Cholinergic Drugs Flashcards
what is the main neurotransmitter of cholinergic drugs
acetylcholine
what are the precursors of acetylcholine
acetyl coenzyme A
choline
where is acetyl coenzyme A derived and synthesized from
derived: pyruvate
Synthesized: mitochondria
True or False:
choline uptake is a rate limiting step
true
what are the choline transport systems
high affinity transport system
synaptic vesicles by vesicular transporters
what is the inhibitor of the high affinity transport system of choline
hemicholinium
what is the inhibitor of the synaptic vesicles of ACh transport
vesamicol
how is acetylcholine released
exocytosis
what can inhibit the release of acetylcholine
botulinum toxins
what can bind to the receptors of cholinergic nerve terminals to interupt the SNARE complex components
clostridium toxins
which animal uses clostridium toxins to their advantage to kill
black widow spiders
what enzyme is used to hydrolyze ACh
acetylcholinesterase
what is the purpose of AChE
recycling of choline to increase ACh synthesis
where is AChE synthesized
autonomic ganglia
neuromuscular motor endplates
visceral neuroeffector junctions
what is the pseudo chE
butyrylcholinesterase
where is butyrylcholinesterase synthesized
liver
what is the purpose of butyrylcholinesterase
metabolism of certain drugs
what occurs if there is an inhibition of AChE
accumulation of ACh in nerve terminal
which receptors are involved with cholinergic receptors
nicotinic and muscarinic receptors
what type of receptor are nicotinic receptors
ligand gated ion channel
what is the main result of activating a nicotinic receptor
skeletal muscle contraction
where are nicotinic receptors found
autonomic ganglion
adrenal medulla
CNS
what type of receptors are muscarinic receptors
GPCR
what are the responses of activating muscarinic receptors
excitatory
inhibitory
where are non-innervated muscarinic receptors found
vascular endothelium
which muscarinic receptor is normally found as non-innervated in blood vessels
M3
where are M1 receptors found
ganglia
secretory glands
where are M2 receptors found
myocardium
smooth muscle
where are M3 & M4 receptors found
smooth muscle and secretory glands
where are M5 receptors found
CNS
what is the most common muscarinic receptor
M5
which muscarinic receptors activate Gq proteins
M1
M3
M5
(odd receptors)
what type of responses are expected with the activation of M1, M3 or M5 receptors
excitatory
what muscarinic receptors are responsible for “relaxation”
M2
M4
which muscarinic receptors act on Gi protein
M2
M4
what is the result of M2 receptor activation of the heart muscle
decreased HR
decrease impulse conduction / contraction
what is the effect of activating M3 receptors of smooth muscle
increase in contraction (GI system)
what is the effect of activating M3 receptors of secretory glands
increased secretion
how do M3 receptors in vascular endothelium cause vasodilation
release of NO
what are the 2 types of cholinergic agonists
direct and indirect
how do indirect cholinergic agonists work
inhibit cholinesterase to cause accumulation of ACh
what are the direct acting agonists
carbachol
bethanechol
pilocarine
what are the reversible indirect cholinergic agonists
physostigmine
neostigmine
edrophonium
pyridostigmine
what is the irreversible indirect agonist
organophosphate
how do low doses of acetylcholine impact the cardio vascular system
rapid fall in pressure –> reflex tachycardia
muscarinic receptors of vascular endothelium are activated (M3 creates vasodilation)
what are the effects of high doses of acetylcholine
vasodilation –> decreased peripheral resistance and BP
slow HR (- chronotropic effect)
- inotropic effect
slow SA and AV node conduction
decreased cardiac output
how does acetylcholine impact smooth muscle
increase motility
increase GIT secretion
increase bronchial muscle contraction
increase urinary bladder contraction
how does acetylcholine effect exocrine glands
increase secretion
how does acetylcholine impact the eye
reduces intraocular pressure
contraction of iris muscle
what can be induced in the eye with acetylcholine
miosis
what are the choline ester direct-acting parasympathomimetic agonists
carbachol
bethanechol
what are the natural alkaloid direct-acting parasympathomimetic agonists
pilocarine
which direct-acting agonist is a very potent nicotinic and muscarinic agonist that is resistant to hydrolysis by AChE
carbachol
True or False:
Carbachol has a longer duration of action
true
what is the pathway of carbachol
stimulate autonomic ganglia = acetylcholine release
when should one administer carbachol
impaction colic in horses
glaucoma in dogs
rumen atony and impaction in cattle
when should you NOT administer carbachol
in cases of maybe solid impactions - can cause bowel ruptures
which direct-acting agonist is very potent and selective for muscarinic receptors and resistant to hydrolysis to AChE
bethanechol
when would you administer bethanechol
GI paralytic ileus
urinary retention associated with bladder muscle atony
what should you be aware of when thinking about using bethanechol
