ANS Flashcards
Ganglionic neurons for Parasympathetic (Length)
pre: long
post: short
Ganglionic neurons for Sympathetic (Length)
pre: short
post: long
In BOTH parasympathetic and sympathetic neurons - ______ is released to activate _______ receptors on ___ganglionic neurons
Ach; nicotinic; post
In Parasympathetic neurons - _______ receptors on target organs are activated by
muscarinic; Ach;
In sympathetic neurons ________ receptors on target organs are activated by
adrenergic; norepinephrine
3 exceptions to the sympathetic nervous system “rules”
sweat glands; kidneys; adrenal gland
Sweat Glands:
- If stress-related (sweaty palms) ________ is excreted
- if thermoregulation _______ is released to work on _______ receptors
norepinephrine; Ach; muscarinic
Kidneys:
________ is released by postganglionic neurons to work on the smooth muscle of the renal vascular bed which cause _________
dopamine; vasodilation
Adrenal gland:
- Do the preganglionic neurons synapse in paravetebral sympathetic ganglion?
- Preganglionic neurons release _____ to activate _______ receptors ON the adrenal gland
- the adrenal gland will release ________ into systemic circulation
Nope;
Ach; nicotinic
epinephrine
Types of cholinergic receptors
Nicotinic; muscarinic
Nicotinic receptors are a ______ type of receptor
and
Muscarinic receptors are a ______ type of receptor
ligand gated ion channel;
GPCR
2 main types of Muscarinic Receptors and where they are found
M3 - glands and smooth muscle
M2 - found in heart
Which G protein pathways do M3 and M2 use?
M3 - Gq (makes DAG and IP3)
M2 - GI (inhibits adenylycyclase)
Main kinds of Adrenergic Receptors
alpha 1; alpha 2; beta (1 and 2)
where are alpha 1 and alpha 2 receptors found
alpha 1 - VASCULAR smooth muscle - BP regulator
alpha 2 -receptors in brain stem/ off switch
where are Beta 1 and Beta 2 receptors found
Beta 1 - heart and kidneys
beta 2 - lungs/smooth muscle/ bronchioles
What kind of G protein does alpha 1 receptors use
Gq
what kind of G protein does alpha 2 receptors use
GaI
what kind of G protein does beta receptors use
GaS
which receptor causes vasodilation of skeletal muscle when activated
B2 (adrenergic receptor)
which receptor cause constriction of arteries when activated
alpha1
which receptor cause bronchodilation of the lungs when activated
B2
which receptor cause bronchoconstriction of the lungs when activated
M2/M3
which receptor causes the salivary glands to increase secretion when activated
BOTH PARA AND SYM!
alpha1; M3
which receptor decreases secretion (of acid) from GI tract when activated
alpha2
which receptor increases secretion (of acid) from GI tract when activated
M2/M3
which receptor is activated to prevent prelabor contractions
beta 2
why do anticholinergics cause dry mouth?
anticholinergics work on muscarinic receptors; muscarinic receptors when activated will cause salivary excretion
which receptor will cause “goosebumps” when activated
goosebumps = piloerection; contraction
alpha1
what does the canal of schlemm do and where is it found
found in eye…
it acts as the “drain” for aqueous humor
what is canal of schlemm opening controlled by
cilliary muscle
ciliary muscle controls what things
opening for canal of schlemm
AND
focusing of the lens in the eye
what receptor is found on the ciliary muscle
muscarinic
what makes aqueous humor in the eye
ciliary epithelium
what does the ciliary epithelium do
makes aqueous humor
what receptor is in the circular muscle and what does the muscle cause when contracted
muscarinic; miosis
what receptor is in the radial muscle and what does the muscle cause when contracted
Alpha; myDriasis
radial has the letters a and d in it…
Miosis vs mydrasis
miosis = constrict pupils mydriasis = dilate pupils
When a muscarinic (3) receptor is activated in the eye - what happens
contracts ciliary muscle and circular muscle -cause pupil constriction and more drainage of aqueous humor
What happens when the alpha 1 receptor is activated in the eye
contract radial muscle - causes mydriasis/pupil dilation;
what happens when Beta 2 receptor is activated in the eye
relaxation of ciliary muscle AND increase secretion of aqueous humor (aka hella aqueous humor)
where does alpha 1 receptor work/what does it do there
vasoconstrictor of arteries and veins; radial eye constrictor; goosebumps - piloerection stress sweat increase salivation contracts sphincter
where does alpha 2 receptor work/what does it do there
vasoconstrict veins; relax GI wall; inhibits acid secretion
