Nagelhout: autonomic nervous system
in general, the parasympathetic response tends to be ____, and the sympathetic
response tends to be ____, with the exception of the ____ which is ____.
(inhibitory or excitatory) - ANSWER-in general, the parasympathetic response tends to
be excitatory, and the sympathetic response tends to be inhibitory, with the exception of
the heart which is excitatory.
explain the negative feedback response for the sympathetic nervous system -
ANSWER-catecholamine NE is released from the nerve and typically attaches to
adrenergic receptors at the target tissue = produces sympathetic activity
there is, however, a #2 receptor site on the pre-ganglionic side (autoreceptor) that
causes a negative feedback response mechanism. when NE binds to the pre-ganglionic
receptor it causes sympatholytic effect by controlling/preventing further NE release
true or false; the parasympathetic and sympathetic nervous systems communicate by
way of epi release - ANSWER-false; they communicate by way of NE release. (when
NE release, it can also affect the parasympathetic side and/or communication with
other)
basic sequence of the synthesis of endogenous catecholamines - ANSWER-Tyrosine
converted by tyrosine hydroxylase > Dopa
Dopa converted by aromatic L amino acid decarboxylase > Dopamine
Dopamine converted by Dopamine B hydroxylase > NE
NE converted by phentylethnolamine N methyltransferase > Epi
dietary amino acid that is necessary for catecholamine synthesis - ANSWER-tyrosine
how are catecholamines metabolized? - ANSWER-by 2 enzymes
1. COMT (catechol-o-metiltransferase) found in synapse
2. MAO (mono-amine oxidase) found in mitochonidria of nerve cell in
(many metabolites formed and some can be used)
forgive the spelling.. i just don't care
review of the PNS and SNS - ANSWER-...
explain the PNS beginning with the parasympathetic nerve - ANSWER-1. long
preganglionic fiber
2. synapse at ganglia
3. neurotransmitter is ACh
4. nicotinic-cholinergic receptor at the ganglia
,5. muscarinic cholinergic receptor post ganglia (at effector tissue)
6. short post ganglionic fiber (ganglia very close to the actual tissue)
explain the SNS beginning with the sympathetic nerve - ANSWER-1. short
preganglionic fiber
2. synapse at ganglia
3. neurotransmitter is ACh pre-synaptic
4. nicotinic cholinergic receptor at ganglia
5. long post ganglionic fiber (ganglia close to the cord)
6. neurotransmitter is NE post-synaptic
7. adrenergic receptor at effector tissue (can be alpha, beta, or dopa)
how does precedex/dexmetatomidine work? - ANSWER-selectively attaching to the
presynaptic alpha 2 receptors and therefore producing sympatholytic (negative
feedback response) and leading to sedation and decrease in BP
what are the 10 mechanisms by which we can mess with an autonomic nerve -
ANSWER-1. interfere with synthesis of neurotransmitter
2. metabolic transformation by same pathway as precursor of transmitter (false
transmitter)
3. blocking transport system at nerve terminal membrane
4. blocking transport system at storage vesicles
5. promotion of exocytosis or displacement of transmitter from axonal terminal
6. preventing release of transmitter
7. mimicry of transmitter at post-junctional sites
8. blocking post-synaptic receptor
9. inhibition of enzymatic breakdown of transmitter
10. interference with 2nd messenger system
explain how we could cause mechanism #1
1. interfere with synthesis of neurotransmitter - ANSWER-the rate limiting enzyme for
catecholamine synthesis = tyrosine hydroxylase. it converts tyrosine (essential dieteary
amino acid) to Dopa and ...blah blah blah (notecard #1)
if we have a drug that inhibits the enzyme tyrosine hydroxylase then tyrosine can't be
converted to dopa
what kind of overall action will we see if tyrosine hydroxylase is inhibited? - ANSWER-
less catecholamine production = sympatholytic response
this is the only tyrosine hydroxylase inhibitor - ANSWER-metyrosine (Demser)
explain how we could cause mechanism #2
2. metabolic transformation by same pathway as precursor of transmitter (we give a
drug that acts like a false transmitter/ give the nerve the wrong thing to synthesize) -
, ANSWER-giving methyldopa instead of dopa > instead of making NE, the nerve will
make a-methyl-NE instead of NE
giving methyldopa (false transmitter) will make a-methyl-NE instead of NE. what is a-
methyl-NE, what drug is it similar to, and what overall effect will we see? - ANSWER-is
an alpha 2 agonist (negative feedback)
similar to clonidine
reduces sympathetic outflow > causes sympatholytic response
explain how we can cause mechanism #3
3. blocking transport system at nerve terminal membrane - ANSWER-by blocking
transport at the nerve terminal, you are blocking the reuptake of neurotransmitter back
into the nerve for re-use.
