NMB Reversal Agents Flashcards
What are the two classes of reversal agents?
- acetylcholinesterase inhibitors/anticholinergics
- selective relaxant binding agent
What reversal agents are considered acetylcholinesterase inhibitors/anticholinergics?
- neostigmine
- edrophonium
- pyridostigmine
Which acetylcholinesterase inhibitor is NOT actually used for reversal? What is it used for?
- physostigmine
- used to treat anticholinergic crisis
What class of reversals does sugammadex fall under?
selective relaxant binding agent
How do anticholinesterases work?
block/inhibit the breakdown of acetylcholine by blocking acetylcholinesterase (which normally breaks down ACh). this increases number of available ACh at the synaptic cleft, giving it a better chance of binding to receptors than NMBAs
What is acetylcholinesterase (AChE)?
enzyme responsible for hydrolysis/breakdown of acetylcholine
Blocking ___________ is a mechanism used to reverse NMBAs
acetylcholinesterase (AChE)
Myasthenia gravis can be diagnosed and treated by?
administrating acetylcholinesterase inhibitor; prevents breakdown of acetylcholine and increases # of ACh to produce muscle response
What is myasthenia graves? What agent can be used for diagnosis and treatment?
- autoimmune disease where the immune system attacks the NMJ
- acetylcholinesterase inhibitor
What are some side effects of anticholinesterase agents? (neostigmine, edrophonium, physostigmine)
- unwanted muscarinic stimulation (SLUDGE)
- cholinergic crisis
- bronchospasm
- increased secretions
- bradycardia (slowing conduction velocity at AV node)
What are some side effects of cholinergic crisis?
- SLUDGE
- bronchospasm
- bradycardia
- hypotension
- muscle cramping
- weakness
- restless, anxiety, confused, seizures, coma
Cholinergic crisis means too much or too little acetylcholine?
too much ACh
When are cholinesterase inhibitors used?
- reversal of NMBAs
- myasthenia gravis dx or tx
- anticholinergic syndrome tx (atropine overdose)
What are S/S of mild, moderate, and severe anticholinergic syndrome?
- Mild: tachycardia, flushed face, mydriasis (dilation), blurry vision, dry mouth, dry skin, fever
- Moderate: agitated/delirium, urinary retention, HTN, hyperthermia
- Severe: CNS depression, coma, seizures, dysrhythmias, hypotension, rhabdomyolysis
Anticholinergic syndrome is too much or too little acetylcholine?
too little ACh
What are some basic signs and symptoms of anticholinergic crisis?
- mad as a hatter (delusional)
- dry as a bone (skin, mucous membranes)
- red as a beet (flushing)
- hot as a hare (fever/hyperthermia)
- blind as a bat (mydriasis/dilation)
picture Alice with anticholinergic crisis)
Overdose of what agents can lead to anticholinergic crisis?
- atropine
- scopalamine
- antihistamines
- tricyclic antidepressants
- antispasmodics
- jimson weed
- meclizine
What can be used to treat anticholinergic crisis?
physostigmine
- increases amount of ACh
Physostigmine is a _______ (tertiary/quaternary) amine and ________ (can/cannot) cross the BBB
- tertiary amine
- CAN cross the BBB
Neostigmine is a quaternary or tertiary ammonium? Can it penetrate the BBB?
- quaternary ammonium
- CANNOT penetrate the BBB
How does neostigmine work?
inhibits hydrolysis of ACh by AChE by blocking AChE at all cholinergic synapses
- causes PNS effects
Neostigmine is usually given with ______________ to decrease muscarinic side effects
glycopyrrolate (anticholinergic)
Neostigmine Dosing
0.04-0.07 mg/kg
Ceiling dose: 70 mcg/kg
Neostigmine onset and duration
Onset: 3-5 min
Duration: 30-60 min
Which NMB reversal agent has a ceiling effect? What is this ceiling effect?
- neostigmine
- 70 mcg/kg
- will worsen muscle weakness
What is the ceiling effect dose of neostigmine?
