Neuroscience Week 8: Depression Drugs Flashcards
(132 cards)
1
Q
Learning issues
A
2
Q
Mood Disorder drugs: Prototypes
12 listed
A
3
Q
Antidepressants: prototypes
8 listed
A
- Fluoxetine
- Venlafaxine
- Bupropion
- Buspirone
- Mirtazepine
- Amitryptyline
- Nortyptyline
- Tranylcypromine
4
Q
Mood Stabilizers: Prototypes
4 listed
A
- Lithium
- Valproic Acid
- Lamotrigine
- Olanzepine
5
Q
Mood Stabilizers: classes
3 listed
A
- Lithium
- Anticonvulsants
- Antipsychotics
6
Q
Antidepressants: Classes
8 listed
A
- SSRIs
- SNRIs
- Amphetamine-related
- 5HT1A/α1 partial agonist
- 5HT2/α2 Antagonists
- Tertiary Amine TCAD’s
- Secondary Amine TCAD’s
- MAOIs
7
Q
Antidepressants: Fluoxetine related agents
5 listed
A
- Paroxetine
- Setraline
- Fluvoxamine
- Citalopram
- Escitalopram
8
Q
Antidepressants: Fluoxetine Class
A
SSRI
9
Q
Antidepressants: Venlafaxine related agents
4 listed
A
- Descenlafaxine
- Duloxetine
- Levomilnacipran
- Milnicipran
10
Q
Antidepressants: Venlafaxine Class
A
SNRI
11
Q
Antidepressants: Bupropion class
A
Amphetamine-related
12
Q
Antidepressants: Buspirone class
A
5HT1A/α1 partial agonist
13
Q
Antidepressants: Mirtazapine related agents
A
Trazodone
14
Q
Antidepressants: Mirtazapine Class
A
5HT2/α2 Antagonists
15
Q
Antidepressants: Amitriptyline Class
A
Tertiary Amine TCAD
16
Q
Antidepressants: Amitriptyline related agents
3 listed
A
- imipramine
- Clomipramine
- Doxepin
17
Q
Antidepressants: Nortriptyline related agents
A
- Desipramine
- Amoxapine
18
Q
Antidepressants: Nortriptyline Class
A
Secondary Amine TCAD
19
Q
Antidepressants: Tranylcypromine Class
A
MAOI
20
Q
Antidepressants: Tranylcypromine Related agents
3 listed
A
- Selegiline
- Phenelzine
- Isocarboxazid
21
Q
Mood Stabilizers: Lithium Class
A
Lithium
22
Q
Mood Stabilizers: Valproic acid class
A
Anticonvulsants
23
Q
Mood Stabilizers: Valproic acid related agents
2 listed
A
- Carbamazepine
- Oxcarbazepine
24
Q
Mood Stabilizers: Valproic acid use
A
Mania-normal
25
Mood Stabilizers: Lamotrigine Class
Anticonvulsants
26
Mood Stabilizers: Lamotrigine use
Depression-normal
27
Mood Stabilizers: Olanzapine Class
Antipsychotics
28
Mood Stabilizers: Olanzapine related agents
3 listed
* Quetiapine
* Lurasidone
* Aripiprazole
29
Reserpine and propranolol can cause?
Depression
30
Depression chemical imbalance theory
31
Monoamine hypothesis is overly simplistic
32
Neuroendocrine factors in the pathophysiology of depression
3 listed
* Dysregulation of the HPA axis: ↑ CRF, ↑ Cortisol
* Dysregulation of the thyroid axis: ↓TSH, ↓Thyroxine
* Gonadotropin deficiencies
33
Stress increases evoked _________ release and chronic antidepressant treatment can diminish ___________ release.
Glutamate
Glutamate
34
Ketamine as an antidepressant
* rapid antidepressant effect that can last up to one week after administration - but arent really practical
* NMDA receptor partial agonists OR allosteric modulators of mGluRs
35
Glucocorticoids depress the synthesis of \_\_\_\_\_\_\_\_\_\_, decreasing neurogenesis
BDNF
36
Some antidepressants and electroconvulsive therapy can increase BDNF levels and thereby increase?
