3. Segars Antidepressants and Mood Stabilizers Flashcards
What drug is indicated for nicotine withdrawl?
Buproprion (zyban)
What drug is indicated for enuresis (involuntary urination)?
Imipramine - Tertiary amine TCA
What drug is indicated for:
- diabetic peripheral neuropathy
- fibromyalgia
- stress incontinence
- chronic MSK pain?
Duloxetine -SNRI
What are the 5 R’s of Antidepressant Efficacy?
- Response–> more than 50% reduction in sx (not well, just better)
- Remission –> sx free (well functioning state) less than 6 months
- Recovery –>not cured, 6-12 months of remisssion
- Relapse –> return of sx after remission but before recovery
- Recurrence –> return of sx after recovery
What do you do if a patient doesn’t respond fro an antidepressant after ~ 8 week trial?
Switch to another antidepressant with a different MOA
What are signs of an antidepressant withdrawal syndrome?
FINISH
- Flu like sx
- Insomnia
- Nausea
- Imbalance
- Sensory Disturbances
- Hyperarousal
Citalopram Escitalopram Fluoxetine Paroxeitine Sertraline Vilazodone Vortioxetine
are what type of drugs?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Citalopram is what?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Escitalopram is what?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Fluoxetine is what?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Paroxetine is what?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Setraline is what?
SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
Vilazodone is what?
- SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
- partial agonist on 5-HT 1A
Vortioxetine is what?
- SSRI -selectivly inhibit the pre-synaptic reuptake of Serotonin via presynaptic transporter SERT
- Partial agonist off 5-HT1B and full agonist on 5-HT-1D
Do SSRIs or TCAs have more side effects?
TCA- SSRIs have less impact on histamine, muscarinic, and adrenergic receptors
- CNS (sedation or insomnia/agitation/nervousness)
- Sexual dysfunction (change in libido/impotence)
- Weight gain (adults) / Weight loss (mild; adolescents)
- Acute withdrawal reactions (concern w/ all categories)
Are primary side effects of what drug class?
SSRI
What is serotonin syndrome? What can cause it?
- Sx: sweating, hyperreflexia, Akathisia/myoclonus, shivering/tremors
- Serious dose dependent side effect of SSRI
What are rare dose dependent toxicities of SSRI?
- QT prolongation
- Hyponatremia (SIADH)
- Serotonin syndrome
- suicidality ( high risk in children, adolescents, and young adults
What SSRI has the most interactions with CYP450?
Fluoxetine - strong and broad CYP450 inhibitor
Which SSRI has the least amount of Reactions with CYP450? (2)
Vortioxetine and Escitalopram
What SSRIs are mild CYP 450 inhibitors? (3)
- Citalopram
- sertraline
- vilazodone
What are SNRIs (including TCA)?
Selectivly inhibit the pre-synaptic reuptake of serotonin via SERT and Norepinephrine via NET
How do tertiary amines TCAs clomipramine, amitriptyline, Doxepin, and Imipramine TCAs work?
inhibit both NE/5-HT relatively equally
(Clomiprmaine/ Amitriptyline impact 5HT more)
- more anticholinergic effects than secondary TCAs
How do secondary amine TCAs work?
Amoxapine, Desipramine, Nortriptyline
Inhibit NE>5HT
Do SNRIs generally affect 5HT or NE reuptake more?
5HT>NE
What is tertiary TCA Amine is metabolized to secondary amine TCA Nortriptyline?
Amitriptyline
What tertiary amine TCA is metabolized to Despiramine?
Imipramine
What receptors do TCAs impact in addition to NET and SERT?
- Histamine (H1)
- Muscarinic (cholinergic)
- alpha 1 (adrenergic)
What are TCA side effects?
- Cardiovascular (a1)–> tachycardia, orthostatic hypotension, dysrhytmias
- Anticholinergic (muscarinic)–> Dry mouth, Urinary retention/Constipation, Blurred vision/ increased intraoccular pressure
- CNS (histamine) – >Sedation/fatigue, dizziness/seizures
What can result from toxic ingestion of TCAs?
3 C’s:
- Coma
- Cardiotoxicity (conduction abnormalities)
- Convulsions
What type of drugs are Nefazodone, and Trazodone?
