15 - Antidepressants Flashcards
The underlying pathology of depression is unknown, however it is thought to involve _____ and/or __________ (as inferred from antidepressant mechanisms).
The underlying pathology of depression is unknown, however it is thought to involve 5-HT (seratonin) and/or noradrenaline (as inferred from antidepressant mechanisms).
The synthesis of noradrenaline is identical to that of dopamine, except for the further conversion of __________ to __________ (bonus: by the enzyme _________ __-________)
The synthesis of noradrenaline is identical to that of dopamine, except for the further conversion of dopamine to noradrenaline (bonus: by the enzyme dopamine β-hydroxylase)
Outline the product at each step of 5-HT (serotonin) synthesis…
- Tryptophan
- 5-HTP
- 5-HT (serotonin)
Monoamine oxidase breaks down…
a) Noradrenaline
b) 5-HT (serotonin)
c) Both NA and 5-HT
d) GABA
Monoamine oxidase breaks down…
a) Noradrenaline
b) 5-HT (serotonin)
c) Both NA and 5-HT
d) GABA
List the subtypes of noradrenergic receptor…
- α1 - ↑DAG ↑Ca2+ (excitatory)
- α2 - ↓ cAMP , open K+ channels (inhibitory)
- β1-3 - ↑ cAMP (excitatory)
Both NA and 5-HT receptors can be linked to…
G-proteins
List the 5-HT receptor subtypes…
5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 3, 4, 5, 6, 7
Which 5-HT receptor subtype is linked to ligand gated channels (ionotropic)?
3
5-HT 1 and 2 type receptors are linked to…
G-Proteins
Autoreceptors are present at:
a) Both NA and 5-HT terminals
b) NA terminals
c) 5-HT terminals
d) Monoamine reuptake transporters
Autoreceptors are present at:
a) Both NA and 5-HT terminals
b) NA terminals
c) 5-HT terminals
d) Monoamine reuptake transporters
Name the NA and 5HT autoreceptors…
- NA = α2
- 5-HT = 5HT1A
Both NA and 5HT have autoreceptors at the terminals to inihibit release AND on…
Cell bodies to inhibit firing
High affinity reuptake transporters remove neurotransmitters from the…
Synaptic cleft
In the 1950s it was found that the anti-TB drug Iproniazid elevated mood in patients. It acts as a…
MAO inhibitor
Imipramine (orginally an antihistamine) was also found to elevate mood in patients. This is thought to occur due to its inhibition of…
Noradrenaline and 5-HT reuptake
(Imipramine is a TCA)
The effectiveness of iproniazid and imipramine and their respective mechanisms of action formed the basis for the…
Monoamine Theory of Depression
The monoamine theory of depression suggests the pharmacotheraputic aim in treating depression should be to increase…
Noradrenaline and 5-HT neurotransmission
Antidrepressants can be divided into two broad classes based on mechanism of action…
- Monoamine Oxidase Inhibitors (MAOIs)
- Monoamine Reuptake Inhibitors (such as TCAs, SSRIs and SNRIs)
Monoamine oxidase inhibitors may be reversible or irreversible and ________ or __________
Monoamine oxidase inhibitors may be reversible or irreversible and selective or non-selective
Monoamine reuptake inhibitors can be either ______ or ________
Monoamine reuptake inhibitors can be either selective or non-selective
Outline how MAOIs increase 5HT neurotransmission…
- MAO is inhibited
- Intracellular metabolism of monoamines by MAO is reduced
- This increases 5-HT in vesicles
- This increases 5-HT released
MAOIs are effective antidepressants, however their downsides include…
- Stimulant effect (↑DA transmission)
- Risk of ‘cheese reaction’ (↑Sympathomimetic amines)
- Interactions with reuptake inhibitors can lead to serotonin syndrome
- Effects outlast drug clearance (Irreversible)
MAOIs also inhibit MAO enzymes in the perifery. This can lead to too much ________ (from dietary sources) which has a sympathomimetic effect (acts like noradrenaline), which leads to increases in ____ ________ . This is known as the cheese reaction.
MAOIs also inhibit MAO enzymes in the perifery. This can lead to too much tyramine (from dietary sources) which has a sympathomimetic effect (acts like noradrenaline), which leads to increases in blood pressure. This is known as the cheese reaction.
Give an example of a TCA…
Amitriptyline
TCAs inhibit the ________ of 5-HT and NA
TCAs inhibit the reuptake of 5-HT and NA
TCA side effects include…
- Sedative effect (H1 antagonism)
- Dry mouth (mAch antagonism)
- Postural hypotension (α1 antagonism)
Which of the following statements about SSRIs is true?
a) They have fewer side effects and higher efficacy than TCAs
b) They have greater side effects but higher efficacy than TCAs
c) They have fewer side effects and similar efficacy than TCAs
d) They have similar side effects and efficacy to TCAs
Which of the following statements about SSRIs is true?
a) They have fewer side effects and higher efficacy than TCAs
b) They have greater side effects but higher efficacy than TCAs
c) They have fewer side effects and similar efficacy than TCAs
d) They have similar side effects and efficacy to TCAs
Serotonin syndrome may result from the combination of a MAOI with a _______ __________ (TCA or SSRI).
Synergistic increase in serotonin at the synapse leads to…
Serotonin syndrome may result from the combination of a MAOI with a reuptake inhibitor (TCA or SSRI).
Synergistic increase in serotonin at the synapse leads to malignant hyperthermia
The pharmacological actions of antidepressants are delayed by 4-6+ weeks. Theories as to why include…
- Post-synaptic receptor adaptation
-
Autoreceptor desensitisation
- Autoreceptors must be desensitised for synaptic 5-HT to increase
-
Synthaptic remodelling
- 5-HT acts as a trophic factor
- Increased 5-HT causes synaptic remodelling, which takes time
