Pharmacology lecture 15
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- Created by: willmiddleham
- Created on: 09-04-15 18:31
What contains the NAergic cell bodies?
Locus coeruleus
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Where do the noradrenergic pathways project to?
Hypothalamus, midbrain, hippocampus and cortex
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What contains serotonergic cell bodies?
Dorsal and median raphe nuclei
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Where do the serotonergic pathways project to?
Hypothalamus, hippocampus and cortex
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What is NA and 5-HT metabolised by?
MAOa and MAOb
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NA receptors: What do the alpha 1 receptors do?
Stimulate PI cycle (excitatory)
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NA receptors: What do the alpha 2 receptors do?
Inhibit adenylate cyclase, opens K+ channels
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NA receptors: What do the beta 1,2,3 receptors do?
Stimulate adenylate cyclase
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Name the 5-HT receptors? What kind of receptor is it?
1A, 1B, 1D, 1E, 1F, 2A, 2C, 3, 4, 5, 6, 7. G-protein linked
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What do the 5-HT1 (A-F) do?
Inhibit adenylate cyclase
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What do the 5-HT2(A,C) do?
Stimulate PI cycle
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What do autoreceptors in the terminals of NA and 5-HT do? What receptors are they?
Inhibit transmitter release. NA terminal auto receptors are alpha 2. 5-HT terminal receptors are 5-HT1B
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What do autoreceptors in the cell bodies of NA and 5-HT do? What receptors are they?
Inhibit firing. NA cell body auto receptors are alpha 2. 5-HT cell body auto receptors are 5-HT1A.
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What is responsible for termination of neurotransmitter effects?
Monoamine reuptake transporters
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What does Iproniazid inhibit?
MAO
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What does Imipramine inhibit?
NA/5-HT reuptake
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What are MAOIs?
Monoamine inhibitors
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What do the MAOIs do?
Inhibit intracellular metabolism of 5-HT. INCREASE vesicular 5-HT. INCREASE 5-HT release.
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Name the types of MAOIs
Reversible (MAOa), irreversible (MAOa/b), selective, non-selective
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What are the side effects of MAOIs?
INCREASE DA transmission. INCREASE actions of sympathomimetic amines (cheese reaction)
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What is the cheese reaction?
Tyramine and other amines are normally metabolised by MAO. With MAOIs amine levels INCREASE. They act as indirect sympathomimetics provoke HYPERTENSIVE crisis
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What do monoamine reuptake inhibitors do?
Prevent removal of transmitter from synaptic cleft. Levels of transmitter in cleft INCREASE. Magnitude and duration of receptor activation INCREASE
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What are the properties of selective MAOIs?
Fewer side effects. Lower efficacy
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What are the properties of reversible MAOIs?
Lower interaction with other antidepressants. Lower efficacy
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What do tricyclic antidepressants do? What are the side effects?
Inhibit reuptake of 5-HT and NA. H1 antagonism - sedation. mAch antagonism - dry mouth. alpha1 antagonism - postural hypotension
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What is the serotonin syndrome?
Synergistic INCREASE in synaptic 5-HT provokes malignant hyperthermia.
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What are the 3 theories of delayed antidepressant action?
1) Postsynaptic receptor adaptation 2) Desensitisation of autoreceptors 3) Synaptic remodelling
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What happens during postsynaptic receptor adaptation?
Increase of synaptic levels of transmitter causes desensitisation of receptors. Desensitisation crucial in the therapeutic response.
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What happens during desensitisation of autoreceptors?
ADs inhibit firing and terminal release via auto receptors. Synaptic 5-HT levels NOT increased. Auto receptors desensitise firing and terminal release are restored --> synaptic 5-HT increases
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What happens during synaptic remodelling?
ADs cause increase in 5-HT. This increase causes synaptic remodelling (5-HT is a trophic factor) which takes time
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Other cards in this set
Card 2
Front
Where do the noradrenergic pathways project to?
Back
Hypothalamus, midbrain, hippocampus and cortex
Card 3
Front
What contains serotonergic cell bodies?
Back
Card 4
Front
Where do the serotonergic pathways project to?
Back
Card 5
Front
What is NA and 5-HT metabolised by?
Back
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