Chapter 17 & Chapter 18

What drug class do these fall under?

-Citalopram

(Celexa)

-Escitalopram

(Lexapro)

-Fluoxetine

(Prozac)

-Sertraline

(Zoloft)

-Paroxetine

(Paxil)

-Fluvoxamine

(Luvox)

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA of Selective Serotonin Reuptake Inhibitor (SSRI)

Specifically block the reuptake of serotonin, leading to increased concentrations of the neurotransmitter in the synaptic cleft.

Uses/Indications of Selective Serotonin Reuptake Inhibitor (SSRI)

1. 1st line for MDD (Major Depressive Disorder)

2. 1st line for GAD (Generalized Anxiety Disorder)

- OCD

-PTSD

-Panic

disorder

-Social Anxiety

-PMDD (Premenstural disorder)

SE of Selective Serotonin Reuptake Inhibitor (SSRI)?

-Sexual dysfunction

-Seizures (all antidepressants may lower seizure threshold)

-Serotonin syndrome (hyperthermia, muscle rigidity, sweating, myoclonus, changes in mental status and vital signs)

-Discontinuation syndrome (flu-like symptoms)

Considerations for Selective Serotonin Reuptake Inhibitor (SSRI)?

-Metabolized by cytochrome P450 (that's why you can't drink grapefruit juice if you're on an SSRI) 🍊

-Food increases absorption of sertraline

What drug class does this medication fall under?

Escitalopram (Lexapro)

Selective Serotonin Reuptake Inhibitor (SSRI)

Use of Escitalopram (Lexapro)?

Childhood depression (Kids get ESCited to get the FLU)

What drug class does this medication fall under?

Fluoxetine (Prozac)

Selective Serotonin Reuptake Inhibitor (SSRI)

Use of Fluoxetine (Prozac)?

-Childhood depression (Kids get ESCited to get the FLU)

-Childhood OCD

-Bulimia nervosa (Fluoxetine only)

SE of Fluoxetine (Prozac)?

-Stimulating effect ☀️

-Lowest risk of causing discontinuation syndrome d/t longer half-life and active metabolite

The perfect paper airplane flew for a long time, stimulating the crowd to applaud

What drug class does this medication fall under?

Sertraline (Zoloft)

Selective Serotonin Reuptake Inhibitor (SSRI)

Use of Sertraline (Zoloft)?

Childhood OCD

SE of Sertraline (Zoloft?

Stimulating effect ☀️

What drug class does this medication fall under?

Paroxetine (Paxil)

Selective Serotonin Reuptake Inhibitor (SSRI)

SE of Paroxetine (Paxil)

Sedating effect 🌜 Picture a sleepy parrot

What drug class does this medication fall under?

Fluvoxamine (Luvox)

Selective Serotonin Reuptake Inhibitor (SSRI)

Use of Fluvoxamine (Luvox)

Childhood OCD

SE of Fluvoxamine (Luvox)

Sedating effect 🌜

Turn the V sideways to make a crescent moon

What drug class does this medication fall under?

Citalopram (Celexa)

Selective Serotonin Reuptake Inhibitor (SSRI)

SE of Citalopram (Celexa)

May cause QT prolongation

What drug class do these fall under?

-Venlafaxine (Effexor)

-Desvenlafaxine (Pristiq)

-Duloxetine (Cymbalta)

-Levomilnacipran (Fetzima)

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

MOA of Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

Inhibit the reuptake of BOTH serotonin and norepinephrine

Uses of Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

-Depression

-Chronic pain accompanying depression Duloxetine like dual, as in it has dual purposes for both depression and pain

-Pain syndromes (diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain.)

SE of Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

-Nausea

-Sexual dysfunction

-Dizziness/Diaphoresis

-Discontinuation Syndrome

CI + DI + Considerations for Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

The SNRIs, unlike the TCAs, have little activity at α-adrenergic, muscarinic, or histamine receptors and, thus, have fewer receptor-mediated adverse effects than the TCAs

MOA of Venlafaxine (Effexor) & Desvenlafaxine (Pristiq)?

-Inhibits serotonin uptake

-Inhibits norepi uptake at high doses

SE specific to Venlafaxine (Effexor) & Desvenlafaxine (Pristiq)?

-Nausea, HA, sexual dysfunction, dizziness, insomnia, sedation, constipation

High doses: increase in blood pressure and heart rate

Faxine = fax machine; those things never work right, it pisses me off and my heart rate/BP increase when I try to use them

CI + DI + Considerations for Venlafaxine (Effexor) & Desvenlafaxine (Pristiq)?

