3- autonomic Flashcards
what are 4 choline esters
acetylcholine
carbachol
bethanechol
methacholine
how are choline esters absorbed in the GI tract
poorly
what is the main effect of muscarinic agonists
parasympathomimetic (stimulates the parasympathetic system)
what is the main effect of nicotinic agonists
parasympathetic and sympathetic effects in autonomic ganglia and skeletal muscle
is ACh nicotinic or muscarinic
both
is carbachol nicotinic or muscarinic
both
is bethanecol nicotinic or muscarinic
muscarinic
what makes carbachol and bethanecol different from ACh
they are not hydrolyzed by acetylcholinesterase
what is the methacholine challenge for asthma
Methacholine is a non-selective muscarinic receptor agonist that acts directly on airway smooth muscle receptors to induce bronchoconstriction. It is administered to test how sensitive lungs are to the PSNS
what are 3 muscarinic agonists
muscarine
oxotremorine
pilocarpine
what is acetylcholine
a choline ester
what is carbachol
a choline ester
what is bethanechol
a choline ester
what is muscarine
muscarinic agonist
what is oxotremorine
muscarinic agonist
what is pilocarpine
muscarinic agonist
what are the main effects of muscarinic agonist
parasympathomimetic
what do muscarinic agonists do to the cardiovascular system
slow HR, decrease force&rate of contraction
what do muscarinic agonists do to endothelium
the muscarinic receptors in the endothelium that cause release of NO that causes relaxation
when does ACh not cause relaxation in the endothelium
when the endothelium is not intact
muscarinic receptors are no longer present and endothelial cells can no longer release NO
what do muscarinic agonists do to the respiratory system
contraction of bronchiole smooth muscle, increased secretion of mucous
why can muscarinic agonists be bad for asthmatics
lots of mucous and bronchiole contraction makes respiration less efficient
what do muscarinic agonists do to the GI tract? what messenging system would this require?
increases saliva and stomach acid secretion, motility and peristalsis
likely Gq (M1, M3) system since effects are stimilatory which would require Ca2+ release
what does muscarinic agonists do to the bladder
stimulates detrusor muscle, relaxes trigone and internal sphincter (promotes voiding)
what are the CNS effects of nicotine
mild stimulation, can cause emesis, coma at high doses
how does nicotine act as an insecticide?
overstimulates the neuromuscular junction, leading to paralysis
does nAChR stimulate the sympathetic or the parasympathetic branch
both of them (found in the ganglia of both)
what does nicotine do to the cardiovascular system
hypertension, sympathetic effects on heart
what is nicotine’s effect on the GI tract
parasympathetic
increase secretion and motility
what are the skeletal muscle effects of nicotine
depolarization and excitation
-it can cause a small disorganized twitch or even a strong contraction o
what do anticholinesterases do to nicotinic and muscarinic receptors
indirectly stimulate by preventing hydrolysis of ACh, causing ACh to bind to the nicotinic/muscarinic receptors
name 4 acetylcholinesterases
edrophonium
neostigmine
malathion
soman
what is edrophonium
a simple alcohol anticholinesterase
what is neostigmine
carbamic esters of alcohols with quaternary or tertiary ammonium group
-an anticholinesterases
what is malathion
insecticide anticholinesterase
organophosphate
what is soman
nerve gas
anticholinesterase
organophosphate
are anticholinesterases well absorbed in the body
yes, via skin gut lung and conjuctiva
what effects are anticholinesterases similar to
direct acting cholinergic agonists
what would anticholinesterases do to respiration
constrict bronchiole, increase secretion (they are like cholinergic agonists which are like parasympathetic agonists)
what would anticholinesterases do to gut
increase motility
they are like cholinergic agonists which are like parasympathetic agonists
what would anticholinesterases do to heart
slow heart rate, decreased cardiac output
they are like cholinergic agonists which are like parasympathetic agonists
what do anticholinesterases do to neuromuscular transmission
increase strength of contraction -can lead to depolarizing neuromuscular blockade
what do acetylcholinesterases do to the vascular systen
little overall change in BP since an increase in upstream SNS activity cancels out parasympathomimetic effects
what is depolarizing neuromuscular blockade
when neurons are chronically stimulated and depolarized to the point that they cannot make AP
what happens to the body in nerve gas / insecticide poisoning
cardiac arrest, fluid in lungs, bronchioconstriction, blockage of respiratory muscle contraction
what drug can be used to limit the effects of nerve gas? what class of drug is it?
