Psychopharm of antidepressants/anxiolytics Flashcards
Monoamine hypothesis
Monoamines are depleted in depression and that ADs work by boosting levels of these NTs
Downstream effects of ADs
Induce neuronal adaptations
Down-regulate/normalize receptors
Promote growth regulation factors
4 general mechanisms of primary AD action
Block reuptake of NTs
Antagonize receptors controlling NT release
Stimulate receptor activity
Interfere with NT breakdown
First line antidepressants
SSRIs: fluoxetine, citalopram, escitalopram, sertraline, paroxetine, fluvoxamine
SNRIs: venlafaxine, duloxetine, desvenlafaxine
Others: buproprion, mirtazapine, vortioxetine
Second line antidepressants
SNRIs: levomilnacipran
TCAs
Others
SSRIs
Selective serotonin reuptake inhibitors Blocks SERT (the reuptake pump)
Side effects of SSRIs
CNS: initial agitation/worsening of anxiety, tremors, insomnia, sedation, serotonin syndrome GI: diarrhea, constipation GU: sexual dysfunction Cardiac: QTc prolongation Endocrine: hyponatremia Heme: bleeding
Problems with paroxetine
Most problematic for medication interactions, worse discontinuation effects, highest risk of weight gain
What drug causes the most pronounced GI effects
Sertraline
Especially nausea and diarrhea
What drug is the easiest to taper? Why?
Fluoxetine
Has the longest half life
SSRI Discontinuation Syndrome
Symptoms may include flu-like symptoms, GI disturbance, headaches, dizziness, paraesthesias, sleep disturbance, fatigue, sweating
Taper medications slowly makes this syndrome less likely
Serotonin Syndrome
Syndrome of excess serotonin
Most often occurs within hours of medication change/addition
Often resolves within 24 hours following cessation of implicated agents
More likely in cases of polypharmacy
May occur with med combos with than ADs
Can use a 5HT2a (ciproheptadin) to treat
Clinical presentation of serotonin syndrome
Triad:
Autonomic (sweating, tachycardia, etc)
Cognitive (delirium, etc)
Neuromuscular (clonus, hyperreflexia, etc)
SNRIs
Serotonin and Norepinephrine Reuptake Inhibitors
Blocks both SERT and NET
Side effects of SNRIs
Same as SSRIs
Plus peripheral noradrenergic effects (sweating, increased BP and HR, urinary retention)
NDRI (what does it stand for, example, how does it work, side effects)
Norepinephrine Dopamine Reuptake Inhibitor
Ex: Buproprion
Blocks NET and DAT
Side effects: nausea, vomiting, decreased appetite, agitation, headache, seizure, rash)
SNS (what does it stand for, example, how does it work, side effects, pearl)
Serotonin modulator and stimulator
Ex: Vortioxetine
Some direct actions: blocks SERT and 5HT 3 and 7, stimulates 5HT-1A/B
Side effects: same as SSRIs but nausea may be more significant. Dizziness and pruritis common
Possible benefit for cognitive symptoms
NaSSA (what does it stand for, example, how does it work, side effects, pearl)
Noradrenergic Serotonin Specific Antidepressant
Ex: Mirtazapine
Action: Blocks a2 receptors (increases release of 5-HT and NE), and blocks other serotonin receptors and histamine
Side effects: similar to SSRIs and SNRIs plus sedation, dizziness, constipation, increased appetite, weight gain
Sedation is greater at lower doses
SARI (what does it stand for, example, how does it work, side effects, pearl)
Serotonin antagonist and reuptake inhibitor
Ex: trazodone
Action: SSRI, 5HT-2, alpha adrenergic and histamine blockade
Side effects: sedation, dizziness, orthostatic hypotension and priapism
Primarily used off label as a sedative
SPARI (what does it stand for, example, how does it work, side effects, pearl)
Serotonin partial agonist and reuptake inhibitor
Ex: vilazodone
Action: partial agonist of 5HT1A, blocks SERT
Side effects: nausea, diarrhea, insomnia
Basically a combo of SSRI and buspirone
May have less weight gain and sexual side effects vs SSRIs/SNRIs
TCAs (what does it stand for, example, how does it work, side effects)
Tricyclic ADs
Ex: amitriptyline (SNRI), desipramine (NRI) and clomipramine (SSRI)
Action depends on agent
Side effects: constipation, sedation, dizziness, orthostatic hypotension, tachy, seizures, coma, blurry vision, arrthymias, urinary retention
Can be potentially deadly in overdose, so they are second line
4 NTs of key interest in anxiety
Serotonin
NE
GABA
Glutamate
Buspirone (action, side effects)
For anxiety
Action: partial 5-HT1A agonist
Side effects: dizziness, nausea, drowsiness, initial nervousness, fatigue
No abuse/depedence potential, no sedation or cognitive effects
Gabapentin/pregabalin (action, side effects)
For anxiety
Action: blocks the a2 delta subunit of calcium channels –> decreases Ca flow and the presynaptic release of glutamate
Side effects: sedation, tremors, dizziness, diplopia, dry mouth, peripheral edema
Benzodiazepines (examples, action, effects)
Ex: -pam
Action: binds to post synaptic GABA-A receptor and increased GABAergic transmission
Sedative/hypnotic, muscle relaxant, anticonvulsant, amnestic and anxiolytic
Side effects of benzos
Dependence, tolerance and addiction
Cognitive/neuromuscular function may be impaired
Disinhibition
Paradoxical reactions
Abrupt discontinuation after chronic use can cause seizures
Why are TCAs second line?
Can be potentially deadly in overdose
