SSRIs (Anti-Depressants)

Question 1

Name the SSRI’s (6 of them)

Answer 1

Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram.

Question 2

PK of SSRI’s

Answer 2

Oral, well absorbed, Tmax 2-3 hours, high plasma protein bound, in general nothing noteworthy.

Question 3

Metabolism of SSRI’s

Answer 3

CYP metabolism particularly 2D6

Question 4

Half lives of SSRIs and which are the special ones?

Answer 4

18-48 hours for chronic use, x1 daily dosing. Fluoxetine is 4-6 days half life, norfluoxetine is 9 days,

Question 5

Which SSRIs are strong 2D6 inhibitors?

Answer 5

Fluoxetine and Paroxetine

Question 6

Which SSRI’s are strong 1A2 and 2C19 inhibitors?

Answer 6

Fluvoxamine.

Question 7

Which SSRI is the only one which doesn’t really inhibit other CYPs?

Answer 7

Escitalopram, which is a weak 2D6 inhibitor but otherwise doesn’t mess with other CYPs.

Question 8

What is the MOA of SSRI’s?

Answer 8

Allosteric inhibiton of the SERT, leading to prolonged serotonergic neurotransmission.

Question 9

What is the INITIAL effect of these SSRI’s and how is it resolved?

Answer 9

Since a bunch of serotonin will be available its going to hit ALL of 5-HT receptors, including their inhibitory autoreceptors. This effect is gradually downregulated and desensitized.

Question 10

What else can be downregulated by SSRI’s besides the autoreceptors?

Answer 10

The 5-HT2 receptors can also be downregulated which can mess w/ efficacy. All the other 5-HT receptors stay responsive.

Question 11

Which SSRI has a relatively higher anticholinergic effect than other SSRIs?

Answer 11

Paroxetine (Paxel)

Question 12

Tx of SSRIs?

Answer 12

MDD, Anxiety disorders, Pain Bulimia nervosa (fluoxetine) and obsessive compulsive disorder (fluvoxamine)

Question 13

Which SSRIs are used for bulimia nervosa? Obsessive Compulsive disorder?

Answer 13

Fluoxetine (prozac) and Fluvoxamine (luvox), respectively.

Question 14

What are the GI and CNS adverse effects of SSRI’s? Rare complication of SSRIs?

Answer 14

Nausea diarrhea vomitting (abates). Headaches, insomnia (common, seen early on), hypersomnia (opposite of insomnia), restlessness, weight gain <– common complaint. SIADH is the rare complication (causes hyponeutremia).

Question 15

Why do SSRI’s make ppl more prone to bleeding?

Answer 15

Decreased serotonin mediated platelet aggregation, specifically we are blocking the serotonin receptors which serotonin needs to bind to to induce platelet aggregation. Not really a big deal on its own but becomes a problem with other anti-coag.

Question 16

Why does SSRI’s cause sexual dysfunction?

Answer 16

Activation of spinal 5-HT2 receptors.

Question 17

Which SSRI is more prone to have the most withdrawal syndrome? Least?

Answer 17

Paroxetine has the highest withdrawal syndrome, fluoxetine the least (because its long acting).

Question 18

In terms of side effects, why are SSRI’s considered first line?

Answer 18

They do not cause CV side effects, antimuscarinic effects or orthostatic hypotension.

Question 19

Which is the only SSRI thats preg category D? What are the rest?

Answer 19

Paroxetine is Category D, all others are category C. Its category D due to increased risk of CV and other congenital malformations.

Question 20

Class drug-drug interactions with SSRIs?

Answer 20

MAOI’s and others that cause serotonin syndrome if taken with SSRIs. The antipsychotics (Thioridazine and pimozide) will cause QT prolongation w/ SSRIs. Anti-coags will increase risk of bleeding. Other drugs that are metabolized by CYPs.

Question 21

What do SSRI’s stand for?

Answer 21

Selective Serotonin Re-uptake Inhibitors.