atropine, a muscarinic antagonist
what are 4 conditions that cholinomimetics work well for
glaucoma
urinary retention
postoperative ileus (low GI motility)
myasthenia gravis (decreased nAChR at the NM junction)
what are cholinomimetics
muscarinic agonist or anticholinesterases
what causes myasthenia gravis
autoimmune disease with decreased nAChR expression at neuromuscular junction
what are the symptoms of myasthenia gravis
weakness, fatigue, difficulty opening eyes, respiration
how would you treat myasthenia gravis
anticholinesterases (work better than cholingeric agonists for some reason)
what are 3 neuromuscular blockers (nicotinic antagonists)
succinylcholine
D-tubocurarine
α-bungarotoxin
what is succinylcholine
nicotinic antagonist/neuromuscular blocker, used for paralysis during surgery
what is D-tubocurarine
nicotinic antagonist
poison in blow darts, curari
what is α-bungarotoxin
nicotinic antagonist
protein in snake venom which causes paralysis
list 3 muscarinic antagonists
atropine
scopolamine
ipratropium
what is atropine
muscarinic antagonist
what causes parkinsons
excess cholinergic activity, lack of dopaminergic activity
lack of dopamine activity
how can atropine help with parkinsons
antimuscarinics can help control with parkinsons tremors (lessens ACH cause parkinsons has excess)
what is scopolamine (drug class)
muscarinic antagonist
what can scopolamine treat
vestibular disturbances (motion sickness) -muscarinic antagonist
what do muscarinic antagonists do to cardiovascular system and why
drug like atropine would stop the parasympathetic breaks-increases HR, force of contraction
what do muscarinic antagonists do to respiratory system and why
slight bronchodilation and decreased secretion (block of parasympathetic tone)
what is ipratropium and what is it used for
muscarinic antagonist
COPD (chronic obstructive pulmonary disease)
what are directly acting sympathomimetics (definition)
α or β adrenoceptor agonists
what are 3 examples of directly acting sympathomimetics
adrenaline
noradrenaline
isoproterenol
what are indirectly acting sympathomimetics (definition+examples)
displace stored catecholamines from vesicles (amphetamines and tyramine, cocaine and)
inhibit catecholamine reuptake (cocaine + TCAs)
what do alpha receptors have highest and lowest affinity for
A>=N»I
adrenaline stronger than noradrenaline than isoproterenol
what do beta receptors have highest and lowest affinity for
I>A>=N
isoproterenol then adrenaline than noradrenaline
how to remember beta and alpha affinities
aggressive ANI (alpha) beaten IAN (beta)
what is vasomotor reversal
given adrenaline, BP goes up due to alpha contraction
as NE decreases, the vessel dilates due to beta activity
whic givving NE with an alpha antagonist, an initial drop in BP is observed
what affinity do β1 receptors have for A vs NA
equal
what affinity do β2 receptors have for A vs NA
higher affinity for A than NA
what does prazosin do
blocks α1 adrenoceptors
what does yohibine do
blocks α2 adrenoceptors
are α or β receptors more sensitive to agonists
β are more sensitive to agonists
what is phenylephrine
α1 agonist (nasal decongestion)
what is clonidine
α2 agonist
what is isoproterenol (INA)
all β agonist
what is dobutamine
β1 agonist
what is salbutamol
β2 agonist (asthma puffer)
what is phentolamine
all α antagonist
what is prazosin
α1 antagonist
what is yohimbine
α2 antagonist
what is propanolol
allβ antagonist
what is metoprolol
β1 antagonist
what g protein pathway for α1 receptors
Gq
if α1 and M3 are both Gq, why do they have opposing effects on vascular smooth muscle?
CELL SPECIFIC EXPRESSION
M3 relax via receptors on endothelial cells that cause eventual NO release
α1 receptors are directly smooth muscle and cause it to contract
what G pathway for α2 receptors
Gi
what G pathway for β receptors
Gs
what does α1 do to blood vessels
vasoconstrict
what does α2 do to blood vessels
vasoconstrict
what does β do to blood vessels
vasodilate