Neurogenesis in the dentate gyrus and enhance synaptic connectivity
37
Neurotrophic hypothesis of depression
38
MOA of common antidepressant medications
39
SNRI MOA
blocks NET reuptake thereby increasing noradrenergic transmission
SNRIs
40
Fluoxetine and related agents MOA
SSRI
block 5HT reuptake transporter thereby increasing
41
Mirtazepine MOA
5HT2/α2 Antagonists which block autoreceptor response to increase the release of NE and SE
42
Buproprion MOA
enhances noradrenergic release
and
dopamine
43
Buspirone MOA
5HT1A/α1 partial agonist so they are NE and SE partial agonists
44
Fill in the table
45
Side effects of SSRIs organ systems
3 listed
* Gut
* Spinal/Supraspinal
* CNS
46
Side effects of SSRIs: Gut
3 listed
* Nausea
* GI Upset
* Diarrhea
47
Side effects of SSRIs: spinal/supraspinal
3 listed
* sexual dysfunction (30-40%) (some tolerance, takes longer)
* ↓ libido, ↓ decreased arousal
* ↓ or delayed orgasm
48
Side effects of SSRIs: Higher CNS
3 listed
* Headaches / insomnia / somnolence
* Anxiety / agitation
* Weight gain (especially with paroxetine)
49
Discontinuation Syndrome of SSRIs
* Nausea
* dizziness
* anxiety
* tremor
* palpitations
* less pronounces with longer-acting agents such as fluoxetine and sertraline
50
Teratogenic potential of SSRIs
* teratogenic potential remains unresolved
* Sertraline is preferred among the class during pregnancy and nursing
51
SSRIs Drug interactions
* High plasma protein binding (80-90%)
* Inhibit drug metabolism by CYP450s: (1A2, 2C19, 2D6, 3A4)
* MAOIs contraindicated - 5HT syndrome
52
Serotonin Syndrome
occurs when the excess of serotonin
53
Serotonin Syndrome symptoms
* Cognitive (delirium, coma)
* Autonomic (hypertension, tachycardia, hyperthermia)
* Somatic (myoclonus, hypereflexia, tremor, muscle rigidity)
* Treatment with benzodiazepines
54
Other complications of SSRIs overview
4 listed
55
Buspirone MOA
56
Buspirone effects at MCRs or H1 receptors
no relevant effects
57
Buspirone contraindicated with
MAOIs
58
Buspirone side effects
4 listed
* Tachycardia
* Tremors
* Insomnia
* Constipation
59
Buspirone clinical use
not first-line but has some utility as an adjunct for use with SSRIs to offset sexual and anxiogenic side effects of SSRIs
60
SNRI MOA
61
SNRIs side effects
SSRI side effects +
* CNS activation / agitation
* can elevate HR and BP
62
SNRI Efficacy
similar to SSRIs but better response in some patients who do not respond to or tolerate SSRIs
63
SNRI other complications
also discontinuation syndrome and SSRI complications
64
SNRI plasma binding
lower plasma protein binding (27%)
65
SNRI half-life
shorter half-life than SSRIs or TCADs
66
SNRI caveat
can be helpful with concomitant pain syndromes
67
Buproprion MOA
Hydroxybuproprion (active metabolite) enhances NE (and DA) release
68
Buproprion adrenergic (muscarinic) and noradrenergic (α1) or H1
no relevant effects
69
Buproprion caveats
* lower incidence of sexual dysfunction and weight gain
* can be combined with SSRI to reduce sexual and weight effects
70
Buproprion contraindications
* higher incidence of tremors and seizures (dose-dependent)
* Can aggravate propensity for psychosis
* Not used when depressive symptoms are accompanied with anxiety
* MAOIs
71
Buproprion drug interactions
high plasma protein binding (84%)
72
Buproprion efficacy for depression
efficacy similar to SSRIs as a monotherapy
73
Buproprion contraindicated with MAOIs
yes it is contraindicated
74
Buproprion overview
75
Mirtazapine Overview
76
Mirtazapine MOA
* 5HT2/α2 adrenergic receptor Antagonists
* (enhances 5HT and NE release via "autoreceptors" blockade)
77
Mirtazapine muscarinic or α1 activity
no effects
78
Mirtazapine H1 receptor effects
Very potent H1 receptor antagonist
So it (↑appetite, weight gain, altered lipid profile)
79
Mirtazepine can offset some SSRI/SNRI side effects
* Drowsiness
* Weight gain
* Dry mouth
* Increased appetite
* Constipation
* Lack of energy
* Weakness
* Dizziness
* Serum triglycerides increased
* Dream disorders
* Disturbance in thinking
* ALT increased
* Swelling of extremities
* Muscle pain
* Confusion
* Urinary frequency
* Tremor
* Back pain
* Shortness of breath
80
Mirtazapine can offset some?
SSRI/SNRI side effects
81
Mirtazapine discontinuation syndrome?
Yes
82
Mirtazapine drug interactions
high plasma protein binding (85%)
83
Mirtazapine safety profile
similar to SSRIs
84
Mirtazapine contraindicated with?
