Lecture 76: Antidepressants Flashcards Preview

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Flashcards in Lecture 76: Antidepressants Deck (49):
1

MAOIs (key, 3)

Phenelzine, tranylcypromine, selegiline

2

What is special about selegline?

Patch delivery

3

Are MAOIs first line? What population might they be used?

No--after trying other anti-depressants first; atypical depression: sleep/eat a lot

4

MAOI mechanism

MAO located in presynaptic neuron and degrades monoamines --> MAOIs inhibit enzyme, inhibiting degradation of monoamines

5

Important MAOI mechanism notes

More NT in both presynaptic neuron AND cleft; irreversible (MAOIs take 2 weeks to recover)

6

Describe types of MAOs and targeted catecholamines. Which one is in the gut? Which one degrades tyramine? Which are targeted by MAOIs?

MAOa: 5-HT, NE, Epi, DA; MAOb: DA; MAOa; both; both

7

2 MAIN (scary) side effects of MAOI and mechanism

1. Also inhibit breakdown of Tyramine --> NE release (hypertensive crisis) if combined with tyramine diet or adrenergic agonists; 2. Serotonin syndrome if combined with other serotonergic drugs

8

Other SEs of MAOIs (5)

Orthostatic hypotension, weight gain, insomnia, sexual dysfunction, rare hepatoxicity

9

Describe symptoms serotonin syndrome (11)

Abdominal pain, diarrhea, sweating, hyperthermia, tachycardia, hypertension, myoclonus, tremor, irritability, delirium, death

10

What can you NOT take with MAOIs because of serotonin syndrome (3)

Other antidepressants, dextromethorphan (cough medicine) and opiates

11

What else can you NOT take with MAOIs? Why?

Decongestants, stimulants because they can cause hypertensive crisis (BP > 120 mm Hg) due adrenergic agonists

12

What food items must be avoided with MAOIs? Why?

Tyramine inhibition in GUT via MAOa but if tyramine gets access to NE sympa neurons, these MAOa are ALSO blocked leading to NE release; soy, beer, red wine, aged cheese, dried sausage, liver, smoked fish, sauerkraut

13

How long must a patient wait to resume normal diet after stopping MAOI?

2 weeks

14

Describe Selegiline's hope

At low doses only inhibits MAOb, but turns out at antidepressant levels, also inhibits MAOa so STILL requires dietary restriction

15

TCAs (key, 1) and secondary amines (key, 2)

Amitriptyine; nortriptyline, desipramine

16

Mechanism of TCAs (?)

Inhibit re-uptake of NE and 5-HT

17

TCA therapeutic uses (4)

Depression, neuropathic pain, anixety, migraine

18

How are tertiary amines different?

Also inhibit 5-HT reuptake

19

TCA SEs via receptor

H1 blocker: sedation, weight gain; Alpha1 blockers: orthostatic hypotension; M1 blocker (anticholinergic) constipation/urinary retention, dry mouth, blurred vision; Na channel blockers: type 1 antiarrythmic effects; Serotonin Reuptake inhibitors (same as SSRIs)

20

Problem with TCAs being a NA channel blocker (2)

1. If you have bad ischemic heart disease, TCA can CAUSE arrythmias; 2. Can lead to overdose

21

Which TCAs are the LEAST anticholinergic and alpha1 blockers

Secondary amines

22

TCA: avoid in...

People with narrow angle glaucoma, recent cardiac events, children, elderly (orthostatic hypotension --> falling)

23

TCA is active in what liver system?

Metabolized BY cytochrome p450

24

SSRIs (key, 5)

Fluoxetine, sertraline, paroxetine, citalopram, escitalopram

25

SSRIs major indications (4)

MDD, anxiety, OCD, bulimia

26

SSRI mechanism (main)

Inhibit reuptake of 5-HT into presynaptic neuron --> more 5-HT in synapse

27

SSRI secondary effects. Important?

Some NE and DA reuptake effects; potential SEs

28

Paroxetine secondarily

Inhibits NE reuptake

29

Sertraline secondarily; why important

Inhibits DA reuptake --> activating good for tired patients

30

SSRIs common SE

GI, weight gain, tremor, headache, sweating, sexual

31

SSRIs less common SE

Dry mouth, bruising/bleeding (important for surgery), hyponatremia, vivid dreams, serotonin syndrome, mania if underlying BP disorder

32

Fluoxetine has the most...What else is special about this drug (2)?

Drug:drug interactions due to p450 inhibition; longest half-life (once weekly formula, best for people who don't take drugs daily); "activating" --> insomnia

33

Citalopram and Escitalopram has the fewest...importance?

Drug:drug interactions; perhaps fewest SEs

34

Paroxetine half-life is...causing...What else is noteworthy about this drug?

Short; withdrawal symptoms; NE reuptake blockade and anticholinergic activity; more sedation, dry mouth, weight gain

35

Describe SSRI withdrawal and how long. Drug least and most likely

Abrupt discontinution of SSRI --> dizziness, nausea, paresthesias, flu-like, muscle aches, headaches; 3 weeks; fluoxetine = least and paroxetine = most

36

SSRI advantages

Standard dosing, clinical response at starting dose, not lethal in OD, no arhythmias, no changes in BP, no seizures, fewer drug-drug interactions

37

Problem with SSRIs and new drugs?

Perhaps SSRIs are not effective enough because of the lost of NE, but trying to be less dirty (= SNRIs)

38

SNRIs (key, 2)

Venlafaxine, duloxetine

39

SNRI therapeutic use (3)

Neuropathic pain, depression, anxiety

40

SNRI SEs

Increases diastolic BP at higher doses, otherwise similar to SSRIs

41

Duloxetine (describe and 2 SEs)

Affinity for 5HT and NE at all doses with many pain and psych indiactions; small amount get hepatoxicity and elevated BP is possible

42

Advantage of Buproprion and therapeutic use. Mechanism? Avoid in what 3 patients?

No weight gain/sex issues; MDD, smoking cessation, ADHD; weak NE and DA inhibitor AND inhibits nACh but NOT 5-HT; avoid in anxious patients, alcoholics (seizure), eating disordered

43

Buproprion SEs (scary one and others)

Seizures at high doses; anxiety, rare psychosis

44

Mirtazapine mechanism. Avoids what SEs but not?

Alpha2 antagonist (presynaptic) --> more NE and 5-HT NT but blocks 5-HT subtypes that causes SEs (GI, sexual); avoids sexual and GI SEs but STILL causes sedation/weight gain

45

Mirtazapine should be used in what patients...

People who are NOT eating or sleeping

46

Trazadone is too...so now just used for? SEs?

Sedating; insomnia; priapism

47

Anti-depressant response rate (%)

60%

48

Four theories for antidepressant action

1. Therapeutic delay --> downregulation of receptors; 2. Enhance neuronal regeneration; 3. Restore cortical dendrites; 4. Increase expression of neurotrophic factors

49

Comorbid pain, think...

SNRIs

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