Term
| explain the process of cholinergic activation up until NT release |
|
Definition
1. Uptake of choline via Na cotransport RATE LIMITING
2. Choline acetyl transferase (CAT) and acetylCoA synthesizes acetylcholine
3. Storage of acetylcholine inside vesicle and H+ is effluxed
4. Depolarization: Ca channels open and lets Ca in
5. Ca mediated vesicle fusion: vesicles migrate and fuse to release contents |
|
|
Term
| what are the fates of ACh after release from neuron |
|
Definition
a. Diffuse across synapse and bind to post-synaptic receptor (N or M) or pre-synaptic receptor (M)
b. Bind to pre-synaptic auto receptor for negative feedback
c. Rapidly metabolized by acetylcholinesterase into acetate and choline which is taken back into nerve (Causes short half-life) |
|
|
Term
| explain how the pre-synaptic autoreceptor works |
|
Definition
i. M2 receptor on original nerve
ii. Inhibitory Gi protein causes cAMP to go down and Ca channels close
iii. Stopping release of neurotransmitter |
|
|
Term
| botox: where does it come from, what does it do |
|
Definition
Produced by clostrum botulinium
Gets inside nerve and inhibits vesicles from fusing with membrane
Blocks release of ACh |
|
|
Term
| latrotoxin: where does it come from, what does it do |
|
Definition
Spider venom
Causes flood of ACh to be released |
|
|
Term
| muscarinic receptors: innervated by, NT is |
|
Definition
Cholinergic receptor on end organ
Affinity for ACh and agents that mimic ACh (cholinomimetics) |
|
|
Term
| what does a muscarinic receptor have the highest affinity for |
|
Definition
| Highest affinity for muscarine (in poisonous mushrooms) |
|
|
Term
| in one sentence describe the purpose of muscarinic receptors |
|
Definition
| Innervate parasympathetic nervous system effects onHeart, smooth muscle, endocrine glands |
|
|
Term
| where is m1 located, what type of receptor |
|
Definition
|
|
Term
|
Definition
| phospholipase C > PIP2 > IP3 + DAG |
|
|
Term
| where is m2 receptor located |
|
Definition
heart
Auto receptors on pre/post-ganglionic or pre-synaptic cholinergic nerves |
|
|
Term
| what type of receptor is m2, how does it work |
|
Definition
Gi receptor
Heart: decrease K+ conductance
Presynaptic: decreases cAMP |
|
|
Term
| in general, what do M2 receptors do |
|
Definition
Decreases HR and force of contraction (due to decreased K conductance)
Decreases ACh release |
|
|
Term
| where are m3 receptors located, what type of receptor, what do they do |
|
Definition
everywhere but heart and brain
Gq receptor
constrict smooth muscle |
|
|
Term
| where are m4 receptors, what type of receptor |
|
Definition
|
|
Term
| where are m5 receptors, what type of receptor |
|
Definition
|
|
Term
| what does a muscarinic agonist do |
|
Definition
| stimulate muscarinic receptor by mimicing ACh but with longer half life |
|
|
Term
| why do muscarinic receptor agonists have a longer half life |
|
Definition
no acetylcholinesterase issue
they only do M receptor (not n) so fewer side effects and uptake issues |
|
|
Term
| what are the 4 muscarinic agonists and their relative nicotinic effects |
|
Definition
bethanechol - little
carbachol - lots causes SE
methacholine - little
pilocarpine |
|
|
Term
| what does benthanecol work on |
|
Definition
| stimulates GI and urinary tract |
|
|
Term
| how is bethanecol administered, why |
|
Definition
| oral, because it isnt absorbed well and limits SE |
|
|
Term
|
Definition
postop and post partum non-obstructive urinary retention
neurogenic atony of bladder with retention
gastric atony
urinary retention; caused by diabetic lack of GI tone, decreased bladder tone due to drugs (ANTI-PSYCHOTICS) ith anti-muscarinic effects |
|
|
Term
| what is carbachol used for |
|
Definition
|
|
Term
| what is methacholine used for |
|
Definition
bronchoconstriction - diagnostic for subclinical asthma
methacholine challenge test; asthma pt is more sensitive to methacholine induced bronchoconstriction |
|
|
Term
|
Definition
| stimulate salivary secretion |
|
|
Term
| what are the ways pilocarpine is administered, why for each (3) |
|
Definition
IV/IV: it isnt, this increases toxicity
