Slattery: Mood Disorders

Question 1

What is euthymia

Answer 1

normal, non-depressed, reasonably positive mood.

Question 2

Describe the monoamine hypothesis

Answer 2

depression is associated with changes in serotonin or NE signaling (or both) with significant downstream effects.

Question 3

Neurotrophic hypothesis.

Answer 3

nerve growth factors such as brain-derived neurotrophic factor (BDNF) are critical in the regulation of neural plasticity, resilience, and neurogenesis.
DEPRESSION: loss of neurotrophic support.
Effective therapies: Increase neurogenesis and synaptic connectivity in cortical areas such as hippocampus (increase BDNF)
A mutated BDNF gene is associated with altered anxiety and depressive behavior.

Question 4

What are the two Tricyclic Antidepressants (TCA’s) we need to know?

Answer 4

Desipramine and Imipramine.

Question 5

Describe the MOA of Desipramine.

Answer 5

Blocks re-uptake of NE.

Question 6

Describe MOA of Imipramine.

Answer 6

Blocks re-uptake of NE and 5-HT.

Question 7

Which neuron are Desipramine and Imipramine working on?

Answer 7

presynaptic

Question 8

What effect do TCA’s have on normal subjects?

Answer 8

no change in mood, sleepiness, antimuscarinic effects.

Question 9

Why aren’t TCA’s used very often anymore?

Answer 9

Because lethal if you overdose even *5. so we avoid giving patients access to many pills: usually give 1 week dose at a time.

Question 10

What metabolizes TCA’s? And if you gave a TCA with Fluoxetine, what could happen?

Answer 10

CYP2D6. Fluoxetine inhibits CYP2D6 so you could get TCA toxicity.

Question 11

Name a Monoamine Oxidase Inhibitor and describe how it works.

Answer 11

Phenelzine. It irreversibly blocks oxidative deamination of monoamines (leading to increase of NE, 5-HT, and DA).

Question 12

What must be avoided in a patient taking Phenelzine?

Answer 12

Tyramine

Question 13

Why can’t you start an SSRI within 14 days of using Phenelzine?

Answer 13

Patient at risk for Serotonin syndrome. Over activation of 5-HT-2A receptor. Hyperthermia, muscle rigidity, tremors, confusion….may cause coma or death.

Question 14

Name 3 SSRI’s.

Answer 14

Fluoxetine. Sertraline. Escitalopram.

Question 15

What is the “black box warning” on Fluoxetine?

Answer 15

Worsening symptoms/suicide attempts.

Question 16

What receptor does Serotonin bind that leads to a clinical improvement of mood?

Answer 16

5-HT-2A.

Question 17

How does Venlafaxine work?

Answer 17

It is an SNRI (serotonin-norepinephrine re-uptake inhibitor). It does not affect adrenergic, histaminergic, or cholinergic receptors (TCA’s do!)

Question 18

When is Venlafaxine contraindicated?

Answer 18

In patients who are on MAOIs and vice versa.

Question 19

What is the only antidepressant that has improved efficacy with an increased dose?

Answer 19

Venlafaxine

Question 20

Describe the MOA of Mirtazapine.

Answer 20

Blocks presynaptic alpha2 receptors on adrenergic and serotonergic neurons. So you get an Increase in NE and 5 HT!

Question 21

What is the difference between an auto receptor and a heteroreceptor?

Answer 21

Autoreceptor: triggered by their own NT. Ex. Serotonin binds auto receptor to inhibit the release of Serotonin.

Heteroreceptor: a NT from a neighboring synapse is acting on an alpha2 receptor to inhibit 5-HT release. Ex. NE binds heteroreceptor to inhibit 5-HT release.

Question 22

What is the standard treatment of Bipolar disorder?

Answer 22

Lithium Carbonate

Question 23

Going from low to medium to high doses, what monoamines does Venlafaxine inhibit the re-uptake of?

Answer 23

Low: Serotonin
Medium: NE
High: DA

Question 24

How does an alpha2 receptor work?

Answer 24

A NT binds alpha2 to inhibit NT release.

Question 25

What is the effect of Lithium carbonate in normal subjects?

Answer 25

None

Question 26

If someone is taking a diuretic with Lithium Carbonate, how do you need to adjust their dose?

Answer 26

Diruetics will reduce the renal clearance of Lithium by 25 % so more is reabsorbed.

Question 27

What are the toxic effects of lithium?

Answer 27

Impaired consciousness and coma. Tremor, muscle rigidity, hyperactive reflexes.

Question 28

Describe the tolerance to Lithium.

Answer 28

Tolerance acuired to most symptoms but not hand tremor or excessive urination and thirst.

Question 29

Why do people on Lithium have excessive urination and thirst?

Answer 29

Blocks the release of ADH.

Question 30

Why can't a patient with bipolar disorder be put on an SSRI monotherapy?

Answer 30

May cause rapid onset of mania. They need a prophylactic mood stabilizer to prevent this.

Question 31

What drug is superior to lithium in patients with rapid cycling bipolar disorder?

Answer 31

Valproic acid

Question 32

What happens if you give someone on an MAOI some aged cheese?

Answer 32

Could go into HYPERTENSIVE CRISIS

Question 33

Why can Tyramine induce hypertensive crisis when consumed in a patient on an MAOI?

Answer 33

Tyramine accumulates in adrenergic nerve endings and induces norepinephrine and epinephrine release. These catecholamines stimulate postsynaptic receptors in the periphery, increasing blood pressure to dangerous levels.

Question 34

How is Tyramine metabolized?

Answer 34

Hepatic MAO

Question 35

What are two uses of Carbamazepine we have learned?

Answer 35

Anticonvulsant: Bipolar disorder, seizures

Question 36

Why are the newer antidepressants better than the older ones?

Answer 36

The older ones weren't precise as they were "shotgun drugs" . The newer ones exert clinical effects by binding the 5-HT 2A receptor so they are more precise.