Flashcards in M&R Session 10 Deck (104):
Is the ANS efferent, afferent or both?
What type of input regulates the ANS?
Where do parasympathetic nerves originate from?
Lateral horn of medulla and sacral spinal cord
Describe parasympathetic pre-ganglionic neurones.
Describe parasympathetic post-ganglionic neurones.
Where are the ganglia in the parasympathetic division of the ANS?
Where do sympathetic nerves originate in the sympathetic nervous system?
Lateral horn of lumbar and thoracic spinal cord
Describe sympathetic preganglionic nerves.
Describe sympathetic postganglionic nerves.
Where are sympathetic ganglia found?
Which neurotransmitter is used in all preganglionic neurones?
What type of receptors are found on postganglionic neurones in both the sympathetic and parasympathetic nervous systems?
Which neurotransmitter and corresponding receptor do postganglionic parasympathetic neurones use?
Which type of neurotransmitter and corresponding receptor do postganglionic sympathetic neurones utilise?
Alpha and beta adrenoceptors
How may genes code for adrenoceptors in the human genome?
Are all sympathetic postganglionic neurones noradrenergic?
Which sympathetic postganglionic neurones are cholinergic?
When can NANC transmitters be released?
Coreleased w/NA or ACh
Give four examples of NANC transmitters.
How is ATP used as a NANC transmitter?
Copackaged into vesicles, especially w/NA
What does ATP use as a NANC transmitter regulate?
Give two examples of neuropeptides used as NANC transmitters.
Vasoactive intestinal peptide
What do sympathetic postganglionic neurones in the adrenal glands differentiate to form?
Neurosecretory chromaffin cells
What is the function of chromaffin cells?
Release adrenaline into blood
What type of receptors are found in chromaffin cells?
Which area/s of the heart does parasympathetic ACh release act on?
Atria - sparse if any input to ventricles
What two effects does activation of M2 receptors by ACh have in the heart?
SAN --> bradycardia
AVN --> decrease cardiac conduction velocity
Which receptor subtype is found in the lungs and GI tract and is activated by ACh?
What is the affect of ACh release on the lungs and GI tract?
Lungs - bronchial contraction
GI - increased mobility and secretion
What are the effects of ACh release on the GU tract?
Penile erection (increased bloodflow)
What is the affect of ACh release on the eye?
Ciliary muscle and iris sphincter contraction
What causes the increase in bloodflow which causes penile erection?
Which receptor type is found in glandular tissue which is activated by ACh release?
What is the affect of M1/3 activation by ACh in glandular tissue?
Control level and composition of secretion
Which component of the lungs, GI tract, GU tract and eye is affected by ACh release?
What does the ANS exist in parallel but separate to?
Somatic nervous system
What effects does NA release have on the heart?
SAN --> +ve chronotropy
Ventricle --> +ve inotropy
Which receptors are activated in the heart by NA?
What does the balance of beta-1 and beta-2 receptors in the heart depend on?
What affect does NA release have on the smooth muscle of the vasculature?
Arteriolar relaxation in some vascular beds
What type of receptors constrict visceral BV upon NA release?
What type of receptors dilate BV in exercising tissue?
What subtype/s of receptor cause smooth muscle relaxation in the lungs, GI tract and GU tract upon NA release?
What does the activation of receptors (thought to be beta-3) in the GU by NA cause the bladder sphincter to do?
What does alpha-1 activation by NA cause in the eye?
Radial muscle contraction
What increases viscous secretion in the salivary glands?
What causes renin release in the kidney?
How is the prostate gland innervated by the ANS?
Parasympathetic on epithelial cells controlling generation of secretion
Sympathetic on smooth muscle contraction --> release of secretory products
What additional medication were prostate cancer patients with a better prognosis noted to be taking?
What is seen in all prostate cancers irrespective of age of patient that affects the rate of development and metastasis?
What constantly modulates efferent ANS neurone activity?
Afferent/sensory ANS inputs
What monitors carbon dioxide, oxygen, arterial pressure, GI tract content and chemical composition?
What is sensed by the carotid body/ chemoreceptors at carotid artery bifurcation?
Blood oxygen, carbon dioxide and pH
How are the inputs to the carotid body/ chemoreceptors at carotid artery bifurcation coordinated?
Glossopharyngeal nerve --> CNS
What forms the nucleus tractus solitarius (nTS)?
Primary sensory neurones acting on second order sensory neurones in medulla oblongata
What is the function of area postrema?
Detect toxins in blood and CSF
Essential for chemical-induced vomiting
Essential for conditional taste aversion
What integrates all visceral afferent information?
Nucleus tractus solitarius
What are the 12 basic steps in neurotransmission?
