Pharmacology - Cholinomimetics
Terms
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- two types of cholinomimetic drugs - mode of action
-
direct-acting -bind M2,M3receptors
indirect-acting-inhibit acetylcholinesterase (anti) - acetylcholinesterase
- enzyme that rapidly degrades Acetylcholine in the synaptic cleft at the NMJ
- indirect acting - mode of action
-
anti-cholinesterase
inhibit the enzyme
reversibly and irreversibly - direct acting cholinomimetics MODE OF ACTION
- receptor agonists - bind to and activate muscarine M2,M3 receptors
- direct acting drugs of choline esters
-
Ach (miochol)
bethanechol
carbachol
methacholine -
direct acting drugs -
alkaloids -
muscarine (M)
pilocarpine (M)
nictotine (N) - memory trigger for choline ester
- beth, meth, carb and Ach all went to see cholinester
- memory trigger for alkaloids
- nic piled in his muscarine and vroomed away
- indirect acting drugs cholinomimetics
-
anti-cholinesterases
antagonists - reversible indirect-acting
- Tensilolon (edrophonium)
-
reversible indirect-acting
carbamates (4) -
demacarium
neostigmine
physiostigmine
pyridostigmine - reversible indirect-acting drugs for Alzheimers disease
-
donepezil
galantamine - memory trigger for the AD drugs
- she's a DONE GAL
-
IRreversible indirect-acting anticholinesterases
--Organophosphates -
echothiphate (phospholine)
Malathion
parathion
soman -
memory trigger
- think military call-out - echo, mala, para, soma
- what are the two main types of Glaucoma?
-
acute narrow angle
chronic open (wide) angle - what issues do these glaucomas create?
- both increase intra-occular fluid pressure
- how is aqueous humor produced?
- by the ciliary body behind the peripheral edge of the iris
- where does this aqueus humor flow?
- medially to the posterior chamber, then anteriorly to the anterior chamber
- describe flow pattern
- medially toward pupil in space b/t back of iris and front of the lens, then fwd thru pupil, to speace b/t front of iris and back of cornea
- what is the function of the aqueous humor?
- nourish the lens of the eye
- what happens if it does not exit the anterior chamber?
- fluid pressure builds up and causes the riris to bulge forward creating a "narrow angle"
- what happens when the aqueous humor does exit the anterior chamber?
- it is absorbed by a network of trabeculae and drained into a conjunctival vein
- what is the name of the conjunctival vein?
-
the canal of schlemm
(sinus venosus sclerae) - where is this "angle" of the eye located?
- where the back of the cornea meets the front peripheral edge of the iris - and is usually wide and 'open'
- what is a narrow angle?
- when the irish bulges
- how is a narrow angle detected?
- by shining a penlight from the lateral side of the eye across the front
- what is present when detecting the angle?
- the bulging iris casts a shadow on the medial side of anterior chamber
- what is the risk of a narrow angle?
- rapid build up of fluid pressure if the pupil becomes significantly dilated
- what issue is created by this risk?
- as the iris contracts radially it can cause acute obstruction of fluid outflow and rapid increase in intra-ocular pressure
- what causes significant eye dilation?
-
dark places (movie theater)
stress
drugs used in eye exams
pre-op atropine
antidepressants
nebulized brhochodilators (B2 agnosists) - how does stress affect dilation?
- increased EPI secretion and sympathetic tone
- what drugs are used during eye exam to cause dilation?
-
mydriatic drugs - mydriacyl (topicamide)
cyclogyl (cyclopentolate) - Mydriasis
- dilated eyes
- why is pre-op atropine an issue?
- it is an anti-cholinergic drug
- why do antidepressants affect dilation?
- anticholinergic effects
- how do nebulized bronchodilators dilate the eye?
- these Beta 2 agonists cross react with Alpha1 receptors of radial muscle of iris
- what are negative effects of long-term dilation?
