Mood disorder drugs Flashcards
What are the mechanism of moo disorders?
- Amine hypothesis
2. Neurotropic hypothesis
What is the amine hypothesis?
Lack of necessary NT’s for normal mood
- NE, 5ht, and DA
- mania if there excess
Why is the amine hypothesis incomplete?
Mismatch between time course
Postmortum studies show no decrease in amines
Most antidepressants down regulate amine Receptors
What is the neurotropic hypothesis?
Depression is associated with loss of neurotrophic support
What are the factors involved with neurotrophic support?
Nerve growth factors like
- Brain-derived neurotrophic factos
- which are important for neural plasticity, resilience and neurogenesis
Is the neurotrophic theory accurate if so why?
Yes
- antidepressants increase BDNF
- effective treatment increase neurogenesis and synaptic connectivity
- mutations in BDNF lead to increased anxiety and depressive behavior
what are the 2 drugs classes to treat mood disorders?
Antidepressants and mood stabilizers
What are the drugs involved with antidepressants?
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- Selective serotonin reuptake inhibitors
- dual- mechanisms drugs
What are the drugs involved with mood stabilizers?
- Lithium carbonate
- Anticonvulsants
- Atypical antipsychotics
what is the mechanism of action of TCA’s?
Block reuptake of of NE and or 5HT
- Desipramine= NE selctive
- Imipramine = NE and 5HT
What are the effects of TCA’s?
Elevation in mood (2-3 delay)
Sleepiness and light headedness
Antimuscarinic effects
- dry mouth, blurred vision, constipation and urinary retention
What are the adverse effects of TCA’s?
Orthostatic HoTN
Weight gain
Tachy and arrhythmias
Antimuscarinic effects- more severe in old people
What does blocking of histamine receptors cause?
weight gains
What does blocking of alpha-1 receptor cause?
lightheadedness and decreased BP
What does blocking NA+ channels cause?
Arrhythmias, cardiac arrest and seizures
When would you use TCA’s?
After first line drugs like SSRI’s and SNRI’s arent working
- of note they are lethal with overdose
What are some of the pharmakokinetics of TCA’s?
long half life
5-10 TI which is low
metabolized by CRP2D6
What should you give if you suspect TCA toxicity?
FLuoxetine (Prozac)
- which inhibits CYR2D6 (potent)
what is the mechanism of action of MOA?
Irreversibly blocks MAO-a (NE and 5HT) Blocks MAO-b (DA) - leads to increased mood (2-3) later - NT change occurs without 24-48hrs - low TI
Why should you wait 14 days after discontinuation of MAO to start SSRI’s?
To prevent serotonin syndrome
What is serotonin syndrome?
Too much serotonin which leads too:
- hyperthemia
- muscle rigidity
- tremors
- autonomic instability
- confusion
- irritability and agitation
What doe MAOI’s potentiate?
sympathomimetic amines
- most specifically Tyramine which is metabolized by MAO’s
- systemic Tryamine leads to release of NE and EPi (adrenergic)
- leads to dangerous levels of HTN
Name some foods rich in Tyramine?
Beer, wine, aged cheese, broad beans, yogurt, avocados, shream, bananas
- cold meds like ephedrine and pseudoephedine
What are some SSRI’s?
Fluoxetine Sertraline Paroxetine Fluvoxamine Citalopram Escitalopram
