Term
| What are the Norepinephrine and Serotonin pathways in the brain |
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Definition
Serotonin:Raphe Nucleus to Spinal cord(pain, visceral, motor) and Forebrain(mood, cognition, neuroendocrine)
Norepinephrine: Locus Ceruleus to Spinal cord(pain) and Forebrain(mood, cognition, arousal) |
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Term
| How is serotonin and norepinephrine released from neurons |
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Definition
| Through varicosities into projecting areas |
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Term
| Describe the synthesis of Norepinephrine |
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Definition
| Tyrosine(tyrosine hydroxylase)->DOPA(AAADC)->Dopamine(Dopamine B-hydroxylase)-> Norepinephrine |
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Term
| What is the mechanism of Reserpin |
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Definition
| Inhibits Norepinephrine transport into vesicles causing cytoplasmic degradation by MAO-A on mitochondrial membrane |
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Term
| What is the feedback inhibition for Norepinephrine and Serotonin releasing neurons |
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Definition
Norepi bind Alpha-2 adrenergics decreasing cAMP in both Noradrenergic and Serotonergic neurons
Serotonin binds 5HT1A(Somatodendritic) and 5HT1B/D(Presynaptically) decreasing cAMP to serotonergic neurons, also 5HT2A decreases norepinephrine release |
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Term
| What are the major hypotheses of depression |
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Definition
Monamine Hypothesis
Neurotrophic hypothesis: Low BDNF
Neuroendocrine: Increased cortisol, thyroid defieciency, sex hormone defeciency |
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Term
| What are the transporters used to uptake serotonin and norepinephrine from the synapse and also into the vesicle |
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Definition
NET: Noreepi selective(cocaine blocks)
Serotonin Selective Reuptake Transporter
VMAT: Serotonin and Norepi into vesicles(blocked by reserpine) |
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Term
| What are the major SSRI's |
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Definition
Fluoxetine(prozac)
Sertraline(zoloft)
Citalopram(celexa)
Fluvoxamine(luvox)
Paroxetine(paxil) |
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Term
| What is the cause of therapeudic lag in SSRI treatment |
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Definition
Presynaptic: overactivity of 5HT1A decreases as receptors desensitize
Postsynaptic: Increased activation of 5HT2 causes desensitization that is eventually overcome |
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Term
| What are the uses of SSRI's |
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Definition
Depression
Anxiety
Panic
OCD
PTSD
PMDD |
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Term
| What SSRI has the longest half life and how does this effect its use |
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Definition
Active metabolic Norfluoxetine has a 8 day half life
Switching from Fluoxetine requires a 4 wk interval before switching to a MAO-I |
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Term
| What are the Major Side effects of SSRI's and how are they caused? |
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Definition
Nausea(5HT3)Area Postrema and afferent vagus
Diarrhea(5HT4)
Sex Dysfunction(5HT2A) Block orgasm and decrease doapmine
Anxiety, Agitation, Insomnia(5HT2A)
Bleeding if with NSAIDs or Aspirin(5HT2)
Serotonin Syndrome: CV collapse, Flushing, Hyperthermia, Muscle rigidity
Sweating
Suicide
Tingling, Numbing, Dizzy: Discontinuation of Zoloft or Paxil |
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Term
| What Antidepressants are metabolized by the p450s and which are potent inhibitors |
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Definition
Trazodone: CYP3A4
Fluvoxamine: CYP3A4
Fluoxetine: CYP2D6 (potent)
Paroxetine: CYP2D6(potent)
Duloxetine: CYP2D6(moderate)
Tricyclics: CYP2D6 |
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Term
| What are the uses of NSRI |
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Definition
Depression
Anxiety
Stress Incontinence
Vasomotor of Menopause
Pain of Diabetic neuropathy |
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Term
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Definition
Duloxetine(Cymbalta)
Venlafaxine(Effexor) |
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Term
| What is desvenlafaxine(Pristiq) |
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Definition
| Active metabolite of venlafaxine |
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Term
| Which antidepressant has a high protein binding capacity |
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Definition
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Term
| What are the adverse effects of SNRIs? |
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Definition
Serotonin Syndrome
Discontinuation Syndrome
Insomnia, Agitation, Anxiety
Increase BP, HR |
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Term
| Which tricyclic antidepressants have the most anti-cholinergic effects |
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Definition
| Tertiary Amines: Amitryptyline, Imipramine, Clomipramine |
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Term
| What are the major tricyclic anti-depressants |
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Definition
Nortriptyline
Amitriptyline(Tertiary amine)
Desipramine
Imipramine(tertiary amine)
Clomipramine |
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Term
| What are the uses of tricyclic anti-depressants |
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Definition
Resistant Depression
Pain at low dose
Imipramine(Nocturnal Enuresis)
Clomipramine(OCD) |
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Term
| Adverse Effects of Tricyclic Anti-depressants |
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Definition
Serotonin Syndrome
Discontinuation Syndrome
Sex Dysfunction(Clomipramine)
Alpha Block: Postural Hypotension
Anticholinergic
Antihistamine: Weight Gain and Sedation
Toxicity: Coma, Covulsions, Cardiotoxicity, Confusion and Hallucinations(elderly) |
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Term
| What is the mechanism and use of Trazodone |
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Definition
5HT2A Antagonist
Postsynaptic 5HT1A 5HT2 agonists
SSRI
Low dose: Only antihistamine, anti-alphaadrenergic
Use: Hypnotic |
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Term
| What is the mechanism of tricyclic antidepressant toxicity, how would you recognize it and how is it treated? |
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Definition
Sodium channel blockade
Signs: Coma, Convulsions, Cardiotoxicity
Confusion and Hallucinations in Elderly
Tx: Sodium Bicarb |
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Term
| What is the mechanism and use of Mirtazapine |
|
Definition
Block: 5HT2A/2C, 5HT3
Presynaptic alpha 2
Use: Melancholic Depression or Depressed with sleep disturbances |
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Term
| Adverse effects of Mirtazipine |
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Definition
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Term
| What is the uses of Bupropion |
|
Definition
Smoking cessation
Atypical Depression |
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Term
| What drug is contraindicated with bupropion? |
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Definition
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Term
| What are the major MAO-I's and which is MAO-B selective |
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Definition
Phenelizine
Tranylcypromine
Isocarboxazid
Selegiline-MAO-B selective |
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Term
| What are the uses of MAO-I's |
|
Definition
Resistant Depression
Anxiety
Social Anxiety
Panic Disorder |
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Term
| What are the adverse effects of MAO-I's |
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Definition
Serotonin Syndrome
Tyramine Foods-> Norepi-> Increased BP
CNS Stimulation
Postural Hypotension(Octopamine or dopamine)
Weight Gain |
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Term
| What anti-depressant should be used in a patient with concerns about daytime tiredness? |
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Definition
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Term
| What drug is used in bed Wetting |
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Definition
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Term
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Definition
Reversible Inhibitor of Monoamine Oxidase Type A
MAO-A inhibitors are more effective as anti-depressants |
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Term
| What is the mechanism of the CNS stimulation and the postural hypotension of MAO-Is |
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Definition
CNS Stimulation: resembles Amphetamine
Postural Hypotension: Octopamine metabolite is a false neurotransmitter |
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Term
| What side effect is specific to SSRI mecahnism? Which trycyclic displays the most SSRI action and which tricyclic displays the most Norepi reuptake block |
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Definition
SSRI: sex dysfunction(Clomipramine)
Norepi reuptake Block: Desipramine
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