1.1 Pharmacology of antidepressant drugs and mood stabilisers Flashcards Preview

Psychiatry- Carol > 1.1 Pharmacology of antidepressant drugs and mood stabilisers > Flashcards

Flashcards in 1.1 Pharmacology of antidepressant drugs and mood stabilisers Deck (32)
Loading flashcards...
1
Q

What drug class is iproniazid from?

A

MAOi

2
Q

What drug class is imipramine from?

A

TCA

3
Q

What was lithium initially approved for?

A

Mania

4
Q

What is the mechanism of action of fluoxetine?

A

Inhibitor of 5HT reuptake.

5
Q

What is the mechanism of action of MAOi?

A
Slows breakdown of: 
NA
5HT
DA
by inhibiting the mitochondrial enzyme monoamine oxidase.
6
Q

Is depression simply hyposerotoninsm?

A

No

7
Q

What are the precursor molecules of serotonin?

A

Tryptophan (from legumes, cheeses, chocolate, red meat)

5-hydroxytryptophan (5HT)

8
Q

Which of the 5HT1/2/3 receptor types are inhibitory or excitatory?

A
5HT1- inhibitory 
5HT2/3- excitatory 
5HT4- excitatory 
5HT5- inhibitory
5HT6/7- excitatory
9
Q

What are the key receptor types involved in mood + 5HT?

A

5HT1A, 5HT1B, 5HT2A, 5HT2C, 5HT4, 5HT6, 5HT7

10
Q

Which drug groups target the 5HT1A receptors?

A

Antidepressants
Anxiolytics- eg. buspirone
Psychosis - Negative symptoms

11
Q

Which drug groups target the 5HT1B and 1D receptors?

A

Migraine- Tryptans

12
Q

What drug groups target the 5HT- 2A, 2B, and 2C receptor groups?

A

Antipsychotics (atypical antipsychotics for 5HT2a)

Antidepressants

13
Q

Which drug groups target the 5HT3 receptors?

A

Anti-emetics

some antidepressants and antipsychotics

14
Q

Which drug groups target the 5HT4 receptors?

A

GI pro-kinetic drugs, esp in IBS, chronic constipation

15
Q

What is the long term neurobiological effect of SSRIs?

A

change relative balance of positive to negative emotional processing, providing platform for subsequent cognitive and psychological consolidation
5HT1a receptors are autoreceptors throughout CNS

With antidepressant treatment, the reuptake of 5HT is inhibited, increased 5HT increases 5HT1A autoreceptor stimulation, which results in inhibition of firing (initially)

Chronic stimulation of the 5HT1a causes it to desensitise. Return of normal firing. Leading to more serotonergic transmission due to reuptake blockade. (later = more serotonin)

16
Q

Which SSRIs inhibit the CYP450 enzymes?

A

fluoxetine

paroxetine

17
Q

What are the most coomon adverse effects related to 5HT- SSRIs?

A

sexual dysfunction - reversed by traxodone
GI: nausea, dyspepsia, constipation, diarrhoea
short term anxiety

18
Q

What cases may TCAs be preferred for?

A

Hospitalised or severe depression (maybe)

19
Q

What three receptor types on the post-synaptic membrane do TCAs act on?

A

adrenergic receptor
histamine receptor
muscarinic acetylcholine receptor

20
Q

What are the main adverse effects of TCAs?

A
Constipation
Dry Mouth
Blurred vision
Effects on cardiac function- do ECG in overdose
postural hypotension
21
Q

What is the mechanism of action of MAOIs?

A

irreversible inhibitors (phenelzine, isocarboxazid, tranylcypromine) inhibit monoamine oxidase A and B
MAO-A- metabolises NA, 5HT, tyramine
MAO-B- metabolises DA, tyramine and phenylthylamine
This results in increased storage and availability of 5HT and NA for release.
Sympathomimetic effects - esp tranylcypromine

22
Q

What are the adverse effects of MAOIs?

A

Hypertensive crisis- tyamine containing foods and drugs cause release of NA.
Foods: cheese, yoghurt, yeast extract, meat, alcohol, broad beans, pickled herring
Drugs: sympathomimetics, OTC cold remedies, pethidine

Symptoms of hypertensive crisis: flushing, headache, increased BP
-rarely, CVA

Treatment: alpha blockade with PENTOLAMINE, CHLORPROMAZINE

23
Q

What are the dopamine related side effects of some antidepressants?

A
By blocking dopamine, EPS may occur: 
tremor
dystonia
akathisia
tardive dyskinesia 

primarily due to antagonism of DA receptors- D2 esp.

24
Q

What is the action of GABA in adult vs. developing brains?

A

GABA is the main inhibitory NT in mammalian brains
BUT
GABA Is primarily excitatory in developing brains!

binds and allows Cl- into cell or K+ out of cell
= hyper polarisation

25
Q

Name 4 agonists and 1 antagonist of the GABAa receptor (ligand gated ion channel)

A

Agonists:

  1. Ethanol
  2. Benzodiazapines
  3. Propofol
  4. Anaesthetics

Antagonists:
1. Flumazenil

26
Q

Name 2 agonists of the GABAb receptor - the GPCR that opens ion channels via intermediate G proteins

A
  1. baclofen

2. propofol (both GABA a and b)

27
Q

Name 2 GABA analogues

A
  1. pregabalin

2. gabapentin

28
Q

Which anticonvulsant drugs may be used as a mood stabiliser?

A
  • carbamazepine
  • valproate
  • semisodium valproate
  • lamotrigine
29
Q

Which atypical or second generation antipsychotics may be used as a mood stabiliser?

A

Olanzapine
risperidone
aripiprazole
quetiapine

30
Q

How does lamotrigine work in mood stabilising?

A
  • blocks Na+ channels- anticonvulsant activity
  • reduces excitability - not via GABA
  • may inhibit 5HT, NA, and DA uptake
31
Q

What is the mechanism of action of lithium?

A
Not exactly known
-inhibit 5HT(1a?) autoreceptors
-increase anti-apoptotic factor bcl-2
-inbhibit glycogen synthase kinase-3****
deplete insoditol
-upregulate glutamate re-uptake
32
Q

What is the main mechanism of action in antipsychotics? Where?

Why are there EPS side effects?

A

D2 - dopamine blocker
-mesolimbic circuits

adverse effects are due to DA blockade in the n igrostiatal and tuberinfundibular pathways

Second generation drugs have 3 main mechanisms of action:

  1. increased D2 receptor binding affinity
  2. Increased 5HT2c and 5HT2a receptor binding
  3. Increased 5HT1a receptor binding

all reduce antipsychotic efficacy