Affective Disorders Flashcards
Which NTs are involved in the monoamine hypothesis of depression?
NA
5HT
What 2 main symptoms must a treatment resolve?
Low mood
Reduced psychomotor drive
What does reserpine do and what is its effect?
Depletes monoamines
Causes depression
What does iproniazid do and what is its effect?
Inhibits nerve terminal MAO-A
Increases cytoplasmic 5HT and NA
NT efflux via reuptake transporter - increases external 5HT and NA
Euphoria/antidepressant effect
What are the 2 types of MAO and what do they metabolise?
MAO-A - 5HT and NA
MAO-B - DA
Name an early irreversible non-selective MAOI
Phenelzine
Name a new reversible selective MAO-AI
Moclobemide
What is the name of the 5HT reuptake transporter?
SERT
What is the name of the NA reuptake transporter?
NET
What is the general mechanism of tricyclic antidepressants?
Inhibit 5HT and NA reuptake
What are the disadvantages of TCAs?
Effect takes 2-3 weeks Initial sedation - eventually desensitise Lack of selectivity Acute cardiotoxicity Overdose risk
Which receptors do TCAs affect and what are the resulting side effects?
Alpha1-adrenoceptor antagonism - postural hypotension
H1-receptor antagonism - sedation
mAChR antagonism - dry mouth, blurred vision
What is the action of SSRIs?
Selectively inhibit SERT
What are the disadvantages of SSRIs?
Rash
Tremor
Gastrointestinal problems
What are the advantages of SSRIs?
No alpha1/H1/mAChR antagonism
No acute cardiotoxicity
Safer in overdose
What are the types of 3rd gen antidepressants, what are their main actions, and name a drug
NRIs - selectively inhibit NET - e.g. maprotiline
SNRIs - inhibit SERT and NET - e.g. venlafaxine
What is the mechanism of monoamine release negative feedback antagonism?
Presynaptic alpha2-adrenoceptors and 5HT1A receptors on soma and terminal - activate Gi/o - inhibit NA and 5HT release
Antagonism of alpha2 and 5HT1A - increases NA and 5HT release - antidepression
What is mirtazapine and how does it work?
3rd gen tetracyclic
NRI
Alpha2 antagonist - less presynaptic feedback inhibition of NA and 5HT release
What is the disadvantage of mirtazapine?
H1-receptor antagonist - sedative
What is the advantage of mirtazapine?
No alpha1/mAChR antagonism
What is mianserin and how does it work?
3rd gen tetracyclic
Alpha2 antagonist - less presynaptic feedback inhibition of NA and 5HT release
5HT3R antagonist - less presynaptic feedback inhibition of NA and 5HT release and postsynaptic effects
What is trazodone and how does it work?
Serotonin antagonist and reuptake inhibitor (SARI) - SSRI and 5HT2R antagonist
What is the advantage of trazodone?
No mAChR antagonism
What are the disadvantages of trazodone?
H1 antagonist - sedative
Alpha1 antagonist - postural hypotension
What is rolipram and how does it work?
Phosphodiesterase inhibitor - increases cAMP and PKA - increases NA synthesis and release
How does ECT work?
Increases CNS sensitivity to 5HT and NA
What is the evidence against the monoamine hypothesis of depression?
Amphetamine, cocaine, L-DOPA increase NA - no antidepression
Iprindole - tricyclic antidepressant - no effect on 5HT/NA
Levels of 5HT and NA equal in CSF of depressed and non-depressed
What is the therapeutic lag hypothesis?
Long-term SSRI use - presynaptic 5HT1ARs gradually desensitise - no feedback inhibition of NA and 5HT release - increased postsynaptic firing
Describe the types of bipolar depression
Type I - mania cycling with major depression - infrequent cycling
Type II - hypomania cycling with major depression - frequent cycling
What is the main treatment for bipolar depression and how does it work?
Lithium
Mechanism unknown
Why can SSRIs not be used for type I bipolar depression?
Cause switch to mania
Why can an antidepressant alone not be used for type II bipolar depression?
Increases suicide risk
