Lecture 15 - ANS #2 Flashcards
outline the basic steps of neurotransmission
- uptake of precursors and synthesis of transmitter
- vesicular storage of transmitter
- degradation of transmitter
- depolarization by action potential
- influx of Ca2+ from depolarization
- Ca2+ triggers exocytosis of transmitter
- interaction with post-synaptic receptors
- inactivation of transmitter ie Ach esterase
- re-uptake of transmitter (inactive)
- possible interaction with pre-synaptic receptors
what steps are most common sites for drug action ?
NOTE: dont memorise these just get the jist of it
degradation of the transmitter in pre synapse
interaction with post-synaptic receptors
inactivation of transmitter
re-uptake of transmitter (inactive)
possible interaction with pre-synaptic receptors
How is Ach synthesised and degraded ?
acetyl CoA and Choline are catalysed by Choline Transferase to make Ach and CoA
Ach is degraded to an inactive form - acetate and choline by acetylcholineesterase
how can we used drugs to block receptors in the ANS
we can block nAchR’s specifically at the autonomic ganglia as opposed to neuromuscular junction do to different receptor structures - trimethaphan blocks as autonomic ganglia
5 muscarinic receptors - only limited selectivity - so drugs will act on all of them- not ideal most of the time
however toterodine is a good mAchR for overactive baldder
why do only have limited cholegenric drug use ?
get the jist of a couple only
a lack of selectivity in cholergenic drugs gives unwanted side effects
a non selective mAchR agonist will cause :
Heart -decrease in heart rate and cardiac output
Smooth muscle
bronchoconstriction - bad for asthma sufferers
GI peristalsis increase
exocrine glands
sweating and salivation increases
What is SLUDGE Syndrome ?
Massive discharge of parasympathetic nervous system
can be caused by organophosphates, drug overdose
often due to chronic overstimulation of muscarinic Ach receptors, or mess with acetylcholine estherase - idea is too much mAch stimulation
treat with atropine/pralidoxime - blocks muscarininc receptors
Salvation - stimulation of salivary glands
Lacrimation - stimulate lacrimal glands
Urination - relax urethral sphinchter - pee alot
Defecation
Gastrointestinal upset - smooth muscle problems in GI - can cause diarrhoea
Emis - vomiting
what are the clinical uses of mAch receptor agonists ?
Not Vital
pilocarpine - treat glaucoma and bethanechol -stimulate baldder emtying
local use is better than systematic - too many side affects
what are the clinical uses of mAch receptor antagonists?
Not Vital
ipratropium and tiotropium to treat some asthma and COPD
Tolterodine - overactive bladder
The majority of postganglionic sympathetic neurones use noradrenaline
Post-ganglionic sympathetic neurons possess a highly branching axonal network with numerous varicosities, each of which is a specialized site for Ca2+ -dependent noradrenaline release - a web mesh system that allows signal to command a large area
important for context only
Outline how noradrenaline works within a neuron/synapse
Noradenaline is porduced from precursor Tyrosine
steps are - Tyrosine - DOPA - Dopamine - Noradernaline
NA is stored in vesicles within the cell
Following depolarization - Ca2+ is taken into cell which triggers exoyctosis - NA is released
NA interacts with adrenoreceptors on the postsynaptic membrane- initiates a signal to the effector tissue
NA will also interact with adrenorecptors on the pre synaptic membrane to regulate NA release
NA is it rapidly removed from the synaptic cleft by noradrenaline transporter proteins
this terminates interaction - by re-uptake into the pre-synaptic terminal by a NET (Na+ dependent, high affinity transporter)
NA not re-captured by NET is taken up by uptake 2
Metabolism
Within the pre-synaptic terminal NA not taken up into
vesicles is susceptible to metabolism by two enzymes
• monoamine oxidase (MAO)
• catechol-O-methyltransferase (COMT)
these are important as if we inhibit with drugs we can increase the amount of NA in the system
what do we use to treat asthma- why is this effective ?
β2
adrenoceptor-selective agonists (e.g. salbutamol) are used in asthma to reverse/oppose bronchoconstriction
this is useful as b2 - lungs b1- heart so side affects are limtied
a non selective b agonist would give a dangerous increase in heart rate - selective b2 agonist does not
how can we alter the cardiovascular disorders using adrenorecptors ?
α1 adrenoceptor-selective antagonists
and β1 adrenoceptor-selective antagonists
are used to treat a number of cardiovascular disorders,
including hypertension.
