Anticholinesterase/Chol.Agonist/Sugga COMP Flashcards
Anticholinesterase Drugs
facilitate speed of recovery from skeletal muscle effects produced by NDNMBS
Anticholinesterase drugs are:
Edrophonium
Neostigmine
Pyridostigmine
What is the drug that crosses the BBB and is use to produce nonspecific antagonism of the CNS effects or certain drugs and iS NOT IONIZED?
PHYSOSTIGMINE
Anticholinesterase drugs use to treat 3 conditions
Myasthenia Gravis
Glaucoma
Alzheimer’s
Exelon patch is
Neogstimine, may interact with REVERSAL agent (like giving more of a drug)
MOA of anticholinesterases
Enzyme inhibition –> Inhibits acetylcholinesterase
Presynaptic effects and direct effects @ NMJ
Anticholinesterase role
Rapid hydrolysis of acetylcholine
ACH compete for
receptor sites
What is the most efficient enzymes in the body why?
Anticholinesterase; One mol hydrolyzes 300000 ate molecules
Neostigmine and pyridostigmine MOA
inhibit breakdown of ACH by acting as a substrate for acetylcholinesterase and altering its structure making it LESS EFFECTIVE
Edrophonium MOA ? Long or short acting?
Short acting
works by forming a reversible electrostatic attachment to acetylcholinesterase
What is Edrophonium reversal always given with
ATROPINE, because of the very fast onset of action, need faster onset of action anticholinergic.
Anticholinesterase drugs are classified according to the mechanism by which they inhibit the activity of cholinesterase. Which ANTICHOLINESTERASE work by IRREVERSIBLE ACTIVATION?
REVERSIBLE ?
Organophosphates
Formation of carbamyl esters
Electrostatic binding
Are anticholinesterase drugs lipid soluble?
What happens when acetylcholinesterase is carbamylated?
very lipid soluble
carbamylated acetylcholinesterase cannot Hydrolyze Ach
Poisons resemble what kinds of blockade
Depolarizing Blockade
Clinical uses of Edrophonium (3)
Antagonissm of NDNMS
Diagnosis of assess therapy for Myasthenia Gravis
Evaluated presence of mixed block associated with Such
What are the Anticholinesterase Drugs that work by Formation of carbamyl Esters?
Physostigmine
Neostigmine
Pyridostigmine
MOA of Anticholinesterase Drugs that work by Formation of carbamyl Esters? Half life of_____
produces reversible inhibition of acetylcholinesterase by formation of carbamyl esters complex
half life of complex 30 mins
How does the Organophophase anticholinesterase work?
What is the Organophosphate poisoning antidote?
Form a stable inactive complex that does not undergo Hydrolysis
ATROPINE
After bolus concentration, the plasma concentration of EDROPHONIUM, NEOGSTIMINE, and PYRIDOSTIGMINE peak and decrease ________
5-10 mins
What should be given along with Neogstigmine?
Glycopyrrolate
Anticholinesterase clearance has much longer half life of these patients?
Renal disease
Quarternary compounds are:
Lipid solubility is? What happens at physiologic pH?
Can it penetrate lipid membrane of the GIT and CNS?
What does QUARTERNARY Means?
Pyridostigmine, Edrophonium, Neogstimine (PEN)
POOR Lipid soluble, ionized at physiological pH
NO
Nitrogen bonded to 4 molecules
Can’t be used for toxicity
TERTIARY AMINE compounds are
Lipid solubility is? What happens at physiologic pH?
Can it penetrate lipid membrane of the GIT and CNS?
What does TERTIARY Means?
Use to treat anticholinergic agent ?
