Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Infectious Final > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

What was the first TCA?

A

Imipramine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe imipramine activity:

A

It is a combo of both imipramine and desimpramine activity. Desimpramine is a 2ndary amine formed through N-demethylation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the half-life of imipramine? Desipramine?

A

8-12 hours and 7-60 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What drug is 50X more potent than imipramine? How?

A

Clomipramine. It is more selective for the 5HT reuptake.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which drug is the only halogenated TCA used to treat depression? What is the function?

A

Clomipramine. To increase selectivity for inhibiting serotonin reuptake.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What TCA has the highest antimuscarinic and sedative SE’s?

A

Amitriptyline (dibenzocycloheptane)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is amitriptyline’s t1/2?

A

16-90 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the metabolite of amitriptyline achieved through N-demethylation?

A

Nortriptyline (2ndary amine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Compare amitriptyline and nortriptyline:

A

Amitriptyline has a symmetrical ring system, and nortriptyline is less sedating with fewer antimuscarinic SE’s.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What mixture is doxepin used as? What isomer is more active?

A

It is a mixture of 85% E and 15% Z, Z isomer is more active.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the half-life of doxepin? It’s metabolite?

A

t1/2 = 15 hours to get to N-desmethyldoxepin. The half-life of the metabolite is ~30 hours.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are Zonalan and Silenor?

A

They are doxepin used in a topical cream (5% Zonalan) and a sleep aid (Silenor -central effects). They take advantage of doxepin’s SE profile.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the 2nd generation TCA that is tetracyclic?

A

Maprotiline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What benefits do this extra ring give Maprotiline?

A

Less flexibility, more rigidity. This gives more selectivity for inhibiting NET over SERT (~500 fold)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does a 2ndary amine give a TCA?

A

Selectivity for NET over SERT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Does maprotiline have antimuscarinic effects? What theory is used to hypothesize why?

A

Reduced sedation and antimuscarinic effects, but still some. Possibly because of 2ndary amine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q 
Tell me about tranylcypromine: 
what kind of core?
Structurally what is it related to?
Reversible inhibition?
Problems with other enzymes?
A

It is an MAO with a phenylethylamine core, with a cyclized amphetamine.
Irreversibly covalently modify MAO active site.
High selectivity means doesn’t cause problems at other enzymes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the radical process of tranylcypromine:

A

Cyclized part splits apart and a double bond forms at the nitrogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What MAOI is believed to be a prodrug?

A

Isocarboxazid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What releases the active drug from Isocarboxazid?

A

Amide hydrolysis releases benzyl hydrazine, which then inactivates MAO.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What type of drug is phenylzine?

A

An MAOI with a phenyl ethyl and a hydrazine. A reactive radical results in irreversible MAO inactivation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What transdermal patch is used to treat Parkinson’s?

A

Selegiline, an MAO-B inhibitor. Interferes with dopamine metabolism and serotonin receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Do SSRI’s have 2ndary or tertiary amine selectivity?

A

No, it does not seem to change selectivity in a pattern.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What type of amine is fluoxetine? What is the selectivity?

A

A secondary amine. Selective ~30 fold SERT over NET.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the active metabolite of fluoxetine formed from N-dealkylation?

A

Norfluoxetine (primary amine).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Compare fluoxetine and norfluoxetine:

A

t1/2 = 1-3 days acute, 4-6 days chronic for fluoxetine
t1/2 = 4-16 days
Both are 2D6 inhibitors with potential for interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What SSRI can be dosed once weekly?

A

Prozac weekly: 90mg capsule DR takes advantage of long half-life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What do all SSRI’s have in common regarding metabolism?

A

P450 metabolism, especially 2D6. Usually multiple.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How do you use them with MAOI’s?

A

Wait 2 weeks after MAO therapy to start fluoxetine. Wait 5 weeks after fluoxetine has stopped to start MAOI therapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What kind of inhibitors are MAOI’s?

A

Irreversible inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are EWG’s good for with SSRI’s?

A

Good for activity, selectivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How many possible isomers does sertraline have?

A

4 possible, but only 1S, 4S enantiomer used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What selectivity does sertraline have?

A

1400 fold selective for SERT over NET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the half life of sertraline? It’s metabolite?