Desvenlafaxine is the active, demethylated metabolite of venlafaxine

MOA of Duloxetine (Cymbalta)?

Inhibits serotonin and norepinephrine reuptake at ALL doses

Dual action - both ser and norepi at all doses

SE specific to Duloxetine (Cymbalta)?

-GI side effects are common (nausea, constipation)

-Dry mouth, insomnia, dizziness, somnolence, sweating, sexual dysfunction

-May increase blood pressure or heart rate

CI + DI + Considerations for Duloxetine (Cymbalta)?

CI: Avoid in patients with liver dysfunction

DI: Moderate inhibitor of CYP2D6 isoenzymes and may increase concentrations of drugs metabolized by this pathway, such as antipsychotics

CYP2D6 has a D in it

SE for Levomilnacipran (Fetzima)?

Similar to other SNRIs - nausea, HA, dry mouth

What drug class does this medication fall under?

Brexanolone (Zulresso)

Atypical Antidepressant

MOA of Brexanolone (Zulresso)

Positive allosteric modulator of GABAA receptors

Uses of Brexanolone (Zulresso)

Postpartum depression

(brexanolone is analog of a neurosteroid, alloprenanolone, which declines after delivery, and may be related to PPD)

SE of Brexanolone (Zulresso)

Excessive sedation, sudden loss of consciousness, and hypoxia - NEEDS SUPERVISION

CI + DI + Considerations for Brexanolone (Zulresso)

administered as an intravenous infusion over 60 hours in an inpatient setting

What drug class does this medication fall under?

Bupropion (Wellbutrin)

Atypical Antidepressant

MOA of Bupropion (Wellbutrin)?

Weak dopamine and norepinephrine reuptake inhibitor

Uses of Bupropion (Wellbutrin)?

-Depression

-Smoking cessation (maybe bc decreases stimulant effects of nicotine on nicotinic acetylcholine receptors)

SE of Bupropion (Wellbutrin)?

-Dry mouth

-Sweating

-Nervousness

-Tremor

-Dose-dependent increased risk for seizures

CI + DI + Considerations for Bupropion (Wellbutrin)?

CI: Avoid in patients at risk for seizures (including electrolyte abnormalities or hx of anorexia or bulimia)

LOW incidence of sexual dysfunction

What drug class does this medication fall under?

Esketamine (Spravato)

Atypical Antidepressant

MOA of Esketamine (Spravato)

NMDA receptor antagonist

Uses of Esketamine (Spravato)

-Adjunctive therapy for management of treatment-resistant depression or MDD with suicidal ideation or behavior

-Faster acting than standard antidepressants

SE of Esketamine (Spravato)

-Sedation

-Nausea and vomiting

-Dissociation and hallucinations

-Increased blood pressure

CI + DI + Considerations for Esketamine (Spravato)

-Intranasal admin

-Administered in controlled environment, patient monitored for 2 hours

-Controlled substance

What drug class does this medication fall under?

Mirtazapine (Remeron)

Atypical Antidepressant

MOA of Mirtazapine (Remeron)

-Enhances serotonin and norepinephrine neurotransmission by serving as an antagonist at central presynaptic α2 receptors

-5-HT2 receptor antagonist

SE of Mirtazapine (Remeron)

-Sedation (bc potent antihistaminic activity)

-Dry mouth

-Increased appetite

-Weight Gain

**Does NOT cause sexual dysfunction (like SSRIs) or antimuscarinic side effects (like TCAs)

What drug class do these medications fall under?

Nefazodone (Rexulti)

Trazodone (Remeron)

Atypical Antidepressants

MOA of Nefazodone (Rexulti) & Trazodone (Remeron)?

-Weak inhibitors of serotonin reuptake and norepinephrine reuptake

-5-HT2a receptor antagonist

Use of Trazodone (Remeron)?

Trazodone often uses off-label for insomnia management

SE of Nefazodone (Rexulti) & Trazodone (Remeron)?

-Sedation (bc H1-blocking activity)

-Nausea

-Dry Mouth

Priapism - Trazodone

Hepatotoxicity - Nefaxodone

CI + DI + Considerations for Nefazodone (Rexulti) & Trazodone (Remeron)?

Both agents are metabolized by CYP3A4; nefazodone is also a CYP3A4 inhibitor

What drug class does this medication fall under?

Vilazodone (Viibryd)

Atypical Antidepressant

MOA of Vilazodone (Viibryd)

-Serotonin reuptake inhibitor

-5-HT1a receptor partial agonist

The villain wants to be different - would just be an SSRI if it weren’t for the 5-HT1a agonism

SE of Vilazodone (Viibryd)?

