Anticholinesterase & Anticholinergic Drugs Flashcards
What do anticholinesterases do?
Inhibit the enzyme that breaks down Ach, which then increases the amount of Ach available in the synapse, increases concentration at both nicotinic and muscarinic receptors, stimulates presynaptic receptors to release more Ach
What are the implications of inhibiting both acetylcholinesterase and pseudocholinesterase?
acetylcholinesterase: increases ach at nicotinic and muscarinic receptors.
pseudocholinesterase: can’t break down succ so it causes a prolonged effect. Also can’t break down ester local anesthetics or remifentanil
What type of receptors are Nicotinic receptors?
Ligand gated ion channels
What type of receptors are muscarinic receptors?
G protein coupled receptors
With reversal, which receptors are we trying to maximize and which are we trying to minimize the side effects of?
maximize: nicotinic
minimize: muscarinic
Stimulation of muscarinic receptors results in:
parasympathetic effects: Diarrhea Urination Miosis Bradycardia Bronchoconstriction Emesis Laxation (peristalsis) Lacrimation Salivation
What are 3 examples of muscarinic receptor antagonists?
atropine, scopolamine, pilocarpine
What are 3 ways anticholinergics inhibit acetylcholinesterase?
Electrostatic attachement
Formation of carbamyl esters
Phosphorylation
The duration of action for anticholinesterase drugs is determined by the _____ of the bond that is formed during hydrolysis.
Strength
What is the only anticholinesterase that crosses the blood brain barrier?
Physostigmine
Anticholinesterases are ______ amines except or physostigmine which is a _____ amine.
Quaternary, tertiary
Anticholinesterases are primary excreted by _____
kidneys
All anticholinesterases have a “ceiling effect”. What does that mean?
There is no therapeutic effect after the max dose
Neostigmine: Dose: Onset: Duration: Administered with: Uses:
Dose: 0.05 mg/kg (max dose 5mg)
Onset: <3 min
Duration: 40-60min
Administered with: glycopyrrolate 0.2mg per 1mg of neo
Uses: antagonize (reverse) non depolarizing neuromuscular blocking drugs, treatment of myasthenia gravis
Physostigmine: Dose: Onset: Duration: Administered with: Uses:
Dose: 0.01-0.03 mg/kg
Onset: 3-8 min
Duration: 30min-5hr
Uses: reverse scopalamine, tx of anticholinergic syndrome (atropine poisoning), reverse prolonged somnolence, treat post op shivering, antagonize opioid induced respiratory depression.
Which anticholinesterase is metabolized by plasma esterases, unlike the others which are primarily renal and hepatic?
Physostigmine
What type of bond is formed between organophosphates and Ach?
Irreversible bond
What is ecothiophate used to treat?
Glaucoma
What are muscarinic signs of anticholinesterase poisoning?
(SLUDGE) salivation, lacrimation, urination, diaphoresis, GI upset, emesis. Can progress to bronchospasm, blurred vision, bradycardia or tachycardia, hypotension, confusion and shock
What are nicotinic signs of anticholinesterase poisoning?
Skeletal muscle fasciculations followed by weakness then paralysis. Severe reactions can result in ventilatory failure and death (cholinergic crisis)
What is the treatment for anticholinesterase poisoning?
Atropine and Pralidoxime (an acetylcholinesterase reactivator)
What is central cholinergic sydrome?
aka cholinergic crisis. Overdose of cholinesterase inhibitors causing excessive Ach in brain
What are the other names for anticholinergics?
Antimuscarinics, parasympatholytics
What is the mechanism of action for anticholinergics?
reversibly bind with muscarinic cholinergic receptors; preventing ach binding to these sites, then causes PNS effects
Which anticholinergic does not cross the blood brain barrier?
Glycopyrrolate
Which anticholinergic has the most effect on causing tachycardia?
Atropine
Which anticholinergic has the most effect on causing sedation?
Scopolamine
What effects on the respiratory system do anticholinergics have?
Bronchodilation and decreased secretions
What effects on the eyes do anticholinergics have?
pupil dilation, cycloplegia (paralysis of ciliary muscle causes loss of accommodation or blurred vision)
What effects on the cardiac system do anticholinergics have?
Increases rate of SA and AV node
What effects on the GI/urinary system do anticholinergics have?
Decreased GI motility and urinary retention
What are clinical uses of anticholinergics?
use with anticholinesterases, parkinsons, motion sickness, bradycardia, cholinergic poinsoning
What are the side effects of atropine poisoning (Central Anticholinergic Syndrome)?
“Dry as bone, blind as a bat, red as a beet, mad as a hatter”
dry mouth, mydriasis, tachycardia, hot/flushed skin, agitation, delerium
What is the treatment for atropine poisoning (Central Anticholinergic Syndrome)?
Physostigmine 15-60mcg/kg
What are contraindications to using anticholinergic drugs?
Glaucoma, gastric ulcer
Atropine
Dose:
Onset:
Duration:
Dose: 0.4-0.8mg every 3-5min
Onset: 45-60sec
Duration: 1 hr
Never less than ____mg of Atropine for bradycardia to adults, and never less than ____mg of Atropine to peds
0.4, 0.1mg
Glycopyrrolate
Dose:
Onset:
Duration:
Dose: 0.01mg/kg (0.2 mg for each 1mg of neostigmine)
Onset: <1min
Duration: 2hr
Scopolamine
Dose:
Onset:
Duration:
Dose: 0.2-0.6mg sedation/amnesia
Onset: <1 min
Duration: 2-6hr
Also for PONV prevention
Dose: 0.1mg transdermal patch
Onset: 2-4hr
Duration: 24hr
Which Anticholinergic pairs with the following Anticholinesterase drug?
Neostigmine
Pyridostigmine
Edrophonium
Physostigmine
Neostigmine–Glycopyrrolate
Pyridostigmine–Glycopyrrolate
Edrophonium–Atropine
Physostigmine–not necessary (crosses BBB)
What is sugammadex’s mechanism of action?
encapsulates the neuromuscular blocker (steroidals NOT benzyls or succs) and makes it ineffective and unable to bind with nicotinic receptors
What are the nondepolarizing neuromuscular blockers that sugammadex can reverse?
Rocuronium, vecuronium, pancuronium
How much of sugammadex is metabolized?
None
Which organ excretes sugammadex?
kidneys
How long is the onset of Sugammadex?
3-5 min
What are side effects of Sugammadex?
Bradycardia, anaphylaxis, bleeding, makes hormonal contraceptives ineffective for 7 days, not recommended with severe renal impairment
Sugammadex:
dose with 2 twitches
dose with 0 twitches
2mg/kg
4mg/kg
