ANS 2

effects of anticholinesterases 1-______ of ACh at receptors

accumulation

anticholinesterase co-admin with?

anticholinergic

organophosphate poisoning treatment - - -

atropine pralidoxime (2-PAM) supportive care

scopalamine and atropine cross the BBB and enter the CNS and produce a blockade of muscarinic receptors leading to

central anticholinergic syndrome

alzheimers causes a marked decrease in what part of ACh synthesis -sensitive to ________ CNS effects of certain drugs -tx with what class

choline acetyltransferase -antimuscarinic -anticholinesterase donepezil tacrine-hepatotoxic

toxicity of muscarinic receptor agonists causes -heart = (4) -lungs = --contraindicated in -glands = (2) --sialogogic effect = -gu/gi = (3) --contraindicated in treatment =

heart = -bradycarida -bronchoconstriction --restrictive airway -syncope -orthostatic hypotension -disrythmias glands= -sialogogic effect = salivation -diaphoresis GU/GI = -gut urgency -urinary urgency -abdominal cramping --peptic ulcer tx = atropine

key point muscarininc channel type

-GPCRs

vascular endothelium: muscarinic activation via ______ receptor -requires ________ endothelium to cause vasodilation

-M3 -intact

key point muscarininc cholinergic locations

-PNS post gang and target tissue -SNS post gang to sweat glands - eccrine

myasthenia gravis test

edrophonium challenge

key point 1-effects of nicotinic stimulation (cholinomimetic) or blockade vary depending on the predominance of _____ or _____ in that organ system 2-stimulation occurs at the peripheral ______ of the post synaptic neuron body--goes on to synapse with***: -all PNS neurons (now muscarininc) and all SNS adrenergic neurons + medulla -skeletal motor neuron *** have to be cautious when administering becasue of ______ effects

-SNS -PNS -downstream

cholinomimetics: direct acting/cholinergic agonists- -choline esters (3)

-ach -methacholine -bethanechol

nicotinic ligand gated receptor 1-need____ molecules of ______ or a _____ _______ or one of each bind to 2-_______ subunit 3-channel opens = _____ influx 4-______ occurs 5-_____outflux = repol

1- 2 -ACh -direct cholinomimetic 2-alpha 3-sodium 4-action potential 5-potassim

central anticholinergic syndrome treatment -OD on anticholinergic so need more ACh so give_____ -particularly?--crosses BBB?

-anti cholinesterase -physostigmine

myasthenia gravis treatment -rx class -typical rx -combo? -surgery -____ therapy

-anticholinesterase -pyridostigmine and an anti-cholinergic -thymectomy -immunosuppressive

anticholinergics most: -tachycardia -bronchodilation -sedation -antisialagogue

-atropine>glyco -atropine = glyco -scopal>atropine 0-glyco -scopal = glyco > atropine

myasthenia gravis -type of disorder -____ or ____ of ACh receptors at ____ -results in -incidence

-autoimmune -destruction or inactivation -weakness and easy fatigueability -1 in 7500

cholinomimetics: direct acting/cholinergic agonists- synthetic (1)

-cevimeline

cholinomimetics: direct acting/cholinergic agonists- 3 categories =

-choline esters -alkaloids -synthetic

CHOLINOMIMETICS indirect acting = cholinesterase inhibitors -inhibits the breakdown of ACh by inhibiting ________ -characterized by the ______ of the bond they form with _______ -increases the _____ that ACh is in able to circulate in the cleft

-cholinesterase -strength -acetylcholinesterase -time

key point organophosphate = classified as what?

-cholinesterase inhibitor/anti-cholinesterase -indirect acting cholinomimetic

the eye: muscarinic activation via PNS -contraction of _____ muscle aka _____ ______= ______ (pupil) -contraction of _____ muscle = a-______ for near vision b-______ r/t ___ _____ of aquious humor r/t ________ on ______ meshwork

-circular -pupillary constrictor -miosis -ciliary a-accommodation b-decreased IOP -increased drainage -stretch -trabecular

key point cholinomimetics are divided into - - via inhibition of ______ which quickly breaks down _____ in miliseconds

-direct acting -indirect acting -cholinesterase -ACh

in somatic NS--ACh is released from _______ into the ______ to _____ receptors on skeletal muscle to produce a _____

-efferent motor neurons -NMJ -Nm -contraction

**organophosphate poisoning pralidoxime 2-PAM -time window? -reverses effects at _____ and ____ _____ -only reverses _____ effects -still need supportive care for CNS related ventilation issues

-give quick to break bond -NMJ -autonomic ganglia -perpheral

muscarinic subtypes M3 = - - - -mechanism? -which is not innervated by parasympathetic nerves --what is its mechanism

-glands + (sympathetic eccrine sweat) = increased secretion -airway smooth muscle = bronchoconstriction -vascular endothelium --nitric oxide NO = smooth muscle dilation -IP3/DAG -- Ca

muscarinic subtypes M2 target organ = M2 autoreceptor = M2 heteroreceptor = -mechanism?

