Autonomic Nervous System 2 Flashcards
Briefly outline the basic steps of neurotransmission.
Uptake of precursors Synthesis of transmitter Vesicular storage of transmitter Degradation of transmitter Depolarisation by propagated action potential Depolarisation-dependent influx of Ca2+ Exocytotic release of transmitter Diffusion to post-synaptic membrane Interaction with post-synaptic receptors Inactivation of transmitter Re-uptake of transmitter Interaction with pre-synaptic receptors
Where in the steps of neurotransmission is the most common site for drugs to intervene?
On degradation of transmitter Interaction with postsynaptic receptors Inactivation of transmitters Re-uptake of transmitters Interaction with pre-synaptic receptors
What types of receptors are found in sympathetic preganglionic receptors?
Cholinergic
What types of receptors are found in sympathetic postganglionic receptors?
Cholinergic but mostly adrenergic receptors
What types of receptors are found in parasympathetic preganglionic receptors?
Cholinergic
What types of receptors are found in parasympathetic postganglionic receptors?
Cholinergic
How is acetylcholine synthesised?
Acetyl CoA + Choline -> acetylcholine + coenzyme A
With the help of the enzyme choline acetyltransferase
How is acetylcholine degraded?
Acetylcholine -> acetate + choline
With the help of the enzyme acetylcholinesterase
What are the consequences of cholinergic drugs?
They usually lack selectivity. This means that if you try to treat something there may be unwanted side-effects.
What is a non-selective muscarinic ACh receptor agonist likely to cause? Give examples.
Autonomic side-effects such as: Heart: Heart rate and cardiac output going down Smooth muscle: Bronchoconstriction and GI-tract peristalsis increases Exocrine glands: Sweating and salivation going up
What is SLUDGE syndrome?
A mnemonic for the pathological effects indicative of massive discharge of the parasympathetic nervous system which is a consequence of organophosphate poisoning where acetylcholinesterase is inhibited. Salivation Lacrimation Urination Defecation Gastrointestinal upset Emesis
How can SLUDGE syndrome come about?
Drug overdose
Ingestion of magic mushrooms
Expose to organophosphorus insecticides
Why do you get the symptoms of SLUDGE?
Du to chronic overstimulation of muscarinic acetylcholine receptors in organs and muscles innervated by the parasympathetic nervous system.
How can SLUDGE be treated?
Anti-cholinergic agents such as atropine and pralidoxime
mACh receptor agonists and antagonists can be used clinically. Give examples of how the agonists can be used.
Agonists such as pilocarpine and bethanechol are respectively used to treat glaucoma and acutely to stimulate bladder emptying
Gives examples of how the antagonists can be used.
To treat some forms of asthma and chronic obstructive pulmonary disease (COPD)
Also to treat an overactive bladder
How do noradrenergic varicosities work in release of neurotransmitter?
Tyrosine goes into the varicosity and becomes DOPA and then dopamine. It is then stored in a vesicle and turns into noradrenaline. Noradrenaline is the released and acts on a post-junctional adrenoceptor.
Where is noradrenaline converted into adrenaline?
Within the adrenal medulla in the chromaffin cells.
What are the two fates of noradrenaline in noradrenergic transmission?
Termination or metabolism
Outline how termination works.
NA actions are terminated by re-uptake into the pre-synaptic terminal by a Na+-dependent high affinity transporter.
NA that is not recaptured by the Na+ transporter is taken up by a lower affinity non-neuronal mechanism.
Outline how metabolism works.
Within the pre-synpatic terminal NA that is not taken up into vesicles again and reused is susceptible to metabolism by monoamine oxidase and catechol-O-methyltransferase.
Where can you pharmacologically manipulate noradrenergic transmission?
Inhibiting metabolism (MAO inhibitors). Inhibit NA synthesis by inhibiting Tyrosine converting into DOPA. alpha2-receptor antagonists and agonists to either increase or decrease re-uptake of NA. Inhibition of post-synaptic receptors to bind to NA.
Why are beta2-adrenoceptor-selective agonists’ selectivity important?
It is used in asthma for example to cause bronchodilation.
However if they weren’t selective they could act on beta1-adrenoceptors found in the heart as well causing tachycardia and positive inotropy.
However there are also b2-adrenoceptors in the heart so it is not entirely possible to limit side-effects.
Why would you use alpha1-adrenoceptor-selective antagonists and beta1-adrenoceptor-selective antagonists?
Used to treat a number of cardiovascular disorders such as hypertension.