topical: reduce side effects (eye drops)
oral: xerostomia (increased SE) |
|
|
Term
|
Definition
openangle and closed angle glaucoma: increases aq humor drainage and decreased production
xerostoma |
|
|
Term
| what causes xerostomia, what is it |
|
Definition
| difficulty swallowing due to head and neck radiation or sjogerns |
|
|
Term
| what is sjogerns and what are the symptoms |
|
Definition
autoimmune disease
decreased secretions: lacrimation, saliva, vaginal |
|
|
Term
| effects of muscarinic agonist on GI tract |
|
Definition
increase tone, constraction, peristalsis, secretions
nausea, belching vomiting, intestinal cramps, defecation |
|
|
Term
| effects of muscarinic agonist on urinary tract |
|
Definition
increase urethral peristalsis
contract detrusor
relax trigone and sphincter
increase voiding pressure
decrease capacity of bladder |
|
|
Term
| effects of muscarinic agonist on cardiovascular system |
|
Definition
decrease HR - neg chronotrophic
decrease conduction at SA/AV - negative domotrophic
decrease contraction force (neg inotrophic)
vasodilation |
|
|
Term
|
Definition
|
|
Term
|
Definition
| conduction at SA/AV nodes |
|
|
Term
|
Definition
|
|
Term
| explain how muscarinic agonist cause vasodilation |
|
Definition
Vessels have M3 receptors on endothelial cells WITHOUT nerve attached (no physiological purpose!)
if you could activate them they release NO causing vasodilation (because the receptor is on endothelial cells DIFFERENT CELL TYPE = DIFFERENT RESPONSE) |
|
|
Term
| what is the overall cardiovascular response to the changes muscarinic agonist make |
|
Definition
decreased HR, conduction, force, vasodilation causes decreased BP
sympathetic responds to this increasing BP |
|
|
Term
| what is the effect of muscairinic agonist on secretions, sweat, lungs, eyes |
|
Definition
increase secretions: salivary, lacrimal, digestive, exocrine, tracheobronchial
sweat glands: (sympathetic but have non innervated M3)
bronchoconstriction
miosis and accommodation for near vision
stimulate chemoreceptors on carotid and aortic bodies |
|
|
Term
| side effects of muscarinic agonist |
|
Definition
miosis, bradycardia, bronchoconstriction (avoid in asthma), increased gastric acid (avoid in ulcers), diarrhea, urination
flushing: due to vasodilation increasing blood flow
salivation, lacrimation, sweating (sympathetic!!) |
|
|
Term
| what are the antidotes to musarinic OD |
|
Definition
atropine sulfate - muscarinic antagonist
epinepherine |
|
|
Term
| atrophine sulfate: admninistration, use |
|
Definition
IV/SC
treat toxic reaction of muscarinic agonist |
|
|
Term
| how does epinepherine work |
|
Definition
physiologic antagonist works on different receptor
overcomes cardiovascular and bronchoconstrictor receptors |
|
|
Term
| reversible acetylcholinesterase inhibitor |
|
Definition
| breaks down acetylcholinesterase and increases M and N receptor action all over body in parasympathetic, sympathetic, and somatic NS |
|
|
Term
| reversible acetylcholinesterase inhibitor drugs (8) |
|
Definition
physpstigmine
pyridostigmine
neostigmine
edrophonium
ambenomium
donpezil
rivastigmine
galatamine |
|
|
Term
| irreversible acetylcholinesterase inhibitor drugs (6) |
|
Definition
military nerve agents: sarlin nerve gas, soman, tabun
insecticides: parathion, malathion (organophosphates)
lice topical: malathion |
|
|
Term
| acetylcholinesterase inhibitor antidotes (2) |
|
Definition
pralidoxime (PAM)
atropine |
|
|
Term
|
Definition
stimulates Nn and Nm receptors
activates sympathetic and parasympathetc NS (mostly parasympathetic) |
|
|
Term
|
Definition
|
|
Term
| cholinergic antagonist MOA |
|
Definition
binds to cholinergic receptors and stops ACh
stops parasympathetic and muscarinic transmission |
|
|
Term
| what are the two types of cholinergic antagonists and their general function |
|
Definition
ganglionic blockers: show preference for blocking nicotonic of sympathetic and parasympathetic GANGLIA
NMJ blockers: block different impulses to SKELETAL MUSCLE
antimuscarinic and antinicotinic |
|
|
Term
| MOA of antimuscarinic agents |
|
Definition
