Exam I - Antidepressants

Question 1

ADDs and Monoamines

Answer 1

-all ADDs incr. plasma monoamines
-however, spike in monoamines precedes therapeutic
effect by 1-3 wks

Question 2

Serotonin Biosynthesis

Answer 2

• ECL(>90%), platelets, Raphe nuclei (brain stem)
• pineal gland
• metab’d by MAO
• 7 receptor subtypes; n=13

Question 3

Drug List

SSRIs

Answer 3

• fluoxetine (prozac)

- sertraline (zoloft)

Question 4

Drug List

SNRIs

Answer 4

-duloxetine (cymbalta)

Question 5

Drug List

TCAs

Answer 5

• amitriptyline

- desipramine

Question 6

Drug List

MAOIs

Answer 6

-tranylcypromine

Question 7

Drug List

Other

Answer 7

• bupropion (wellbutrin)
• mirtazapine
• trazodone

Question 8

SSRI

Mechanism

Answer 8

-selectively block serotonin transporter (SERT),
inhibiting reuptake
-increase quantity/duration of 5HT at synapses
-enhanced serotonergic transmission over time
-gradual improvement of depression sx in 1-6 wks
-pos response in 75%

Question 9

SSRI

Indication

Answer 9

• 1st line for depression
• also for anxiety, bulimia, PMDD, ADD/HD
• well tolerated
• do not affect other monoamines
• do not act directly on NT receptors

Question 10

SSRI

Adverse

Answer 10

• initial GI upset, CNS stim, restlessness, akithisia, sex dysfxn
• most sx improve in time
• withdrawal rxns
• higher drug-drug interactions with fluox

Question 11

SSRI

ADME

Answer 11

• good absorption, majority protein bound
• CYP3A4 oxidation, phase 2 glucuronidation
• fluox is a prodrug
• t1/2 = 24 hrs or longer

Question 12

SNRI

Mechanism

Answer 12

-same as SSRI, but at high dose also block NE uptake (NET)

Question 13

SNRI

Indication

Answer 13

• neuropathic pain

- also GAD, fibromyalgia, depression

Question 14

SNRI

Adverse

Answer 14

• same as SSRI, but also HTN

- greater risk of withdrawal sx d/t shorter t1/2

Question 15

Serotonin Syndrome

Answer 15

• from OD
• enhanced by co-rx w/ MAOIs, other ADDs, triptans
• hyperthermia, musc rigidity, myoclonus, akathisia, mental status

Question 16

Serotonin Receptor Antagonist

Answer 16

Trazodone

Question 17

Dopamine Reuptake Inhibitor

Answer 17

Bupropion

Question 18

Autoreceptor Antagonist

Answer 18

Mitrazipine

Question 19

Trazodone

Answer 19

• 5HT2A receptor blockade
• mCPP metabolite 5HT agonist
• sedative effect; sleep aide
• risk of orthostatic HoTN, priapism

Question 20

Bupropion

Answer 20

• blocks DA and NE reuptake
• smoking cessation
• ADD (mild psychostimulant)
• adverse: CNS stim, wt loss, seizures, anxiety
• no/low sexual side effects

Question 21

Mirtazapine

Answer 21

• a2 agonist, enhances NE release
• Sedative effect w/ SOME anticholinergic effects
• some antihistamine acitvity (incr appetite, wt gain)
• low sexual side effects

Question 22

TCA

Mechanism

Answer 22

• block SERT and NET
• 3* metab’d to 2*
• also block receptors for many other NTs

Question 23

TCA

Adverse

Answer 23

• initial drowsiness, dry mouth, anxiety, dysphoria
• delayed therapeutic response
• heart: tachycardia, palps, arrhythmias, blocks
• vasc: HoTN
• incr appetite, wt gain
• sexual side effects
• low tx index (arrhythmias; tx w/ lidocaine)
• despiramine has higher tx index

Question 24

TCA

Indications

Answer 24

• Anxiety Disorders
• enuresis
• neuropathic pain, migraine

Question 25

MAOIs

Mechanism

Answer 25

• irreversibly inhibit MAO
• incr 5HT and NE in synapses, both periph and brain
• non-selective

Question 26

MAOIs

Indications

Answer 26

• 3rd line antidepressant

- atypical depression (does not respond to TCAs)

Question 27

MAOIs

Adverse

Answer 27

• CNS stim, post HoTN, GI sx, sex dysfxn
• many drug-drug interactions (can lead to OD)
• allow 2-5 wks after cessation to start new ADD
• cannot initiate tx until 2 wks after discontinuation of other ADD
• tyramine (in cheese, wine) can cause acute hypertensive crisis

Question 28

ADDs and Pregnancy

Answer 28

CONTRAINDICATED:

• tranylcypromine (HTN)
• fluoxetine, sertraline (malformations)
• amitriptyline (limb malformation)