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Pharm III - Exam 4 > Antidepressants > Flashcards

Flashcards in Antidepressants Deck (76)
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1

What do the symptoms of MDD reflect changes in?

Norepi
Serotonin (5HT)
Dopamine

2

Hospitalization of MDD patients is based on:

-Suicide risk
-Physical state of health
-Support system
-Presence of psychotic features

3

Treatment phases of MDD

1. Acute: lasts 6-8 wks, goal is remission of symptoms
2. Continuation: lasts 4-9 mos, eliminate residual symptoms and prevent relapse
3. Maintenance: lasts 12-36 mos, goal is to prevent recurrence

4

Response to antidepressants

-65-70% of pts improve
-Well documented placebo effect
-ADEs may occur immediately
-Resolution of symptoms may take 2-4 wks or longer
-Adherence is essential to success

5

Black box warning of antidepressants

ALL carry warning of increased suicidality risk in 18-24 yo during initial stages of treatment

6

How do TCAs work?

-Potentiate activity of NE and 5HT via reuptake blockade
-Block M1, a1, H1 receptors

7

What can TCAs be used to treat besides depression?

-Enuresis
-Migraines
-Nausea w/chemo
-Neuralgia
-Urticaria
-OCD

8

Which TCAs block 5HT reuptake more than NE reuptake?

Amitriptyline
Clomipramine

9

Which TCAs block NE reuptake more than 5HT reuptake?

Desipramine
Nortriptyline

10

TCA metabolism?

Hepatic - CYP1A2, 3A4, 2D6

11

TCA ADEs

-Tachy
-Orthostatic hypotension
-Cardiac rhythm changes
-Wt gain
-Sedation
-Lowers seizure threshold
-Sexual dysfunction
-Narrow therapeutic index

12

How do tertiary amine TCAs compare to secondary amine TCAs?

-More pronounced anticholinergic, antihistaminergic, hypotensive effects
-Avoid in elderly due to postural hypotension, risk of fall, and other CV effects

13

TCA contraindications

-BPH
-Closed angle glaucoma
-Cardiac disease
-Hepatic impairment
-Elderly

14

TCA drug interactions

-Avoid other CYP450 drugs
-May increase vasopressor response to direct acting sympathomimetics
-Additive adverse effects w/other agents w/serotonergic, anti-ACh, sedative or hypotensive properties

15

Examples of MAOIs

Phenelzine
Tranylcypromine
Selegiline transdermal patch

16

How do MAOIs work?

Block metabolism of NE, 5HT, DA via inhibition of MAO enzyme

17

Common ADEs of MAOIs

-Orthostatic hypotension
-Dizzy
-Mydriasis
-Edema
-Piloerection
-Tremor
-Wt gain
-Insomnia

18

Rare ADEs of MAOIs

Allergic reactions
Hepatic dysfunction
Blood dyscrasias

19

Describe hypertensive crisis caused by MAOIs

-Occurs after ingestion of tyramine containing foods/drugs
-Tyramine is metabolized in gut by MAO enzymes (causes release of NE from presynaptic sites)
-Medical emergency
-HTN, occipital HA, neck stiffness, diaphoresis

20

What MAOI does not require as much dietary restriction?

Selegiline transdermal patch at 6 mg/24 hrs

21

MAOI drug interactions

-Drugs that can precipitate HTN crisis (ephedrine, pseudoephedrine, phenylephrine)
-Serotonin syndrome w/other antidepressants, narcotics

22

When is a washout period of 14 days required?

Switching from one MAOI to another antidepressant
Switching from other antidepressant to an MAOI

23

When is a 5 wk washout period required?

Switching from fluoxetine to an MAOI

24

Switching from MAOI to another antidepressant requires a ___ washout period

14 days

25

Switching from fluoxetine to an MAOI requires a ____ washout period

5 week

26

SSRI agents:

-Fluoxetine
-Sertraline
-Paroxetine
-Citalopram
-Fluvoxamine

27

What is Fluvoxamine and what is it FDA approved for?

SSRI
FDA approved ONLY for OCD

28

Which SSRI is only approved for OCD use?

Fluvoxamine

29

What is 1st line pharm treatment of MDD?

SSRI

30

What can SSRIs be used for besides MDD?

-Anxiety disorders (OCD, PTSD, GAD, etc.)
-Bulemia
-Premenstrual Dysphoric Disorder

31

Common ADEs of SSRIs

-Nausea
-HA
-Sleep disturbances
-Agitation/anxiety
-Sexual dysfunction
-Tremor

32

Why are SSRIs more favorable than TCAs or MAOIs?

Less sedating and cause less weight gain

33

Overdose of SSRIs?

Not lethal

34

What is discontinuation syndrome of SSRIs?

-Potential for withdrawal w/abrupt d/c of short acting SSRIs
-Vivid dreams/nightmares, tremor, dizzy, crying spells, nausea, poor concentration
-Occurs as early as 1-4 days or up to 25 days after d/c
-Taper dose slowly over 7-10 days

35

How should SSRIs be d/c?

Taper dose slowly over 7-10 days to avoid discontinuation syndrome

36

How should most SSRIs be administered?

Recommended morning dosing d/t "energizing" effect

37

Which SSRI can be dosed in morning or evening?