give examples of 2 drugs that are responsible for causing the adrenergic mechanism
#3: blocking transport system at nerve terminal
give example of cholinergic drug and how it works - ANSWER-adrenergic: cocaine and
tricyclics (imipramine and amitrptylline used for migraines)
they work by blocking the reuptake of NE back into the nerve
cholinergic: hemicholinium blocks choline uptake with consequent depletion of ACh and
causes sympathomimetic
what occurs when NE is not able to re-enter the nerve cell bc it's being blocked? what
overall effect will we see - ANSWER-left in synapse longer > blocks the negative
feedback loop > nerve won't know to stop releasing NE > more NE in synapse >
sympathomimetic effect bc it can then only be broken down by COMT
explain how cause mechanism #4
4. blocking transport system at storage vesicles - ANSWER-blocking the storage of ACh
or NE in their storage vesicles inside the nerve cell (they are knocked out of their home
and into the axoplasm of the nerve cell where MAO can get to them and metabolize
them)
give example of cholinergic and adrenergic drugs that can cause mechanism #4
(blocking transport system at storage vesicles); how they work; and their overall
response - ANSWER-1. cholinergic drug is Vesamicol that blocks ACh storage
2. Adrenergic drug Reserpine: blocks NE from entering vesicles in nerve cell > left in
axoplasm > metabolized by MAO found in the mitochondria of nerve cell.
both of these cause sympatholytic response
(reserpine fyi: old drug used to treat HTN, but had high rate of suicide and thought to be
bc of so little catecholamines available)
explain how we can cause mechanism 5
in general, the parasympathetic response tends to be ____, and the sympathetic
response tends to be ____, with the exception of the ____ which is ____.
(inhibitory or excitatory) - ANSWER-in general, the parasympathetic response tends to
be excitatory, and the sympathetic response tends to be inhibitory, with the exception of
the heart which is excitatory.
explain the negative feedback response for the sympathetic nervous system -
ANSWER-catecholamine NE is released from the nerve and typically attaches to
adrenergic receptors at the target tissue = produces sympathetic activity
there is, however, a #2 receptor site on the pre-ganglionic side (autoreceptor) that
causes a negative feedback response mechanism. when NE binds to the pre-ganglionic
receptor it causes sympatholytic effect by controlling/preventing further NE release
true or false; the parasympathetic and sympathetic nervous systems communicate by
way of epi release - ANSWER-false; they communicate by way of NE release. (when
NE release, it can also affect the parasympathetic side and/or communication with
other)
basic sequence of the synthesis of endogenous catecholamines - ANSWER-Tyrosine
converted by tyrosine hydroxylase > Dopa
Dopa converted by aromatic L amino acid decarboxylase > Dopamine
Dopamine converted by Dopamine B hydroxylase > NE
NE converted by phentylethnolamine N methyltransferase > Epi
dietary amino acid that is necessary for catecholamine synthesis - ANSWER-tyrosine
how are catecholamines metabolized? - ANSWER-by 2 enzymes
1. COMT (catechol-o-metiltransferase) found in synapse
2. MAO (mono-amine oxidase) found in mitochonidria of nerve cell in
(many metabolites formed and some can be used)
forgive the spelling.. i just don't care
review of the PNS and SNS - ANSWER-...
