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
What is fluoxetine?
Prozac
What is Sertraline?
Zoloft
What is Paraxetine?
Paxil
What is Fluvoxamine?
Luvox
What is citalopram?
Celexa
What is escitalopram?
Lexapro
How many primary subtpes of serotonin receptors are there?
7- which have sever subtypes
What is 5HT3?
May mediate Gi and sexual adverse effects
What is 5HT 2c?
May mediate agitation and restlessness
WHat is 5HT2a?
May be involved in anxiety and mood
What are some adverse effects of SSRI’s?
N, D, WL, sexual dysfunction, anxiety, nervousness, insomnia
- Suicide- black box warning
- should not be taken alone in bipolar disorder
What are some atypical (dual/mixed) action antidepressants?
Venlafaxine
Duloxetine- Cymbalta
Mirtaxepine
Buproprion
What is Venlafaxine and what is the mechanism of action of it?
Effexor
It is a NE and 5HT reuptake inhibitor
What drug that isnt a TCA has the same mechanism?
Effexor
- doesnt effect adrenergic, histamine or cholinergic receptors
- dont give to patients on MAOI’s
What happens to the NT’s affects by dosing of Effexor?
Changes which NT it actions
Low to high dosing
- 5HT–> NE–>DA
What is desvenlafaxine (pristiq)?
Metabolite of Effexor
- more balanced Ne/5HT reuptake inhibition
What is Mirtazapine?
Remeron
It affects both adrenergic and and serotonergic neurons
What is Buproprion?
Wellbutrin
- Enhances both NE and DA NT (moderate inhibition of reuptake and increased release)
- also used for smoking cessation
- AE: agitation, anorexia and insomnia
what is the mechanism of action of Ketamine?
NMDA receptor antagonist
- nightmares and hallucination
what is the mechanism of action of Lithium carbonate?
Most likely involved postysynaptic
- decrease in IP3 and DAG
- can inhibit sensitive adenylyl clyclase
- uncouple receptor recognition site fro mGTP by competing with MG
- ALters gene expression for long-term neuroplastic events
What are Lithobid and Eskalith?
Lithium drugs
- 60-80% effecive
- 5-21 days until you see effects
Where is most of lithium excreted?
95% from kidneys
- reasopbed about 25% with diuretics
What are some adverse effects of lithium?
Fatigue, weakness, slurred speech, ataxia, tremor, excessive thirst/urination
Toxic: LOC, coma, regidity, hyperreflexia, Muscle fasciculations
TI is very low
what is the mechanism of action of Valproic acid?
Anticonvulsant
- Depakene
- Depacon–> sodium valproate
- similare efficacy to lithium
- if neither work alone use together
