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Psychiatry > Pharmacology of Antidepressants and Mood Stabilisers > Flashcards

Pharmacology of Antidepressants and Mood Stabilisers Flashcards

1
Q

What is the MOA of monoamine oxidase inhibitors (MAOIs)?

A

Slows down the breakdown of NA, 5-HT and DA by inhibition of the mitochondrial enzyme monoamine oxidase

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2
Q

What is the MOA of antidepressants generally?

A

Blocking reuptake of monoamine neurotransmitters (5-HT, NA,DA)
Preventing breakdown of monoamine neurotransmitters
In short term increased neurotransmitter availability

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3
Q

What are Na selective antidepressants?

A 
Maprotiline
Desipramine
Reboxetine
Protriptyline
Nortriptyline
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4
Q

What are non-selective antidepressants?

A

Amitriptyline
Imipramine
Clomipramine

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5
Q

What are 5-HT-selective antidepressants?

A 
Venlafaxine
Paroxetine
Fluvoxamine
Sertraline
Fluoxetine
Citalopram
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6
Q

What are the appetitive/approach systems in the brain?

A

Function to mediate seeking and approach behaviours (incl. pleasure)
Ascending dopamine systems- mesolimbic/cortical projection
Ventral striatum
Dorsal striatum (movement)Amygdala (conditioning/learning)
Anterior cingulate (attention/ conflict/
response selection)
Orbitofrontal cortex (relative reward preference/ rule learning)

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7
Q

What are the aversive/defensive systems in the brain?

A 
Function to promote survival in event of threat (fear/pain)
Ascending serotonin systems
Na/CRF/Peptide transmitters
Central nucleus of amygdala
Hippocampus
Ventroanterior and medial hypothalamus
Periaqueductal gray matter
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8
Q

Describe the 5-HT1 receptor

A

Found in CNS and blood vessels
Inhibitory effect
Agonists: Quetiapine and trazodone
Antagonists: Nefazodone, Vortioxetine

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9
Q

Describe the 5-HT2 receptor

A

Found in blood vessels, CNS, PNS, GIT, platelets, smooth muscle
Excitatory effect
Agonists: LSD, mescaline
Antagonists: Most atypical antipsychotics, Mirtazapine, Agomelatine, Fluoxetine, Paroxetine, Nefazodone, Trazodone, Mianserin

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10
Q

Describe the 5-HT3 receptor

A

Found in CNS, PNS, GIT
Excitatory effect
Agonist: Quizapine
Antagonists: Mianserin, Clozapine, Mirtazapine, Olanzapine, Quetiapine, Vortioxetine

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11
Q

Describe the 5-HT4 receptor

A

Found in the CNS, PNS,GIT
Excitatory effect
No agonists/antagonists

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12
Q

Describe the 5-HT5 receptor

A

Found in CNS
Inhibitory effect
No agonists/antagonists

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13
Q

Describe the 5-HT6 receptor

A

Found in the CNS
Excitatory effect
No agonists
Antagonists: Amitriptyline, Clomipramine, Clozapine, Olanzapine, Aripiprazole

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14
Q

Describe the 5-HT7 receptor

A

Found in CNS, GIT, blood vessels
Excitatory effect
Agonist: Aripiprazole
Antagonists: Amitriptyline, Clomipramine, Mirtazapine, Vortioxetine, Clozapine, Olanzapine

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15
Q

What 5-HT receptor types are involved in mood?

A

5-HT 1A,B,2A,C,4,6,7

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16
Q

What 5-HT receptor types are involved in sleep?

A

5-HT 1A,2A,2B,5A,7

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17
Q

What 5-HT receptor types are involved in appetite?

A

5-HT 1A,2A,2B,2C,4

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18
Q

What 5-HT receptor types are involved in anxiety?

A

5-HT 1A,1B,1D,2A,2B,2C,3,4,6,7

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19
Q

What 5-HT receptor types are involved in aggression?

A

5-HT 1B

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20
Q

What 5-HT receptor types are involved in memory?

A

5-HT 1B,2A,3,4,6,7

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21
Q

What 5-HT receptor types are involved in learning?

A

5-HT 1B,2A,3,4,6,7

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22
Q

What 5-HT receptor types are involved in addiction?

A

5-HT 1B,2C,3

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23
Q

What are drugs used for that act on the 5-HT1A receptor?

A

Antidepressant
Anxioytic e.g. buspirone
Psychosis (-ve symptoms)

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24
Q

What are drugs used for that act on the 5-HT1B receptor?

A

Migraine eg triptans

25
Q

What are drugs used for that act on the 5-HT1D receptor?

A

Migraine eg triptans

26
Q

What are drugs used for that act on the 5-HT2A receptor?

A

Atypical antipsychotics

Antidepressants

27
Q

What are drugs used for that act on the 5-HT2B receptor?

A

Some antidepressants e.g. agomelatine

Some antipsychotics e.g. asenapine

28
Q

What are drugs used for that act on the 5-HT2C receptor?

A

Antidepressants

Antipsychotics

29
Q

What are drugs used for that act on the 5-HT3 receptor?

