Lecture 11 - Antidepressants Flashcards Preview

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Flashcards in Lecture 11 - Antidepressants Deck (71)
1

Drugs used as antidepressants

amitriptyline
imipramine
fluoxetine
paroxetine
sertraline
mirtazapine
buprorion
venlafaxine
phenelzine

2

List 3 types of depressive disorders

1 - reactive (secondary depression)

2 - bipolar disorder

3 - major depression

3

Describe:
1 - reactive (secondary depression)

-temporary rxn to real stimuli such as grief or illness
-treatment is largely by psychotherapy

4

Describe:
2 - bipolar disorder

-recurrent major depressive episodes with intervening manic, hypomanic, or mixed episodes

5

Describe:
3 - major depression

-one or more major depressive episodes free of manic, mixed or hypomanic episodes

6

Lifetime prevalence in males?

9.6%

7

Lifetime prevalence in females?

20.4%

8

____% of the population are at risk of experience a major depressive episode at any given time

3-5

9

Onset?

most frequently 25-44 years of age

10

____ % have a single episode

30-50

11

recurrent episodes in ____%

50-70

12

If a first degree relative has depression, how much more likely are you to get depression?

1.5-3 times more likely

13

Risk of major depression determined by inheritance = ?

39%

14

Risk of major depression determined by environment = ?

61%

15

List the 4 types of symptoms of major depression

1-emotional
2-physical
3-cognitive
4-psychomotor

16

Describe:
1-emotional

-diminished ability to experience pleasure
-loss of interest in usual activities
-pessimistic outlook
-anxiety (90%)

17

Describe:
2-physical

-chronic fatigue
-terminal insomnia
-appetite disturbances

18

Describe:
3-cognitive

-poor concentration
-slow thinking
-poor short-term memory

19

Describe:
4-psychomotor

-slowed physical movements and speech
-agitation

20

Diagnosis for depression?

have to have at least 5 symptoms of these over a period of 2 weeks to be diagnosed with depression

21

List 2 non-pharmacologic therapies for major depression

-psychotherapy
-ECT (electroconvulsive therapy)

22

Describe pharmacologic therapy for major depression

-50-60% of Pts responsive
-newer drugs well-tolerated and present little risk for OD
-all drugs have similar efficacy

23

Describe the amine hypothesis

depression is related to reduced synaptic levels of NE and 5-HT

24

What supports the amine hypothesis?

1) 1950's - Reserpine was proven to reduce NE and 5-HT metabolism and caused depression in 15% of patients

2) Most antidepressant drugs appear to work by enhancing synaptic monoamines (by blocking reuptake)

25

How long is the therapeutic lag for antidepressants?

1-4 weeks

26

Antidepressants have ___-term synaptic effects that influence synaptic strength

long

27

Describe Phase 1 amine enhancement

short-term (min-hrs)
uptake inhibition

28

Describe Phase 2 amine enhancement

long-term (weeks) effects of phase 1 enhancement - produces further enhanced amine levels to reach therapeutic significance

29

Explain "understand Phase 2"

-normal scenario - pre-synaptic receptors that feedback inhibit to stop amine release

-phase 1 causes homeostatic agonist down regulation of these receptors to maintain "normal" agonist:receptor interaction levels

-results in reduced negative feedback and phase 2 amine increase

30

Give examples of TCAs

**amitriptyline
**imipramine
clomipramine
doxepin
protriptyline
desipramine

**most important

31

Describe the mechanism of how TCAs work

-mixed norepinephrine and serotonin reuptake inhibitors

32

Other than depression, what else can TCAs be used for?

neuropathic pain

33

TCAs also cause some blockade of ??

cholinergic, histaminergic, and alpha 1 adrenergic receptors

34

What do the other blockades result in?

adverse effects

35

Adverse effects of tricyclic antidepressants

-antimuscarinic effects
-cardiovascular (orthostatic hypotension, conduction defects)
-sedation
-sympathomimetic (tremor, insomnia)
-neurologic - seizures
-metabolic - weight gain, sexual disturbances
-overdose - extremely dangerous cardiac arrhythmias

36

Pharmacokinetic drug interactions

CYP 2D6 inhibitors
highly protein bound

37

Pharmacodynamic drug interactions

sedatives
sympathomimetic antimuscarinic

38

Describe a pharmacokinetic drug interaction

one drug affects the other's absorption, distribution, metabolism, or excretion

39

Describe a pharmacodynamic drug interaction

two drugs have additive or antagonistic effects

40

Give examples of SSRIs

fluoxetine
paroxetine
sertraline
citalopram

41

Describe the mechanism of SSRIs

-block serotonin reuptake 300-700 fold more effectively than NE

42

Are SSRIs anymore effective than TCAs?

