PHARM - Antidepressants Flashcards
briefly - what is the pathogenesis of stress?
cortisol release in the absence of a non-threatning stimulus
d/t chronic activation of adrenal HPA
mediated by the amygdala
what are the main theories that explain the etiology of depression?
why is this important?
- monoamine neurotransmitter hypothesis: insufficient NE and 5-HT
- neurotrophic hypothesis: stress induced BDNF depletion
many depression drugs increase monoamine NTs, which can in turn increase BNDF expression
BDNF?
- what is it?
- where / how is it produced ?
- how does stress decrease its levels?
- how do anti-depressents increase its levels?
- brain derived neurotrophic factor
- made in hippocampus
- 5-HT and NE bind respective receptors on neuron
- CREB becomes phosphorylated
- upregulation of BDNF & TrkB
- stress: chronic elevated glucocorticoids → atrophy of hippocampus
- anti-depressants: decrease 5-HT & NE reuptake
SSRIs
- includes which drugs?
- MOA
- PK
- AE/CI
selective serotonin reuptake inhibitors
- drugs: fluoxetine, escitalopram
- MOA:
- selectively increases synaptic 5-HT by
- inhibiting 5-HT reuptake
- upregulating 5-HT receptors
- increase in BDNF (slow onset)
- selectively increases synaptic 5-HT by
- PK: delayed onset
- AE: same as SNRIs
- sexual dysfunction
- weight gain
- suicidal ideations
- C/I: MOA-inhibitors
which SSRI is the “most” selective?
escitalopram
SNRIs
- includes which drugs
- MOA
- PK
- AE/CI
serotonin / NE reuptake inhibitors
- drugs: venlaxafine
- MOA:
- increases synaptic 5-HT and NE
- thus increasing BDNF
- PK: slow onset
- AE: same as SSRIs
- sexual dysfunction
- weight gain
- suicidal ideations
- C/I: MAO inhibitors
TCAs
- includes which drugs
- MOA
- AE/CI
- drugs: - pramines: desipramine, imipramine
- MOA: blocks a variety of receptors
- blocks NE and 5-HT reuptake
- also blocks: histamine, muscarinic & alpha-1 receptors
- PK: slow onset
- AE: more severe than SSRIs/SNRIs
- drowsiness (histamine)
- muscarininc:
- dry mouth
- blurry vision
- tachycardia
- constipation / urinary retention
- ED
- orthostatic hypotension (alpha-1)
- cardiac toxicity
- seizures
- diaphoresis
- CI: MAO inhibitors
which drugs are strictly C/I with MAO inhibitors?
why?
what is a commonly used MAO inhibitor?
SSRIs, SNRIs, TCAs
all of these drugs increase vasoconstrictive monoamines, and adding a MAO-I can lead to a hypertensive crisis
tranylcypromine
tranylcypromine
- what kind of drug?
- clinical use
- MOA
- AEs
- drug/MOA: is a MOA inhibitor
- clinical use: second line drug for atpyical depression
- AE/CI:
- hypertensive crisis (C/I with SSRIs, SNRIs, TCAS)
- orthostatic hypotension
which drug combinations can lead to a hypertensive crisis?
- MAO-I with SSRIs, SNRIs, TCAs
- MAO-I with tyramine containing foods - yeast, cheese, cold cuts
- SSRIs (fluoxetine) with CYP-3A4 inhibitors (ritonavir)
compare / contrast the AEs of SSRIs, SNRIs, and TCAs
why do they differ?
- SSRIs / SNRIs = sexual dysfunction, appetite, suicidal ideation
- TCAs = more severe, b/c it blocks histamine, muscarinic and alpha-1 receptors on top of 5-HT & NE
- drowsiness (HA)
- othostatic hypotension (alpha-1)
- dry mouth, blurry vision, ED, constipation / retention, tachy (cholinergic)
- paradoxic diaphoresis
- cardiac toxicity
- seizures
compare / constrast the onset of action of SSRIs, SNRIs and TCAs.
why is this the case?
all have delayed onset of action
this is because the neuronal plasticity following BNDF secretion
fluoxetine is what kind of drug?
SSRI
(prozac)
escitalopram is what kind of drug?
SSRI
(lexapro)
velaxafine is what kind of drug?
SNRI