where does Beta 2 receptor work/what does it do there
lungs - bronchodilator
eye - relaxes ciliary muscle; increases aqueous humor production
relaxes GI wall;
uterus - relaxes it
where does M3 receptor work/what does it do there (M3 only)
increases saliva; releases EDRF
what does M2 do own its own and where
heart - decrease HR rate contraction
where does Beta 1 receptor work/what does it do there
heart and kidney
increase HR and increase Renin secretion
What are ways to enhance/mimic the cholinergic system
nicotinic agonist
muscarinic agonist
AchE inhibitor
ways to block or inhibit the cholinergic system
nicotinic antagonist muscarinic antagonist inhibit choline uptake inhibit vesicular storage inhibit release
In the cholinergic system - what drug is used to prevent uptake of choline
Hemocholinium
In the cholinergic system - what drug is used to prevent vesicular storage
vesamicol
In the cholinergic system - what drug is used to prevent release (of Ach)
botulism
How is Ach made in the cholinergic system
Choline and Acetate are made into Ach via ChAT (choline acetyl transferase)
Main groups Direct Acting Cholinergic Agonists
Esters, Alkaloids, Synthetic analogs
Examples of Direct Acting Cholinergic Agonists - Esters
Acetylcholine; Carbachol; Methacholine; Bethanechol
Examples of Direct Acting Cholinergic Agonists - Alkaloids
Muscarine; Nicotine
Examples of Direct Acting Cholinergic Agonists - Synthetic Analogs
Pilocarpine
Reactions (amino acid properties) found in the active site of Ach binding to muscarinic receptors
Two aromatic rings - pi cation interaction with the + amine in the Ach
Do all the muscarinic receptors have the same amino acids in there active site?
No! - therefore can use this factor to create selectivity
Stereochemistry of Ach
trans and cis points
cis - more stable
trans - stereochemistry present when Ach is bound to the receptor
Why are antimuscarininc drugs contraindicated in glaucoma?
antimuscarinics prevents the canal of schlemm from opening/draining aqueous humor via paralyzing the ciliary muscle
Main components of Ach
+ amine; choline chain (alpha and beta carbons); ester
what are the two sites in AchE
anionic and esteraic sites
What happens when you modify the choline chain - alter number of atoms…
5 is best
4 atoms will cause it to lose activity
what happens when you substitute a methyl group on the alpha carbon vs the beta carbon in Ach
alpha = more nicotinic reactive beta = more muscarinic selective and more resistant to metabolism bc carbon group is near ester
AN and BM
What happens if you alter the acetyl group in Ach by adding carbons
violating 5 atom rule –> makes it more nicotinic selective (muscarininc doesn’t like extra bulk)
What happens if you alter the acetyl group in Ach by making the end group a carbamyl group
makes carbachol drug = non selective still but will decrease metabolism
What happens if you alter the acetyl group in Ach by making the end group a carbamyl group AND adding a methyl group at the beta carbon
makes it more muscarinic selective AND more resistant to metabolizing
What are ways to mimic/activate the adrenergic system
- adrenergic receptor agonists
- increase release (NE transporter working backwards)
- block uptake in two diff places (preventing breakdown or block NE uptake into the post synaptic region)
- decrease metabolism
Ways to reduce/block the adrenergic system
- adrenergic receptor antagonist
- decrease release of
- deplete vesicular stores
- decrease synthesis
Synthesis steps for making Catcholamines
1- tyrosine - DOPA (via tyrosine hydroxylase)
2 - DOPA - dopamine (decarboxylate)
3 - dopamine - NE (hydroxylase)
4 - NE - Epi (add a methyl)
What step in the making of catecholamines is the rate limiting step
first step: tyrosine to DOPA
NE is metabolized by what enzymes?
MAO and COMT
What is the end product of NE metabolism
VMA = vanilymandelic acid
Example drugs of alpha 1 agonists
phenylephrine
methaoxamine
oxymetazoline
(also NE and Epi can activate alpha 1 just not selectively)
what pathway is stimulated via alpha1 agonists
Gq pathway
Example drugs of alpha 2 agonists
clonidine methyldopa guanfacine guanabenz tizanidine
what pathway is stimulated by alpha 2 receptors
GI/O (less adenlylcyclase - less cAMP - less PKA)
Example drugs of beta non-selective agonists
isoproterenol
Example drugs of beta 1 selective agonists
dobutamine
dopamine
Example drugs of beta 2 selective agonists
terbutaline metaproterenol albuterol salmeterol ritodrine
what adrenergic receptors does NE activate
alpha and beta1