3.1 Antidepressants

Question 1

What system do ALL antidepressants affect?

Answer 1

Monoamine System

Question 2

Depression is related to a deficiency in what? (3)

Answer 2

• Serotonin (5-HT)
• Norepinephrine (NE)
• Dopamine (DA)

Question 3

Pts responsive to serotonergic antidepressants can relapse with what?

Answer 3

Low-Tryptophan Diet

Tryptophan is a pre-cursor to synthesize serotonin

Question 4

What class of antidepressants is currently used in patients unresponsive to SSRIs/SNRIs?

Answer 4

Tricyclic Antidepressants (TCAs)

Question 5

What is the mechanism of action of the TCA class of antidepressants?

Answer 5

• Block neuronal reuptake of 2 monoamine transmitters:
  
  • Norepinephrine (NET)
  • Serotonin (SERT)

​More available to work on post-synaptic terminal

Question 6

What is the most dangerous adverse effect of TCAs?

Answer 6

• High overdose potential
  
  • Lethal Arrhythmias
    
    • ​Cardio-toxic actions
  • < 7 days of drug supply should be given

Question 7

Name 2 TCA’s.

Answer 7

• Imipramine
• Amitriptyline

Question 8

What are the most common adverse effects of TCA’s?

Answer 8

• Sedation
• Orthostatic hypotension
• Anticholinergic effects

Question 9

What class of antidepressants are most commonly Rx’d?

Answer 9

Selective Serotonin Reuptake Inhibitors (SSRIs)

Question 10

What is the mechanism of action of SSRI’s?

Answer 10

• Inhibit transport (re-uptake) of serotonin via SERT
• Prolong post- and pre-synaptic activity of 5-HT

Produces CNS Excitation

Question 11

Co-administration of SSRI’s with MAOI or Amphetamines can lead to what?

Answer 11

Serotonin Syndrome

• Eventual coma
• Death

Question 12

What class of antidepressants has relativley few adverse effects? Why?

Answer 12

SSRI’s

• Due to their selectivity
• As effective as TCAs - but do not cause hypotension, sedation, or anticholinergic effects

Question 13

What are the 2 SSRI’s we need to know?

Answer 13

• Fluoxetine (Prozac, Sarafem)
• Sertraline (Zoloft)

Question 14

What is the most widely Rx SSRI in the U.S.?

Answer 14

Fluoxetine (Prozac, Sarafem)

Question 15

What is the mechanism of the SSRI, Sertraline (Zoloft)?

Answer 15

Blocks uptake of serotonin and dopamine

Question 16

What are second-generation antidepressants?

Answer 16

Serotonin/Norepinephrine Reuptake Inhibitors (S/NRIs)

Question 17

What are S/NRIs also useful for besides tx depression?

Answer 17

Pain Management (Fibromyalgia)

Question 18

What is the mechanism of action of S/NRIs?

Answer 18

Blocks NE and Serotonin uptake

• BUT doesn’t block cholinergic, histaminergic, or alpha1-adrenergic receptors
  
  • aka TCAs have > adverse effects

Question 19

What drug is a S/NRI?

Answer 19

Venlafaxine (Effexor)

Question 20

Serious reactions occur if Venlafaxine (Effexor) is combined with what drug class?

Answer 20

MAOIs

Question 21

What is the main adverse effect with Monoamine Oxidase Inhibitors (MAOIs)?

Answer 21

• Risk of triggering Hypertensive Crisis if pt eats foods rich in Tyramine (aged cheeses, red wine, tap beer)
  
  • Tyramine accumulation in adrenergic nerve endings causes NE release
  • Causing massive vasoconstriction and excessive stimulation of the heart

Question 22

RECALL: what is MAO responsible for?

Answer 22

Degradation of 5-HT

Question 23

What is the mechanism of action of MAOIs?

Answer 23

• Irreversibly bind MAO-A and MAO-B
• Prevent inactivation of NE and Serotonin
  
  • Leads to inc availability of 5-HT and NET

Question 24

What MAOI is non-selective?

Answer 24

Phenelzine

Question 25

What MAOI is MAO-B selective, and is also an Anti-Parkinson’s Drug?

Answer 25

Selegiline (Emsam)

Question 26

What drugs can have interactions with MAOIs?

Answer 26

Antidepressants: TCAs + SSRIs

Question 27

What is the 1st transdermal treatment for depression?

Answer 27

Selegiline (Emsam)

MAOI