Antidepressants Flashcards
What is the theory that explains what causes depression?
Deficits in monoamine neurotransmitters cause depression
Are monoamines the only cause of depression?
Most likely monoamines are important but there are complex interactions with other neurotransmitter systems as well
What are the functions of MAO-A and MAO-B?
5HT is mainly broken down by MAO-A
NA and dopamine - MAO-B
MOA of MAOIs
Increase bioavailability of monoamines by inhibiting the enzyme that degrades the neurotransmitters
How does selegiline work?
MAO-B selective inhibitor, works to preserve dopamine
What is phenelzine?
Non-selective for MAO-A and MAO-B
Irreversible MAOI
Adverse effects of MAOIs
Postural hypotension (due to sympathetic block by accumulation of dopamine in the cervical neck ganglia, where it acts as a inhibitory transmitter) Restlessness and insomnia Should not be combined with other drugs enhancing serotonergic function (e.g. pethidine)
What is the cheese reaction?
Drug food interaction leading to acute hypertension
Major danger from cheeses and concentrated yeast products
Amines (eg tyramine) in foods are usually broken down by MAO in the intestines and liver. MAOIs can lead to accumulation of tyramine and sympathomimetic effect (tyramine competes with noradrenaline for the vesicular compartment, leads to more release of NA)
With what agents is the cheese reaction less likely to occur?
Less likely to occur with reversible MAO-A selective (eg moclobemide) than irreversible non-selective MAOIs (phenelzine)
MAO-B can still work, and mechanism is reversible
Types of antidepressants
MAOIs TCAs SSRIs NARI SNRI NaSSA NDRI Melatonin receptor agonist Glutamate NMDA antagonist Multimodal serotonergic antidepressant
MOA of TCA
Prevent monoamine from being reuptake into the synapse to let them stay in the synapse for longer → increases levels of monoamines
TCAs
Imipramine, amitryptiline, nortryptiline
Adverse effects of TCAs
Sedation (H1 antagonism) Postural hypotension (alpha adrenergic sympathetic block) Dry mouth, constipation, blurred vision (muscarinic receptor antagonism)
SSRIs vs TCAs
SSRIs have greater 5HT reuptake transporter selectivity than TCAs
Fewer side effects (but still antimuscarinic, sedation and postural hypotension)
ADVANTAGES:
- Improved adverse effect profile of SSRIs leads to better compliance and prescription of more adequate doses
- Safer in overdose
SSRIs
Fluoxetine, citalopram
Advantages of SSRIs
Low affinity for alpha-adrenoceptors
Lack of effect at histamine receptors
Low affinity for muscarinic
AEs of SSRIs
Nausea and insomnia
Sexual dysfunction
Sedation (citalopram)
Serotonin syndrome - caused by what and what are the effects?
Severe reaction from drug-drug interactions with other drugs increasing serotonergic activity
Tremor, hyperthermia, cardiovascular collapse
NARI
reboxetine
NARI adverse effects
dry mouth, constipation, insomnia, tachycardia
Mirtazipine
NaSSA
Norepinephrine and specific serotonin antidepressant
Antagonist of adrenergic alpha2-autoreceptors and 5-HT receptors
Bupropion
Noradrenaline dopamine reuptake inhibitor
Ketamine
Glutamate NMDA receptor antagonist used as an anesthetic, currently evaluated for rapid-onset antidepressant effect
Vortioxetine
Multimodal serotonergic antidepressant
Additional receptor affinities may result in further release of serotonin and other neurotransmitters
May be efficacious in patients resistant to other antidepressants
May also have pro-cognitive effects
May increase risk of suicidal thoughts or actions in children and teens