-
*acute eye pain
*blurred vision
*see halos around light
*nausea/abd pain
*conjunctivitis
*stamy cornea
*dilated pupil that is unreactive to light
*permanent vision loss 2-5 days - T/F acute narrow angle glaucoma is a medical emergency?
- TRUE - must treat immediately by reducing the pressure - by re-constricting the puil and reopening the angle
- what drug treatment is used to treat narrow angle glaucoma?
- muscarinic agonist combined with anticholinesterases
- what is the effect of the general treatment?
- cause ciliary muscle contraction, stretching the trabeculae, allowing for draining of fluid
- what muscarinic agonists are used?
- pilocarpine drops or carbachol drops
- what anticholinesterases are used to treat narrow angle?
-
physostigmine - opth. ointmnt
echothiophate drops
demecarium drops - what other drugs are used to decrease fluid pressure?
-
carbonic anhydrase inhibitors
Acetazolamide
brinzolamide - why are carbonic anhydrase inhibitors used?
- to decrease the fluid production
- what is the effect of prostaglandins?
- increase drainage of aqueous humor
- what prostaglandins are used?
-
Lumigen (bimatroprost)
rescula (unoprostone) - does surgical treatment work?
- Yes - laser peripheral iridotomy is a permanent cure
- describe Chronic open angle glaucoma
- simple, wide angle glaucoma - with increased intra-ocular pressure doe to inadequate drainage of trabeculae
- is this a true angle problem>
- no, it is an issue of inadequate drainage
- what is the etiology?
- unknown - idiopathic, could be familial or cx by diabetes
- what secondary events could cause chronic open glaucoma?
- uveitis or trauma
- which glaucoma is considered to be bilateral?
- chronic open angle
- is surgical treatment a viable option for chronic open angle?
- typically no, but laser trabeculopplasty may come into play on some
- what is the recommendation for drug treatment for chronic glaucoma? (timeframe)
- long term is required using alpha-agonists, beta-blockers, caronic anyhdrase inhibitors and prostaglandins
- how do cholinomimetics work to treat COG?
- enhance drainage of fluid by contracting ciliary muscles and stretching trabeculae
- what cholinomimetic drugs are used?
-
muscarinic agonists
*pilocarpine, carbachol
anti-cholinesterase
-physostigmine - what carbonic anhydrase inhibitors are used?
-
acetazolamide
brinzolamide - what alpha agonists are used?
-
nonselective =EPI, and propine
alpha2 = iopidine & alphagan - what affect do the alpha agonists have?
-
non-selective
**INCREASE DRAINAGE
selective alpha 2
**DECREASE humor PRODUCTION - What beta blockers are used?
-
betaxolol (betoptic)
timolol(timoptic, betomil) - what is the function of beta blockers for this?
- DEcrease humor production
- what drugs decrease humor production?
-
*beta blockers betoptic, betomil, timoptic
*aplha2 agonists-iopidine, brimonidine - what cholinomimetics are used to counteract GI and UT smooth muscle activity depression?
-
muscarinic agonist
*bethanechol (uricholine)
indrect-acting (anti-cholins.)
*neostigmine - what is Post-Op Ileus?
- atony or paralysis of stomach or bowel after surgery
- depressed muslce activity causing urinary retention occurs from?
-
*post-op
*postpartum
*after spinal cord injury/disease
"neurogenic bladder" - reflux esophagitis (GERD) is treated with?
- H2 blockers, bethanechol, neostigmine
- What is used to treat DRY MOUTH cx by sjorgren's syndrom or other sicca syndromes?
-
muscarinic agonist -
cevimiline (Evoxac) - what is the relationship b/t Myesthenias gravis and receptors?
- Ab-mediated reduction in the # of FX nicotinic Nm receptors of NMJ
- what is used to treat MG for this?
-
ONLY indirect-acting anticholinesterases
-pyridostigmine
-neostigmine
-ambenomium
demercarium
LONG TERM - how is MG diagnosed?
- by giving Tensilon to pt - will see decreased fatigue w/in 5 min,
- how is Tensilon used regarding MG?
