Flashcards in Lecture 30 - Antidepressant Drugs Deck (17):
what are the monoamines?
NE and 5HT
what is the Monoamine Hypothesis of Depression
Depression results from the pathologically decreased or depleted levels of 5HT and/or NE
where is 5HT synthesized ? what is the precurosr amino acid?
where is NE synthesized ?
5HT -- raphe Nucleus synthesis; Precurosor - Tryptophan
NE - Locus ceruleus synthesis; Precurosor -- Tyrosine
Describe the interactions between 5HT and NE?
Brainstem -- NE neurons of the LC synapse on 5HT neurons of the RN to stimulate 5HT synthesis and release
Ascending projections to the Frontal Cortex -- Alpha2 NE receptors located on both the terminals of the 5HT and NE neurons reducing activity
what 5HT receptors are implicated in depression? where are they located
5HT1D -- classic autoreceptor (presynpatic terminal)
5HT1A -- autoreceptor on the dendrite; decrease AP firing
5HT2A -- post synaptic
what are the 4 classes of anti-depressant drugs? name a few examples of each
which are the first line?
TCAs -- amytriptyline, deispramine, imipramine
Monoamine oxidase inhibitors -- Isocarboxazid, phenelzine
SSRIs --fluoxetine, sertraline, paroxetine, citalopram
Atypical anti-depressants -- New generations
bupropion, mirtazapine, trazodone, venlafaxine
Block Reuptake Pumps for 5HT and NE
Side effects: also antagonizes M1, H1 and Alpha 1
M1 - Antimuscarinic -- (DRY -- mydriasis, dry mouth, urinary retention, constipatin)
H1 -- antihistamine -- sedation, weight gain
Alpha 1 blocker -- orthostatic hypotension, relfex tachy, drowsiness
Monoamine Oxidase Inhibitors
- which of the two enzymes ?
- of classic vs non classic? -- name a few
what is the risky side effect?
Common side effects
never use these with...
MOA-a -- metabolism of NE, 5HT, tyramine
Classic = Irreversible, non selective; (Isocarboxazid)
can have the wine and cheese HTN crisis with Tyramine
Non classic -- reversible and selective (Moclobemide, Bfeloxatone)
no tyramine htn crisis
§ Blurred vision, dizziness, sleep disturbances, fatigue, weakness and increased sweating
§ Sexual dysfunction
Don't use with...SSRIs --- serotonin syndrome
Mechanism -- Antagonist 5HT1A (autoreceptor of dendrites)
Pros -- relatively few side effects
Cons -- takes 3-6 weeks to work;
Don't use with MAOIs -- Serotonin Syndrome
Side effects -- Nausea, Decreased sex drive
what is the reason for the delayed onset of the benefits from SSRIs?
Intially low serotonin, so there is an upregulation of 5HT1A receptors on the Dendrite (which slows APs)
When Blocked, by the drug, more Serotonin becomes available per receptor; still a slowed firing of APs
Eventually the overwhelming amount of serotonin downregulates the5HT1A receptors
Overload of serotonin (a side effect of serotonergic drugs) can lead to what common symptom that is a reason for non-adherence with the medication?
what are some symptoms of serotonin syndrome
Decreased Libido/sexual dysfunction
Hypertension, muscle rigidity, rapid changes in mental status
what are the 4 types (mechanisms) of "Atypical" antidepressants?
SARI -- 5HT2a Antagonist and Reuptake Inbitirors '
NDRI -- NE/DA Reuptake Inhibitor;
Noradrenergic and Specific 5HT
Serotonin/Ne Reuptake Inhibition
5HT2a Antagonist and Reuptake Inhibitors
Blocks serotonin reuptake
but alleviates some 5HT side effects
No sexual dysfunction
Also some Antihistamine and Anti-alpha 1 properties
sedation and orhtostatic hypotension
NE and DA reuptake inhibition
no sexual dysfunction
good for poeple who can't tolerate serotonin side effects
3rd Gen Heterolytic
Noradrenergic and Specific Serotonergic Antidepressants
blocks NE Alpha 2 in the LC, therefore increased NE reselase onto the RN, therefore increased 5HT
But also blocks post synaptic 5HT receptors --
and reduces some side effects of anxiety and sexual dysfunction
Side effects --
Some H1 antagonism -- sedation, weight gain
3rd Gen heterolytic
Serotonin/NE Reuptake Inhibition --
Name: Venlafaxine (Effexor)
Mechanism: Combined selective reuptake inhibition of NE and Serotonin
Lacks Side effects: bc they are very selective