-heart = bradycardia -vagal nerve to lungs = bronchoconstriction -adrenergic nerve = decreased NE release -inhibition of cAMP

GU/GI contain multiple types of muscarinic receptors. list effects for -in general -secretions? -elimination? -stomach

-increased activity = rest and digest -increased contraction of SM and decreased tone of sphincters -increased H secretion

effects of anticholinesterases at the NMJ -prolonged ACh = _____ effects 1- increased ____ of contraction 2- increased concentration = _____ of muscle relaxants 3-treatment for ______ -PYridostigmine long term -test rx? 4-higher doses may result in muscle ______ or a _______

-intensified 1-strength 2-reversal 3-myasthenia gravis -edrophonium -fibrillation -depolarizing nmb

key point nicotinic channel type

-ligand gated ion channels

**organophosphate poisoning key point -highly _____ soluble = -rapidly absorbed from outside via - - - -most typically (2) -rapidly diffused across _____ producing intense ______ effects

-lipid -skin -alveoli -GI tract -BBB -CNS

anticholinesterase co-admin with anti cholinergic why? -to prevent ______ effects which occur at ______ conc of ACh than necessary to act at NMJ 1- 2- 3- -onset of anticholinergic should be _____ -examples -edrophonium and -neostigmine and

-muscarinic -lower -quicker 1-bradycardia 2-bronchocostric 3-salivation/N/V -atropine -atropine or glycopyrrolate

**organophosphate poisioning atropine -only treat ____ symptoms -give every -large dose

-muscarinic 3-10min

nicotinic subtypes = - - -Nn = -Nm = -channel type?

-neuronal/CNS -muscle type -Nn = postgang cells in all ANS ganglia, CNS, and adrenal medulla -Nm= NMJ

Nm receptors are blocked by what class of drug? -4 examples

-nicotinic antagonist --Curare -non-depolarizing neuromuscular blocker NMBA -nimbex -roc -vec -cisatricurium

Nn receptors can also be blocked (yikes-ganglionic) -1 example

-nicotinic antagonist --non-depolarizing ganglionic blocker -hexamethonium was used to treat HTN

cholinomimetics: direct acting/cholinergic agonists- -alkaloids (1)

-pilocarpine

central anticholinergic syndrome symptoms - - - -

-restlesness -hallucinations -somnolence -unconsciousness

effects of anticholinesterases CNS -depending on dose= -activation of ______ -advancement to _____ -resp?

-seizures -coma -resp arrest

nicotinic receptors discovery -______ contraction could be reproduced by administering _____ extract -could be blocked by ______

-skeletal -tobacco--nicotine -tubocurarine

muscarininc discovery -other responses like ______ contraction or _______ could be reproduced by administering ______ extract ______ -could be blocked by atropine

-smooth muscle -glandular secretion -mushroom -muscarine

key point -activation of M3 on the vascular endothelium results in _________ relaxation and _______ via the action of _______ 1-ACh released in _____ to vascular endothelial cell and binds to it's ____ receptor 2-causes release of _____ from endothelial cell 3-NO diffuses over to ________ ______cell and stimulates ______ ______ 4-this increases ________ which caues _________ -in the absence of intact/healthy endothelium (______)the ______ may occur =

-smooth muscle -vasodilation -nitric oxide 1-in close proximity -M3 2-NO 3-vascular smooth muscle cell -guanylate cyclase 4-cGMP -vasodilation -CAD/coronary arteries -opposite -vasoconstriction

muscarinic subtypes M1 main target organ= -other target = M1 autoreceptor = -mechanism?

-stomach = production of hydrogen ions -nerves -heart = tachycardia -IP3/DAG

anticholinergic co-admin effects -HR -lungs -glands -GI.GU -CNS

-tachycardia -bronchodilation -decreased salivation -decreased n/v -sedation

muscarinic GCPR 1-need____ molecules of _____ or a ____ ____ or one of each bind to 2-______ subunit 3-intracellular g protein subunit complex recognizes binding and _____ replaces ______ on alpha subunit = splits into a- b- 4-alpha +GTP effector enzymes a- b- 5- a-adenylyl cyclase 2nd mess = b-PLC 2nd mess = 6- a-IP3 = b-cAMP =

1-2 ACh direct cholinomimetic 2-alpha 3-GDT to GTP a-alpha + GTP b-beta + gamma 4- a-adenylyl cyclase b-phospholipase C 5- a-cAMP b-IP3 and DAG 6- a-increased ICF Ca b-provides energy for multiple processes

key point 1-myasthenia gravis is an ______ disorder resulting in a-_______ or b-_______ of _________ receptors at the _____ = 2-it is often treated with an _______ which is classified as _______ which causes what

1-autoimmune a-destruction b-inactivation -ACh -NMJ -Nm 2-anticholinesterase -indirect cholinomimetic -increased ACh in the cleft

key point: effects of nicotinic stimulation: -nicotinic receptors found in post gang neurons of ALL ANS (ganglia) and skeletal muscle in somatic NS 1-Nn then to adrenergic receptor SNS is T1-L4 so predominantly ______ effects. OD causes --2 main things = - - 2-Nn then to M: PNS post gang = cranio-sacral s2-s4 with predominance in ______ systems. OD causes 3 main things - - 3-Nm SOMATIC NS = Nm in the NMJ (depolarizing NMB/sux) -resp? -cardiac? 4-CNS -excitement = seizures -late stage = coma treatment=

1-cardiovascular --htn and tachycardia 2-GU/GI -nausea -vom -urination/diarrhea 3- -resp = respiratory paralysis -cards - arrhythmias tx -atropine for muscarinic PNS effects -anticonvulsant for CNS effects -respiratory support

muscarinic subtypes M4 and M5 = -

CNS

what channel type do muscarinic receptors use

GCPR

key point nicotininc cholinergic locations

Nm- NMJ somatic efferent to muscle tissue Nn - ganglia adrenal medulla

cardiac effects: muscarinic activation M2 a-slows pacemaker rate by inhibiting ____/____ conduction b-decreases contractility in ventricles --small effect r/t limited _____ M2 heteroreceptor = accentuated antagonism of adrenergic neurons occurs via inhibition of NE release and thus SNS stimulation

a-AV/SA node b- --limited innervation adrenergic and cholinergic neurons close together

key point the clincial usefulness of direct acting cholinomimetics is dependent on their a- ________to cholinesterase and b-_______ for various cholinergic receptors

a-suseptibility b-affinity