Similar to SSRIs:

-Nausea

-Diarrhea

-Sexual dysfunction

-Dizziness

-Risk for discontinuation syndrome if abruptly stopped

What drug class does this medication fall under?

Vortioxetine (Trintellix)

Atypical Antidepressant

MOA of Vortioxetine (Trintellix)?

-Serotonin reuptake inhibition

-5-HT1a agonism

-5-HT3 and 5-HT7 antagonism

SE of Vortioxetine (Trintellix)?

-Nausea

-Constipation

-Sexual Dysfunciton

(Makes sense bc of serotonergic mechanisms)

CI + DI + Considerations for Vortioxetine (Trintellix)?

DI: primarily metabolized by CYP2D6

-Reduce dose if coadministered with strong CYP2D6 inhibitors

What drug class do these medications fall under?

-Clomipramine (Anafranil)

-Trimipramine (Surmontil)

-Nortriptyline (Pamelor)

-Protriptyline (Vivactil)

Tricyclic Antidepressants (TCAs)

MOA of:

-Clomipramine (Anafranil)

-Trimipramine (Surmontil)

-Nortriptyline (Pamelor)

-Protriptyline (Vivactil)

-Inhibit norepi and serotonin reuptake

-Also block serotonergic, alpha-adrenergic, muscarinic, and histaminic receptors

Uses of:

-Clomipramine (Anafranil)

-Trimipramine (Surmontil)

-Nortriptyline (Pamelor)

-Protriptyline (Vivactil)

-Major depression

-Panic disorder

SE of:

-Clomipramine (Anafranil)

-Trimipramine (Surmontil)

-Nortriptyline (Pamelor)

-Protriptyline (Vivactil)

Blockade of muscarinic receptoqrs leads to anticholinergic effects:

-Blurred vision

-Dry mouth

-Urinary retention

Sinus tachycardia

-Constipation

-Aggravation of angle-closure glaucoma

May precipitate life threatening arrhythmias in overdose

Blockade of alpha-adrenergic receptors causes:

-Orthostatic hypotension

-Dizziness

-Reflex tachycardia

Blocking Histamine H1 receptors causes:

-Sedation

-Weight gain

-Sexual dysfunction (but less than SSRIs)

CI + DI + Considerations for:

-Clomipramine (Anafranil)

-Trimipramine (Surmontil)

-Nortriptyline (Pamelor)

-Protriptyline (Vivactil)

CI: Use with caution for patients with Bipolar disorder - May cause switch to manic behavior

DI: Drugs that induce or inhibit CYP450 enzymes 🍊

Consider: Narrow therapeutic index

-MOA is similar to SNRIs. Main difference is worse side effects for TCAs because they also affect several other receptor types

-Takes 2 weeks or longer to start working

-Taper off to avoid discontinuation syndrome and cholinergic rebound effects

-Well-absorbed upon oral admin, but have variable first-pass metabolism in liver, so low and inconsistent bioavailability

What drug class does this medication fall under?

Imipramine (Tofranil)

Tricyclic Antidepressant

MOA of Imipramine (Tofranil)?

-Inhibit norepi and serotonin reuptake

-Also block serotonergic, alpha-adrenergic, muscarinic, and histaminic receptors

Use of Imipramine (Tofranil)?

Bed-Wetting

What drug class does this medication fall under?

Amitriptyline (Elavil)

Tricyclic Antidepressant

MOA of Amitriptyline (Elavil)?

-Inhibit norepi and serotonin reuptake

-Also block serotonergic, alpha-adrenergic, muscarinic, and histaminic receptors

Uses of Amitriptyline (Elavil)?

Prevent migraine headache and treat chronic pain syndromes (e.g. neuropathic pain)

What drug class does this medication fall under?

Doxepin (Silenor)

Tricyclic Antideprssants (TCAs)

MOA of Doxepin (Silenor)?

-Inhibit norepi and serotonin reuptake

-Also block serotonergic, alpha-adrenergic, muscarinic, and histaminic receptors

Use of Doxepin (Silenor)?

Insomnia

What drug class do these medications fall under?

Desipramine (Norpramin) & Maprotiline (Ludiomil)

Tricyclic Antidepressants (TCAs)

MOA of Desipramine (Norpramin) & Maprotiline (Ludiomil)?

-Relatively selective inhibitors of norepi

-Also block serotonergic, alpha-adrenergic, muscarinic, and histaminic receptors

What drug class does this medication fall under?

Amoxapine (Asendin)

Tricyclic Antidepressants (TCAs)

MOA of Amoxapine (Asendin)?