-
diagnosis
assess level of longterm tx with anitcholinesterases - what is the result of overmedicating the pt?
- depolarizing blockade and excessive stimulation of muscarinic receptors
- what are the signs of an overmedicated pt?
-
miosis
bradycardia
excessive salivation and bronchial secretions
abd pain cramps and diarrhea - how do you know if pt is over or under medicated?
-
by giving Tensilon -
if weakness does not improve - overmedicatd
if weakness does improve - undermedicated - are cholinomimetics useful in treating Alzheimer's Disease?
- NO - but people use as a last hope and some results have been positive SHORT TERM
- What cholinomimetics are prescribed for AD?
-
anticholinesterases
-donepezil
-galantamine - T/F AD is the result of too little Ach due to a reduction of brain neurons?
- TRUE
- what is the action of anesthetics during surgery?
- neuromuscular blockade - imposing dysfunction of the motor endplate - cx muscle paralysis via NT dysfunction at NMJ
- what drugs are used to impose this skeletal muscle paralysis? (general class)
-
anti-cholinergics
deoplarizing and nonpolarizing - what depolarizing drugs are used?
- succinylcholine
- what nonpolarizing drugs are used?
-
curare
attracurium
pipecuronium
pancuronium
vecuronium
(remember 3 curoniums) - trigger- who are the 3 curonium brothers and their sister?
- pipe, panc, vec and sister curare
- which anti-cholinergic class is used most frequently and what is its action?
- non-depolarizing - they block the Nm receptors by competing w/ Ach, thereby preventing depolarization of muscle fiber membrane
- T/F the muscle paralysis induced by these drugs is caused by upper/lower motor neuron dysfunction?
- FALSE - it is from neurotransmitter dysfunction at the NMJ
- what drug class is used to reverse this process?
- anti-cholinesterases- aimed at increasing amount of Ach (and icreasing half-life) at the motor end plate
- what are these drugs?
-
neostigmine
pyridostigmine
Tensilon - what ailments are cholinomimetics used for?
-
acute narrow angle glaucoma
chronic wide angle glaucoma
GI and UT activity depression
Alzheimer's Disease
Dry mouth
Myasthenias Gravis
reversal of surgical NM block
antidotes for insecticides and humanocides -
What does DUMBELS represent?
( OR...DUMB3ELS) -
Diarrhea
Urination
Miosis
Bronchorrhea
Bronchospasm
Bradycardia
Excitation (anxiety, fasciculation, seizures)
Lacrimation
Salivation - what is the other name for cholinomimetics?
-
parasympathomimetics
or cholinoreceptor activating drugs - what is the action of insecticides?
- organophosphates kill via irreversible anticholinesterase activity-causing excessive parasympathetic activity-
- what parasympathetic activity is induced from ingestion of insecticides?
-
vegetative manifestations:
miosis
salivation
hyperactive bowel sounds
lethargy
bradycardia (muscarinic axn)
or tachycardia (nicotinic axn) - death can occur from?
- respiratory depression - you can NOT take IN another breath
- what is the mnemonic used to describe the effects of insecticides?
- DUMBELS
- what does DUMBELS stand for?
-
Diarrhea
Urination
Miosis
Bronchorrhea
Bronchospasm
Bradycardia
Excitation: anx,fasciulations, seizures
Lacrimation
Salivation - what are the antidotes for DUMBELS?
-
Atropine
pralidoxime(Protopam 2-PAM) - what is the action of Atropine?
-
competitive muscarinic receptor blocker
M1,2,3 etc.
