Antidepressant drugs

Question 1

Monoamine hypothesis of depression

Answer 1

Depleted monamines –> depression

• MAOIs = antidepressants
• Reserpine (HTN drug) induces depression by depleting monoamines

Question 2

How can reserpine lead to depression?

Answer 2

–| VMAT (transporter for monoamines). Monamines in cytoplasm don’t get packaged –> get degraded instead –> depleted monoamines –> depression

Question 3

Why do antidepressants (and opp resertine) take weeks to have their effects?

Answer 3

Presynaptic autoreceptors react to changing NTs. Long term –> downregulation of autoreceptors –> effect

Question 4

What is taken up by the presynaptic neuron to be converted to 5-HT?

Answer 4

Tryptophan

Question 5

What gets taken up by presynaptic neuron to be converted to dopamine then NE?

Answer 5

Tyrosine

Question 6

Indications of SSRIs

Answer 6

• anxiety
• MDD
• OCD
• PTSD
• bulimia
• social anxiety disorder

Question 7

Side effects of SSRIs

Answer 7

• weight gain
• sexual dysfunction
• drowsiness
• SIADH
• EPS symptoms (early)
• seizures
• serotonin syndrome (if taken with MAOI)

Question 8

Fluoxetine

Answer 8

SSRI

• • | CYP34A
• crazy long half life

Question 9

Paroxetine

Answer 9

SSRI

–| 2D6

Question 10

Sertraline

Answer 10

SSRI

Question 11

Citalopram

Answer 11

SSRI

Question 12

Escitalopram

Answer 12

SSRI

Question 13

Fluvoxamine

Answer 13

SSRI

Question 14

SNRI Indications

Answer 14

• MDD
• chronic pain
• fibromyalgia
• neuropathic pain
• menopausal symptoms

Question 15

SNRI side effects

Answer 15

Same as SSRI plus

• anticholinergic
• anti H1: sedation

Question 16

Venlafaxine

Answer 16

SNRI

• • | CYP 2D6
• HTN side effect

Question 17

Duloxetine

Answer 17

SNRI

Question 18

Serotonin syndrome

Answer 18

Caused by mult mechanisms to elevate 5HT signaling

• altered mental status
• fever
• tachycardia
• HTN
• agitation
• tremor
• clonus
• hyperreflexia
• ataxia
• incoordination
• diaphoresis (sweating)
• shivering

Question 19

Treat serotonin syndrome

Answer 19

Cyproheptadine: 5-HT2 antagonist

Question 20

Why do you have to taper off SSRIs and SNRIs?

Answer 20

Otherwise have withdrawal symptoms = flu-like symptoms

Question 21

Mechanism of TCAs

Answer 21

Same as SNRIs + some ACh antagonists

Question 22

TCA Indications

Answer 22

• resistant MDD
• diabetic neuropathy
• chronic pain
• migraine prophylaxis
• OCD

Question 23

TCA adverse effects

Answer 23

Same as SNRIs but more anticholinergic and anti-H1 and anti-alpha effects. Contraindicated in elderly

• sexual dysfunction
• weight gain
• seizures
• arrhythmias: block cardiac fast Na+ channels –> widened QRS

Question 24

Imapramine

Answer 24

TCA

-Targets 5-HT > NE

Question 25

Amitriptyline

Answer 25

TCA

Question 26

Clomipramine

Answer 26

TCA for OCD

Question 27

Desipramine

Answer 27

TCA - Targets NE > 5-HT - fewer anticholinergic effects

Question 28

Nortriptyline

Answer 28

TCA | -fewer anticholinergic effects

Question 29

TCA Overdose

Answer 29

Dangerous! Prescribed in small quantities w/ no refill | -Treat arrhythmia: sodium bicarbonate

Question 30

MAOI indications

Answer 30

Resistant depression

Question 31

MAOI adverse effects

Answer 31

- HTN reactions - hyperthermia - CNS stimulation

Question 32

What foods do you avoid when on MAOIs and why?

Answer 32

Tyramine-containing foods b/c they're normally metabolized by MAO-A in GI tract. If MAO-A is inhibited, tyramine enters circulation --> sympathomimetic --> HTN crisis

Question 33

Phenelzine

Answer 33

MAOI | Binds irreversibly- long-lasting inhibition

Question 34

Tranylcypromine

Answer 34

MAOI

Question 35

Isocarboxazid

Answer 35

MAOI

Question 36

MAO-A

Answer 36

Breaks down 5-HT, NE, DA

Question 37

MAO-B

Answer 37

Breaks down DA only

Question 38

Selegiline

Answer 38

MAO-B inhibitor (selective!) --> increases DA

Question 39

Treat HTN crisis from tyramine toxicity

Answer 39

Phentolamine: a1 and a2 antagonist

Question 40

5-HT2A antagonists

Answer 40

- treats depression and hypnosis | - 5-HT2A found in cerebral cortex

Question 41

5-HT2A antagonist adverse effects

Answer 41

- sedation | - orthostatic hypotension

Question 42

Nefazodone

Answer 42

--| 5-HT2A | Black box warning: hepatotoxicity

Question 43

Trazodone

Answer 43

--| 5-HT2A | Prodrug

Question 44

Heterocyclic antidepressants (atypical) indications

Answer 44

- MDD | - sedation

Question 45

Buproprion

Answer 45

Heterocyclic antidepressant - -| NET (NE uptake) and --| DAT (DA uptake) --> enhanced NE and DA signaling - for smoking cessation - lowers seizure threshold (bad!)

Question 46

Mirtazapine

Answer 46

``` Heterocyclic antidepressant --| 5-HT2A --| H1 --> sedation = 1st line for MDD with insomnia -antagonizes a2 autoreceptor --> enhances release of NE and 5-HT ```

Question 47

Typical half life of antidpressants

Answer 47

12-24 hrs

Question 48

Why should you be cautious giving bipolar patients antidepressants?

Answer 48

Increasing catecholamines --> could induce mania

Question 49

Lithium

Answer 49

Treats acute mania and chronically- maintenance

Question 50

Lithium mechanism

Answer 50

Unknown but enters via Na+ channels and acts like Na+

Question 51

Adverse effects of Lithium

Answer 51

- Narrow therapeutic index! - tremor - hypothyroidism (weight gain, hair loss) - diabetes insipidus (polydipsia, polyuria) - teratogenic - inhibits K+ entry to myocytes

Question 52

Contraindications of Lithium

Answer 52

- dehydration, hyponatremia - cardiovascular probs - renal impairment - lactation

Question 53

How is Lithium excreted?

Answer 53

In urine

Question 54

What decreases the clearance of Lithium?

Answer 54

Diuretics and NSAIDs (increase reabsorption from kidney)