Antidepressants Flashcards
what are the two ways of inhibiting different reuptake transpoerters?
- Short-term (acute) effect → Increased neurotransmitter availability in the brain.
- Long-term effect → Adaptive changes in receptor sensitivity and neuronal signaling.
Antidepressants predominately increase synaptic levels of which neurotransmitters?
Norepinephrine (NE)
Serotonin (5-HT)
Dopamine (DA)
what is the goal of antidepressant?
To promote long-term adaptions in serotonergic (5-HT) neurotransmission or noradrenergic (NE) neurotransmission that results in improvement of depression
what is the ONE medication that targets the dopaminergic (DA) systems?
bupropion
what are the classes of anti-depressants?
- selective serotonergic reuptake inhibitors (SSRIs)
- serotonin antagonists
- serotonergic-noradrenergic reuptake inhibitors (SNRIs)
- Tricyclic antidepressants
- MAO inhibitors
- atypicals
what are the SSRIs?
fluoxetine (Prozac), Sertraline (Zoloft) & escitalopram (Lexapro)
what is the MOA for SSRIs?
Inhibit reuptake of 5-HT immediately – immediate increase in synaptic 5-HT due to SERT block
what are the therapeutic indications for SSRIs?
- Major Depression: SSRIs major 1st line choices
- Chronic Anxiety Disorders
*takes time to work
what are the pharmacokinetics for SSRIs?
All undergo complex cyp450 metabolism
what are drug-drug interactions of SSRIs?
- fluoxetine strongly inhibits CYP2D6 and moderately inhibits CYP3A4; sertraline and escitalopram are weaker cyp inhibitors
- this decreases metabolism of other drugs, could lead to toxicity
what are the adverse effects of SSRIs?
- discontinuation syndrome (sertraline/escitalopram more severe)
- nausea
- anxiety
- weight changes
what is the SSRIs black box warning (SNRIs, TCA also) ?
Serotonin Syndrome – occurs with high doses SSRI (OD), poor CYP2D6 metabolizers, concurrent use with other agents that increase serotonin
- Toxidrome: hyper is the word, Hypertension, Hyperthermia, Hyperreflexia, Hyperstimulation
what is the treatment for serotonin syndrome?
Cyproheptadine (Periactin)
MOA: antagonist of 5HT 2 receptors, blocks ability of 5HT to stimulate post-synaptic receptors
what SSRIs are used in pediatrics and for pregnant people?
fluoxetine for kids
sertraline for pregnant women
what are the SNRIs?
venlafaxine (Effexor): duloxetine (Cymbalta)
commonly prescribed
what is the MOA for SNRIs?
Inhibits SERT & NET = increases synaptic 5-HT & NE interactions
* Similar to a TCA but SNRIs lack antimuscarinic effects
what are SNRIs used for?
Same as SSRI: Highly effective for neuropathic pain, chronic pain and fibromyalgia
what is Venlafaxine most commonly used for?
used more depression ~benefit less drug
interactions
what is Duloxetine used for?
widely used for neuropathic & chronic pain
how do SNRIs decrease chronic pain and what medication is usually prescribed?
by increasing norepinephrine in the spinal cord, activating alpha-2 receptors, and reducing pain transmission
- Duloxetine (Cymbalta) is one of the most prescribed for neuropathic and musculoskeletal pain
what are the adverse effects of SNRIs?
- same as SSRIs
- Can worsen anxiety more then SSRI
- Can worsen headaches
- Cardiovascular
what are Bupropion’s atypical MOAs?
- blocks dopamine and norepinephrine transporters (DAT, NET) causing an increase in synaptic dopamine (DA) &
norepinephrine (NE) - nicotinic cholinergic antagonist (reduces nicotine cravings)
what is Bupropion (Wellbutrin) used for?
- major depression
- obesity
- smoking
- ADHD
what are the benefits of Bupropion (Wellbutrin)?
- no sedation
- no sexual dysfunction
- no anticholinergic effects
what are the major adverse effects of Bupropion (Wellbutrin)?
