder > Flashcards

Class 4- depressive disorder Flashcards

1
Q

DRUGS THAT MAY BE INVOLVED depression

A 
o Anticonvulsants
o Benzodiazepines
o Betablockers, a lot of fatigue when you start them
o Corticosteroids
o Interferon alpha or beta
o Isotretinoin acutnae
o Opioids
o Varenicline champs
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2
Q

MONOAMINES HYPOTHESIS

A
  • Depletion of neurotransmitters = depressive symptoms

* Does not account for delayed onset of effect on mood in relation to increased synaptic neurotransmitters concentration

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3
Q

DYSREGULATION HYPOTHESIS

A
  • Dysregulation of neurotransmitters = alteration in both pre- and post- synaptic receptors = depressive symptoms
  • Normalization of receptors in response to antidepressant therapy is delayed in relation to change in synaptic neurotransmitter concentration
  • Better accounts for delay in onset of antidepressant action
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4
Q

Examples of medications to avoid, minimize or stop during ECT

A 
o Anticonvulsants (e.g. divalproex): increased threshold for convulsions
o Benzodiazepines: increased threshold for convulsions
o Lithium (controversial): increased risk of delirium and/or prolonged seizures
o High-dose bupropion? : lowering the threshold for convulsions
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5
Q

SSRI – MECHANISM OF ACTION

A

• Selective inhibition of 5-HT recapture via SERT
receptor inhibition
• ↑ 5-HT in the synapse

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6
Q

Prolongation of QTc interval SSRI

A
  • Maximum doses of 40 mg for citalopram and 20 mg for escitalopram
  • In the elderly > 60 years, maximum doses of 20 mg for citalopram and 10 mg for escitalopram
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7
Q

Fluoxetine

A

Activation effect

  • Possible release of DA and NA
  • Taken in the morning
  • Long half-life
  • a lot of interactions
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8
Q

Fluvoxamine

A
  • Anxiolytics

- Short half-life (can be given BID)

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9
Q

Sertraline

A

Take while eating for better absorption

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10
Q

Paroxetine

A

Anticholinergic effects ++

  • Calming and sedative effect
  • More side effects
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11
Q

SSRI – SIDE EFFECTS

A 
• Gastrointestinal
• Headache
• Drowsiness or insomnia
• Possible anxiety at the beginning of treatment
• Sexual dysfunction
• Weight gain: 5-10 lbs
• Hyponatremia: in the elderly
diaphoresis
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12
Q

Pharmacokinetics interactions SSRI

A

• Some are at higher risk (e.g. paroxetine via CYP2D6)

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13
Q

Pharmacodynamic interactions SSRI

A
  • Decrease in platelet aggregation (with all antidepressants having an effect on serotonin) = increase risk of bleeding
  • Clinical impact if administered with AINS? Clopidogrel?
  • Examples of risk factors: thrombopenia, H. Pylori
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14
Q

SNRI – MECHANISM OF ACTION

A

• Selective inhibition of 5-HT and NE recapture via
inhibition of SERT and NET receptors
• ↑ 5-HT and NE in the synapse

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15
Q

SNRI

Lots of similarities with SSRIs, benefits for some indications:

A

o Pain

o Vasomotor symptoms of menopause (small doses; e.g. venlafaxine XR)

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16
Q

Venlafaxine

Effexor XRTM

A

5-HT > NE

  • First IRSN on the market
  • The higher the dose, the more you have an effect on NE
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17
Q

Desvenlafaxine

A

5-HT > NE

- Not covered by RAMQ

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18
Q

Duloxetine

A 
5-HT > NE
- Also indicated in treatment of :
• Neuropathic pain secondary to
diabetes
• Fibromyalgia
• Low back pain
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19
Q

Levomilnacipran

A

NE > 5-HT

  • New drug
  • Not covered by RAMQ
  • contra-indicated if heart problems
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20
Q

SNRI – SIDE EFFECTS

A 
Similar to SSRIs, + :
• Constipation
• Dry mouth
• Sweating
• Increased blood pressure (mostly)
Few drug interactions
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21
Q

BUPROPION – MECHANISM OF ACTION

A

• Selective inhibition of NE and DA recapture via
inhibition of DAT and NET receptors
• ↑ NE and DA in synapse

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22
Q

BUPROPION

Also indicated in :

