Cholinergics Flashcards
name 4 reversible inhibitors of cholinesterase
1) edrophonium
2) physostigmine
3) neostigmine
4) donepezil
name 3 irreversible inhibitors of cholinesterase
1) isoflurophate
2) parathion
3) soman (+ other organophosphates)
name 1 reactivator of cholinesterase
Pralidoxime (PAM)
name 1 nicotinic agonist
nicotine
name 3 muscarinic agonists that are cholinesters
1) Ach
2) carbachol
3) bethanechol
name 3 muscarinic agonists that are natural alkaloids
1) Pilocarpine
2) muscarine
what part of the body is in charge of overall ANS integration?
Hypothalamus
which part of the body specifically controls pupil size, respiration, heart rate, bp, etc?
brainstem (midbrain, pons, medulla oblongata)
which part of the body specifically controls urination, defecation, erection, ejaculation reflexes?
spinal cord
What are 3 survival reflexes?
1) flight or fight
2) freeze
3) faint and look dead
hyperthyroidism results in an increase or decrease of sympathetic and parasympathetic systems?
increase in both sympathetic and parasympathetic nervous systems
cholinergic neurons release what NT?
ACh
which two cholinergic receptors bind ACh?
Nicotinic and Muscarinic
ACh is inactivated by what enzyme?
acetylcholinesterase
What is the mechanism of action of the M2 receptor at the SA node?
Gi activates K+ channel which reduces cAMP, PKA and availability of L-type Ca flow
What is the mechanism of action of nicotinic transmission at skeletal neuromuscular junction?
allows Na+ influx to produce an EPSP which depolarizes muscle membrane, generating an action potential and triggering contraction.
what drug is used if a physician suspects a patient is an asthmatic to see if there is increases bronchoconstriction sensitivity?
Methacholine
what receptor does ACh act on to decrease BP?
M3
What is the mechanism of action of M3 receptors for decreasing BP?
M3 sites in endothelial cells produces NO. NO diffuses to vascular smooth muscle cells to stimulate protein kinase G production which leads to hyperpolarizaiton and smooth muscle relaxation via phophadiesterase-3 inhibition
Bethanechol is selective for muscarinic or nicotinic receptors?
muscarinic
what are the Routes of Administration of Bethanechol?
oral and SC (CANNOT cross BBB)
what is the main use for Bethanechol?
stimulation of GI motility and tone as well as urine expulsion (increases tone of detrusor muscle)
What is the Route of Administration of Carbachol?
SOLUTION! (applied locally- usually to the eye). Not avail orally
what is the main use of Carbachol?
constricts iris and ciliary bodies in eye and reduces intraocular pressure
what receptors does carbachol act on?
muscarinic AND nicotinic (could stimulate cardiac and GI, will increase release of Epinephrine)
what receptors does Pilocarpine act on?
MUSCARINIC agonist (only)
what is the route of administration of Pilocarpine?
solution or spray (eye or mouth only)
what is the main use for Pilocarpine?
Glaucoma (for emergency!!!)
1) decreases intraocular pressure
2) contracts iris sphincter and ciliary muscle (M3)
AE’s of Pilocarpine?
night blindness and blurred vision
what drug causes mydriasis and what receptor does it act on?
Atropine (alpha 1)
Ciliary body is responsible for what and what happens when parasympathetic acts on ciliary muscle?
accommodation, aqueous humor production and resorption.
When PNS acts on it, lens becomes thicker and eye focuses on near objects.
What happens when PNS acts on sphincter of Iris?
Miosis (M3)– i.e. contraction of sphinchter of iris
Treatment of Glaucoma
What 2 cholinomimetics can be used?
carbachol
pilocarpine (emergency use)
Treatment of Glaucoma
What nonselective alpha agonist can be used?
epinephrine
Treatment of Glaucoma
What selective alpha-2 agonist can be used?
apraclonidine
Treatment of Glaucoma
What 2 beta blockers can be used?
timolol
betaxolol
Treatment of Glaucoma
What Prostaglandin can be used?
latanaprost
can diuretics be used to treat glaucoma?
yes
what three classes of drugs can decrease aqueous humor production?
sympathetic system alpha agonists (i.e. epinephrine, apraclonidine), Beta antagonists (i.e. timolol, betaxolol), and diuretcs
what is the mechanism of action of physostigmine?
blocks AChE. This increases ACh at muscarinic and nicotinic receptors. Reversible.
can cross BBB
what 3 conditions is physostigmine used for?
1) glaucoma
2) Alzheimers
3) delayed gastric emptying
AEs of physostigmine?
high doses cause convulsions, decreased CO, paralysis of skeletal muscle
How is Neostigmine different from Physostigmine?
neostigmine does NOT cross BBB
Clinical Uses of Neostigmine
1) improve muscle tone in people with myasthenia gravis
2) in anesthesia to reverse the effects of non-depolarizing muscle relaxants such as rocuronium and vecuronium at the end of an operation
3) used for urinary retention resulting from general anesthesia (i.e. it can stimulate GI and bladder smooth muscle)
What is the MOA of Neostigmine?
blocks AChE. This increases ACh at muscarinic and nicotinic receptors. Reversible.
what is the main use of edrophonium?
myesthenia gravia (rapidly increases muscle strength)
which reversible anticholinesterase has the shortest duration of action?
edrophonium (10-20 minutes)
What is Donepezil used for? and what is its mechanism of action?
alzheimers
reversible AChE inhibitor
what is the MOA of edrophonium?
reversible AChE inhibitor
what is the mechanism of action of irreversible anticholinesterases?
1) covalent modification of AChE (at this point 2-PAM can rescue, if it does not displace organophosphate, see step 2)
2) 6-8 hrs –> isopropyl groups released –> AChE is irreversibly blocked
what is isoflurophate used for?
It is an organophosphate (that crosses BBB) and is used for open angle glaucoma when no other treatments work
what is parathion?
it is an insecticide that acts as an irreversible AChE inhibitor
What is Soman?
it is a nerve agent that acts as an irreversible AChE inhibitor
what is the duration of action of organophosphates?
100 hours! (long time)
what should you give if a black widow spider bites? (mass amount of Ach released)
atropine OK to give
if poisoned by Amanita muscaria (mushroom neurotoxin) don’t give what drug?
don’t give atropine
