L10: Drugs affecting SYM NS 1 Flashcards
3 branches in the peripheral nervous system
1) Somatic NS
2) Autonomic NS
3) Enteric NS
What does sympathetic NS prepare us for?
Flight or fight
How does efferent nerves of the sympathetic NS leave?
Spinal cord in the thoracic & lumbar regions
Role of adrenal medulla
Controls hormones that initiates fight or flight responses
Main hormones secreted by the adrenal medulla
1) Epinephrine (Adrenaline)
2) Norepinephrine (Noradrenaline)
What acts as neurotransmitters in the sympathetic NS?
ACh & noradrenaline
What do post-ganglionic nerves in the SNS release?
Noradrenaline as their neurotransmitter = noradrenergic nerves
Features of the postganglionic nerves
Varicosities: ‘swellings’ along their length wich releases noradrenaline
1st step of synthesis pathway for noradrenaline
Begins with amino acid tyrosine
What is the 2nd step; “rate-liming step”
Conversion of tyrosine to DOPA by enzyme** tyrosine hydroxylase ** which is the slowest step
3rd step of synthesis of noradrenaline
Synthesis of dopamine occur in the cell cytoplasm
4th step; conversion of dopamine
conversion of dopamine to noradrenaline by enzyme dopamine beta-hydroxylase in synaptic vescicles within varicosity
Role of the drug carbidopa
Inhibits the enzyme DOPA decarboxylase
5th stage of synthesis of noradrenaline & adrenaline
Noradrenaline to adrenaline
**Chomaffin cells ** of the adrenal medulla contain **phenylethanolamin N-methyl transferase (PNMT) ** that converts noradrenaline to adrenaline
6th step: what happens when it is stimulated?
Adrenal medulla releases a mix of adrenaline (95%) & noradrenaline (5%) into the blood stream
Role of drug a-methyl tyrosine
Inhibits tyrosine hydroxylase which secretes a lot of adrenaline
Release of noradrenaline
How is exocytosis triggered?
Increase in intracellular conc of Ca2+ ions caused by Ca2+ entering the channels, opened by an AP
Release of noradrenaline 2
How does the released noradrenaline act?
Act on receptors found on target tissue but some act on a2-adrenoreceptors found on varicosity
How can release of noradrenaline be inhibited?
“Noradrenergic neurone blocking” drug guanethidine
How do noradrenaline & adrenaline produce their effects by doing?
Activating “adrenoceptors”
Define adrenoceptors
A group of nine 7-transmembrane receptors comprising of 3 main types: a1, a2, and a3
Which 4 main types of adrenoceptor is used to explain drug action?
a1, a2, b1, b2
All GPCRs (G-protein coupled receptors)
Removal of noradrenaline
1st step of removal
Once released, about 75% of noradrenaline is removed from synapse & taken back into the varicosity by Uptake-1 carried out by the norepinephrine transporter (NET)
Removal of noradrenaline
2nd step: What happens to the remaining 25% of noradrenaline?
Taken up into other cells by Uptake-2 carried out by extraneuronal monoamine transporter (EMT)
What 2 things can happen to the noradrenaline when it is inside the varicosity?
1) Taken back up into the synaptic vesicles by VMAT
2) Destoryed by enzyme Monoamine Oxidase (MAO)
What does NET stand for?
Norepinephrine transporter
Role of norepinephrine transporter (NET)
Remove neurotransmitters from synapses
1 drug that inhibits NET
Cocainel; increase extracellular concentration of noradrnealine in both peripheral & CNS
How can recycled noradrenaline be can increased further?
By **monoamine oxidase ** which repackages them into vesicles
What food do patients who take MAOIs cannot have?
Cheese
Why does this “cheese reaction” occur?
MAO is found in cells of gut for breaking down dietary tyramine
1. Normal intake of cheese results in little tyramine
2. MAOI drug, tyramine reaches blood stream
Tyramine is a “indirectly acting sympathomimetic” drug
1. Taken up to sympathetic nerves (through NET) into synaptic vesciels where it displaces noradrenaline out of vesicles
Role of amphetamine
Increase extracellular concentration of noradrenaline in the CNS
How does amphetamine do its job?
- Act like tyramine
- Inhibiting MAO, enzyme busy breaking down amphetamine & can’t break down noradrenaline
Role of antidepressant fluoxetine
Inhibits uptake of neurotransmitter seronin in the brian