- decreases seizure threshold
- may worsen hypertension
what is refractory depression?
refers to major depressive disorder (MDD) that does not respond to first-line treatments, such as SSRIs or SNRIs (about 30%)
- patients experience persistent symptoms, leading to poor quality of life and increased health risks like Substance Use Disorder (SUD), Alcohol Use Disorder (AUD), Opioid Use Disorder (OUD)
*increased risk of suicide
what are Tricyclic Antidepressants (TCA) and why are they limited?
- highly effective antidepressants but have a greater toxicity profile comapred to SSRIs, limiting their use
- Anticholinergic & antihistamine properties
- come with significant side effects.
- high toxicity in OD
what are the alternative drugs for TCAs?
mirtazapine, trazodone
what are the alternative treatments for Refractory Depression?
MAO Inhibitors (MAOIs) → Effective but have severe dietary and drug interactions, limiting their use.
what is the TCA?
Amitriptyline (Elavil)
what are the MOAs for TCA?
- Both block SERT & NET – NET with high affinity
- Antagonist α1 adrenergic receptor
- Antagonist at muscarinic and histamine receptors
what are the pharmacokinetics of TCAs?
primarily metabolized by CYP3A4 or CYP2D6
- less CYP enzyme inhibition, meaning they are less likely to interfere with the metabolism of other drugs
What are TCAs used for?
Refractory depression
neuropathic/chronic pain
enuresis (bed wetting)
what are the adverse effects of TCAs?
- Alpha-1 Adrenergic Antagonism hypotension
TCAs (Mnemonic)
* Tachycardia
* Cardiac Effects
* Anticholinergic effects
* sedation/sexual dysfunction
why are high doses of TCAs not good?
High dose = Tachycardia, fast Na+ channel myocyte block = infamous prolonged QRS =dangerous arrhythmias including fatal V fib
*Therapeutic index =3 so dangerous in overdose
What are the dangerous adverse effects of TCAs if a patient overdoses?
- death
- serotonin syndrome
- 3 C’s:
cardiac death
convulsions
coma and stupor
what do you give if a patient is overdosing on TCAs?
TCA are weak bases = Administer sodium bicarbonate ASAP ~can save patient’s life if done quickly
what is the MOA for Mirtazapine (Remeron)?
α2 Autoreceptor Antagonist → increases NE neurotransmission and increases serotonin levels
5-HT2A Receptor Blockade → modulates serotonin activity/ stimulation
what is Mirtazapine (Remeron) used for?
effective antidepressant if insomnia
what are the adverse effects for Mirtazapine (Remeron)?
highly sedative, weight gain, vestibular effects
what is the MOA for TRAZODONE (DESYREL) ?
- SERT Inhibitor (more in the cleft, weak)
- 5-HT2A Antagonist (reduces excessive serotonin stimulation)
- 5-HT1A autoreceptor (enhances serotonin and NE neurotransmission)
what is TRAZODONE (DESYREL) used for?
alternative antidepressant if co-morbid insomnia: commonly used as hypnotic: highly sedative
what are the adverse effects of TRAZODONE (DESYREL)?
- Antihistamine Effects → Very sedative, causes weight gain.
α1 Antagonist Effects: - Orthostatic hypotension (dizziness when standing up too fast).
- Priapism (rare but serious prolonged erection in males).
- Nasal congestion (in about 6% of patien
what is the MAO-I?
Phenelzine (Nardil)
what is the MOA for Phenelzine (Nardil)?
inhibits Monoamine Oxidase A (MAO-A), an enzyme that normally breaks down norepinephrine (NE), serotonin (5-HT), and dopamine (DA)
what is Phenelzine (Nardil) used for?
Used for refractory depression for patients not responding to SSRIs or SNRIs
what are the adverse effects of Phenelzine (Nardil)?
- Antihistamine – very sedative, weight gain
- Sympathomimetic effects ~ avoid other stimulants (including using epinephrine)
- hypertensive crisis & tachycardia risks
- CNS agitation & anxiety
- Increases seizure risk (lowers seizure threshold)
what are considerations you must be aware of if taking Phenelzine (Nardil)?
Avoid Tyramine-Rich Foods: Tyramine is normally broken down by MAO
- could lead to hypertension
Avoid Other Serotonergic Drugs
Avoid Other Sympathomimetic Agents