MAOIs
85
Mirtazapine efficacy
* better than SSRIs / SNRIs/ Buproprion
* but less than TCADs or MAOIs
* Has a substantial anxiolytic effects
86
Mirtazapine caveats
* H1 receptor antagonists
* substantial anxiolytic effect
* can offset some SSRI/SNRI side effects
87
Tricyclic Antidepressants overview
88
Tricyclic Antidepressants AKA
TCADs
89
Tricyclic Antidepressants subtypes
* Tertiary amine TCADs
* Secondary amine TCADs
90
TCAD: Tertiary amine MOA
1o preference as a 5HT reuptake inhibitor
2o Muscarinic, α1 adrenergic & H1 receptor antagonist
91
TCAD: secondary amine MOA
* 1o preference as a NE reuptake inhibitor
* 2o Reduced affinity as Muscarinic antagonists BUT similar affinity to α1 adrenergic & H1 receptors as antagonist
92
TCAD: secondary amine example
Nortriptyline
93
TCAD: Tertiary amine example
Amitriptyline
94
TCAD Side effects organ systems
* GI distress
* Sexual dysfunction
* Sedation
* Weight gain
* Cardiovascular (orthostatic hypotension → tachycardia)
95
Which subtype of TCAD have more pronounced side effects
3o amine TCADs
96
TCADs toxic range
* incorporate into excitable membranes
* Cardiovascular (arrythmias / AV block / Cardiac arrest)
* CNS (confused states / seizures / coma)
97
TCADs drug interactions
High plasma protein binding \>85%
98
TCAD discontinuation syndrome
Yes
99
TCAD side effects overview
100
CNS & autonomic system effects
* Muscarinic antagonism
* α1 antagonism
* H1 antagonism
101
MAOIs subtypes
irreversible MAOIs
reversible MAOIs
with selectivity
102
Non-selective MAOIs
* Phenelzine
* Iproniazide
103
Irreversible Type A MAOIs MOA
NE/5HT/DA
104
Irreversible Type A MAOIs
Clorgyline
105
Irreversible Type B MAOIs
Selegiline
106
Irreversible Type B MAOIs MOA
DA
107
Reversible Non-selective MAOI
Tranylcypromine
108
Reversible Type A MAOI
Moclobemide
109
Reversible Type A MAOI MOA
NE/5HT/DA
110
MAOI Acute side effects therapeutic range
* Acute:
* sexual dysfunction (worst of all classes)
* Restlessness / insomnia (amphetamine-like effects
111
MAOI long-term side effects therapeutic range
* weight gain
* postural hypotension
* reflex tachycardia via downregulation of α1 adrenergic receptors
112
MAOI side effects toxic range
* CV: hypotension/Arrhythmias
* CNS: ataxia / confused states / convulsions / coma
113
MAOIs Drug interactions overview
114
MAOIs plasma binding
High plasma protein binding
115
MAOIs serotonin syndrome
YES
116
MAOIs hypertensive crisis
especially with irreversible MAOIs
* tyramine containing foods (some cheeses, beers, soy products)
* Decongestants in cold medications (ephedrine, pseudoephedrine, phenylprolamine)
117
MAOIs clinical use
* limited to treatment-resistant cases of depression
* because of intense side effects
* but
* advent of newer selective reversible agents?
* Development of transdermal preps would avoid the 1st pass metabolism
118
St. Johns Wort
119
St John's Wort active agents
* Hypericin
* Hyperforin
* Flavinoids
* and other active agents
120
St John's Wort MOA
weak NE, DA & 5HT reuptake inhibitor
Weak MAO inhibition (types a & B)
glutamate, GABA & adenosine receptor antagonism
121
St John's Wort plasma protein binding
potential for drug interactions
122
St John's Wort efficacy
some efficacy for mild to moderate depression
123
St John's Wort dosing issue
continuing problem of variable dosing
124
St John's Wort contraindications
Antidepressants
125
Treating Major Depressive disorder I
126
considered a disease of 3rds
Major Depressive disorder I
* 1/3 are properly diagnosed
* 1/3 of the diagnosed are properly treated
* 1/3 of the treated don't respond significantly
127
Major Depressive disorder I adjuncts or switching drugs
adding an adjunct or switching can increase efficacy
128
Treatment of Major Depressive disorder I concerns
* need to ensure sufficient dose
* Non-pharmacological interventions in milder cases
* Drugs more effective in more depressed patients
* some agents are more effective with certain types of depression
* Consider side effects you most want to avoid
* Greater efficacy & compliance when combined with other therapies
129
Treating Major Depressive disorder II
130
Depression comorbidity
131
Challenges with Antidepressant therapy
132
Other uses of antidepressants
