Pharm1E1 Cholinergic Agonists Flashcards
muscarinic receptors
only in CNS?
inhibitory?
stimulatory?
M4, M5
M2, M4 (M2 decreases effects on heart)
M1, M3, M5
M1 and M3 receptors are coupled to stimulatory ? proteins
- leads to an increase in ? and ?
- leads to an increase in intracellular ?
Gq/11 G-proteins
IP3, DAG
Ca2+
M2 receptors are coupled to inhibitory ? proteins
- inhibits production of ?
- leads to ? through the opening of K channels
Gi/G0
cAMP
hyperpolarization
nicotinic receptors are ?, ? channels
muscarinic is 7 transmembrane G
pentameric, ion
both Nn and Nm mediate fast ? ? potentials resulting in the activation of the post synaptic cell
excitatory, postsynaptic
direct effects of muscarinic agonists on the CV system can be altered through ?
EX: IV infusion of a low dose of Ach will cause a drop in blood pressure that is detected by ?, resulting in an ?
-a larger dose of Ach will ? due to a slowed firing rate w/in the ? and a decreased conduction velocity of the ?
reflex arcs
baroreceptors, increase in SNS stimulation on the heart- increase HR- reflex tachycardia
result in bradycardia, SA node, AV node
muscarinic agonists on the ? terminals decrease the release of ? or ?
presynaptic nerve
Ach, NE
Nm receptors responds to both ? and ?
nicotine, acetylcholine
continued exposure to a nonhydrolyzable agonist like ? will lead to ? and eventually a ?
nicotine, depolarization blockade, flaccid paralysis
hyperthyroidism, asthma, CAD (hypotension), acid peptic disorders (increased gastric secretion), obstructive urinary retention
contraindications of choline esters
acetylcholine
bethanechol
carbechol
methacholine
choline esters
only high IV doses for short term effects
reduce postop IOP
last about 20 min
used in sweat spot test for diabetics
acetylCHOLine
longer lasting than Ach, more resistant to AchE
used to Dx bronchial airway hypersensitivity via bronchoconstriction
methaCHOLine (provoCHOLine)
is mostly NICOTINIC (other esters are M3)
increase in skeletal muscle activation
limit to opthalmic applications
IF YOU GIVE ATROPINE- it will block ? and you will see all of the effects of ?
carbaCHOL
muscarinic receptors
nicotine (it can only bind here)
promotes urination, NONobstructive urinary retention
only choline ester given SYSTEMICALLY
bethaneCHOL (URecholine)
CAN cross BBB
some are highly soluble and readily absorbed i.e. ?
some are quarternary amines and less readily absorbed i.e.?
cholinomimetic alkaloids
nicotine
muscarine
muscarINE
pilocarpINE
nicotINE
vareniclINE
alkaloids
no clinical uses
psychodelic effect- amanita muscaria (mushroom)
muscarINE
initial, acute treatment of open angle GLC
sjogren’s syndrome- xerostomia
reverses mydratic actions
rapid miosis
dont use in IOP that are >45 because it can close the angle further!
pilocarpINE
increase HR, secretions of NE&Epi
increase tone and motility of GI
(both PNS and SNS b/c it’s nicotinic)
clinically used as a smoking cessation agent
nicotine
ALSO NICOTINIC
partial agonist at neuronal nicotinic receptors
neuropsychiatric changes i.e. agitation, depressed mood, suicidal thoughts
vareneclINE
endothelium intact
vasodilation from release of nitric oxide
endothelium not intact
vasoconstriction
quarternary alcohols and carbamates are ?
reversible
organophosphates are ?
- last ? due to the ? bonding
- if given early enough- ? (cholinesterase regenerator) can treat patients suffering from organophosphate poisoning
irreversible
hundreds of hours, covalent
PAM (pralidoxime)
moderate doses of cholinesterase inhibitors (indirect) will reduce HR/CO and increase ?, BUT large/toxic doses will result in marked bradycardia, reduced CO and ?
blood pressure
hypotension
edrophonIUM physosSTIGmine neoSTIGmine Aricept COGnex REMINyl EXelon (rivaSTIGmine) pyridoSTIGmine ambenonIUM HUMORsol carbaCIDE (carbaryl)
indirect acting reversible cholinesterase inhibitors
Dx of myasthenia gravis- increase in muscle strength is positive
assesses the long term anticholinesterase therapy used in MG (pryidoSTIGmine)
short DOA
edrophonIUM
*decrease in muscle strength would indicate that they have been exposed to an anticholinesterase insecticide; driven from stimulation to depolarizing inhibition
antidote for anti-muscarinic toxicity
miosis, accomodation, decrease in IOP
nonobstructive paralytic ileus, postop atony of bladder
physoSTIGmine
MG
post-op bladder retention
REVERSES anaesthesia by reversing NM blockade
neoSTIGmine
MG gravis FIRST LINE Tx
NM blockade reversal
**prophylactic Tx of NERVE GAS
pyridoSTIGmine
Alzheimers disease Tx- 3
Aricept
COGnex
REMINyl
derived from daffodils
reminyl
PD w/ dementia
pseudo-irreversible
EXelon
used for MG
4-8 hours
mytelase
rarely used due to liver toxicity
COGnex
echothiphate
malathion & parathion
nerve agents (gases)
irreversible cholinesterase inhibitors- mostly pesticides
low lipid solubility
used in GLC
echothiophate
opthal drops for GLC
HUMORsol
treats lice
carbaCIDE
organophosphate poisoning can be treated with ? (nucleophile) via regenerating the enzyme if given before ? occurs
PAM, aging
rapidly metabolized by birds and mammals to non-toxic metabolites but not insects or fish
malathion
NOT rapidly detoxified in vertebrate; more dangerous and not available
parathion
sarin
soman
tabun
VX
nerve agents- death from respiratory failure
