Miscellaneous Quiz / Anti-depressants

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Can you name the Anti-depressants?

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Fluoxetine class
MOA: Potent 5-HT reuptake blockade, acts like SSRI at low doses, NE & DA as well at higher doses.
Use: Major depression, rarely used. Good for depression in psychotic pts.
SE: Hypotension, insomnia. OD --> agitation, delirium, seizures, shock, hyperthermia.
SE: Lowers seizure threshold, akathisia, parkinsonism, amenorrhea, tardive dyskinesia. OD --> seizures & severe neurotoxicity.
P-kinetics: Well absorbed, long t1/2s, significant 1st pass metabolism, highly lipid soluble & PRO binding. Active metabolites: Imipramine -> desipramine; Amitriptyline -> nortrypt
MOA: NET > SERT inhibition. Some DA receptor antagonism.
Duloxetine class
Phenelzine class
SE: Lacks many SE, higher acceptance. Sexual dysfunction, decreased libido, nausea, GI s/s. Low liklihood of fatalities from OD.
Effects: Presynaptic release of catecholamines but no effect on 5-HT
MOA: Irreversible, selective MAO-B inhibition (low dose)
Interactions: May potetiate the action of several other rxs (opiates, ephedrine, adrenaline
Use: Major depression, chronic pain, fibromyalgia, perimenopausal s/s. Venlazfaxine & Duloxetine also used for anxiety, generalized anxiety, social phobia.
Paroxetine class
SE: Anticholinergic, α-blocking effects, sedation, weight gain.
MOA: NET > SERT inhibition
Maprotiline class
P-kinetics: Well absorbed, extensive 1st pass metabolism. MAO inhibition persists even after plasma levels become undetectable (slow elimination).
P-kinetics: Conjugated --> not oxidative metabolism, 45% excreted in urine unchanged
Use: Major depression, sedation
Effects: Like SNRIs plus significant blockade of ANS & histamine receptors
Amitriptyline class
Interactions: Some CYP2D6 inhibition
Effects: Resemble TCAs.
Desvenlafaxine class
SE: Modest α- and H1-receptor blockade. Unpredictable efficacy.
Isocarboxacid class
P-kinetics: Drugs chemically unrelated. Venlafaxine & duloxetine have extensive hepatic metab. Active metabolites: Venlafexine -> desvenlafaxine (both have lowest PRO bind ~ 30%).
Effects: Transdermal absorption achieves levels that inhibit MAO-A. Also available SL.
HintAnswer
Amoxapine class
Sertraline class
Txing OD: Lidocaine, propanolol, & phenytoin; Na bicarb (relief of conduction block); physostigmine (small boluses to awaken pts).
Milnacipran class
MOA: Increased NE and DA activity
Effects: Forms a metabolite (m-cpp) that blocks 5-HT2A receptors.
Interactions: Other indirect sympathomimetics -- serotonin syndrome w/ serotoneric agents, meperidine. Interaction w/ SSRIs.
SE: Antihistamine --> sedation, weight gain, few adverse sexual side effects
Use: Major depression, smoking cessation
P-kinetics: Extensive hepatic metabolism, high 1st pass. Very efficacious but poor compliance.
MOA: Highly selective blockade of serotonin transporter (SERT). Little effect on NE transporter (NET)
Use: Major depression, anxiety, panic disorder, PTSD. Fluoxetine; perimenopausal vasomotor symptoms, bulimia, OCD. Usually first-choice despite costs
SE: OD --> seizures, arrhythmias, coma, shock, resp depression, agitation (note suicide risk - prescribe few pills, no refills).
Citalopram class
Trazodone class
P-kinetics: Rapidly absorbed, extensive hepatic metabolism, high PRO binding, short t1/2 (2-6 hrs), Active metabolites also exhibity 5-HT2 antagonism
P-kinetics: Well absorbed, peak plasma 4-8 hrs, t1/2 7-9 days (low risk of withdrawal s/s). Fluoxetine -> norfluoxetine (active, longest t1/2 180 hrs)
MOA: Blockade of MAO-A and MAO-B, nonselective
SE: Anticholinergic, sedation, HTN. Withdrawal symptoms from receptor downregulation, so withdraw slowly
MOA: Blockade of MAO-A and MAO-B
Fluvoxamine class
Use: Major depression, rarely used
Doxepin class
P-kinetics: 3 active metabolites, biphasic elimination (1 hr/14 hrs).
MAOI elimination 2-3 weeks
Trimipramine class
Venlafaxine class
Imipramine class
SE: Dose-dependent seizures, cardiotoxicity (OD)
MAOI elimination 7 days
HintAnswer
Dangerous interaction w/ MAOIs --> serotonin syndrome (hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status & VS)
Interactions: Hypertensive crisis w/ tyramine [MAO-A oxidation of NE, 5-HT, tyramine allows accumulation of tyramine (avoid aged cheese, red wine, liver)]
Clomipramine class
Tranylcypromine class
MOA: Moderately selective blockade of NET & SERT
Tricyclic w/ high sedation (additive w/ other sedation drugs, ETOH); antimuscarinic: blurred vision, constipation, confusion
Interactions: Inhibits CYP34A
Escitalopram class
MOA: Mixed/variable NET/SERT block. 'Dirty rxs' varying selectivity (NMDA antag; α2 agonist; α1 antag; adenosine reuptake block [alter opiod binding]; inhibit Na, K, Ca channels
Use: Major depression unresponsive to other rxs. Helpful in pts w/ atypical deprssion: attendant anxiety, phobic features, hypocondriasis.
Effects: Acute increase of serotonergic synaptic activity & slower changes in several signaling pathways & neurotrophic activity
Significant interactions w/ other antidepressants. Some CYP inhibition (fluoxetine, fluvoxamine, paroxetine).
Use: Major depression (not responsive to other rx), chronic pain disorders, incontinence, OCD (clomipramine), ADHD (imipramine & desipramine), enuresis
MOA: Increased release of NE, 5-HT
Proptriptyline class
Selegiline class
Desipramine class
Mirtazapine class
SE: Fewer adverse sexual effects
Nortriptyline class
Interactions: Interactions with CYP inhibitors & inducers
P-kinetics: At high doses may be more efficacious than SSRIs
Use: Major depression, sedation, hypnosis (trazadone)
P-kinetics: Variable bioavailability, half-life; active metabolite (7-hydroxyamoxapine) potent D2 blocker (antipsychotic)
Effects: Acute increase in serotonergic & adrenergic activity. Otherwise like SSRIs
Bupropion class
SE: Lowers seizure threshold
Nefazodone class

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