Cholinergic Agonisits Flashcards
What is the rate limiting step of ACH synthesis
Choline uptake
Release of Ach
- membrane depolarizes
- open Ca2+ channels and Ca2+ rushes in
- this causes the vesicles to move to the membrane and release Ach into the synapse
What are the 3 fates of ACH once it is in the synapse?
- Binds postsynaptic receptor
- Metabolized by acetylcholinesterase
- Ach binds to presynaptic nerve (same nerve that releases)
What does Ach bind to postsynaptically
Nicotinic or muscarinic receptors
How is Ach metabolized
By acetylcholinesterase
-breaks it into choline and esterase
What happens to the choline once acetylcholinesterase has metabolized Ach
It gets recycled, it never takes in whole Ach, has to be choline
Why does Ach have a short half life
Because acetylcholinesterase metabolizes it so quickly
What happens when Ach binds to the presynaptic cleft?
- regulation by negative feedback
- usually an M2 receptor (GI)
- decreases CAMP, which decreases Ca2+ channels opening, which stops Ach release.
All NT releasing neurons have to be regulated by
Negative feedback
What receptors do NE bind to regulate with negative feedback
A2
What receptors do dopamine have to bind to to regulate via negative feedback
D2
What does an acetylcholinesterase inhibitor act like
Muscarinic agonist
Increases the half life of Ach
What does Botox do to the release of Ach
Decreases it
What does Botox do to a somatic muscle nerve
Muscle wont contract,relaxes it
Botox and sweat glands
Inject into sweat glands to decrease sweat, sweat is activated by Ach
What does spider venom do to Ach
Causes very increased released of Ach
Can bind acetylcholine and the alkaloid muscarine
Muscarinic receptors
What are the subclasses of muscarinic receptors
M1,M2,M3,M4,M5
We dont talk much anoint 4 and 5
M1 receptors located mainly in the
CNS
M2 receptors mainly located in the
Heart and presynaptic preganglionic nerves
Where are M3 receptors found
Just about everywhere except the heart and CNS
Properties of muscarinic receptor agonists
- show selectivity for muscarinic receptors
- mimic the actions of Ach but have longer 1/2 life
- parasympathetic effects + sweating (symp)
Muscarinic receptor agonist drugs
- bethanechol
- carbachol
- methacholine
- pilocarpine
- cevimeline
GI system effects of muscarinic agonists
-stimulates the GI tract
Increases just about everything
-may be accompanied by nausea, belching, vomiting, intestinal cramps, and defacation
Urinary effects of muscarinic agonists
Increased urination
- increase ureteral peristalsis
- contract dertusor muscle
- relax the trigone and sphincter muscle
- increase max voluntary voiding pressure
- decrease capacity of the bladder
Muscarinic receptors in urinary tract
M3
Muscarinic receptors in the GI Tract
M3
Cardiovascular effects of a muscarinic agonist
M2
-decrease HR, contractility, and rate of conduction
M3
-vasodilation with drugs only
M3 receptors in the blood vessels
- physiologically inactive
- pharmacologically useful
- there are 3 receptors in BV, a1, b2, m3
- a1 is innervated and activated by epi and b2 is activated by epi from adrenal medulla
- m3 has no nerve and does not get Ach from any other source.
- can only be activated pharmacologically
- releases NO onto smooth muscles to cause vasodilation
- activated by muscarinic agonist
Miscellaneous effects of muscarinic agonists
Increased secretions
Bronchoconstriction
Miosis and accommodation
Why are acetylcholine and carbachol not good for the GI tract
They are not very selective and will also bind nicotinic receptors
Used to stimulate the smooth muscle of the GI tract and bladder. Used for urinary retention and gastric atony
Bethanechol
“Bowels and bladder”
Carbachol and decreasing IOP
Used to decreased IOP, but it is as last choice drug for that.
Why is carbachol’s use restricted
Because of nicotinic effects at autonomic ganglia. Rarely used because it is not selective enough
What is methacholine important for
Helps dx asthma
- causes bronchoconstriction
- can dx astham in subjects who do not have clinically apparent asthma (methacholine chllange test)
- asthma patients more sensitive to this
Pilocarpine and glaucoma
Used for open angle glaucoma and angle closure glaucoma. Not first choice. Low priority
What are pilocarpine and cevimeline important for
Xerostomia
- occurs after head and neck radiation tx or with sjogrens sysndrom.
- stimulates salivary secretions which eases swallowing
What is a drug you would give to someone who is having difficulty swallowing due to a dry mouth
Pilocarpine or cevimeline
This is an autoimmune disease causing decreased secretion (dryness)
Sjogren’s
What does glaucoma treatment usually involve
Decreased the production or increased the drainage of aqueous humor
-muscarinic agonists increase fluid drainage
Toxicity of muscarinic agonists
Miosis, bradycardia, bronchoconsitrion (dont give to asthma patients), increased gastric acid production (avoid in ulcers), diarrhea, increased ruination, flushing, salivation, lacrimation, sweating
How are muscarinic agonists given to avoid toxicity
Topically
What is given to treat serious toxic reactions to muscarinic agonists
Atropine sulfate or epinephrine
What kind of binding is atropine sulfate in the case of a muscarinic agonist overdose
Pharmacological
What kind of binding is epinephrine in the case of a muscarinic agonist overdose
Physiologic
Binding symp receptors while the agonist is binding parasympathetic
Why is reversible drugs more therapeutic than nonreversible
Because they are less dangerous
They have temporary inhibition, binds and lets go
This group of drugs inhibits achase
Acetylcholinesterase inhibitors
How can acetylcholinesterase inhibitors be exerted
At either nicotinic or muscarinic receptors
