Nervous Systems Flashcards
What is the Autonomic Nervous System?
all the neural pathways that leave the brain and don’t innervate voluntary muscles
Sympathetic?
Fight or Flight
Short preganglionic and long postganglionic
Parasympathetic?
Rest and Digest
Long preganglionic and short postganglionic
Ganglion?
Point of contact between first and second efferent neurones in the pathway.
Group of nerve cell bodies that lie outside the CNS
Sympathetic ganglia?
Preganglionic neurone is located in the midbrain, medulla or lateral horn of spinal cord.
Provides diffuse innervation of target tissues (not very precise).
Parasympathetic ganglia?
Preganglionic neurone is located in the medulla or sacral segment of spinal cord.
Provides discrete innervation of target tissue.
Ganglia are in the target tissue.
Role of amygdala?
main limbic region for emotions
Role of hypothalamus?
main integration centre
Role of reticular formation?
most direct influence over autonomic function
Where is dopamine released in the ANS?
Postganglionic neurones to the smooth muscle of the renal (kidney) vascular bed release dopamine
Where in the ANS is there no postganglionic neurone?
In the paravertebral sympathetic ganglion. Directly onto the adrenal gland, releasing acetylcholine and activating nicotinic receptors on the adrenal gland. The gland releases epinephrine into system circulation.
Neurotransmission at the ganglia?
acetlycholine acting on nicotinic acetylcholine receptors
Neurotransmission at postganglionic sympathetic synapse?
noradrenaline acting on a/b- adrenoreceptors
Neurotransmission at postganglionic parasympathetic synapse?
acetylcholine acting on muscarinic receptors
Effects of sympathetic system?
Dilate pupil and bronchi, speeds up heart rate, inhibits peristalsis and urination
Effects of parasympathetic system?
Constricts pupil and bronchi, slows down heart rate, stimulates peristalsis and urination
Enteric Nervous System?
Myenteric Plexus receives the sympathetic/parasympathetic innervation. They synapse to the submucosal plexus. Sensory neurones can send local information back to local layers and CNS.
Regulates GI tract. Wide diversity of neurotransmitters. Local reflex pathways which regulate gut activity, independently of neural input from higher centres.
What is dysautonomia?
Damage to autonomic nerves.
Usually dizziness/fainting upon standing up. Inability to alter heart rate for exercise. Sweating abnormalities. Digestive problems. Urine, sex and vision problems.
What is the Valsalva Maneuver test?
tests the body’s ability to compensate for changes in the amount of blood that returns to the heart.
What is a receptor agonist?
Mimics neurotransmitters and activates receptors
What is a receptor antagonist?
Blocks neurotransmitters and stops endogenous neurotransmitters from activating the receptors
What did Von Euler demonstrate?
Noradrenaline is the main endogenous catecholamine in the sympathetic nerves
Another name for noradrenaline?
Norepinephrine
Another name for adrenaline?
Epinephrine
Finkleman preparation?
Uses intestine. NA stimulates sympathetic nerves. Catecholamine
When is noradrenaline not the transmitter at postganglionic sympathetic synapses?
in sweat glands, acetylcholine
resistance blood vessels in skeletal muscle - vasodilation
other neurotransmitters, non-adrenergic and non-cholinergic
How are false transmitters made?
If DDC is used instead of tyrosine hydroxylase, then tyramine is made.
DBH would make octopamine.
PNMT would make synephrine.
What is a competitive inhibitor of tyrosine hydroxylase?
a methyl-tyrosine
used in treatment of pheochromocytoma
What can interfere with noradrenaline transmission?
a methyl-DOPA leads to synthesis of flase transmitter a methyl-noradrenaline
Treatment of Parkinson’s Disease?
Carbidopa inhibits DDC (L-DOPA –> dopamine) and is administered with L-DOPA.
No peripheral metabolism of L-DOPA.
Carbidopa doesn’t cross the BBB. Prevents L-DOPA from being converted into dopamine prematurely in the bloodstream.
How is noradrenaline stored?
In vesicles. ATP driven proton gradient pumps the noradrenaline into the vesicles.
Stored with ATP and chromogranin.
Reserpine
Inhibitor of noradrenaline storage. Side effect of antihypertension from treating depression.
Guanethidine?
Inhibitor for incorporation of noradrenaline into presynaptic vesicles. Side effect - orthostatic hypotension
High affinity noradrenaline uptake?
Low capacity. Noradrenaline transporter (NAT). On nerve terminal. Requires Na+ gradient and ATP. Active so high affinity. Substrate specificity.
Low affinity noradrenaline uptake?
High capacity.
Present on extraneuronal tissue. Inhibited by cortisol. Passive. Cotransport with Na+
Drugs which block noradrenaline transporter?