block M receptors blocking parasympathetic and sympathetic NS mediated by ACh (thats sweating for sympathetic)
no nicotinic receptor activation
competitive agonist - can be out competed
target organ depends on lipid solubility |
|
|
Term
| what are competitive muscarinic agonists / muscarinic antagonist antidotes |
|
Definition
| thiostigmine, ACh inhibitor, muscarinic agonist |
|
|
Term
| what strucure of antimuscarinic agents makes it more lipid soluble, what diseases is this required for |
|
Definition
qaternary N is more polar and less likley to penetrate BBB or cornea so needs to have tertiary amine
parkinsons and opthalmology needs lipid soluble (gut and bronchi dont) |
|
|
Term
|
Definition
tropicaamide
scopolamide
bnstropine
atropine
tolterodine
oxybutynin |
|
|
Term
| physpstigmine distribution |
|
Definition
| tertiary amine: lipid soluble |
|
|
Term
|
Definition
antidote for muscarinic blockers (anticholinergic toxicity) like atropine
reversible acetylcholinesterase inhibitor |
|
|
Term
|
Definition
|
|
Term
| pyridostigmine/neostigmine MOA |
|
Definition
quarinary amine (positive) water soluble
only used for Nm at NMJ
reversible acetylcholinesterase inhibitor increases ACh can outcompete binding of antibodies in myasthenia gravis |
|
|
Term
| use pyridostigmine/neostigmine |
|
Definition
myasthenia gravis: autoimmune disease with antibodies to Nm causes weakness mostly in facial region, the more they excert the weaker they get, symptoms improve with rest
reversal of non-depolarizing blocking agents like tubocurarine |
|
|
Term
|
Definition
IV short acting 10-20min reversible acetylcholinesterase inhibitor to diagnose myasthemia gravis
if muscle activity returns then they have it |
|
|
Term
|
Definition
| back up drug for myasthenia gravis if they cannot tolerate bromides |
|
|
Term
| donepezil/rivastigmine/galantamine distribution |
|
Definition
| tertiary amines: enter CNS |
|
|
Term
| donepezil/rivastigmine/galantamine use |
|
Definition
alzheimers (mostly doneprezil)
neurodegenerative disorder with loss of memory and cognative function
pt looses cholinergic neurons in cortex (mynert's nuclei)
increasing ACh is many strategy for tx |
|
|
Term
| parathion/malathion: MOA, SE, use |
|
Definition
insecticides, malathion is for lice
prodrugs, activated by P450
active form is hydrolyzed by plasma carbxylesterases which causes death in insects but sucks in us only in high doses |
|
|
Term
| SE acetylcholinesterase inhibitors and the receptor involved |
|
Definition
diarrhea - M3
urination - M3
miosis - M3
bronchoconstriction - M3
bradycardia - M2
excitation of skeletal M - Nm
excitation of CNS - M1, Nn
lacrimation - M3
salivation - M3
sweating - M3 - sympathetic! |
|
|
Term
| what SE of acetylcholinesterase inhibitors are deatly |
|
Definition
excitation of skeletal muscle / CNS
causes paralysis of diaphragm |
|
|
Term
|
Definition
| breaks bone between irreversible acetylcholinesterase inhibitor and ACh, regenerating the enzyme so it can work again |
|
|
Term
| what is chemical aging, why is it a problem |
|
Definition
change in structure of irreversible acetylcholinesterase inhibitor makes it so pralodoxime can no longer remove the drug
due to hydrolysis reaction pulling alkyl grop off
rate depends on agent - can be minutes
releases enzyme so it breaks down ACh and stops effects at skeletal M |
|
|
Term
|
Definition
| inhibits everything in acetylcholinesterase SE except excitation of heart |
|
|
Term
| nicotinic receptors: MOA, locations, types |
|
Definition
binds ACh and nicotine
nitotine initially stimulates then blocks receptor
locations: CNS, adrenal medulla, autonomic ganglia, NMJ
types: autonomic ganglia Nn, skeletal muscle Nm |
|
|
Term
|
Definition
stimulates Nn and Nm receptors
stimulating parasympathetic and sympathetic (vessels, and sweating) |
|
|
Term
| SE/MOA high doses of nicotine |
|
Definition
| desensitization of receptors at organs leads to inability to cause parasympathetic response and thus causes sympathetic response |
|
|
Term
| what causes problems in cigarette smoke, why |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| MOA cholinergic antagonist |