SARA
- two agents that that act like SSRIs
- selectively block at post synaptic a1 receptors on norAdrenergic neurons
- block post synaptic 5-HT2 receptors
- Also bloc H1 and cause sedation
What type of drug is Mirtazapine?
SARA
- blocks presynaptic a2 receptors on norAdrenergic and Serotonergic 5HT neurons
- blocks post synaptic 5-HT(2/3) receptors
- Blocks H1
- No SERT/NET activity
What are the SARA side effects (H1/a1)?
- CNS: sedation (most with Trazodone/Mirtazapine)
- Orthostatic HTN (most with Trazodone)
- weight gain (most with mirtazapine)
What are NDRIs?
antidepressants that selectively inhibit presynaptic Reuptake of NE (via NET) and Dopamine (via DAT)
- enhanced, prolonged NE and DA neurotransmission to post-synaptic receptors
- enhances presynaptic release of NE and DA via VMAT2
What type of drug is buproprion?
NDRI
- Agitation/Insomnia (stimulating)–> HTN/Tachycardia/tremors
- Weightloss
- Seizures (dose-dependent or those at risk)
are side effects of what drugs?
NDRI’s
What do MAO inhibitors do?
- Increase levels of monoamines in neuronal vesicles
2. increase the amount of NE, 5-HT and DA released
Isocarboazid, Phenelzine, Selegiline, and Tranylcypromine are what type of drugs?
MAOI’s
What type of MAOI’s are irreversible?
Oral agents
All MAOIs are nonselective against MAO A/B except what?
Selegiline is B selective–> nonselective at high doses
What MAOI is a patch?
Selegiline
- Isocarboxazid
- Phenelzine
- Selegiline (patch)
- Tranylcypromine
are what types of drugs?
MAOIs
MAOI’s can interact with what drugs?
5-HT/NE affecting drugs
-there is a 2 week wash out period for fluoxetine, can take 5 weeks for it to leave the system making interactions possible
A major concern of MAOI’s is what?
Hypertensive Crisis
Signs:
- severe headache
- sweating/severe anxiety
- nosebleeds
- tachycardia
- chest pain
What miscellaneous antidepressant is an NMDA receptor (glutamate) antagonist) that is indicated for treatment-resistant depression in conjunction with ongoing antidepressant therapy?
Esketamine- S isomer of ketamine
- nasal administration by an REMs authorized physician and must be monitored 2 hrs post dose for blood person, and cognitive impairtment
What miscellaneous antidepressant is a GABA (A) receptor positive allosteric modulator that is identical to endogenous alloprenanolone and used to treat post partum depression?
Brexanolone
sounds like pregnenolone
How long does GABA(A) receptor positive allosteric modulatorBrexanolone last?
efficacy lasts up to 30 days post does
Anti-seizure agents carbamazepine, Lamotrigine, and valproic acid; and lithium are used to treat what aspect of mood disorders?
Mood stabalizers
What are the targets of lithium as a mood stabilizer?
- Brain Structure
- Neurotransmitter modulation
- Intracellular changes
What neurotransmitter transmission is inhibited by lithium?
dopamine
-Li+ interferes with Gs anGi activity keeping them in the inactive state
What receptor is down regulated by lithium?
NMDA receptor in chronic use
Lithium increase the neuronstransmission of what?
GABA
What drug is a monovalent ion that compete with Na+ for kidney reabsorption?
Lithium
-
Accumulation of Lithium in the principle cells of the collecting duct can lead to what?
- resistance to ADH
- Polyuria/Polydipsia
**Nephrogenic Diabetes insidious is a big side effect
What drugs interact with lithium?
- Diuretics
- ACEIs
- NSAIDs
What are the indications of Lithium?
- acute maintenance and treatment of mania/ bipolar I disorder
- Augmentation for patients in unipolar depressive patients with inadequate response to antidepressant therapy
- Off label reduces risk of suicide and mortality in patients with mood disorders
What is the use of Valproic acid/Divalproex as a mood stabilizer?
acute bipolar I (with or without psychotic features)
What is the use of Lamotrigine as an mood stabilizer?
lamotrigine is used for maintenance of Bipolar I and II
What is the use of carbamazepine as a mood stabilizer?
acute maintenance treatment of acute mania and mixed episodes of bipolar I
- carbamazepine is a major CYP450 inducer