A

o Seasonal depression

o Smoking cessation

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23
Q

BUPROPION – SIDE EFFECTS

A

• Agitation
• Insomnia
• Gastrointestinal effects
• Decrease in convulsion threshold
Ø Caution if uncontrolled epilepsy, eating disorders, electrolytic disorders
• Less weight gain or sexual dysfunction than SSRIs and IRSNs
Some drug interactions via CYP2D6

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24
Q

MIRTAZAPINE – MECHANISM OF ACTION

A
  • Alpha2 receptor antagonist
  • 5-HT2A/2C receptor antagonist
  • 5-HT3 receptor antagonist
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25
Q

• Alpha2 receptor antagonist

A

Alpha2 receptor: It is a self-receptor, its stimulation is a “brake” to the release of NE

Alpha2 receptor antagonist: - Blocking this receptor increases the release of NE
- The increase in NE also acts on alpha receptors located on serotonin neurons, thus increasing the transmission of 5-HT
FINAL EFFECT = ↑ NE and 5-HT

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26
Q

5-HT2 receptor antagonist

A
  • Contributes to the antidepressant effect
  • Decreased anxiety
  • Weight gain/drowsiness
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27
Q

H1 receptor antagonist

A
  • Antihistamine effect
  • More drowsiness or weight gain
  • Useful if patient has insomnia or has little appetite
    More present in small doses
  • e.g. 7.5 or 15 mg
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28
Q

MIRTAZAPINE – SIDE EFFECTS

A

• Sedation
• Weight gain/increased appetite
• Dry mouth
• Hypercholesterolemia
• Fewer sexual dysfunctions than SSRIs and NSRIs
• Less nausea (via the 5-HT3 antagonistic effect)= tolerate effexor better
Few drug interactions

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29
Q

VORTIOXETINE

A

• Inhibition of serotonin reuptake (such
as SSRIs)
• Partial agonist 5-HT1A• Inhibition of serotonin reuptake (such as SSRIs)
• Partial agonist 5-HT1A

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30
Q

VILAZODONE

A

• Inhibition of serotonin reuptake (such
as SSRIs)
• Partial agonist 5-HT1A, 5-HT1B
• Antagonist 5-HT3, 5-HT1D

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31
Q

MULTIMODAL ANTIDEPRESSANTS; mechanism

A

Mechanism of action is similar to SSRIs
o Clinical effect on other receptors is not very clear
o Possible advantage of vortioxetine over cognitive functions
o Vilazodone should be taken with food

32
Q

MULTIMODAL ANTIDEPRESSANTS: s/e

A
  • Similar to SSRIs

* Vilazodone should be titled very slowly to avoid gastrointestinal effects

33
Q

TRAZODONE – MECHANISM OF ACTION

A

• 5-HT2 and alpha1 receptor antagonist
• Low inhibition of serotonin and norepinephrine reuptake
• Antihistaminic effect at low dose
Rarely used as an antidepressant
o Especially used in the treatment of insomnia at a smaller dose

34
Q

TRAZODONE S/E

A 
oDifficult to tolerate :
• Orthostatic hypotension
• Drowsiness, sedation
• Cognitive disorders
• Increased risk of heart disease
• Priapism (rare)
35
Q

TCA – MECHANISM OF ACTION

A

• Selective inhibition of 5-HT and NE recapture via
inhibition of SERT and NET receptors
• ↑ 5-HT and NE in the synapse

36
Q

Secondary amines

A

Better tolerated
(desipramine, nortriptyline)
NE > 5-HT

37
Q

Tertiary amines

A

(amitriptyline, clomipramine, doxepine, imipramine,
trimipramine)
5-HT > NE

38
Q

TCA – SIDE EFFECTS

A 
• Anticholinergiques ++
Ø Blurred vision, sedation, urinary retention, dry mouth, constipation, orthostatic hypotension, tachycardia, cognitive impairments
• Weight gain
• Sexual dysfunction
• Decrease in convulsion threshold
• Overdose toxicity (arrhythmias)
39
Q