|
Definition
| blinds to cholinergic receptor stopping ACh stopping parasympathetic and muscarinic transmission |
|
|
Term
| types of cholinergic antagonists |
|
Definition
ganglionic blockers
NMJ blockers |
|
|
Term
| where does atropine come from |
|
Definition
| belladone aklaloid, gymsin weed |
|
|
Term
|
Definition
| blocks receptors in PNS and CNS |
|
|
Term
|
Definition
| tertiary amine: lipid soluble, enters CNS |
|
|
Term
|
Definition
short 4-8h
unless in eye 3-5d |
|
|
Term
| CNS effects of antimuscarinic |
|
Definition
| sedation, anti-motion sickness, anti-parkinsons, amnesia, delirium |
|
|
Term
| M1 effecs of antimuscarinic |
|
Definition
GI relaxation, slow peristalsis
exocrine: reduced salivation, lacrimation, sweating, gastric secetion |
|
|
Term
| M2 effects of antimuscarinic |
|
Definition
heart: initial bradycardia then tachycardia decreases in AV conduction
inhibit presynaptic M2 (inhibit inhibitory) and pathway becomes stimulate releasing more ACh -> initial bradycardia
M2 acts on heart a little more slowly and blocks it -> tachycardia |
|
|
Term
| effects of antimuscarinic on M3 |
|
Definition
eye: cycloplegia
bronchi: dilation
GI: relaxation, slow peristalsis
GU: relax bladder wall, urinary retention
vessesl: block muscarinic causing vasodilation (only when muscarinic agonist present or else does nothing)
exocrine: reduced salivation, lacrimation, sweating, gastric secretion |
|
|
Term
| SE of antimuscarinic - hot as a pistol |
|
Definition
| atropine fever: blocks thermoregulatory mechanisms causing hyperthermia (lethal in infants) |
|
|
Term
| SE of antimuscarinic - dry as a bone |
|
Definition
| decreased sweating, lacrimation, salivation, urination, pooing |
|
|
Term
| SE of antimuscarinic - blind as a bat |
|
Definition
| blurred bision, acute angle closure glaucome (esp elderly) |
|
|
Term
| SE of antimuscarinic - mad as a hatter |
|
Definition
| sedation, amnesia, delirium, hallucinations |
|
|
Term
| SE of antimuscarinic - red as a beet |
|
Definition
atropine flush: dilation of cutaneous vessels in arms, head, neck, trunk
diagnostic for OD |
|
|
Term
|
Definition
dilate pupil (mydriasis) for eye exam
paralyze accomodation |
|
|
Term
|
Definition
| motion sickness - block receptors in vestibular apparatus that induce nausea and vomiting |
|
|
Term
|
Definition
| adjunct to L DOPA for parkinsonism (loss of dopaminergic neurons decreases dopamine and increases ACh) |
|
|
Term
| what drug can help with peptic ulcer disease |
|
Definition
|
|
Term
| what drug can be used for bronchodilation in asthma and COPD |
|
Definition
|
|
Term
| use of tolerodine, oxybutynin, |
|
Definition
reduce urgency in cystitis
reduce bladder spasm following urologic surgery
urinary incontence |
|
|
Term
|
Definition
block Nn receptor on autonomic ganglia and adrenal medulla
blocks dominant system (usually parasympathetic) |
|
|
Term
| ganglionic blocker drug and its use and MOA |
|
Definition
mecamylamine
HTN back up drug
decrease sympathetic tone and vasodilates |
|
|
Term
| structure of neuromuscular blockers |
|
Definition
similar to ACh
have 2 quatenary N, unable to get in CNS |
|
|
Term
| uses of neuromuscular blockers |
|
Definition
surgical relaxation
trachea intubation
control ventilation
control motor acrivity in seizure (not tx it) |
|
|
Term
| what category of drugs are best at helping with trachea intubation |
|
Definition
| depolarizing neuromuscular blockers |
|
|
Term
| MOA non-depolarizing neuromuscular blockers |
|
Definition
competitive blocker of ACh and Nm receptor at a subunit
can be outcompeted by acetylcholinesterase inhibitors |
|
|
Term
| what is the antidote to non-depolarizing neuromuscular blocker |
|
Definition
| acetylcholinesterase inhibitors neostigmine and pyridostigmine (because they work in peripherary) |
|
|
Term
| side effect of all non-depolarizing neuromuscular blockers |
|
Definition
motor weakness: small muscles first then large, large first to recover
diaphragm is last |
|
|
Term
| what are the short duration neuromuscular blockers, how long |
|
Definition
10 min