A

Anti-emetics
Some antidepressants e.g. mirtazapine, vortioxetine
Some antipsychotics e.g. clozapine, olanzapine

30
Q

What are drugs used for that act on the 5-HT4 receptor?

A

GI pro-kinetic (IBS, chronic constipation)

31
Q

What are drugs used for that act on the 5-HT5 receptor?

A

None known

32
Q

What are drugs used for that act on the 5-HT6 receptor?

A

Antidepressants

Anxiolytics

33
Q

What are drugs used for that act on the 5-HT7 receptor?

A

Antidepressants

Anxiolytics

34
Q

What are some SSRIs?

A

Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine

35
Q

What are SSRIs used to treat?

A

Depression, panic disorder, social anxiety disorder, PTSD, OCD, chronic pain, eating disorders, stroke recovery, premature ejaculation

36
Q

What is the MOA of SSRIs?

A

By inhibiting the re-uptake of 5-HT, increase synaptic 5-HT within hours
Effect takes 2-3 weeks however to improve mood

37
Q

What may be a mechanism that causes the delayed effect of most antidepressants?

A

5-HT1A receptors- autoreceptors found throughout the CNS that are inhibitory

38
Q

What are the clinical aspects of SSRIs?

A

Almost all can be started at therapeutic dose from day 1
Tolerated well
Safe in overdose
Some (fluoxetine, paroxetine) inhibit CYP450 which causes interactions with other drugs that are metabolised via the same pathways

39
Q

What are some adverse effects of SSRIs?

A

Sexual dysfunction (can be via DA blockade and/or 5-HT2 activation, can be reversed by 5-HT2 antagonists or 5-HT1A partial agonists)
GI S/E- nausea, dyspepsia, constipation, diarrhoea
Short term anxiety
In <25yo, increased risk of self harm and suicide in first few weeks

40
Q

What may patients at higher doses of TCAs need?

A

ECGs (QTc)

41
Q

What are the adverse effects of TCAs?

A 
Constipation
Dry mouth
Blurred vision
Effects on cardiac function
Postural hypotension (cholinergic and adrenergic blockage causing failure of peripheral orthostatic reflexes)
42
Q

What does MAO A metabolise?

A

NA, 5-HT and tyramine

43
Q

What does MAO B metabolise?

A

DA, tyramine and phenylethylamine

44
Q

When are MAOIs often used?

A

Treatment of atypical depression

45
Q

What are the adverse effects of MAOIs?

A

Tyramine inactivated in gut by MAO (it acts by releasing NA)
HT crisis can occur with tyramine-containing foods (cheese, yoghurt, yeast extracts, meat, alcohol, broad beans, pickled herring) and some drugs (sympathomimetics (including OTC cold remedies), pethidine)
Symptoms: flushing, headache, increased BP, rarely CVA

46
Q

What is an MAOI HT crises treated with?

A

Alpha blockade (phentolamine, chlorpromazine)

47
Q

Describe GABA (A)

A

Ligand gated ion channel
Agonists: Ethanol, benzos, propofol, anaesthetics
Antagonists: Flumazenil

48
Q

Describe GABA (B)

A

GPCR- opens ion channels via intermediate G-proteins
Agonists: Baclofen, propofol
No antagonists

49
Q

What are some GABA-transaminase inhibitors?

A

Phenelzine, Valproate, Vigabatrin

50
Q

What are some GABA analogues?

A

Pregabalin

Gabapentin

51
Q

What are mood stabilisers?

A

Most are anti-convulsants

More effective at reducing manic episodes than depressive episodes

52
Q

What are some types of mood stabiliser?

A

Anti-convulsants: carbamazepine, valproate, lamotrigine
Atypical antipsychotics: olanzapine, risperidone, aripiprazole, quetiapine
Others: lithium carbonate, nimodipine (CCB)

53
Q

How do mood stabilisers likely exert their effects?

A

By increasing inhibitory neurotransmission in the brain

54
Q

Describe Lamotrigine

A

Blocks Na channels
Overall effect is to reduce excitability and cell firing
May also inhibit 5-HT, NA, DA uptake as well

55
Q

What are the MOAs of lithium?

A 
Inhibition of 5-HT autoreceptors
Increase in anti-apoptotic factor Bcl-2
Increase in glycogen synthase kinase-3 (GSK-3)
Depletion of inositol
Upregulation of glutamate re-uptake
56
Q

Describe lithium in clinical practice

A

High incidence of adverse effects and toxicity
Toxicity in overdose
Poor adherence
Requires blood monitoring

57
Q

What is the MOA for typical antipsychotics?

A

Affinity for D2 receptor
DA blockade in mesolimbic circuits
Adverse effects (movement disorders, hyperprolactinaemia) due to DA blockage in the nigrostriatal and tubero-infundibular pathways respectively

58
Q

What are the main MOAs for atypical antipsychotics?

A

Increased D2 receptor-binding affinity increases antipsychotic effectiveness
Increased 5-HT2C and 5-HT2A receptor binding affinities increase antipsychotic efficacy
Increased 5-HT1A receptor binding affinity reduces antipsychotic efficacy

Psychiatry (29 decks)

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