70 mcg/kg
When is neostigmine used?
- deep blocks
- moderate blocks (slow acting)
- when spontaneous recovery is evident in the TOF!!!
T/F: There are no recommendations on when to give neostigmine
false
- shouldn’t be given until spontaneous recovery is evident on the TOF
What happens if we give surpass the ceiling effect dose of neostigmine?
may worsen the block and increase weakness; potentially increases the incidence of residual block
How much neostigmine to how much glycopyrrolate?
1 mg neostigmine to 0.2 mg glycopyrrolate
Is edrophonium a quaternary or tertiary amine? Does it cross the BBB?
- quaternary amine
- CANNOT cross the BBB
How does edrophonium work?
inhibits the destruction of ACh by AChE by blocking AChE, thus increasing amounts of ACh
What agent is edrophonium typically administered with? Why?
- atropine
- PROFOUND decrease in HR (down to the 30s) VERY quickly
What is the mix of edrophonium and atropine called?
Enlon-Plus
Edrophonium Dosing
0.5 - 1 mg/kg
How much atropine is mixed per 1 mg of edrophonium?
0.014 mg of atropine per 1 mg of edrophonium
Enlon-plus Dosing
0.05 - 0.1 mg/kg SLOWLY over 1 min
Is Enlon-Plus sufficient enough to decrease risk of bradycardia?
No - typically still need to add more atropine
Cholinergic syndrome is characterized as an overstimulation of _______ and ________ receptors
- nicotinic
- muscarinic
What causes cholinergic syndrome?
- too much anticholinesterase
- organophosphate poisoning (found in pesticides/fertilizers)
- nerve gas agents
How is cholinergic crisis treated?
- atropine (immediate tx)
- benzos (versed/valium)
- pralidoxime/obidoxime (affects acetylcholinesterase)
What are two types of oximes used to treat cholinergic syndrome?
- pralidoxime (2-PAM)
- obidoxime (prevents aging and regenerates AChE)
When should oximes be given?
- to treat cholinergic crisis
- prior to aging of the phosphate bond to the AChE molecule (rate of aging is unique to the organophosphate compound [sarin/VX in min; pesticides/fertilizers in min to days])
Is physostigmine a quaternary or tertiary amine? Can it cross the BBB?
- tertiary amine
- it CAN cross the BBB; the only anticholinesterase that can cross BBB
What is physostigmine used for?
- NOT as a NMB reversal agent
- to treat anticholinergic toxicity
What s/s might we see that warrants physostigmine administration?
- s/s of anticholinergic toxicity
- flushing, dry skin/mucous membranes, mydriasis (dilation), loss of accommodation, AMS, fever, urinary retention, restless, shivers, agitation, disoriented
Physostigmine Dosing
1-2 mg
Overdose of what drugs can lead to anticholinergic toxicity?
- atropine
- scopolamine
- tricyclic antidepressants
- antihistamines
- antipsychotics
When is sugammadex used?
reversal of rocuronium or vecuronium (roc > vec)
What is the generic name for Sugammadex?
bridion
How does sugammadex/bridion work?
- it is a selectrive relaxant binding agent
- ENCAPSULATES roc or vec, prevents its action, and allows it to be excreted in urine
Sugammadex Dosing
- 2 mg/kg: TOF of 2
- 4 mg/kg: no TOF twitches, or 1-2 post tetanic counts
- 16 mg/kg: ONLY ROC; to reverse RSI dose of roc (we will see side effects at this dose)
What are the side effects of sugammadex?
- anaphylaxis
- hypersensitivity
- bradycardia
- coagulopathy probs/bleeding (increased PTT, PT, and INR)
- N/V
- hypotension
- headache
What drugs does sugammadex interact with?
- toremifene (breast cancer drug)
- HORMONAL CONTRACEPTIVES (must educate patient they shouldn’t have sex for 7days)
What is a huge warning that comes with sugammadex that anesthesia providers NEED to educate their patients about?
sugammadex will cause birth control to not work for 7 days. provider liable if patient gets pregnant