articurium
mivacurium |
|
|
Term
| what are the intermediate duration neuromuscular blockers, how long |
|
Definition
25 min
cisatracurium
rochuronium |
|
|
Term
| what are the long duration neuromuscular blockers, how lonw |
|
Definition
|
|
Term
|
Definition
| spontaneously inactivate to metabolite laudanosine (causes seizures, can be used in liver and kidney dysfynction) |
|
|
Term
|
Definition
| same as articurium but when spontaneously inactivated does not produce as much laudanosine so less seizures occur |
|
|
Term
| mivacurium SE, duration, onset of action |
|
Definition
shortest DURATION
short onset of action
causes histamine release > hypotension and reflex tachycardia |
|
|
Term
|
Definition
|
|
Term
|
Definition
| blocks M receptors and causes tachycardia |
|
|
Term
| what drug is a depolarizing neuromuscular blocker, what is its structure |
|
Definition
| succinylcholine - 1 ACh together |
|
|
Term
|
Definition
phase one: simulates ACh and causes muscle contraction
phase two: overstimulation causes de-sensitization of the receptor so membrane repolarizes but it cannot easily repolarize |
|
|
Term
| what is the antidote for succinylcholine |
|
Definition
there isnt one. acetylcholinesterase innhibitor dosent work.
it increases ACh in the phase one which just further mimics the drug
it increases ACh in phase two but at that point it dosent matter how much ACh there is, the receptor dosent work |
|
|
Term
| kinetics and distribution succinylcholine |
|
Definition
short acting, works fast
less lipid soluble, cannot get into CNS |
|
|
Term
| succinylcholine: how long does it take to work, wat are the next two stages of timing, how long does it take to stop, why does it stop |
|
Definition
30s- general anasthesia
90s- arm, back, leg muscle flaccid
more sec- repsiratory muscle flaccid
10 min- hydrolyzed in plasma and liver cholinesterase |
|
|
Term
| side effects of depolarizing neuromuscular blockers, why |
|
Definition
can stimulate M and Nn too causing bradycardia
hyperkalemia in burn pt, head injury, trauma bc Na rushes in and K out at nicotinic receptors which are being fired
muscle pain due to initial contraction
increased risk if inhaled anasthetic |
|
|
Term
| interactions with depolarizing neuromuscular blockers, effect, tx |
|
Definition
inhaled anasthetics: malignant hyperthermia (rare, fatal). due to abnormal release of Ca from skeletal M
tx dantrolene |
|
|
Term
|
Definition
blocks ryanoide receptor (RyR1) on SER blocking Ca release decreasing ability for contraction
decreased muscle contraction decreases body temo |
|
|
Term
| what tx malignant hyperthermia, how is the condition started |
|
Definition
dantrolene
genetic alteration in RyR1 gene + succinylcholine or anesthetics --> prolonged Ca release --> muscle contraction, lactic acid, increased body temp |
|
|
Term
|
Definition
|
|
Term
|
Definition
local facial injection
spasticity - cerebral palsy
strabismus
blepharospasm
hyperhidrosis
migraines |
|
|
Term
| use of CNS skeletal relaxants |
|
Definition
spasticity: increase in tonic stretch reflexes. caused by spinal injury, cerebral palsy, MS, stroke
often involves abnormal function of bladder and bowel |
|
|
Term
| how are BDZ dosed for their usages |
|
Definition
low: anxiety
med: slwwp
high: anasthetic |
|
|
Term
|
Definition
| activate GABAa which increases frequency of Ca channel opening decreasing neuron activity |
|
|
Term
|
Definition
|
|
Term
|
Definition
activate GABAb opening K channel causing hyperpolarization and inhibiting neuron activity
prevent post synaptic propogation of AP |
|
|
Term
|
Definition
| less sedating than diazepam |
|
|
Term
|
Definition
a2 agonist: prevents NT release
(glutamate presynaptic, AP post synaptic)
classif autoreceptor mecanism |
|
|
Term
|
Definition
fewer effects than clonidine and methyldopa (a2 agonist for HTN)
hypotension and drowsiness due to decreased NE release |
|
|
Term
|
Definition
|
|
Term
|
Definition
| slow progression of amytrophic lateral sclerosis (ALS) / Lou Gherig's |
|
|
Term
| what are the CNS muscle relaxants |
|
Definition
riluzole
tyanadine
baclofen
diazepam |
|
|
