Neuropharmacology Flashcards
what are cholinergic drugs?
drugs that mimic the action of acetylcholine
what are adrenergic drugs?
drugs that mimic the action of epinephrine and norepinephrine
what are the general functions of the sympathetic and parasympathetic systems?
oppose each other
discrete vs diffuse action
both excitatory and inhibitory
maintain homeostasis
one may directly inhibit other
what are the events involved in a cholinergic response?
synthesis of acetylcholine
storage of acetylcholine in vesicles
arrival of impulse and calcium uptake
release of acetylcholine into synaptic cleft
interaction of acetylcholine with receptor
hydrolysis of acetylcholine by esterase
reuptake of choline
what are the agonist and antagonist of muscarinic receptors (subtype of cholinergic)?
muscarine is agonist
atropine is antagonist
what are the agonist and antagonist of nicotinic receptors (subtype of cholinergic)?
nicotine is agonist
curare is antagonist
nicotinic receptor is the _________________ and is activated by _____________________________________
sodium channel
2 acetylcholine binding to the 2 alpha subunits
what are the subclasses of muscarinic receptors?
M1
M2
M3
where are M2 receptors located?
heart
where are M3 receptors located?
smooth muscle
secretory glands
what is the receptor action of M1 and M3?
M1: close potassium channel
M3: increased contraction, increased secretion
depolarization
what is the M2 receptor action?
open potassium channels and decrease cAMP to decrease heart rate
if a cholinergic drug’s mechanism of action is at M1, what does it do?
excitatory
close potassium channel
activate phospholipase C
if a cholinergic drug’s mechanism of action is at M2, what does it do?
inhibitory
open potassium channel
inhibit adenylate cyclase
if a cholinergic drug’s mechanism of action is at M3, what does it do?
excitatory
activate phospholipase C
increase ionized calcium concentration
where are cholinergic actions in the body?
cardiovascular system
respiratory system
gastrointestinal system
urinary bladder
eye
skeletal and smooth muscles
what are cholinergic actions in the cardiovascular system?
decrease heart rate
decrease atrial contractility
decrease AV conduction
decrease blood pressure
what are cholinergic actions in the respiratory system?
bronchoconstriction
increase bronchial secretion
what are cholinergic actions in the gastrointestinal system?
increase motility
increase secretion
relax sphincters
what are cholinergic actions in the urinary bladder?
contract detrusor muscle
relax internal sphincter
what are cholinergic actions in the eye?
contract sphincter muscles and iris
contract ciliary muscle
what are cholinergic actions in skeletal and smooth muscles?
contraction: muscle spasms
what are some direct acting cholinomimetics?
natural alkaloids- muscarinic receptor
synthetic- choline esters
what are some natural alkaloids?
muscarine
pilocarpine
arecoline
what are some synthetic cholinomimetics?
choline esters:
carbachol
bethanechol
methacholine
how do indirect acting cholinomimetics work?
inhibit acetylcholinesterase
what are some reversible indirect acting cholinomimetics?
physostigmine
neostigmine
pyridostigmine
edrophonium
what are some irreversible indirect acting cholinomimetics?
echothiophate
malathion
what can organophosphate poisoning be treated with and why?
atropine
antagonist: blocks acetylcholine until can make more acetylcholinesterase proteins
what are the clinical applications of cholinomimetics?
glaucoma
ileus and urinary bladder atony
myasthenia gravis
edrophonium test and atropine
curareform toxicity
anticholinergic toxicity
alzheimer’s disease
what blocks choline uptake and acetylcholine synthesis?
hemicholinium
what blocks release of acetylcholine?
low calcium
excess magnesium
botulinum toxicity
aminoglycosides
local anesthetics
what inhibits acetylcholine-receptor interaction?
curare
atropine
hexamethonium
what inhibits acetylcholine hydrolysis by esterase?
neostigmine
organophosphate
what is atropine’s mechanism of action?
prevents acetylcholine from binding and inducing its effects by interacting with muscarinic acetylcholine receptors
attenuates parasympathetic nerve impulses
what are the actions of muscarinic antagonists on the cardiovascular system?
increase heart rate
increase intranodal conduction
slight increase or no change in blood pressure
(dose dependent decrease in heart rate and second degree AV block can occur)
what are the actions of muscarinic antagonists on the respiratory system?
produce bronchodilation
decrease bronchial secretion
what are the actions of muscarinic antagonists on the gastrointestinal system?
relaxation of GI smooth muscle
decreased secretions
decreased salivation
what are the actions of muscarinic antagonists on the urinary bladder?
relaxes smooth muscle of urinary tract
urinary retention
what are the actions of muscarinic antagonists on the eye?
relax sphincter muscle and iris, dilated pupil
what are some antimuscarinic drugs?
atropine
glycopyrrolate
homatropine
propantheline
ipratropium
what is one autonomic ganglion blocker?
hexamethonium
what are some neuromuscular blockers?
curure
succinylcholine
what are some clinical applications of anticholinergics in the GI?
spasmolytic
peptic ulcer
colic in horses
what are some results of cholinergic drug toxicity?
severe colic and diarrhea
increased exocrine secretion
dyspnea
hypotension, cardiac slowing
death if not treated
when should you be careful while using anti-cholinesterases?
liver disease
respiratory disease
late pregnancy
when should you avoid using anti-cholinesterases?
other anti-cholinesterase
drugs metabolized by cholinesterase
phenothiozines
when should you be careful with anti-muscarinic drugs?
glaucoma
gastric ulcer
what are some competitive non-depolarizing blockers?
D-tubocurarine
gallamine
pancuronium
what are some depolarizing blockers?
succinyl choline
decamethonium
what is the mechanism of action for competitive/non-depolarizing blockers?
bind to receptors
no depolarization
block access of agonist to receptors
action can be reversed
what is the mechanism of action for non-competive/depolarizing blockers?
bind to receptors
cause depolarization
membrane remains depolarized
cannot be reversed with acetylcholinesterase inhibitor
how are D-tubocurarine and pancuronium metabolizd?
liver
excreted in bile and urine
how are gallamine and decamethonium metabolized?
excreted unchanged in urine
minimal tissue distribution
how is succinylcholine metabolized?
hydrolyzed by serum psuedo cholinesterase
what is the order for muscles being relaxed?
toes, ears, eyes
head and neck
limbs
respiratory muscles
what are some pharmacological actions of blockers?
central autonomic effect
contracture of ocular muscles
hypotension
cardiac arrhythmia
what are the clinical applications of blockers?
major and minor surgery
chemical restraint
strychnine poisoning
muscle disorders
how do you treat blocker toxicosis?
artificial respiration
anticholinesterase and atropine
what are some ways that the junctional events in cholinergic junctions can be blocked?
choline uptake and acetylcholine synthesis
release of acetylcholine
inhibition of acetylcholine-receptor interaction
acetylcholine hydrolysis by esterase
what are some clinical applications of anticholinergics in ophthalmology?
mydriasis
cycloplegia
what is a clinical application of anticholinergics in respiratory?
bronchodilator
what is a clinical application of anticholinergics in the cardiovascular system?
sinus bradycardia
what is a clinical application of anticholinergics using no system in particular?
pre-anesthetic
anti-cholinesterase toxicity
what do anti-nicotinic drugs do?
muscle relaxants
neuromuscular blocking agents
how do anti-nicotinic drugs cause hypotension?
blockade of ganglion
histamine release
which anti-nicotinic drug can cause cardiac arrhythmia at high doses?
succinylcholine
