Pharma - Autonomic Nervous System Flashcards
define autonomic nervous system
all the neural pathways that leave the brain that do not innervate voluntary muscle
what fall under the peripheral nervous system
autonomic nervous system
somatic nervous system
what fall under ANS
sympathetic
parasympathetic
what are the roles of the ANS
pupillary dilation
dilation/constriction of blood vessels
force/rate of heart beat
movements of GI tract
secretion of most glands
energy motabolism
where does the point of contact between the first and second efferent neuron occur
ganglion
what is a ganglion
a group of nerve cell bodies that lie outside the CNS
are parasympathetic or sympathetic neurones longer
parasympathetic
what is a receptor agonist
a drug that mimics a neurotransmitter
what is a drug that blocks a neurotransmitter called
receptor antagonist
where are sympathetic preganglionic neurones located
midbrain
medulla
lateral horn of the spinal cord
in the sympathetic NS what do ganglia form
the sympathetic chain
where are parasympathetic preganglionic neurones located
medulla
sacral segment of spinal cord
where are ganglia located in the parasympathetic NS
in the target tissue
what do sympathetic postganglionic neurons to the smooth muscle of the renal vascular bed release
dopamine
at the adrenal gland, where do sympathetic preganglionic neurones not synapse and where do they
don’t - paravertebral sympathetic ganglion
do - directly onto the adrenal gland
what do preganglionic neurones release on the adrenal gland
acetylcholine
activate nicotinic receptors
function of adrenal glands
release epinephrine into systemic circulation
what does all excitatory transmission of all the autonomic ganglia involve
acetylcholine acting on nicotinic acetylcholine receptors
what does transmission of the postganglionic sympathetic synapse usually involve
noradrenaline acting of a-adrenoceptors or b-adrenoceptors
what does transmission at the postganglionic parasympathetic synapse usually involve
acetylcholine acting on muscarinic receptors
where does noradrenaline not act
sweat glands
resistance blood vessels in skeletal muscle
what drug classification does noradrenaline belong to and why
catecholamine
carries a catechol group
name all the metabolites in the synthetic pathway of adrenaline in order
tyrosine
L-DOPA
dopamine
adrenaline
noradrenaline
what converts tyrosine into L-DOPA and what does it do
tyrosine hydroxylase
adds an OH group to the benzene
what converts L-DOPA into dopamine and what does it do
dopadecarboxylase
removes the carboxylic acid from the α-carbon
what converts dopamine into noradrenaline and what does it do
dopaminebetahydroxylase
adds an OH group to the β-carbon
what converts noradrenaline into adrenaline and what does it do
PNMT
adds a methyl group to the amine
(NH-CH3)
what are the false transmitters metabolites
tyramine
octopamine
synephrine
what converts tyrosine into tyramine
DDC
what converts tyramine into octopamine
DBH
what converts octopamine into synephrine
PNMT
what is a competitive inhibitor of tyrosine hydroxylase
α-methyltyrosine
what is α-methyltyrosine used to treat
phaeochromocytoma
what is α-methyl-DOPA used for
interferes with NAdr transmission
leads to synthesis of false transmitter - α-methyl-NAdr
function of carbidopa
inhibits dopa-decarboxylase (DCC)
outline the treatment for Parkinson’s disease
co-administer carbidopa with L-DOPA
L-DOPA - to increase the amount of precursor for dopamine in the brain
carbidopa - inhibits DCC from converting L-DOPA to dopamine in the bloodstream, which cannot cross the BBB
how is NADR stored
stored in vesicles
transport is driven by a proton gradient
stored with ATP and chromogranin
what are drugs that interfere with NADR storgae
reserpine
guanethidine
features of resperine
anti-hypertensive
side effect - depression
features of guanethidine
anti-hypertensive
side-effect - orthostatic hypotension
in terms of NAdr inactivation following release what are the features of uptake 1
NAT - noradrenaline transporter
high affinity, low capacity
present on nerve terminals
requires Na+ gradient and ATP
substrate specificity
in terms of NAdr inactivation following release what are the features of uptake 2
low affinity, high capacity
present on extra-neuronal tissue
what was used to demonstrate the uptake mechanism of NAdr
iversen
what blocks uptake mechanism 2
cortisol
what blocks uptake mechanism 1 and what are they most clinically used as
cocaine
imipramine
desipramine
amitryptaline
what weakly blocks uptake mechanism 1
guanethidine
structure of imipramine
tricyclic antidepressant
first one
what are drugs that stimulate NAdr release