Blocks the same receptors as the other TCAs plus 5-HT2 and dopamine D2 receptors

What happens when TCAs are combined with MAO inhibitors?

Mutual enhancement, leading to:

-Hypertension

-Hyperpyrexia

-Convulsions

-Coma

How do TCAs interact with direct-acting adrenergic drugs?

They potentiate the effects of biogenic amine drugs by preventing their removal from the synaptic cleft

Further explained:

-TCAs (tricyclic antidepressants) block the reuptake of certain chemicals in the brain and body, like norepinephrine and serotonin, so these chemicals stick around longer in the synapse (the space between nerve cells)

-Direct-acting adrenergic drugs are drugs that directly stimulate receptors for these chemicals (like norepinephrine).

-When you give both together, the TCAs increase the effect of the adrenergic drug because the natural chemical isn’t being cleared away as quickly

How do TCAs interact with ethanol or other CNS depressants?

They decrease their effects, causing toxic sedation

How do TCAs interact with indirect-acting adrenergic drugs?

They decrease their effects by preventing the drugs from reaching their intracellular sites of action

What drug class do these medications fall under?

-Phenelzine (Nardil)

-Tranylcypromine (Parnate)

-Isocarboxazid (Marplan)

Monoaminase Oxidase Inhbitors

MOA of:

-Phenelzine (Nardil)

-Tranylcypromine (Parnate)

-Isocarboxazid (Marplan)

-Irreversible inactivation of MAOs, resulitn in increased norepi, serotonin, and dopamine

-Also inhibit MAO in the liver and gut (therefore, lots of drug and food interactions)

Uses of:

-Phenelzine (Nardil)

-Tranylcypromine (Parnate)

-Isocarboxazid (Marplan)

Last line for depression

SE of:

-Phenelzine (Nardil)

-Tranylcypromine (Parnate)

-Isocarboxazid (Marplan)

Real bad!!

Avoid tyramine because MAOIs keep you from degrading it, and tyramine causes the release of catecholamines, resulting in hypertensive crisis:

-Occipital headache

-Stiff neck

-Tachycardia

-Nausea

-HTN

-Cardiac arrhythmias

-Seizures

-Stroke

Selegiline and Tranylcypromine have amphetamine-like stimulant effect. May produce:

-Agitation

-Insomnia

CI + DI + Considerations for:

-Phenelzine (Nardil)

-Tranylcypromine (Parnate)

-Isocarboxazid (Marplan)

DI: Do not coadminister with SSRIs d/t risk of serotonin syndrome

-Combo with sympathomimetics (eg pseudoephedrine) causes significant HTN

Consider: Delay two weeks after stopping MAOIs before starting another antidepressant, because you need time for the MAO to regenerate

-Also delay 2 wks if starting MAOI after SSRI - or 6 wks if fluoxetine bc of the long half life

What drug class does this medication fall under?

Selegiline (Eldeprenyl)

Monoamine Oxidase Inhibitors

MOA of Selegiline (Eldeprenyl)?

More selective for MAO-B at lower doses, but nonselective at higher doses (both MAO-A and B)

Uses of Selegiline (Eldeprenyl)?

Also used for the treatment of Parkinson’s disease

(Think Eldeprenyl -> elder -> Parkinson’s patients are elderly)

CI + DI + Considerations for Selegiline (Eldeprenyl)?

-The only antidepressant available in transdermal

-Produces less inhibition of gut and hepatic MAO because avoids first-pass metabolism

What is monoamine oxidase (MAO) and where is it found?

MAO is a mitochondrial enzyme found in nerves and other tissues such as the gut and liver

What is the primary function of MAO in neurons?

Acts as a "safety valve" by oxidatively deaminating and inactivating excess neurotransmitters (e.g., norepinephrine, dopamine, serotonin) that leak from synaptic vesicles at rest

What neurotransmitters does MAO-A primarily metabolize?

-Serotonin

-Norepinephrine

-Dopamine

What neurotransmitter does MAO-B primarily metabolize?

Dopamine

What drug class do these medications fall under?

-Aripriprazole (Abilify)

-Brexpiprazole (Rexulti)

-Quetiapine (Seroquel)

Second Generation Antipsychotics

MOA of:

-Aripriprazole (Abilify)

-Brexpiprazole (Rexulti)

-Quetiapine (Seroquel)

Block serotonin (5-HT2) and Dopamine (D2) receptors

Uses of:

-Aripriprazole (Abilify)

-Brexpiprazole (Rexulti)

-Quetiapine (Seroquel)

Adjunct therapy for depression