Lecture 30 - Antidepressant Drugs

Question 1

what are the monoamines?

Answer 1

NE and 5HT

Question 2

what is the Monoamine Hypothesis of Depression

Answer 2

Depression results from the pathologically decreased or depleted levels of 5HT and/or NE

Question 3

where is 5HT synthesized ? what is the precurosr amino acid?

where is NE synthesized ?

Answer 3

5HT – raphe Nucleus synthesis; Precurosor - Tryptophan

	NE - Locus ceruleus synthesis; Precurosor -- Tyrosine

Question 4

Describe the interactions between 5HT and NE?

Answer 4

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

Question 5

what 5HT receptors are implicated in depression? where are they located

Answer 5

5HT1D – classic autoreceptor (presynpatic terminal)

5HT1A – autoreceptor on the dendrite; decrease AP firing

5HT2A – post synaptic

5HT2C

Question 6

what are the 4 classes of anti-depressant drugs? name a few examples of each

which are the first line?

Answer 6

TCAs – amytriptyline, deispramine, imipramine

Monoamine oxidase inhibitors – Isocarboxazid, phenelzine

SSRIs –fluoxetine, sertraline, paroxetine, citalopram
(First line)

Atypical anti-depressants – New generations
bupropion, mirtazapine, trazodone, venlafaxine
(second line)

Question 7

Tricyclic Antidepressants:

• mechanism

Side effects

Answer 7

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

Question 8

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…

Answer 8

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
Orthostatic hypotension

Don’t use with…SSRIs — serotonin syndrome

Question 9

SSRIs

Mechanism

Pros

Cons

Interactions

Answer 9

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

Question 10

what is the reason for the delayed onset of the benefits from SSRIs?

Answer 10

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

Question 11

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

Answer 11

Decreased Libido/sexual dysfunction

Hypertension, muscle rigidity, rapid changes in mental status

Question 12

what are the 4 types (mechanisms) of “Atypical” antidepressants?

Answer 12

SARI – 5HT2a Antagonist and Reuptake Inbitirors ‘

NDRI – NE/DA Reuptake Inhibitor;

Noradrenergic and Specific 5HT

Serotonin/Ne Reuptake Inhibition

Question 13

SARI
5HT2a Antagonist and Reuptake Inhibitors

name
side effects
benefits
-

Answer 13

Trazadone

Blocks serotonin reuptake
but alleviates some 5HT side effects
No sexual dysfunction

Also some Antihistamine and Anti-alpha 1 properties
sedation and orhtostatic hypotension

Question 14

NDRI –
name
mechanism
benefits

Answer 14

wellbutrin (bupropion)

NE and DA reuptake inhibition

no sexual dysfunction

good for poeple who can’t tolerate serotonin side effects

Question 15

3rd Gen Heterolytic
Noradrenergic and Specific Serotonergic Antidepressants

name
mechanism
side effects

Answer 15

Mirtazapine

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

Question 16

3rd Gen heterolytic
Serotonin/NE Reuptake Inhibition –

Name
benefits
side effects

Answer 16

Name: Venlafaxine (Effexor)
Mechanism: Combined selective reuptake inhibition of NE and Serotonin
Lacks Side effects: bc they are very selective

Question 17

first line drug for depression

Second line drugs

Answer 17

SSRIs

Atypicals – bupropion, mirtazapine, velafaxine