PHYSOSTIGMINE, Antilirium and ORGANOPHOSPHATES
LIPID SOLUBLE, Nonionized at physiologic pH
Penetrate GIT and Crosses BBB
Nitrogen bonded to 3 molecules
USE To treat ANTICHOLINERGIC AGENTS
EDROPHONIUM (Tensilon) onset (rapid intermediate or delayed)
1-2 minutes (Rapid)
NEOSTIGMINE onset (fast, intermediate or slow)
7-11 minutes (intermediate)
Pyrostigmine onset (fast, intermediate or slow)
16 minutes (delayed)
Duration of action of those drugs affected by __________ and ranging from _______ to ____mns
affected by rate of disappearance
60-76 minutes
Renal clearance % for neostigmine?
Renal clearance of Pyridostigmine and Edrophonium?
Is clerance affected in renal failure?
50%
75%
Yes
Metabolism of Neo, edro and pyridostigmine of hepatic?
Hepatic 50 % Neostigmine
30 % of Edrophonium and pyridostigmine
Pharmacological response by these agents reflects_____________At__________causing_________
__________ receptors
Accumulation of ach at muscarinic POST synaptic parasympathetic activation; Severe BRADYCARDIA
NICOTINIC
POST synaptic Skeletal Muscle Increased strength desired
Pre synaptic : Inhibition of release of ACH undesired, increased weakness
Parasympathetic activation side effects
Bradycardia may lead to asystole Salivation Miosis Hyperperistalsis Bronchoconstriction
NECESSARY To give ________simultaneously with this agent?
Anticholinergic drug
If you give NEOSTIGMINE and Pyridostigmine then SUCC what happens to SUCCINYLCHOLINE EFFECTS? why?
Which one does NOT Inhibit plasma cholinesterase activity?
- effects of SCH is prolonged because enzymes are inhibited.
- Because both Neostigmine and Pyridostigmine Produced -MARKED and PROLONGED Inhibition of PLASMA CHOLINESTERASE ACTIVITY
- EDROPHONIUM
MUSCARINIC Anticholinergic agents effects?
Effects on CV attenuated by giving?
What happens to patient with DENERVATED HEART such as TRANSPLANT PT?
PVR and SVR?
Bradycardia, Escape beats, Sinus Arrest Anticholinergic ASystole ( Denervated heart--Transplant) Decrease SVR, increase PVR
GI effect of Anticholinesterases (increase ach) enhance
Gastric fluid and increase GI motility
ETOMIDATE and N2O increase
Chance of post op N/V
This agent may treat paralytic ileum or atony of bladder ____
Neostigmine.
What is the risk associated with giving ANTICHOLINESTERASE with patients with MYASTHENIA GRAVIS who also received NDNMB?
CHOLINERGIC CRISIS
MG Patients are more sensitive to ________ why? and less sensitive to __________
Non-depolarizing to block because of down-regulation of receptors. More sensitive to ANTAGONIST (NDNMB) and less sensitive to (agonist)
MYOTONIA with anticholinesterase agent
Share some effect of succinylcholine (can produce FASCICULATIONS and AUGMENT Twitch response
Use ANTICHOLINESTERASE with caution with patient that have an ABSOLUTE CONTRAINDICATIONS to Succinylcholine, those patients are patients with (4)
Myotonia
Muscular dystrophies
Burn patint
Spinal cord transection
Clinical uses of the drugs
Antagonized NDNMB drugs Treat CNS effects of drugs Treat MG/ Glaucoma Treat paralytic ileum and atony Treat Alzheimers
Antagonize- Assist REVERSAL of NMB
3 drugs use to reverse NDNMB?
How do they help ?
Edrophonium, Neostigmine, and pyridostigmine used to reverse NDNMB
Increase amount of ACH at the nicotinic receptors which is the result of giving these drugs increases the changes of 2 Ach molecule binding to the alpha subunits of the nicotinic receptors.
More rapid onset of action with ______
Dose of EDROPHONIUM
DURATION Of ACTION are all
EDROPHONIUM
0.5 mg/kg/ IV (1mg/kg if >90% twitch depression when reversal is initiated)
Similar
Dose of NEOSTIGMINE
Neostigmine appears to be preferable when
Can be given with either ______or _______why?
0.043 mg/kg/IV
>90% twitch depression is to be antagonized?