only use when there is no mechanical obstruction in GIT
what receptor does Pilocarine act on
M3
what is the effects of using M3
contraction of iris sphincter and ciliary muscle of the lens
what can pilocarine be used to treat
acute glaucoma
keratoconjunctivitis sicca
what are the therapeutic uses of parasympathomimetic
GI atony / impaction
urinary bladder muscle atony
glaucoma
how do reversible cholinesterase inhibitors work
inhibit ACh binding to AChE
how is physostigmine administered
orally
what is physostigmine used for
glaucoma
atropine toxicity
how is neostigmine administered
orally
what receptors does neostigmine work on
selective for nicotinic receptors at the Nm junction
when is neostigmine used (therapeutic)
myasthenia gravis
reverse neuromuscular blockade (non-depolarizing)
what type of inhibitor is edrophonium
competitive reversible inhibitor
when is edrophonium used (therapeutic)
anti-curare
myasthenia gravis
what is a longer acting drug used for myasthenia gravis
pridostigmine
what are the digestive pharmacologic effects of reversible cholinesterase inhibitors
increase GIT motility
increase frequency / strength of peristaltic waves
what should you be aware of (warnings) before using reversible cholinesterase inhibitors
intestinal spasm
colic
what are the ocular effects of using reversible cholinesterase inhibitors
pupillary constriction
loss of accommodation
when are pharmacologic effects more pronounced in skeletal muscle
low doses
how do reversible cholinesterase inhibitors affect cardiac tissue
hypotension
bradycardia
arrhythmia
how do reversible cholinesterase inhibitors affect the bladder and lungs
bronchoconstriction
contraction of the urinary bladder (detrusor muscle)
what is physostigmine used to treat
glaucoma
impaction in cattle
what drug combination is used to prevent or breakdown of synechia formed between lens and iris
physostigmine + atropine
which reversible cholinesterase inhibitors are used to treat myasthenia gravis and anticurare
neostigmine
pyridostigmine
which reversible cholinesterase inhibitor is used to differentiate myasthenia gravis from cholinergic crisis
edrophonium
when should reversible cholinesterase inhibitors use be avoided
impaction with possible mechanical obstruction
pregnancy
which reversible cholinesterase inhibitor depresses the CNS at large doses and causes convulsions at massive doses
physostigmine
which reversible cholinesterase inhibitor can cause skeletal muscle weakness in cases of overdose
neostigmine
what are some possible respiratory repercussions of reversible cholinesterase inhibitors
respiratory paralysis
increased bronchiolar secretion
what is the antagonist to reversible cholinesterase inhibitors
atropine
what is the irreversible cholinesterase inhibitor
organophosphourous compounds
True or False:
organophosphourous compounds can cross the brain blood barrier
true
what is the antidote used for organophosphorus poisoning
atropine
which organophosphorus compound is used to reactivate ChE
pralidoximine
True or False:
Use of pralidoxime and atropine is a time-sensitive treatment for organophosphate poisoning
true
for what type of poisoning should pralidoxime not be used
carbamate poisoning
what are some precautions that should be taken before administering pralidoxime or atropine
-no exposure to other cholinesterase inhibitor drugs
-history of respiratory illness or hepatic disease
-pregnant patients
how do cholinergic antagonists work
inhibit actions of acetyl choline by blocking cholinergic receptors
what receptors do cholinergic antagonists act on
muscarinic
Nm receptors
what is the response of using a cholinergic antagonist on a muscarinic receptor
muscle relaxation
how do antimuscarinic agents work
inhibit muscarinic actions of acetylcholine and related cholinergic agonists
what is the affect of atropine on the cardio vascular system
tachycardia
increased cardiac output
increased blood pressure
what is the response of atropine in the GIT
relaxation of GIT
decrease in motility
decrease in secretions
what is the affect of atropine on the urinary system
relaxes smooth muscle of bladder
urinary retention
what is the affect of atropine on the respiratory system
decreased secretions
bronchodilation
what is the affect of atropine on the ocular system
increased intraocular pressure
True or False:
atropine has minimal effect on the CNS
true
which species is resistant to atropine
rabbits
what atropine derivative causes slight sedation and antiemetic effects
scopolamine
how is atropine poisoning tested for
drop of urine
mydriasis in cat eyes
what is the treatment of atropine poisoning
neostigmine
physostigmine
which antimuscarinic drug can be used to reduce gastric acid secretion
pirenzepine
which antimuscarinic drug can be used for ophthalmic purposes
tropicamide
what is tropicamide used to treat
adhesion between iris and lens
what is the antidote for cholinergic agonists
atropine
what antimuscarinic drug can be used to prevent motion sickness
scopolamine
which antimuscarinic drug can be used as a preanaesthetic in veterinary medicine
glycopyrrolate
