Slattery: Mood Disorders Flashcards
What is euthymia
normal, non-depressed, reasonably positive mood.
Describe the monoamine hypothesis
depression is associated with changes in serotonin or NE signaling (or both) with significant downstream effects.
Neurotrophic hypothesis.
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.
What are the two Tricyclic Antidepressants (TCA’s) we need to know?
Desipramine and Imipramine.
Describe the MOA of Desipramine.
Blocks re-uptake of NE.
Describe MOA of Imipramine.
Blocks re-uptake of NE and 5-HT.
Which neuron are Desipramine and Imipramine working on?
presynaptic
What effect do TCA’s have on normal subjects?
no change in mood, sleepiness, antimuscarinic effects.
Why aren’t TCA’s used very often anymore?
Because lethal if you overdose even *5. so we avoid giving patients access to many pills: usually give 1 week dose at a time.
What metabolizes TCA’s? And if you gave a TCA with Fluoxetine, what could happen?
CYP2D6. Fluoxetine inhibits CYP2D6 so you could get TCA toxicity.
Name a Monoamine Oxidase Inhibitor and describe how it works.
Phenelzine. It irreversibly blocks oxidative deamination of monoamines (leading to increase of NE, 5-HT, and DA).
What must be avoided in a patient taking Phenelzine?
Tyramine
Why can’t you start an SSRI within 14 days of using Phenelzine?
Patient at risk for Serotonin syndrome. Over activation of 5-HT-2A receptor. Hyperthermia, muscle rigidity, tremors, confusion….may cause coma or death.
Name 3 SSRI’s.
Fluoxetine. Sertraline. Escitalopram.
What is the “black box warning” on Fluoxetine?
Worsening symptoms/suicide attempts.
What receptor does Serotonin bind that leads to a clinical improvement of mood?
5-HT-2A.
How does Venlafaxine work?
It is an SNRI (serotonin-norepinephrine re-uptake inhibitor). It does not affect adrenergic, histaminergic, or cholinergic receptors (TCA’s do!)
When is Venlafaxine contraindicated?
In patients who are on MAOIs and vice versa.
What is the only antidepressant that has improved efficacy with an increased dose?
Venlafaxine
Describe the MOA of Mirtazapine.
Blocks presynaptic alpha2 receptors on adrenergic and serotonergic neurons. So you get an Increase in NE and 5 HT!
What is the difference between an auto receptor and a heteroreceptor?
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.
What is the standard treatment of Bipolar disorder?
Lithium Carbonate
Going from low to medium to high doses, what monoamines does Venlafaxine inhibit the re-uptake of?
Low: Serotonin
Medium: NE
High: DA
How does an alpha2 receptor work?
A NT binds alpha2 to inhibit NT release.
What is the effect of Lithium carbonate in normal subjects?
None
If someone is taking a diuretic with Lithium Carbonate, how do you need to adjust their dose?
Diruetics will reduce the renal clearance of Lithium by 25 % so more is reabsorbed.
What are the toxic effects of lithium?
Impaired consciousness and coma. Tremor, muscle rigidity, hyperactive reflexes.
Describe the tolerance to Lithium.
Tolerance acuired to most symptoms but not hand tremor or excessive urination and thirst.
Why do people on Lithium have excessive urination and thirst?
Blocks the release of ADH.
Why can’t a patient with bipolar disorder be put on an SSRI monotherapy?
May cause rapid onset of mania. They need a prophylactic mood stabilizer to prevent this.
What drug is superior to lithium in patients with rapid cycling bipolar disorder?
Valproic acid
What happens if you give someone on an MAOI some aged cheese?
Could go into HYPERTENSIVE CRISIS
Why can Tyramine induce hypertensive crisis when consumed in a patient on an MAOI?
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.
How is Tyramine metabolized?
Hepatic MAO
What are two uses of Carbamazepine we have learned?
Anticonvulsant: Bipolar disorder, seizures
Why are the newer antidepressants better than the older ones?
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.