Atropine or Glycopyrrolate ; because of slower onset of action.
Dose of Pyridostigmine
What is expected with Pyridostigmine?
0.21 mg/kg/ IV
Initial TACHYCARDIA
When EDROPHONIUM is used, which Atropine DOSE is recommended?
7 MCG/KG.
LESS than the recommended ATROPINE dose CAN CAUSE _______
The dose of atropine is about ______the dose of NEOGstimine. Initial ______Then ____
BRADYCARDIA
1/2
Tachy –> brady
EXCESSIVE NMB: does additional doses of anticholinesterase drugs further antagonize the block?
When is ventilation indicated then?
Once maximally inhibited acetylcholine , giving additional anticholinesteras drugs does not further antagonize the block.
When there is persistent NMB despite large doses of anticholinesterase drugs (NEO >70mcg/kg) , ventilate until NMB wears off , use sedation.
Events that influence reversal
EDROPHONIUM Vs NEO which is more EFFECTIVE in reversing deep NMB produced by continous infusion of Atracurium, Vecuronium and Pancuronium?
Inhibited antagonism by ARHH?
- Intensity of block at time of reversal agent administration
NEO More effectivee; EDROPHONIUM less effective than NEO in reversing deep NMB produced by continous infusion of Atracurium, Vecuronium and Pancuronium.
Inhibited antagonism by ARHH
- Aminoglycosides
- Hyperthermia
- Resp acidosis associated with PaCO2> 50
- Hypokalemia and Metabolic acidosis.
EPHODRIUM may be more effective for reversal of
ATRACURIUM
NEOSGTIGMINE may be more effective for reversal of
VECURONIUM
Hoffman eliminaton dependent
pH and temperature dependent
HOW TO Avoid Residual paralysis
ADUU
- Avoid long acting (PANCURONIUM)
- use INTERMEDIATE ACTING
- USE QUANTITATIVE ObJECTiVE TESTS (TOF <0.9 last twitch)
- DO NOT use clinical tests *Head life, jaw clenching (unreliable)
During anesthetics that do not enhance NMB
A minimal of TOF count of 2 should be present before administration of anticholinesterases
During anesthetics that DO ENHANCE NMB
A TOF count of 4 should be present before administering anti cholinesterase.
What should be done if recovery of TOF>0.9 is documented? why?
Neostigmine administration should be withheld.
May decrease upper airway muscle activitiy and tidal volume
Peripheral Nerve Stimulator (subjective) assessment TOF count of 1 or no TOF response_______
TOF count 2 or 3 ________
TOF with fade (TOF <0.4) _________
TOF no evidence of fade (TOF >0.4)
- Delay reversal
- administer pharmacologic reversal
- administer pharmacologic reversal
- administer pharmacologic reversal consider 20mcg/kg Neogstigmine
Quantitative EVOKED response monitor TOF count of 1 or no TOF response\_\_\_\_\_\_\_ TOF count 2 or 3 \_\_\_\_\_\_\_\_ TOF less than <0.4 TOF = 0.40 to .90) \_\_\_\_\_\_\_\_\_ TOF >0.90
- Delay reversal
-administer pharmacologic reversal - administer pharmacologic reversal
- administer pharmacologic reversal consider 20mcg/kg Neogstigmine
NO REVERSAL recommended
Class of Quarternary ammonium: Example
EDROPHONIUM (no true covalent bond, so ACH can easily compete with edrophohium for binding site)
EDROPHonium onset
1-2 minutes
EDROPHONIUM duration
30-60 minutes
EDROPHONIUM not recommended for
DEEP BLOCK
NEOGSTIMINE is a
Quaternary ammonium (CANNOT ENTER CNS)
NEOGSTIMINE onset
7-11 minutes
NEOGSTIMINE duration
45-90 minutes
How do you mix NEO and GLYCOPYRROLATE
1mg of NEOSTIGMINE with 0.2 mg of GLYCOPYROLATE
1cc and 1cc = total admin 2cc
Most commonly used reversal ______
Used for Diagnosis of therapy for MG is
NEOGSTIMINE.
