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PED1003-Pharmacology > PED1003/L16 Antidepressants > Flashcards

PED1003/L16 Antidepressants Flashcards

1
Q

Give 3 symptoms of depression.

A

Low mood
Hopelessness, despair
Guilt, suicidality
Anhedonia
Altered appetite

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2
Q

What is the pathology of depression?

A

Unknown

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3
Q

What does the pharmacology of effective antidepressant drugs suggest about the pathology of depression?

A

Dysnfunction of 5-HT and/or NA systems

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4
Q

Give another name for serotonin.

A

5-HT

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5
Q

What does the locus coeruleus contain? (3)

A

NAergic cell bodies
Projections to hypothalamus and midbrain
Projections to hippocampus and cortex

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6
Q

What do the dorsal and median raphe nuclei contain? (2)

A

Serotonergic cell bodies
Projectioons to hypothalamus, hippocampus and cortex

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7
Q

Describe the synthesis of noradrenaline (3).

A

Tyrosine -> L-DOPA
L-DOPA -> dopamine
Dopamine -> noradrenaline

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8
Q

Name the 3 enzymes involved in noradrenaline synthesis.

A

Tyrosine hydroxylase
DOPA decarboxylase
Dopamine B-hydroxylase

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9
Q

Describe 5-HT synthesis (2).

A

Tryptophan -> 5-HTP
5-HTP -> 5-HT

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10
Q

Give the 2 enzymes involved in 5-HT synthesis.

A

Tryptophan hydroxylase
5-HTP decarboxylase

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11
Q

How is NA/5-HT stored?

A

In vesicles (vesicular monoamine transporters - VMAT2)

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12
Q

Where is monoamine oxidase present?

A

DA, NA and 5-HT terminals

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13
Q

What breaks down transmitter in cytosol?

A

MAO

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14
Q

What metabolises both NA and 5-HT?

A

MAO(A) and MAO(B)

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15
Q

Describe NA metabolism (2)

A

NA -> DOPEG via MAO and aldehyde dehydrogenase
DOPEG -> MHPG via catechol-O-methyl transferase

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16
Q

Describe 5-HT metabolism. (2)

A

5-HT -> aldehyde via MAO
Aldehyde -> 5-HIAA via aldehyde dehydrogenase

17
Q

Describe release and receptors of NA & 5-HT. (2)

A

Depolarisation causes exocytotic release
Receptors bind of pre- and postsynaptic membrane

18
Q

Give the 3 kinds of NA receptors.

A

A1
A2
B1, 2, 3

19
Q

What do A1 NA receptors do? (2)

A

Stimulate PI cycle
Increased DAG & [Ca2+]

20
Q

What do A2 NA receptors do? (2)

A

Inhibit adenylate cyclase, decreased cAMP
Open K+ channels (GIRK), hyperpolarise

21
Q

What do B1, 2, 3 NA receptors do?

A

Stimulate adenylate cyclase, increased cAMP

22
Q

Give 4 kinds of 5-HT receptor and their actions.

A

5-HT(A-F) inhibit adenylate cyclase, decreased cAMP
5-HT(1A) open K+ channel
5-HT(2(A-C)) stimulate PI cycle, increased DAG & [Ca2+]
5-HT(3) ligand-gated ion channel

23
Q

What kind of receptors are NA and 5-HT terminal autoreceptors?

A

NA - a2
5-HT - 5-HT(1B)
Both inhibitory

24
Q

How is NA/5-HT removed from the synaptic cleft?

A

Transporter proteins

25
Q

Give 2 1950’s drugs found to elevate mood.

A

Iproniazid
Imipramine

26
Q

What is the monoamine theory of depression?

A

Relative decrease in NA and/or 5-HT neurotransmission underlies the symptoms of depression

27
Q

What is the main target of current antidepressants? (2)

A

Presynaptic elements of NA/5-HT neurotransmission
Inhibition of MAO or reuptake

28
Q

What are the issues with MAOIs? (2)

A

Increased DA transmission - stimulant
Increased actions of sympathomimetic amines

29
Q

How do TCAs work?

A

Inhibit reuptake of 5-Ht and NA

30
Q

Give 3 side effects of TCAs.

A

H1 antagonism - sedation
mACh antagonism - dry mouth
A1 antagonism - postural hypotension

31
Q

Give 2 SSRIs/

A

Fluoxetine - Prozac
Parxetine - Seroxat
Sertraline - Zoloft
Escitalopram - Cipralex

32
Q

How do SSRIs work?

A

Inhibit reuptake of 5-HT selectively and no receptor interactions

33
Q

Describe serotonin syndrome. (2)

A

MAOI plus reuptake inhibitor (TCA or SSRI)
Synergistic increase in synaptic 5-HT provokes malignant hyperthermia

34
Q

Why don’t antidepressant work acutely? (2)

A

Autoreceptor desensitisation
Synaptic remodelling

35
Q

Describe acute desensitisation of autoreceptors. (5)

A

Reuptake blocked at cell body and terminal
Autoreceptors activated
Firing inhibited
Terminal release inhibited
Synaptic 5-HT levels are not increased

36
Q

Describe long-term desensitisation of autoreceptors. (4)

A

Autoreceptors desensitise
Firing is restored
Terminal release is restored
Reuptake still blocked
5-HT levels in synaptic cleft elevated

37
Q

What does increased synaptic 5-HT do? (2)

A

Promotes synaptic remodelling
Supports plasticity in forebrain neurones

PED1003-Pharmacology (27 decks)

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