Pharmacokinetic interactions TCA

A
  • Very high interaction potential

* Via CYP1A2 and CYP2D6

40
Q

Pharmacodynamic interactions TCA

A

• Combination with other anticholinergic drugs

41
Q

ATC – THERAPEUTIC MONITORING

A

FOR SAFETY
o Risk of toxicity in overdose
o Risk of arrhythmias and convulsions
o Significant anticholinergic effects (confusion, blurred vision)
o Sedation
** Dosing should be taken 12 hours post dose

42
Q

MAO – A

A

Plays a more important role in the degradation of

5-HT and NE and tyramine in the gut

43
Q

MAO – B

A

Plays a more important role in the degradation of

DA

44
Q

MOCLOBEMIDE

A
  • Reversible

- Specific to MAO-A

45
Q

TRANYLCYPROMINE

PHENELZINE

A
  • Irreversible: binds to receptor and doesn’t move

- Non-specific (inhibits MAO-A and MAO-B)

46
Q

MAOI – SIDE EFFECTS

A 
o Weight gain
o Sexual dysfunction
o Orthostatic hypotension
o Edema
o Insomnia (tranylcypromine) or drowsiness (phenelzine)
o Short half time so BID
HYPERTENSIVE CRISIS
47
Q

HYPERTENSIVE CRISIS

A
  • Dangerous increase in blood pressure with diastolic > 120 mmHg
  • Inhibition of MAO allows the absorption of exogenous tyramine which causes overstimulation of NE receptors, which can cause an increase in blood pressure
    -To minimize the risk: avoid food containing tyramine (nutritionist)
    -Worse with irreversible MAOIs
    -It may also be the result of interaction with drugs that increase NE
    • Oral decongestants
    • Stimulants
    • Antidepressants inhibiting NE reuptake (e.g. SNRIs)
48
Q

Pharmacokinetic interactions MAOI

A

Some via the CYP2C19

49
Q

Pharmacodynamic interactions MAOI

A

o Risk of serotonin syndrome (see section on management of adverse events)
o Risk of hypertensive crisis

50
Q

QUETIAPINE XR – MECHANISM OF ACTION

A
  • 5-HT2C and 5-HT2A receptor antagonist
  • 5-HT1A partial agonist
  • possible inhibition of NE reuptake (norquetiapine)
51
Q

QUETIAPINE XR – SIDE EFFECTS

A

o Metabolic side effects: Weight gain, increased blood pressure, dyslipidemia, insulin resistance
o Sedation
o Orthostatic hypotension

52
Q

ESKETAMINE –

MECHANISM OF ACTION

A

NMDA RECEPTOR ANTAGONIST
o Increased glutamate release
o AMPA activation
o↑ Synaptogenesis

53
Q

ESKETAMINE – SIDE EFFECTS

A
  • Dizziness
  • Sedation
  • Gastrointestinal (nausea, vomiting, dry mouth)
  • Dissociation (derealization, depersonalization, distortion of time and space)
  • Increased blood pressure
54
Q

ESKETAMINE- CONSIDER

A 
INTRA-NASAL ADMINISTRATION
• 1 – 2 times/week
CONSIDER
• Costs
• Side effects
• Treatment/availability supervision
55
Q

ADJUNCTIVE TREATMENTS 1st line

A

ATYPICAL ANTIPSYCHOTICS
Olanzapine, risperidone, quetiapine, aripiprazole

o Lower doses than in mania or schizophrenia
o Consider the risk of metabolic syndrome and extrapyramidal reactions

56
Q

ADJUNCTIVE TREATMENTS 2nd line

A

LITHIUM
o Aim for a lower serum concentration than
bipolar affective disease
o Risk of side effects and interactions

STIMULANTS: don’t treat, only decrease fatigue

57
Q

ST. JOHN’S WORT

A

o Demonstrated in the treatment of mild to moderate depression
Unknown mechanism of action
o Non-standardized and preparations available often vary
Side effects
o Gastric irritation, headache, anxiety
Drug interactions:
o High inducor of CYP3A4
o Reduces the effectiveness of many drugs!!

