CPTP 3.3 Neuropharmacology 1 (Antidepressants) Flashcards Preview

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Flashcards in CPTP 3.3 Neuropharmacology 1 (Antidepressants) Deck (42)
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1

What creates biological vulnerabilities for depression and mood disorders?

• Genetic predisposition
• Early adverse life experiences

2

Are catecholamines monoamines?

Yes

3

list the catecholamines

• NA
• Serotonin
• Dopamine

4

Outline briefly the monoamine hypothesis?

Depression is due to a deficit in central monoamine neurotransmission.

5

What evidence is there against monoamine theory?

• Cocaine inhibits NA uptake, but isn's an antidepressant
• Lowered monoamines aren't seen in patients with depression

6

Outline the biochemical pathway for the synthesis of 5-HT

Tryptophan --TPH--> 5-HTP
5-HTP --AADC--> 5-HT

TPH = tyrptophan hydroxylase
AADC = 5-hydroxytryptophan decarboxylase

7

What occurs to 5-HT after synthesis?

Either stored into vesicles or broken down by MAO into 5-HIAA and extruded

8

What are the most important postsynaptic 5-HT receptors?

• 5-HT 1A
• 5-HT 1B
• 5-HT 2A
• 5-HT 2C

9

What is the 5-HT autoreceptor?

5-HT 1A

10

How is serotonin terminated?

SERT in the presynaptic membrane pumps 5-HT back into the presynaptic neurone.

It can then either be transported back into vesicles or broken down by MAO

11

What two pharmacological targets are there for antidepressants?

The termination step:
• MAO
• SERT

12

Which antidepressants block 5-HT reuptake?

• Tricyclic antidepressants
• SSRIs
• SNRIs (serotonin & noradrenaline)

13

Which antidepressants block NA reuptake?

• SNRIs (serotonin & noradrenaline)
• NARIs

14

What effect do reuptake inhibitors have?

They prolong the effects of the neurotransmitter

15

What are the clinical limitations of TCAs?

• Delayed onset of 2 weeks before effective
• M1 antagonistic effects
• H1 antagonistic effects
• a1-adrenoreceptor antagonistic effects
• Cardiotoxic in overdose

16

What do TCA M1 antagonistic side effects include?

• dry mouth
• blurred vision
• constipation
• urinary retention

17

What do TCA H1 antagonistic side effects include?

• Sedation
• Weight gain

18

What do TCA a1 antagonistic side effects include?

Postural hypotension

19

What do the clinical limitations of TCAs result in?

Feeling worse before you feel better because the side effects are immediate but the therapeutic effects are delayed

This results in poor compliance

20

What are the benefits of TCAs

• Can be used for severe or resistant (other drugs aren't working) depression
• They are cheap

21

In what groups are TCAs not used?

• Elderly
• Young
• Cardiac patients
• Suicidal patients (overdose)
• Drivers (sedation)

22

Why are TCAs not used in cardiac patients?

They increase the chance of conduction abnormalities.

23

What are the 'second generation' antidepressant classes? What is special about these?

• SSRIs
• SNRIs
• NARI
Selective for 5-HT or NA transporters and do not have affinity for postsynaptic receptors so there are fewer side-effects

24

How do SSRI and SNRI efficacies compare to those of TCAs?

The same (but far fewer side-effects) "Clean drugs", high selectivity

25

What do the isoforms of MAO do?

• MAO A breaks down 5-HT and NA
• MAO B breaks down Dopamine

26

What does older MAOIs do? Name the one in the formulary. What are the downsides to these?

Blocks both isoforms of MAO irreversibly.

Phenelzine

• Stimulant effects
• Dangerous in overdose

27

What do new MAOIs do?

Reversible inhibitors of monoamine oxidase A (RIMA)

• Selective for MAO A
• Reversible
• Dont have the downsides of older MAOIs

28

What is the main side effect of MAOIs?

The cheese effect:
• MAO in gut and periphery usually breaks down dietary amines
• If MAOIs are used in a diet high in amines, this leads to a increased amine absorption
• Noradrenaline is displaced by these amines causing a hypertensive crisis

29

What is serotonin syndrome?

Result of drug-drug interaction between MAOIs and SSRIs
• Hyperthermia
• Confusion
• Hypertensive crisis

30

When does serotonin syndrome most commonly occur?

When switching between MAOIs and SSRIs due to the half lives of some of these drugs being high