Clinically used as antidepressants.
Cocaine blocks active uptake.
Imipramine first tricyclical antidepressant. Desipramine and amitriptyline are similar.
Guanethidine also weakly blocks.
Which drugs stimulate noradrenaline release?
Tyramine
Ephedrine
Amphetamine
Important enzymes in noradrenaline metabolism?
MAO (monoamine oxidase)
COMT (catechol-o-methyltransferase)
Important metabolites in noradrenaline metabolism?
VMA and MPHG
Plamsa levels of the metabolites can be useful biomarkers of disease
Drugs that interfere with noradrenaline metabolism?
MAOIs - Monoamine oxidase inhibitors
Iproniazid
What type of receptor are adrenoceptors?
G Protein Coupled Receptors
Adrenoceptor subtypes?
A1, A1, B1, B2, B3
What drives feedback inhibition of noradrenaline release at the synapse?
alpha 2 adrenoceptors
where is alpha 1?
postsynaptic
where is alpha 2?
presynaptic
Alpha adrenoceptor agonists?
phenylephrine a1>a2
methoxamine a1
clonidine a2
How do you block raised blood pressure?
agonise alpha 2
Alpha adrenoceptor antagonists?
phentolamine a1=a2
phenoxybenzamine a1
prasozin a1>a2
yohimbine a2>a1
Antihypertensive?
Block a1
Effect of yohimbine on noradrenaline transmission?
low dose just blocks a1, high dose blocks both
What do b adrenoceptors stimulate?
cAMP formation
effects of b1 adrenoceptors?
cardiac acceleration
lipolysis
decreased gut motility & secretion
renin release
effects of b2 adrenoceptors?
bronchodilation
blood vessels to skeletal muscles vasodilation
glycogen breakdown
beta adrenoceptors agonists?
isoprenaline b1>b2
salbutamol b2>b1
dobutamine b1>b2
Use of isoprenaline
used to treat asthma, high incidence of heart failure
Use of salbutamol
effective bronchodilation by inhalation
Use of dobutamine
cardiac stimulant
beta adrenoceptor antagonists?
propranolol - non selective beta blocker, local anaesthetic action
atenolol - b1 antagonist. cardioselective.
How is choline taken up to nerve terminals?
by choline transporter
How is acetylcholine taken up into presynaptic vesicles?
Active transport process (blocked by vesamicol). Vesicle Acetylcholine Transporter
What blocks choline transporter?
Hemicholinium
How is acetylcholine inactivated?
Acetylcholinesterase breaks down into choline and acetic acid.
2 actions of cholinergic transmission?
muscarine - paralysed by atropine
nicotine - paralysed by nicotine
How can acetylcholine produce 2 different effects on blood pressure?
The same compound triggers two dose dependent opposite responses.
Low affinity receptor can only be triggered with high levels of acetylcholine.
Muscarinic agonists?
Acetylcholine (also nicotinic) Carbachol (also nicotinic) Bethanechol Muscarine Pilocarpine Oxotremorine
Effects of muscarinic agonists?
Decreased HR, CO and vasodilation
Increased GI activity
Increased sweating and salivation
Treatment of glaucoma?
Failed drainage in the eye via the drainage canal. Gets blocked, increases intraocular pressure and the optic nerve gets damaged.
Pilocarpine - ciliary muscle relaxes and relieves the pressure on the drainage canal.
M1 receptor?
Neural - CNS
Increases IP3 and DAG
Gastric acid secretion & Gut motility
M2 receptor?
Cardiac - Atria & presynaptic terminals
Decreased cAMP
Cardiac and neural inhibition
M3 receptor?
Glandular - exocrine glands, smooth muscle and vascular endothelium.
Increases IP3 and DAG
Secretion, smooth muscle contraction and vasodilation via NO.
Muscarinic receptor structure?
Has a central binding site for ACh.
Can be coupled to Gq (excitatory) or G/o (inhibitory)
Muscarinic receptor antagonists?
atropine
pirenzepine
Which receptors have a higher affinity for acetylcholine?
muscarinic
N1 receptor?
Neuromuscular junction. NN
N2 receptor?
Autonomic ganglia, CNS or adrenal medulla. NM
Nicotinic agonists?
acetylcholine
nicotine - stimulates autonomic ganglia
What happens when acetylcholine binds at nicotinic receptors?
Binds to alpha subunits, the channel opens and allows sodium and potassium to flow through.
What blocks ganglionic nicotinic receptors?
Hexamethonium
Reduces bp, dry mouth, constipation, urinary retention, blurred vision, sexual dsyfunction. Better to alter either sympathetic or parasympathetic, not entire ANS.
What series does hexamethonium belong to?
polymethylene bismethonium series
shorter - ganglionic block
longer - neuromuscular block