no

43

Which 2 SSRIs have shorter half lives?

paroxetine
sertraline

44

Which SSRI was used first?

fluoxetine

45

_____ is most SERT-selective

citalopram

46

Adverse effects of SSRIs

-much less cholinergic, histaminergic, adrenergic receptor blockade than TCAs therefore more tolerable side effect profile (& better compliance)
-safer in OD
-associated with mild, short-lived GI symptoms, headache
-sexual dysfunction, fatigue, insomnia
-paroxetine withdrawl can cause dizziness, nausea, tremor, anxiety
-platelet inhibition

47

Pharmacokinetic drug interactions

-Strong CYP 2D6 inhibitors
-TCAs
-antipsychotics
-B blockers interfere with metabolism

48

Pharmacodynamic drug interactions

low non-SERT interactions

49

Describe advantages of SSRIs over TCAs (3)

-equal efficacy with milder side effect profile
-much more favourable therapeutic index
-smaller chance of additive drug interactions (ex. anticholinergic)

50

Examples of SNRIs

venlafaxine
duloxetine
desvenlafaxine

51

Describe the mechanism of SNRIs

inhibit both serotonin and NE reuptake (5-HT>NE)

also weak dopamine reuptake inhibitors

no affinity for muscarinic, alpha 1 adrenergic or histaminergic receptors

52

Adverse effects of SNRIs

-similar to SSRIs
-much lower incidence than TCAs

Adverse effects can include:
-nausea
-sweating
-dizziness
-anxiety
-sexual dysfunction
-hypertension

53

Pharmacodynamic drug interactions for SNRIs?

limited

54

other drug interactions for SNRIs

protein binding varies:
-venlafaxine (30%)
-duloxetine (>90%)

CYP 2D6 substrate (venlafaxine, duloxetine)

55

Potential advantages of SNRIs over TCAs

-same milder side effect profile as SSRIs
-may be useful for depression with neuropathic pain
-fewer drug interactions
-potentially lower safety margin than SSRIs in OD

56

Mirtazapine (Remeron) is an ??

atypical antidepressant

57

Describe the mechanism of mirtazapine

-blocks the alpha 2 adrenergic receptors thus increasing NE release

-has low affinity for muscarinic and alpha 1 adrenergic receptors

-potent blocker of histamine receptors

58

Adverse effects of mirtazapine

sedation
weight gain

no anticholinergic effects

less propensity for sexual side effects than SSRIs and TCAs

59

Any drug interactions for atypical antidepressants?

none known

60

Advantages of mirtazapine?

-they are as tolerable as SSRIs
-anxiolytic/sedative effect can be useful
-antihistamine
-minimal cholinergic/adrenergic drug interactions

61

Major draw back of using mirtazapine?

weight gain

IMPORTANT POINT

62

Mechanism of Buproprion

largely unknown!
-does not inhibit NE or serotonin reuptake
-weakly blocks dopamine reuptake
-mild stimulant - treats comorbid fatigue/poor concentration, ADHD
-low affinity for muscarinic, alpha 1 adrenergic or histaminergic receptors

63

Adverse effects of buproprion

-much lower incidence than TCAs
-can include nausea, headache, dizziness, insomnia, seizures

**no sexual dysfunction or weight gain or sedation

64

Drug interactions with bupropion

-meds that lower seizure threshold, L-dopa
-CYP 2D6 inhibitor

65

Advantages of bupropion

-as tolerable as SSRIs
-stimulant effects may be helpful
-may offer relief from SSRI or SNRI-induced sexual dysfunction or weight gain

66

Examples of monoamine oxidase inhibitors (MAOIs)

phenelzineu
moclobemide
tranylcypromine

67

explain the mechanism of MAOIs

MAO-A breaks down NE and serotonin

MAO-B breaks down dopamine

we are inhibiting these so therefore we would increase NE, serotonin, and dopamine

68

When would you use MAOIs?

they are usually reserved for patients unresponsive to other therapies due to side effects and drug and food interactions

*def not 1st line treatment

69

Adverse effects of MAOIs

-orthostatic hypotension
-antimuscarinic
-mild-moderate sedation
-dose-related sexual dysfunction in males and females
-hypertensive crisis

70

see slide 28

kay man

71

What 2 types of antidepressants are first line therapies?

SSRI
SNRI