indirect sympathominetics:
tyramine
ephedrine
amphetamine
what are the 2 important enzymes and metabolites in NAdr metabolism
monoamine oxidase (MAO)
catechol-O-methyltransferase (COMT)
VMA
MHPG
what does COMT convert norepinephrine into
normetanephrine
what does MAO convert normetanephrine into
mopegal
what converts mopegal into VMA
AD
what does MAO convert norepinephrine into
dopegal
what does AR convert norepinephrine into
DHPG
in NAdr metabolism what happens to DHPG
COMT converts it into MHPG
what converts MHPG into mopegal and what can reverse this process
ADH
AR
what are drugs that interfere with NAdr metabolism
monoamine oxidase inhibitors (MAOI’s)
iproniazid
what are the adrenoceptor subtypes
α- isoforms 1/2
β - 1/2/3
function of autoreceptors
mediates feedback inhibition of neurotransmitter release at the synapse
α1 - predominantly postsynaptic
α2 - predominantly presynaptic
what are all β adenoceptors
are all GPCR’s and stimulate cAMP formation
what do β1 adrenoceptors stimulate
cardiac acceleration lipolysis
decrease gut motility and secretion
renin release
what do β2 adrenoceptors release
bronchodilation
vasodilation of blood vessels to skeletal muscle
glycogen breakdown
why would clonidine (α2) have an antihypertensive action
clonidine will agonise α2 receptors which are located at the presynaptic membrane
causes a block to noradrenaline release
what occurs if you antagonise an α1 adrenocepor
anti-hypertensive effect
what is isoprenaline
a β1 adrenoceptor agonist
used in treatment for asthma
associated with high incidences of heart failure
what is salbutamol
a β2 adrenoceptor agonist
effective bronchodilator by inhalation
what is dobutamine
a β1 agonist
used as a cardiac stimulant
what is propanolol
β adrenoceptor antagonist
non-selective beta blocker
anti-hypertensive
has local anaesthetic action
can cause bronchoconstriction
what is atenolol
β1 adrenoceptor antagonist
cardio-selective
what do atenolol and propanolol both have in their structure
oxymethylene bridge
what are the signalling properties of α1 adrenoceptors
increase in IP3
increase in DAG
mostly excitatory
what are the signalling properties of α2 adrenoceptors
decrease in cAMP
decrease in CA2+ channels
increase in K+ conductance
what are the signalling properties of β1,2,3 adrenoceptors
increase in cAMP
mostly excitatory
what enzyme makes acetylcholine and from what
acetyl CoA and choline
choline acetyltransferase (CAT)
what is the rate limiting step for ACh synthesis
choline being taken into the nerve transmitter by choline transporter
how is ACh taken into presynaptic vesicles and what blocks it
via active transport
vesamicol
what is ACh released in response to
calcium entry into the presynaptic terminal
the synaptic cleft is rich in which enzyme and what is its function
acetylcholinesterase
breaks down ACh into choline and acetic acid
what blocks choline transporter
hemicholinium
how do different doses of acetylcholine receptors affect blood pressure
low doses (2-50μg) causes a drop in blood pressure
higher doses of 5mg cause a rise in blood pressure
what blocks muscarinic and nicotinic action
muscarinic - atropine
nicotinic - excess of nicotine
which drugs have muscarinic and nicotinic action
acetylcholine
carbachol
what drugs are selective for muscarinic action
bethanechol
muscarine
pilocarpine
oxotremorine
muscarinic receptors effect of agonists on cardiovascular system
decreased HR
decreased cardiac output
decreased vasodilation
muscarinic receptors effect of agonists on GI system
increased activity
muscarinic receptors effect of agonists on gland secretion
increased sweating
increased lacrimation
increased salivation
features of muscarinic 1 receptors
type - neural
location - CNS
cellular action:
increase in IP3 and DAG
function - increase gut motility
increase gastric acid secretion
features of muscarinic 2 receptors
type - cardiac
location - atria/presynaptic terminals
cellular action - decrease in cAMP
function - cardiac and neural inhibition
features of muscarinic 3 receptors
type - glandular
location - exocrine glands, smooth muscle, vascular endothelium
cellular action - increase in IP3 and DAG
function - secretion, smooth muscle contraction, vasodilation (via NO)
name 2 muscarinic receptor antagonists
atropine
pirenzepine
what are the effects of nicotine and DMPP
stimulation of autonomic ganglia
what does hexamethonium block
ganglionic nicotinic receptors
what can hexamethonium be used to treat
hypertension - lowers blood pressure
what are the potential side effects of hexamethonium
dry mouth
reduced gastric acid secretion
constipation
urinary retention
blurred vision
postural hypotension
sexual dysfunction