EDROPHONIUM
Neogstimine may cause
MAY INCREASE PONV
Pyridostigmine
Quarternary ammonium’
Only agent able to reverse CNS effect, why?
Physostigmine, crosses BBB
Physostigmine dose
15-60 mcg/kg IV
Physostigmine may reverse depression of
Reverse depression of ventilation associated with opioids but not the analgesia.
How to asses anticholinesterase treatment in treatment of Myasthenia Gravis
Edrophonium 1 mg IV every 1-2 minutes to assess tc
if patient underdose, symptoms will improve
if overdose, symptoms will worsen
POST op shivering you can use this agent ?
PHYSOSTIGMINE 40mcg/Kg at the conclusion of anesthesia
Most often POST OP used for shivering is
Meperidine
Overdose of anticholinesterase
Muscarininc :MDS BBLR
NIcotinic :
Acute overdose Muscarinic symptoms--> Miosis Difficulty focusing Salivating Bronchoconstiction, Bradycardia loss of bladder and rectal control
Skeletal muscle weakness, PARALYSIS
OVERDOSE of Anticholinesterase CNS effects
Confusion, ataxia, seizures
Treatment of anticholinesterase intoxication
Atropine 35-70mcg/kg IV every 3-10 minutes until muscarinic symptoms disappear
What is a ACETYLCHOLINESTERASE Reactivator?
Pralidoxime
What is the dose of pralidoxime (2-PAM) ?
15 mg/kg IV over 2 minutes
Synthetic Cholinergic Agonist are
Act as a agonists at postganglionic PNS nerves
Synthetic Cholinergic Agonist mimics
Ach , act as muscarinic
Synthetic Cholinergic Agonist 3 drugs
Methacholine (usd to diagnose asthma)
Bethanechol (usd for BPH)
Carbachol ( Glaucoma used)
Synthetic Cholinergic Agonist avoid in
PAC
Asthma
CAD
PUD
Carbachol and Bethanechol are _______
Resistant to hydrolysis of acetylcholinesterase
- Used as at stimulant of smooth muscle of the GI tract and urinary bladder
- Use to treat NARROW ANGLE GLAUCOMA
Bethanecol
Carbachol
Pilocarpine
Predominant muscarinic actions
DECRASE IOP
OVERCOME the mydriasis produced by atropine
Sugammadex (Bridion)
selective relaxant binding agent designed to encapsulate the STEROIDAL NMBAs ROCURONIUM and vecuronium
Sugammadex forms an
inclusion complex with these NMBAs, thereby preventing their binding to nicotinic receptors at the NMJ, resulting in reversal of neuromuscular blockade.
Sugammadex effectiveness
Does not work with ____and______
Rapid and effective with BENZYLISOQUINOLINIUM (ATRA and MIVAcurium(
The reversal activity of Sugammadex is
selective for steroidal NMB agents (ROC and VEC only)
Shallow blocks Sugammadex ( reappearance of a 2nd twitch of the TOF)
2mg/kg
Deep block (1-2 post titanic count)Sugammadex dose
4mg/kg
Large block Sugammadex dose (For rescue) CANNOT INTUBATE< CANNOT VENTILATE
16mg/kg
Sugammadex WARNINGS/PRECAUTIONS
Metabolism?
Elimination and clearance
Limited metabolism
ELIMINATED IN URINE UNCHANGED
RENAL PATIENT clearance decrease, elimination half life increase.
Dialysis IS NOT CONSISTENTLY EFFECTIVE
WARNING of SUGGAMADEX
AVOIDED IN PATIENTS with a CrCl < 30ml/min
Most commonly reported adverse reaction,
DYSGEUSIA (metal or bitter taste) after dose of 32mg/kg or higher
Flushing, rash
Possibility that patients may have ______ and ______reaction, advise
Hypersensitivity and Anaphylaxis. Clinician caution.