A

24 hours and N-desmethylsertraline (less active as SSRI) is 62-104 hours.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What does sertraline inhibit?

A

Weak 2D6, not many drug interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What does CYP 2D6 do to paroxetine? What does paroxetine do to the enzyme?

A

Not methylation.
Removes methylene to form inactive catechol metabolite. 50% of the time can irreversibly inhibit the 2D6 from reactive intermediate, which alkylates the enzyme.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the t1/2 of paroxetine?

A

22 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is paroxetine used as?

A

Single 3S, 4R enantiomer

39
Q

What is paroxetine selective for?

A

~300 fold SERT over NET

40
Q

What is the primary amine SSRI?

A

Fluvoxamine

41
Q

What does UV light do to fluvoxamine?

A

It isomerizes to inactive Z isomer.

42
Q

What is the half-life and selectivity of fluvoxamine?

A

14-15 hour, ~600 fold SERT over NET

43
Q

What is the metabolism and inhibition of fluvoxamine?

A

Extensive metabolism leaves no active metabolites. It is a potent inhibitor of 1A2 and 2C19.

44
Q

What are the differences between citalopram and escitalopram?

A

Citalopram is a racemic mixture, while escitalopram is only the s enantiomer. Citalopram has a dosing limit based on Qt prolongation. Escitalopram has fewer histamine SE’s.

45
Q

Which SSRI is most selective for SERT over NET?

A

citalopram/escitalopram are >3,000 times more selective SERT over NET

46
Q

Weakest P450 inhibitor of the SSRI?

A

citalopram/escitalopram

47
Q

What is the half-lfe of citalopram? What does it metabolize to?

A

36 hours to metabolize to desmethylcitalopram, which is active but less so than parent compound.

48
Q

Which multimodal SSRI has an m-chlorophenylpiperazine (mCpp) metabolite that may contribute to the overall antidepressant action? What is the metabolism pathway?

A

Trazodone. 3A4. Nefazodone also.

49
Q

Trazodone: half-life, effects

A

Lacks antimuscarinic effects, t1/2 = 6 hours

50
Q

What is mCpp a partial agonist for?

A

5HT-2c

51
Q

Which multimodal SSRI has both an alpha-hydroxymetabolite and an mCpp metabolite that may contribute to the drug’s action? What metabolism? What are the half-lives for the drug and each metabolite?

A

Nefazodone. 3A4 for both pathways. t1/2 of nefazodone = 2-4 hours, for alpha-hydroxymetabolite 1&1/2 - 4 hours, and mCpp 4-9 hours.

52
Q

Both nefazodone and alpha-hydroxymetabolite inhibit what?

A

3A4

53
Q

What are possible side effects of nefazodone?

A

Hepatic failure/hepatotoxicity

54
Q

What is the multimodal SSRI with a 25 hour half-life and inactive metabolites?

A

Vilazodone. Inactive metabolites from a 3A4-mediated dealkylation.

55
Q

What multimodal SSRI is structurally distinct from the “azodones” and has a half-life of 66 hours, along with an inactive metabolite? How is it distinct?

A

Vortioxetine. No EWG and ring system pattern is missing. CH3 is changed to CO2.

56
Q

What enzyme is involved with Vortioxetine? What does it inhibit/induce?

A

2D6 is a major enzyme involved in forming the inactive product, but there is no P450 induction/inhibition.

57
Q

What are the two metabolites of venlafaxine, and what type of activity do they have?

A

3A4 leads to an N-desmethylvenlafaxine with minimal SNRI activity, while 2D6 leads to a O-desmethylvenlafaxine which has activity and is a separate antidepressant.

58
Q

What is the half-life of venlafaxine?

A

4-5 hours

59
Q

Does venlafaxine have affinity for M1, H1, or alpha1 receptors?

A

No

60
Q

How is desvenlafaxine formed?

A

By venlafaxine undergoes 2D6 O-demethylation

61
Q

What is the half-life of desvenlafaxine? Metabolism?

A

11 hours. Major- glucuronidation. Minor - 3A4 N-demethylation.

62
Q

What SNRI is similar to fluoxetine and has 2D6 inhibition?

A

duloxetine. The inhibition leads to drug interactions.

63
Q

What is the half-life of duloxetine?

A

12 hours

64
Q

What is the metabolism of duloxetine?