58
Q

OMEGA-3 FATTY ACIDS

A

Adjunct
Unknown required doses
Side effects: residual taste in the mouth, dyspepsia and increased risk of bleeding

59
Q

Recovery

A

No symptoms x 12 months

60
Q

Substitute the antidepressant

A
  • First antidepressant treatment
  • Intolerance to initial treatment
  • Non-response to initial treatment (< 25% improvement)
  • Less severe depression and less functional impairment
  • Patient prefers to change antidepressant
61
Q

Add an agent

A
  • ≥ 2 antidepressant treatments attempted
  • Well-tolerated initial treatment
  • Partial response to initial treatment (> 25%
    improvement)
  • Residual symptoms or specific side effects that
    may be targeted
  • More severe depression and significant functional
    impairment
  • Patient prefers to add another drug
62
Q

COMBINATIONS OF ANTIDEPRESSANTS

A 
SSRI + bupropion
SSRI + mirtazapine
SSRI + TCA
SNRI + bupropion
venlafaxine + mirtazapine
Antidepressant + trazodone
63
Q

SNRI +

bupropion

A
  • Complementary mechanisms of action and synergistic effect on NE
  • Increase doses gradually to avoid side effects (e.g. restlessness, anxiety)
  • Monitor blood pressure and pulse
  • Decrease in sexual effects associated with venlafaxine
64
Q

venlafaxoine

+ mirtazapine

A
  • Complementary mechanisms of action and synergistic effect on neurotransmitters
  • Reaches higher doses of venlafaxine, as mirtazapine blocks side effects of SNRI
65
Q

Antidepressant

+ trazodone

A
  • Improved sleep if small-dose trazodone is used

- Possible combination with all antidepressants, but it is best to avoid association with irreversible MAOIs

66
Q

SSRI +

bupropion

A
  • Complementary mechanisms of action
  • Decrease in sexual effects associated with SSRIs
  • Adding bupropion can worsen insomnia if already present
67
Q

SSRI +

mirtazapine

A
  • Complementary mechanisms of action
  • Improved sleep
  • Decrease in sexual effects associated with SSRIs
  • More weight gain
68
Q

SSRI + TCA

A
  • Use of a secondary amine that primarily inhibits NE reuptake to have complementary mechanisms of action
  • Small dose of TCA would be sufficient
  • Higher risk of side effects
69
Q

RESISTANCE TO TREATMENT

A

No response to 2 antidepressant treatments
• appropriate dose and duration of treatment

ESKETAMINE
• Indicated in the treatment of resistant depression, as an adjunctive treatment to an
antidepressant
• Not covered by RAMQ (refusal by INESS)

70
Q

SUBSTITUTION OF ANTIDEPRESSANTS

A

In most cases :
Withdrawal the first drug over a period of one to two weeks and then gradually introduce
the new drug simultaneously

Exception
MAOI involved: withdrawal the first drug completely and wait for 2 weeks (or longer if long
half-life) before the introduction of the second

71
Q

DURATION OF TREATMENT

A
  • 6 – 9 months
- 2 years or more if :
• Recurrent or frequent episodes
• Severe episodes
• Chronic episodes
• Presence of psychiatric or physical comorbidities
• Residual symptoms
• Difficult-to-treat episodes
72
Q

CESSATION OF TREATMENT

A

Gradual withdrawal over a few weeks
o Allows to detect the recurrence of symptoms and facilitate a return to initial treatment as required
o Reduces the risk of withdrawal symptoms
• Especially for medicines with short half-lifes (paroxetine, venlafaxine)
• Anxiety, irritability, insomnia, headache, nausea

73
Q

Sexual side effects

A
  • Reduce dose if possible
  • Add bupropion or mirtazapine
  • Substitute the antidepressant
  • Consider taking a PDE5 inhibitor (e.g. sildenafil)
74
Q

SEROTONIN TOXICITY SYMPTOMS

A 
o Altered mental status and/or agitation
o Autonomic instability
• Hypertension, tachycardia, diaphoresis
o Neuromuscular changes
• Clonus, tremors, hyperreflexia
o Gastrointestinal symptoms
o Hyperthermia
75
Q

SEROTONIN TOXICITY

A
  • Potentially fatal side effect-
  • Especially at risk of occurring in the presence of a drug that increases serotonin levels with a drug that decreases its metabolism (e.g. SSRI and MAOI)
  • Beware of secret IMAOs (e.g. linezolide)
76
Q

SEROTONIN TOXICITY MANAGEMENT

A

o Discontinuer the drug in question

o Support therapy according to severity

77
Q

OTHER TREATMENTS / FUTURE TREATMENTS?

A

o Ketamine IV
o Brexanolone
o Botox?

Pharmaco (11 decks)

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