_reduces symptoms, may need repeated doses - what is the action of Pralidoxime? (protopam, 2pam)
-
competitively INHIBIT binding of organophosphates to acetylcholinesterase
(2-PAM carried by military personnel) - carbachol
-
cholinomimetic direct acting choline ester
Tx: narrow angle glaucoma
fx: M + N,
resistant to AchE, - Acetylcholine
-
cholinomimetic direct-acting
M+N shortest duration - Bethanechol
-
cholinomimetic direct-acting
Fx: Muscarinic
resistant to AchE,
TX: stimulates post op bladder and GI - Pilocarpine
-
Cholinomimetic direct-acting alkyloid
Fx: M
Tx: glaucoma, narrow angle and chronic wide - cevimeline (Evoxac)
-
cholinomimetic direct-acting
fx: M
tx: dry mouth from Sjogrens or sicca syndrome - nicotine
-
cholinomimetic direct-acting
Alkaloid
Fx: nicotinic receptor - endrophonium (Tensilon)
-
anticholinesterase
indirect-acting -reversible
FX: M+N
Tx: diagnostic test for myasthnia gravis
reversal of surgical NM blockade - demecarium (Humorsol)
-
Indirect-anticholinesterase
a carbamate
Fx: inhibit, reversible
Tx: Myastehnias Gravis
wide angle glaucoma - neostigmine
-
indirect-anticholinesterase - carbamate
Fx: inhibit, reversible
tx: myasthenias gravis
GI, GERD, UT post-op
reversal of surgical blockade - physostigmine
-
cholinomimetic indirect-acting
Fx: M+N carbamate=reversible Tx: glaucoma - echothiophate
-
indirect-acting M+N organophosphate
=irreversible
Tx: glaucoma - parathion
-
indirect-acting M+N irreversible organophosphate
longest lasting=most toxic - atropine
-
antidote for organophosphate insecticides
Fx: blocks M1,2,3 etc
no effect on nicotinic - curare,atracurium,pipecuronium,pancuronium, vecuronium
- non-polarizing anti-cholinergic drugs used for surgical NM blockade
- succinylcholine
- depolarizing anti-cholinergic drug used for reversal of surgical NM blockade
- what anticholinesterases are used for reversal of NM blockade post surgery?
-
neostigmine
pyridostigmine
Tensilon
"PEN" - pralidoxime (Protopam, 2PAM)
-
used by military and in hospitals to counteract DUMBELS poisoning
Fx: inhibitrs binding of organophosphates to acetylcholinesterase - what drugs decrease aqueous humor production?
-
beta blockers=
Betoptic, Timoptic,Betimol
carbonic anyhdrase inhibitors =
Diamox, Azopt - what drugs increase drainage of aqueous fluid to trabeculae?
-
non-selective alpha agonists=
EPI, Propine
Prostaglandins =
Lumigan, Rescula - memory trigger for beta blockers
- Tim and Beto Bet-im-ol at the casino, and you beta their wives blocked their receptors
- treatment of myasthenias Gravis can include one of the following
-
indirect -anticholinesterases
reversible
pyridostigmine
neostigmine
ambenonium(Mytelase)
demercarium (Humorsol) - Donepezil (Aricpet)
-
anticholinesterase -indirect, reversible
Tx: alzheimer disease - neurogenic bladder tx
-
treat with cholinomimetic
M =bethanechol (urecholine)
anti-ChE=neostigmine (prostigmin) -
memory trigger
neurogenic bladder and urecholine -
when you 'gotta go'
ur-e-choline for the drugs to help you out - Mytelase
- generic for ambenonium for tx of MG
- Humorsol
-
generic for demecarium
tx for MG, wide angle glaucoma (drops) - trigger for increased draining of aqueous humor
-
ED, please RESCULA my LUMIGAN, I AZOPT it in the DIAMOX drain and it is full o PCP's
p=pilocarpine, C-carbachol p=physostigmine
ED = epi, diivefrin - trigger for decreased humor production (tx for glaucoma)
-
no humor until you do your ABC's
alpha 2 agonists, beta blockers, carbonic anhydrase inhibitors - memory trigger ro decreased humor productionn - specific drug names used
- IOPIDINE THE BRIMONIDINE, BETA clean my diamox beore I azopt for the night.
- CAIs
-
acetazolamide (diamox)
brinzolamide (Azopt) - memory trigger for GI, UT, GERD
- when those go crazy - some people smell like "P U" .
- my mouth is dry, bring me some
- cevimiline