explain the PNS beginning with the parasympathetic nerve - ANSWER-1. long
preganglionic fiber
2. synapse at ganglia
3. neurotransmitter is ACh
4. nicotinic-cholinergic receptor at the ganglia
,5. muscarinic cholinergic receptor post ganglia (at effector tissue)
6. short post ganglionic fiber (ganglia very close to the actual tissue)
explain the SNS beginning with the sympathetic nerve - ANSWER-1. short
preganglionic fiber
2. synapse at ganglia
3. neurotransmitter is ACh pre-synaptic
4. nicotinic cholinergic receptor at ganglia
5. long post ganglionic fiber (ganglia close to the cord)
6. neurotransmitter is NE post-synaptic
7. adrenergic receptor at effector tissue (can be alpha, beta, or dopa)
how does precedex/dexmetatomidine work? - ANSWER-selectively attaching to the
presynaptic alpha 2 receptors and therefore producing sympatholytic (negative
feedback response) and leading to sedation and decrease in BP
what are the 10 mechanisms by which we can mess with an autonomic nerve -
ANSWER-1. interfere with synthesis of neurotransmitter
2. metabolic transformation by same pathway as precursor of transmitter (false
transmitter)
3. blocking transport system at nerve terminal membrane
4. blocking transport system at storage vesicles
5. promotion of exocytosis or displacement of transmitter from axonal terminal
6. preventing release of transmitter
7. mimicry of transmitter at post-junctional sites
8. blocking post-synaptic receptor
9. inhibition of enzymatic breakdown of transmitter
10. interference with 2nd messenger system
explain how we could cause mechanism #1
1. interfere with synthesis of neurotransmitter - ANSWER-the rate limiting enzyme for
catecholamine synthesis = tyrosine hydroxylase. it converts tyrosine (essential dieteary
amino acid) to Dopa and ...blah blah blah (notecard #1)
if we have a drug that inhibits the enzyme tyrosine hydroxylase then tyrosine can't be
converted to dopa
what kind of overall action will we see if tyrosine hydroxylase is inhibited? - ANSWER-
less catecholamine production = sympatholytic response
this is the only tyrosine hydroxylase inhibitor - ANSWER-metyrosine (Demser)
explain how we could cause mechanism #2
2. metabolic transformation by same pathway as precursor of transmitter (we give a
drug that acts like a false transmitter/ give the nerve the wrong thing to synthesize) -
, ANSWER-giving methyldopa instead of dopa > instead of making NE, the nerve will
make a-methyl-NE instead of NE
giving methyldopa (false transmitter) will make a-methyl-NE instead of NE. what is a-
methyl-NE, what drug is it similar to, and what overall effect will we see? - ANSWER-is
an alpha 2 agonist (negative feedback)
similar to clonidine
reduces sympathetic outflow > causes sympatholytic response
explain how we can cause mechanism #3
3. blocking transport system at nerve terminal membrane - ANSWER-by blocking
transport at the nerve terminal, you are blocking the reuptake of neurotransmitter back
into the nerve for re-use.
give examples of 2 drugs that are responsible for causing the adrenergic mechanism
#3: blocking transport system at nerve terminal
give example of cholinergic drug and how it works - ANSWER-adrenergic: cocaine and
tricyclics (imipramine and amitrptylline used for migraines)
they work by blocking the reuptake of NE back into the nerve
cholinergic: hemicholinium blocks choline uptake with consequent depletion of ACh and
causes sympathomimetic
what occurs when NE is not able to re-enter the nerve cell bc it's being blocked? what
overall effect will we see - ANSWER-left in synapse longer > blocks the negative
feedback loop > nerve won't know to stop releasing NE > more NE in synapse >
sympathomimetic effect bc it can then only be broken down by COMT
explain how cause mechanism #4
4. blocking transport system at storage vesicles - ANSWER-blocking the storage of ACh
or NE in their storage vesicles inside the nerve cell (they are knocked out of their home
and into the axoplasm of the nerve cell where MAO can get to them and metabolize
them)
give example of cholinergic and adrenergic drugs that can cause mechanism #4
(blocking transport system at storage vesicles); how they work; and their overall
response - ANSWER-1. cholinergic drug is Vesamicol that blocks ACh storage
2. Adrenergic drug Reserpine: blocks NE from entering vesicles in nerve cell > left in
axoplasm > metabolized by MAO found in the mitochondria of nerve cell.
both of these cause sympatholytic response
(reserpine fyi: old drug used to treat HTN, but had high rate of suicide and thought to be
bc of so little catecholamines available)
explain how we can cause mechanism 5
