L1 Antidepressants Flashcards
5-HT is broken down mainly by
MAO-A
Noradrenaline is broken down mainly by
MAO-A and MAO-B
Dopamine is broken down mainly by
MAO-A and MAO-b
What is the type of MAOi used in Parkinson’s disease?
MAO-B
Phenelzine is: (2)
- non-selective for MAO-A vs MAO-B
- and irreversible MAOi
ADR of MAOis
- postural hypotension - dopamine as inhibitory neurotransmitter, cervical block
- restlessness or insomnia - CNS stimulation
- should not be combined with other drugs with seretoninergic function eg. pethidine - myoclonus, hyperexcitability, loss of consciousness, increased muscular tone
Significant drug-food interaction related to the use of MAOIs (also its major limitation)
the ‘cheese’ reaction
- cheeses and concentrated yeast products eg. marmites
Tyramine has a high affinity for
NA transporters
TCAs were initially produced as
potential antipsychotic drugs in 1949, but found to be ineffective in schizophrenia
Examples of non-selective TCAs
imipramine, amitriptyline, nortriptyline
Example of NET-selective TCA
desipramine
Which one of the non-selective TCAs has the mildest side effect profile?
nortriptyline
ADR of TCAs (4)
- sedation - H1 antagonism, tolerance can be developed in 1-2weeks
- postural hypotension - a-adrenoceptor sympathetic block
- dry mouth, blurred vision, constipation - muscarinic receptor antagonism
- ddi - rely on hepatic metabolism
Which is the first drug class to be developed for the purpose of antidepressant treatment?
SSRIs
What is the mostly widely prescribed antidepressant currently?
Fluoxetine
3 key advantages of SSRIs
- low affinity for alpha-adrenoceptors
- low affinity for muscarinic cholinergic receptors
- lack of effect at histamine receptors
Which SSRIs still retain some level of sedation?
citalopram - still has some histamine receptor antagonism
adr of SSRIs
nausea, insomnia, sexual dysfunction
What drugs can be given to prevent SSRTI-induced sexual dysfunction?
cyproheptadine or other 5HT2 blockers
What is the current first line therapy used for depression?
SSRIs, but it is not perfect:
- only 2/3 achieve remission
- adverse effects, esp at the start
- discontinuation can be a problem in some
Maprotiline
an earlier NARI, had TCA-like adverse effects due to alpha-adrenoceptor and histamine receptor effects and occasionally caused seizures
Examples of SNRIs in clinical use
venlafaxine, desvenlafaxine (synthetic metabolite of venlafaxine), and duloxetine
Withdrawal effects is more common and stronger for SSRIs/TCAs/SNRIs?
SNRIs
Example of a NDRI
bupropion
Example of an anesthetic, currently evaluated for rapid-onset antidepressant effect
Ketamine, a glutamate NMDA receptor antagonist
Example of a NaSSA
mirtazapine, adrenergic a2 autoreceptor antagonist + 5HT2c receptor antagonist
Aglomelatine
agonist of MT1 and MT2 receptors, also has antagonist at 5HT2c receptors
- also helps in sleep disorders
- less TCA/SSRI-associated adr
Vortioxetine
multimodal serotonergic antidepressant + additional receptor affinities
Vortioxetine is generally used in
patients resistant to other antidepressants, pro cognitive effects too, appear to work well with children and young adults
Close monitoring required in initial stages of vortioxetine use due to
increased risk of suicidal thoughts or actions in childrens and teens
Does fluoxetine or citalopram has a higher selectivity for 5-HT?
50-fold vs 1000-fold, citalopram
Does TCA and SSRI bind to the same site?
Yes
- SSRI has greater 5-HT reuptake selectivity though, fewer adverse effects
Adverse effects of TCAs lead to
prescription of subtherapeutic doses
- improved adverse side effect profile of SSRIs lead to better compliance and so prescription of more adequate doses, better efficacy
Symptoms of serotonin syndrome
tremor, hyperthermia, cardiovascular collapse
Why is SSRis safer in overdose?
low affinity for alpha-adrenoreceptors: lack of cardiovascular effects (postural hypotension, bradycardia)
NARI
reboxetine, maprotiline
ADR of SNRI
- similar to SSRI: nausea, insomnia, sexual dysfunction
- ‘serotonin syndrome’ when combined with other serotoninergic drugs and MAOis
- withdrawal effects may be more common and stronger than for SSRIs and TCAs
Which of the following has the fewest adr? TCAs/SSRIs/NARIs
NARI
Does venlafaxine have the same structure as TCA?
NO, fewer adr than TCAs
Adv of velnlafaxine
- different structure to TCAs and fewer side effects
- claimed to work slightly faster, 2-4weeks, work better in treatment-resistant patients
ADR of reboxetine
- dry mouth, constipation
- insomnia: noradrenergic activity on CNS
- tachycardia: increased NA availability
