Drugs acting on the sympathetic nervous system (L11) Flashcards
where does NA act as a neurotransmitter?
sympathetic nervous system only
what is the sympathetic nervous system?
fight or flight response
- short preganglionic fibre
- long postganglionic fibre
- prepanglionic ACh
- postganglioic NA
NA pharmacology
- precursor is AA tyrosine
- its transported into neurone by an AA transporter
- synthesis of NA
- NA kept in vesicles for protection against cytosolic enzymes
- NA taken back up by NA transporter and is then broken down by monoamine oxidase or recycled
3 enzymes involved in the synthesis of NA
tyrosine hydroxylase
DOPA decarboxylase
DA beta-hydroxylase
the 2 classes of NA receptors
alpha
beta
alpha noradrenergic receptors
alpha1,2
located in effector tissues/targets of the sympathetic system
GPCP
slow response - seconds
beta noradrenergic receptors
beta1,2,3
located in effector tissues/targets of the sympathetic system
GPCP
slow response - seconds
what are sympathetic effects on the body
- pupils dilate
- lens of eye adjusts for far vision
- airways in lungs dilate
- HR increases
- blood vessels to limb muscles dilate
- blood vessels to visceral organs and skin constrict
- brain activity general alertness
what sympathetic effects do alpha1 receptors mediate?
- pupils dilate
- blood vessels to visceral organs and skin constrict
- brain activity and general alterness
what sympathetic effects do alpha2 receptors mediate?
- they are presynaptic receptors
- they turn off further release - negative feedback
- inhibits neurotransmitter release - both NA and ACh
autoreceptor = own type of neurone heteroreceptor = different neurone
what sympathetic effects do beta1 receptors mediate?
HR increases
force of contraction increases
what sympathetic effects do beta2 receptors mediate?
- lens of eye adjusts for far vision
- airways in lung dilate
- blood vessels to limb muscle dilate
what sympathetic effects do beta3 receptors mediate?
increases lipolysis - breakdown of triglycerides to fatty acids
noradrenergic agonists
adrenaline clonidine dobutamine salbutamol clenbuterol
adrenaline
noradrenergic agonist
agonist against all NA receptors - not selective
clonidine
noradrenergic agonist
finish
dobutamine
noradrenergic agonist
finish
salbutamol
noradrenergic agonist
finish
clenbuterol
noradrenergic agonist
finish
noradrenergic antagonists
prazosin tamsulson propranolol atenolol timolol
prazosin
noradrenergic antagonist
tamsulson
noradrenergic antagonist
propranolol
noradrenergic antagonist
atenolol
noradrenergic antagonist
timolol
noradrenergic antagonist
drugs affecting NA synthesis
drugs can give a false substrate
methylDOPA (meDOPA) acts as a false substrate for DOPA decarboxylase
drugs affecting NA storage
reserpine disrupts storage of NA in synaptic vesicles
overall decrease in NA neurotransmission
drugs affecting NA release
NA release is subject to auto inhibitory control via presynaptic alpha2 auto receptors
clonidine (alpha2 agonist) causes inhibition of NA release
• overall decrease in NA neurotransmission
• used to treat hypertension
drugs affecting NA reuptake
NA reuptake can be blocked by NA reuptake inhibitors
this will prolong the action of NA in the synapse
drugs affecting NA metabolism
NA is metabolised by monoamine oxidase (MAO) and catecholamine transferase (COMT)
by blocking these enzymes the amount of NA available for release is increased
tranylcypromine blocks MAO and allows more NA to be recycled so increases NA neurotransmission
cheese reaction
tranylcypramine and other MAOIs not only block the metabolism of NA but also block the metabolism of dietary amines (e.g. commonly found in cheese, marmite) and amines found in popular cold remedies
accumulation of dietary amines can have a sympathomimetic effect and result in hypertension
