18. The Autonomic Nervous System Flashcards Preview

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Flashcards in 18. The Autonomic Nervous System Deck (24)

What are the 12 main steps in neurotransmission?

1. Uptake of precursors. 2. Synthesis of transmitter. 3. Vesicular storage of transmitter. 4. Degradation of transmitter. 5. Depolarisation by propagated action potential. 6. Depolarisation-dependent influx of Ca2+. 7. Exocytotic release of transmitter. 8. Diffusion to post-synaptic membrane. 9. Interaction with post-synaptic receptors. 10. Inactivation of transmitter. 11. Re-uptake of transmitter. 12. Interaction with pre-synaptic receptors.


Which steps in neurotransmission are targeted pharmacologically?

Degradation of transmitter, interaction with post-synaptic receptors, inactivation of transmitter, re-uptake of transmitter, interaction with pre-synaptic receptor.


Which enzyme catalyses synthesis of acetylcholine?

Choline acetyltransferase.


Which enzyme catalyses degradation of acetylcholine?



How do drugs have selectivity at autonomic ganglia over nicotinic acetylcholine receptors at the neuromuscular junction?

The structures are different so drugs may only bind to one.


How many types of muscarinic acetylcholine receptors are there?

5: M1-M5.


How can the actions of endogenously released ACh be enhanced?

By AChE inhibitors as ACh is broken down slower so is the neuromuscular junction for longer to act longer.


What limits the useage of cholinergic drugs?

The lack of selectivity, as it means there are unwanted side-effects.


What is SLUDGE?

A mnemonic for the pathological effects indicative of massive discharge of the parasympathetic nervous system.


What are the symptoms in SLUDGE due to?

Chronic stimulation of muscarinic acetylcholine receptors in organs and muscles innervated by the parasympathetic nervous system.


What are the symptoms in SLUDGE?

Salivation, Lacrimation, Urination, Defecation, Gastrointestinal upset, Emesis (vomiting).


How can SLUDGE be treated?

With atropine, pralidoxime, or other anticholinergic agents.


What are some muscarinic ACh receptor agonists and their functions?

Pilocarpine - treats glaucoma. Bethanechol - stimulate bladder emptying.


What are some muscarinic ACh receptor antagonists and their functions?

Ipratropium and tiotropium - some types of asthma and COPD. Tolterodine, darifenacin, and oxybutynin - overactive bladder treatment.


How is noradrenaline synthesised?

In the cytosol: Tyrosine -> DOPA (tyrosine hydroxylase). DOPA -> Dopamine (DOPA decaroxylase). In the vesicle: Dopamine -> Noradrenaline (Dopamine B-hydroxylase).


How does NA act in the post-synaptic membrane?

It diffuses across the synaptic cleft and interacts with adrenoceptors to initiate signalling in the effector tissue.


How does NA act in the pre-synaptic membrane?

It interacts with pre-synaptic adrenoceptors to regulate processes within the nerve terminal.


Why has NA only have a very limited time to influence pre and post-synaptic adrenoceptors?

It is rapidly removed from the synaptic cleft by noradrenaline transporter proteins.


How are NA actions terminated?

Uptake 1 - re-uptake into the presynaptic terminal by a Na+ dependent, high affinity transporter. Uptake 2 - taken up by a lower affinity, affinity, non-neuronal mechanism.


How is NA metabolised?

In the pre-synaptic terminal, if NA isn't taken up it is susceptible to metabolism by two enzymes: MAO (monoamine oxide) or COMT (catechol-O-methyltransferase).


How can neurotransmitter release by inhibited?

By inhibiting Ca2+-dependent exocytosis.


How do indirectly-acting sympathomimetic agents work?

They are taken up into noradrenergic synaptic vesicles and cause NA to leak from vesicles. NA then leaks into the synaptic cleft.


How are effects of activation of B1-adrenoceptors in the heart mediated?

Through activation of the adenylyl cyclase/cyclic AMP signalling pathway.


What are the drugs of choice for chronic heart failure?

Bisoprolol, metoprolol (B1-adrenoceptor selective antagonists). Carvedilol (mixed B1/B2/a1 adrenoceptor antagonist).