Uptake of precursors
Synthesis of transmitter
Vesicular storage of transmitter
Degradation of transmitter
Depolarisation by propagated AP
Depolarisation-dependent influx of calcium ions
Exocytotic release of transmitter
Diffusion to post-synaptic membrane
Interaction w/ post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors
Which steps of neurotransmission can be targeted by drugs?
Degradation of neurotransmitter
Interaction w/post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors
Why is degradation of ACh immediate?
Abundance of AChE
What can be used to irreversibly inhibit AChE in terrorist attacks?
How is ACh formed?
Acetyl CoA + choline --> ACh + CoA
Uses choline acetyltransferase (CAT)
Where can cholinergic function be manipulated in the ANS?
Effector - especially parasympathetic branch
What does interfering with the cholinergic function at the ganglia of the ANS effectively do?
Switch off ANS
Why can nAChR at autonomic ganglia be targeted and the nAChR at the NMJ be unaffected?
Different receptor structures
What is Trimethapan?
Ganglion-blocking drug used in hypertensive emergencies and when hypotension is needed during surgery
How many mAChR subtype specific agonists or antagonists are currently available clinically?
Only a few
What is Tolterodine?
mAChR antagonist used to treat an overactive bladder w/limited tissue selectivity
How can endogenous ACh release be enhanced?
Pyridostigmine and Donepezil are AChE inhibitors. What are they used to treat?
Pyridostigmine - myasthenia gravis
Donepezil - Alzheimer's
What often has to be given with a mAChR agonist to prevent unwanted side effects caused by low specificity?
How can low specificity mAChR agonists and antagonists be used effectively clinically?
Administer locally not systemically
How are mAChR agonists pilocarpine and bethanechol used to treat glaucoma and to stimulate bladder emptying respectively?
Used w/pharmacodynamics to localise drug effects
What are mAChR antagonists ipratrapium and tiotropium used to treat?
What are Tolterodine, clarifenacin and oxybutynin?
mAChR antagonists used to treat an overactive bladder
What do postganglionic sympathetic neuron axons form to allow for specialised sites of calcium-dependent NA release?
Highly branched atonal network w/numerous varicosities which are regularly arranged
(Beads on a string)
What do varicosities allow for?
Coordinated responses on a wide field of the effector organ
Give the intermediates of noradrenaline synthesis
Tyrosine --> DOPA --> dopamine --> noradrenaline
Which enzymes are needed for NA synthesis?
Which stage of NA synthesis takes place in the vesicle?
Conversion of dopamine to NA
What type of receptor forms the auto-regulatory feedback system in NA release?
How does alpha-2 activation prevent further NA release?
Beta-gamma subunits inhibit VOCCs
How can DOPA be sued to treat Parkinson's disease?
Delivered in pharmacokinetic protected dose
How is NA release terminated?
Rapidly by Uptake 1
Rest by Uptake 2
Small amount escapes
What is Uptake 1?
High affinity, sodium dependent NA transporter
What percentage of released NA is recaptured by Uptake 1?
What is Uptake 2?
Lower affinity, non-neuronal NA transporter protein
Why can NA metabolism only occur after uptake?
Lack of extracellular enzymes
What happens to the majority of NA uptaken after release?
~90% is repackaged into vesicles
What happens to the NA uptake that is not repackaged into vesicles?
Metabolised by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)
What are tyramine, amphetamine and ephedrine examples of?
Indirectly acting sympathiomimetic agents
How do indirectly acting sympathiomimetic agents intervene in adrenergic transmission?
Taken up into vesicles --> allow NA leak from vesicles and into synaptic cleft without influx of calcium ions
What are tricyclic antidepressants and selective NA re-uptake inhibitors examples of?
Uptake 1 inhibitors
Where do Uptake 1 inhibitors exert their major therapeutic action?
What must be minimised by drug choice and dosage when using amitryptyline, imipramine or reboxetine for example?
Peripheral actions e.g. tachycardia and cardiac dysrhythmia
What are salbutamol and salmeterol?
Beta-2 selective agonists used to treat asthma
What are doxazosin and atenolol, drugs used for CVS disorders incl. hypertension?
Doxazosin - alpha-1 antagonist
Atenolol - beta-1 antagonist
What are the NICE guidelines for treatment of chronic heart failure?
What do the NICE guidelines for treatment of chronic heart failure using three classes of drugs cause?
Proven mortality and morbidity benefits
Give three examples of proven efficacy drugs which are better than other types of beta-blockers for treatment of chronic heart failure.
Which adrenoceptors do bisoprolol and metoprolol act on in chronic heart failure?
Why is Carvedilol which acts on beta-1, beta-2 and alpha-1 receptors very effective?
Causes uniques adaptations to receptors not seen with other drugs
How does the paradoxical increase in alpha-adrenoceptor subtypes seen when using Carvedilol to treat chronic heart failure present clinically?
Initially patients become very tired but a week later they are much better