Paroxetine (depending on pt response)

38

Fluoxetine drug interactions

-5 wk washout before starting MAOI (2 wk for all other SSRIs)
-Potent inhibitor of CYP2D6
-Weak inhibitor of CYP3A4 and 2C9 (phenytoin, warfarin)

39

Sertraline drug interactions

Weak inhibitor of CYP2D6 at low doses (becomes more potent at higher doses, but still weaker than fluoxetine and paroxetine)

40

Paroxetine drug interactions

Potent inhibitor of CYP2D6

41

Citalopram and escitalopram drug interactions

Possible dose dependent inhibition of CYP2D6

42

Fluvoxamine drug interactions

-Potent inhibitor of CYP1A2
-Weak inhibitor of CYP2C9

43

What are mixed 5HT/NE reuptake inhibitors?

Venlafaxine
Duloxetine
Desvenlafaxine

44

How does Venlafaxine work?

-Potent 5HT/NE reuptake inhibitor
-At lower doses, much higher 5HT reuptake inhibition
-Weak DA reuptake inhibitor

45

Describe Venlafaxine

-Mixed 5HT/NE reuptake inhibitor for MDD
-XR formulation is considered 1st line agent for MDD

46

Metabolism of Venlafaxine

Substantial 1st pass via CYP2D6

47

ADEs of Venlafaxine

Similar SE profile to SSRIs

48

Venlafaxine drug interactions

-Weak inhibitor of CYP2D6
-Serotonin syndrome

49

How does Duloxetine work? What is it indicated for?

-Balanced reuptake inhibitor of 5HT and NE
-FDA approved for MDD, diabetic neuropathy, fibromyalgia

50

Which antidepressant is FDA approved for MDD, diabetic neuropathy and fibromyalgia?

Duloxetine

51

What is Bupropion (Wellbutrin)?

-Potent DA reuptake inhibition
-Very low reuptake inhibition of NE

52

Indications for Bupropion (Wellbutrin)?

Depression
Smoking cessation

53

Which antidepressant is indicated for smoking cessation?

Bupropion (Wellbutrin)

54

Bupropion drug interactions

-Use caution w/drugs known to lower seizure threshold
-Use w/MAOI is CONTRAINDICATED
-Very low inhibition of CYP2D6

55

What is Nefazodone?

-5HT2 blocker AND reuptake inhibitor
-NOT a 1st line agent for depression

56

Nefazodone ADEs

-Black box warning: cases of life threatening hepatic failure
-Potent CYP3A4 inhibitor

57

Describe Trazodone

-5HT2 blocker AND reuptake inhibitor
-Uncommonly used in depression (d/t ADEs)
-Commonly used as sedative
-Rare cases of priapism, QTc prolongation

58

What is Mirtazapine?

Selective, presynaptic a2 receptor antagonist (enhancement of NE transmission)

59

Mirtazapine ADEs

-Sedation
-Dry mouth
-Constipation
-Increased appetite, weight gain

60

Mirtazapine drug interactions

-Other sedating agents
-MAOIs

61

Rare ADE of Vilazodone

May cause new or worsening cataracts with long term use

62

Describe Levomilnacipran

-SNRI (higher selectivity for NE than 5HT)
-Primarily excreted by kidneys
-Role in treatment of depression is unknown (only studied vs. placebo)

63

Describe Vortioxetine

-5HT reuptake inhibitor and agonist
-Role in depression treatment is unknown
-MC ADEs: NV, constipation

64

St. John's wort in the treatment of depression?

-Found to be safe and effective for mild-mod depression
-NOT FDA regulated though
-Significant drug interactions (potent CYP3A4 inducer)

65

How does ECT work?

-Small current used to induce a seizure
-30-60 secs in duration
-Pts are given sedative and paralytic
-6 to 12 treatments (2-3 times per week)

66

Indications for ECT?

-High suicide risk
-Rapid physical decline
-Drug non-response or intolerability
-History of prior response to ECT

67

Contraindications to ECT?

NO absolute contraindications

68

Limitations/ADEs of ECT

-High relapse rate
-Impairments in memory and neurocognitive function
-Treatment-emergent mania
-HA, nausea, muscle aches

69

Describe depression in the elderly

-Often mistaken for another disorder (e.g. dementia)
-Depressed mood may be less prominent than other symptoms
-Increased suicide attempts
-Start LOW and go SLOW

70

Depression treatment in pregnant/lactating patients

-New evidence for potential resp distress and withdrawal syndrome in neonates whose mothers took SSRIs during pregnancy
-ECT can be used safely during pregnancy
-Sertraline and paroxetine appear in low concentrations in breast milk

71

How is response to antidepressants measured?

1. Non-response: less than 25% decrease in baseline symptoms
2. Partial: 26-49% decrease
3. Partial remission: over 50% decrease
4. Remission: return to baseline functioning

72

What is considered an adequate trial of antidepressants?

6-8 weeks at a maximum dosage
(up to 12 wks in elderly)

73

How to prevent relapse with antidepressant treatment?

Continue at full therapeutic dose for 4-9 months after symptom remission (aka continuation therapy)

74

When is lifelong maintenance therapy recommended in depression?

Patients with high risk of recurrence (2 or more previous episodes)

75

Define treatment resistant depression

Remission not achieved after 2 optimal antidepressant trials (6-8 wks)

76

Approaches to treatment resistant depression

1. Switch to another SSRI or antidepressant w/different MOA
2. Augment w/another antidepressant, Li, T3, atypical antipsychotic, ECT, psychotherapy