A

1A2 and 2D6, napthyl ring hydroxylation and then glucuronidation lead to inactive product.

65
Q

Levomilnacipran:

A

T1/2 = 12 hour
Major metabolite is inactive (3A4 mediated, N-deethylation.
Not a P450 inhibitor
single 1S, 2R enantiomer is active

66
Q

What atypical antidepressant has an amphetamine core structure?

A

Bupropion

67
Q

What is the half-life of bupropion?

A

21 hours

68
Q

What metabolism occurs and where? Active?

A

hydroxylation by 2B6 on one of the methyl groups on the turkey foot. Both are active.

69
Q

What are the SE’s of bupropion?

A

Restlessness and insomnia - could be associated with amphetamine core structure. Very little antimuscarinic or sedative SE’s.

70
Q

What does bupropion and its metabolite inhibit?

A

2D6

71
Q

What is the half-life of mirtazipine?

A

20-40 hours

72
Q

How is mirtazipine different than a TCA?

A

N-bearing ring attached to 2-atom bridge

Basic N is closer to tricyclic rings than a TCA, no antimuscarinic effects

73
Q

Does mirtazipine inhibit P450s?

A

No

74
Q

What are the drugs that block NE and 5HT transporters?

A 
TCA's!
Imipramine
amitriptyline
desipramine
doxepin
maprotiline
75
Q

What are the SE’s of the TCA’s?

A

cardiovascular (higher HR, lower BP), histamine receptor antagonism (sleepy), weight gain, decreased seizure threshold, sexual SE.
Toxicities = lethal in overdose, toxic sedative effects in combo with downers, cardiac effects, anticholinergic psychosis

76
Q

What class of drugs block NE and 5HT breakdown?

A

MAOI’s!
phenelzineu
tranylcypromine
isocarboxazid

77
Q

What are MAOI’s useful for?

A

Atypical depression and narcolepsy

78
Q

What are the adverse effects of MAOI’s?

A

dry mouth, impotence, loss of libido, hepatotoxicity, overdose toxicities with serotonin (hyperthermia) and too much NE (hypertension, tachycardia, muscular agitation).

79
Q

What can MAOI’s interact with?

A

They can prolong half-lives of deaminated drugs. Serotonin syndrome, treatable with Dantrolene. Lots of food restrictions.

80
Q

What are the 1st line agents for depression? Which is most efficacious?

A

SSRI’s. They all are equally so.

81
Q

What SSRI is most stimulating?

A

Fluoxetine

82
Q

Which drugs are better for anxiety with depression?

A

Sertraline and paroxetine

83
Q

Which SSRI has the shortest half-life?

A

Fluvoxamine

84
Q

Which drugs has the largest selectivity for SERT over NET?

A

Citalopram and escitalopram.

85
Q

Which SSRI has a side effect of hyponatremia in older patients?

A

Fluoxetine

86
Q

What do the multimodal SSRI’s do? What are they?

A

They have affinity for various 5HT receptor subtypes (in post-synaptic neuron) in addition to blocking SERT. Trazodone and nefazodone.

87
Q

What do SSRI’s do?

A

Block re-uptake of 5-HT

88
Q

Which drugs do not have sexual SE’s?

A

Bupropion, and nefazodone is marketed as having less, a well as mirtazipine.

89
Q

What are the SNRI’s?

A 
They have affinity for both SERT and NET
Venlafaxine
duloxetine
desvenlafaxine
levomilnacipran
90
Q

What are the SEs associated with SNRI’s?

A

Similar to SSRI’s, with additional NE SE’s, such as mild hypertension, dry mouth, increased HR, dilated pupils

91
Q

What is the mechanism for bupropion?

A

Inhibitor of central nicotinic receptors, inhibitor of NE and dopamine re-uptake. Stimulating, no anticholinergic SE’s reported. Safe for bi-polar.

92
Q

What is mirtazipine used for?

A

anxiety with depression (H1 antagonism = sleepy). Useful for treatment-resistant depression.

93
Q

What is the mechanism for mirtazipine

A

Not well-understood. May block presynaptic auto-receptors.

94
Q

What is hyperforin an ingredient in?

A

St. John’s Wort. Standardized to this, but not the active ingredient.

Infectious Final (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions