Norepinephrine Pathways:

Name the nucleus of the brain that uses NE, its location, and 4 locations to which its neurons project

Nucleus = Locus Coeruleus, in the brainstem

Projects to:

Frontal

Limbic

Cerebellum 

Brainstem

Serotonin Pathways

Name the nucleus of the brain that uses serotonin, and 4locations to which its neurons project

Raphe Nucleus

5HT neurons project to:

Frontal

Limbic

Brainstem

Hypothalamus

If Raphael took LSD, he'd become FLaBuH-gasted!

Tyramine - effect on CNS?

Describe the clinical effects of tyramine toxicity

Found in Cheese, alcohol, MSG, cured meat, fava beans, liver

Increases the release of NE

When a person is on an MAOI and also consumes tyramine containing foods/drinks, there is NE overload which can cause hypertensive crisis

Clinical effects:

Hypertension

occipital headache

palpitations

nausea/vomiting

In severe cases:  alteration of consiousness, hyperpyrexia, cerebral hemorrhage, death!

Second line treatment, due to side effect profile

potentially lethal food and drug interactions

Still used for refractory depression

Tyramine (previously discussed)

OTC cold meds can also cause hypertensive crisis

Don't take SSRI's if you're already on a Tricyclic antidepressant

Analgesic narcotics like meperidine can cause hypertension, hyperpyrexia, and coma

Must allow 2 weeks after discontinuation of MAOI before starting a prohibitied medication

1. Significant Overdose Potential due to narrow therapeutic window

- 1 week of meds taken at once can be fatal; this is a huge problem for dosing patients that are depressed/potentially suicidal

2. Cardiovascular Toxicity (potential for fatal cardiac arrythmia)

3. Side effects:

anti-histaminergic (weight gain, drowsiness)

anti-cholinergic (constipation, blurred vision, dry mouth, drowsiness again)

anti-alpha adrenergic (dizziness, decreased BP)

TCAs - amitriptyline (Elavil)

3 indications for use

For pain,

Headache,

insomnia

Name 3 specific TCA's worth knowing

How long does it take for the TCA's to have therapeutic effects?

Amitriptyline (Elavil)

Clomipramine (Anafranil)

Nortriptyline (Pamelor)

Therapeutic effect begins only after 3-4 weeks of administration

Tertiary amines have greater alpha, histamine 1, and muscarinic blockade

Secondary amines are newer, have fewer side effects, are less sedating, and hold less overdose risk

TCA's: clomipramine 

specific affect on CNS, and indication

sold as Anafranil

its highly serotonergic, used to treat OCD

TCA's: nortriptyline

What is it and how does it improve upon another TCA?

aka Pamelor

its demethylated amitriptyline, and it causes the least orthostasis of the TCA's

SSRI's

How are they better than TCA's?

It's a much less 'dirty' drug, less unwanted actions

Much less side effects

Much safer, less toxicity/OD risks

Serotonin vs Norepinephrine

Therapeutic Effects and Side Effects

Overall, Serotonin is more of a calming agent, NE more of a stimulating agent

Serotonin - therapeutically acts on mood, anxiety, and obsessions

NE - acts on mood, attention, and improves low energy states

Serotonin side effects - sexual dysfunction, GI, Insomnia, Akasthesia

NE side effects - Tremor, elevated BP/HR, urinary retention

NE and DA Reuptake Blockers 

Give the name of the specific drug

Indications (4)

Adverse effects/what patients should not be on this drug?

Bupropion (Wellbutrin, Zyban)

Indications:

Depression

Dysthymia

Smoking cessation (Zyban and Wellbutrin are exactly the same, Zyban is just remarked as an anti-smoking drug)

ADHD

Adverse:

Increased risk of seizures in bulemics (don't give to anyone with a history of eating disorder!)

Also increased risk for seizure in patients w/ head injury, or going thru alcohol withdrawl

NRI's

Indications in US vs. in Europe

4 Adverse Affects

To treat ADHD in the US (used to treat depression in Europe)

Adverse:

Tremor

Agitation

Hypertension

Tachycardia

NaSSA

What does it stand for, and what is it?

Specific NaSSA drug?

3 Indications for use?

What are all the reason's its awesome, and what is 1 reason its not awesome?

Noradrenergic and Specific Serotonergic Antidepressant

Its a NE/5HT agonist

Classic NaSSA = mirtazapine, and alpha 2 antagonist

INdications:

Major Depression

Anxiety & Insomnia

Sedation or weight gain can actually be healthy (increased appetite and sleep can be good in old depressed frail people)

Benefits:  Anti-anxiety (anti-agitation), sleep-restoring, antidepressant obviously, and no associated nausea/GI problems/sexual problems!

Weight gain sucks if you don't want it

SARIs

What is it, and how is it different from an SSRI?

Indications

Adverse effects

Serotonin Antagonist & Reuptake Inhibitors

Its an SSRI that also blocks the 5HT2A-R (overall, its less activating and more sedating than the SSRI's)

Used to treat depression, anxiety, insomnia

AND no associated weight gain OR sexual dysfunction!

Adverse:  Sedation, orthostatic hypotention, priapism (rare)

Yet its rarely used, not 1st line

Theory about why Antidepressants take weeks to work

(monoamine hypothesis)