NMBD Reversal Agents (Exam IV) Flashcards
Reversal of NMJ blockade is dependent on these 5 factors:
- Depth of block
- AchE Drug choice (neo vs edro)
- Dose admin
- Rate of plasma clearance of NMBD
- Anesthetic agent choice and depth (post-op residual NM blockade)
NMBD reversal agents - Classification:
AKA: AchE inhibitors, cholinergic agents, and competitive antagonists.
NMBD reversal agents: MOA?
AchE: rapid hydrolysis (catalyze) of Ach
- inhibition = more Acetylcholine available
-Ach binds to alpha subunits
Available @ preganglionic (SNS & PNS) & NMJ
What is the max dosage of neostigmine?
40 - 70 mcg/kg
0.04 - 0.07 mg/kg
(5mg MAX?? double check)
What is the onset and duration of neostigmine?
Onset: 5 - 10 min
Duration: 60 min
What is the dosage of edrophonium?
0.5 - 1 mg/kg
What is the max dosage of edrophonium?
1.5 mg/kg
?? 1 mg/kg listed in PP ??
What is the onset and duration of edrophonium?
Onset: 1-2 min
Duration: 5-15 min
What percentage of neostigmine is renally excreted?
50%
What percentage of both pyridostigmine and edrophonium are renally excreted?
75%
What effect comes from chronic renal failure (CRF) decreases plasma clearance?
Prolonged action of NMBD reversal agent.
How are NMB reversal agents cleared if the patient has no innate renal function? so, hepatic clearance?
30 - 50% cleared hepatically
What are the major side effects of NMBD reversal agents?
From increased nACh and mACh activity.
CV: Bradycardia, dysrhythmias, asystole, ↓SVR
Pulmonary: Bronchoconstriction, increased airway resistance, increased salivation
GI: Hyperperistalsis, enhanced gastric fluid secretion, PONV
Eyes: Miosis
What drugs would be coupled with NMBD reversal agents to prevent adverse side effects from these drugs?
Anti-cholinergic / Anti-muscarinics
- Atropine
- Glycopyrrolate
If you’re concerned about someone’s cardiac status due to an existing disease, which Anticholinergic drug would you use?
Glycopyrrolate may be preferred.
What NMBD(s) reversal is glycopyrrolate used with?
- Neostigmine
- Pyridostigmine
What NMBD(s) is atropine used with?
Edrophonium
What is the dose of Atropine?
7 - 10 mcg/kg
What common side effects are seen right after atropine administration?
- Mydriasis (pupil dilation)
- initial tachycardia
What is the maximum dose of glycopyrrolate?
1 mg max dose
What is the dose for Glycopyrrolate?
7 - 15 mcg/kg
How long does glycopyrrolate need to be administered over?
2 - 5 min
Persistent NM blockade: mechanism and intervention?
Mechanism:
Acetylcholinesterase is maximally inhibited
No further anticholinesterase is effective
Intervention:
Sedation and postop ventilation
Factors Influencing NMBD Reversal
Intensity of block
Which NMBD did you use
Continued volatile anesthetic
Which reversal drug are you using
Patient conditions: Metabolic acidosis, Respiratory acidosis, Hypothermia
What reversal drug is specific to mivacurium?
Purified human plasma cholinesterase
What reversal drug is specific to gantacurium?
Cystiene
What reversal drug is very specific to an aminosteroid drug (rocuronium)?
Sugammadex
What type of drug is sugammadex?
Selective relaxant-binding agent
What should be known about sugammadex’s organic structure and physical properties?
- γ-cyclodextrin
- Dextrose units from starch
- Very H₂O-soluble
What is the MOA of Sugammadex?
very tight reversal by encapsulating rocuronium via:
- Van der Waals forces (intermolecular)
- H-bonds (thermodynamic bonds)
- Hydrophobic interactions
What drugs does sugammadex work with?
Roc > Vec > Pancuronium
How do hydrophobic interactions affect “free drug”?
Hydrophobic interactions bind to free drugs in plasma.
What is the E ½ time of sugammadex?
2 hours
How is sugammedex eliminated?
Urine:
- 70% gone in 6 hours
- 90% gone in 24 hours
- renal impairment: C/I with dialysis.
Differentiate a moderate block vs a deep block.
- Moderate: 2/4 twitches on TOF
- Deep: No twitches to TOF
What is the Sugammadex dose for a moderate block?
2 mg/kg
What is the Sugammadex dose for a deep block?
4 mg/kg
What is the sugammadex dose for an extreme (overdose) block?
8 - 16 mg/kg
recurarization: not observed at appropriate doses.
What are the side effects of Sugammadex?
- marked bradycardia
- dose-related N/V
- dose-related Pruritis
- dose-related Urticaria
- doesn’t work
- anaphylaxis
sugammadex cautions?
- Contraceptives - binds with progesterone (7 days)
- Toremifene - (non-steroidal anti-estrogen): (displaces NMBD from sugammadex)
- Coagulopathy/bleeding (heparin/LMWH; elevated PTT, PT, INR)
- Recurarization (lower than recommended doses)
What is recurarization?
Resumption of NMJ blockade after a period of reversal (a.k.a: re-paralyzed patient)
What s/s would indicate recurarization?
Say you just brought the patient to PACU.
- ↓ SpO₂
- ineffective abdominal and intercostal activity
- Floppy/uncoordinated
- Unresponsive patient
- verbalize: suffocating feeling
- unable to sustain head life or hand grasp
- worst case: pharyngeal collapse and respiratory obstruction.
What drug and dose would be a good choice for a recurarizing patient in the PACU?
Why might this be a good choice?
- Treat urgently and aggressively: re-sedate the patient (we don’t want someone paralyzed and fully conscious) and give additional reversal agents in divided doses.
- Neostigmine 0.05 mg/kg IV
- Longer duration of action (60 mins)
Clinical Duration of Response (min): d-Tobucurarine
81 mins
Clinical Duration of Response (min): Pancuronium
86 mins
Clinical Duration of Response (min): Rocuronium?
36 mins
Clinical Duration of Response (min): Vecuronium?
44 mins
Clinical Duration of Response (min): Atracurium?
46 mins
Clinical Duration of Response (min): Cisatracurium?
45 mins
Clinical Duration of Response (min): Mivacurium?
16.8 mins
Long-acting ND-NMBD?
d-Tubocurarine
Pancuronium
Intermediate-acting ND-NMBD?
Rocuronium, Vecuronium, Atracurium, Cisatracurium
Short-acting ND-NMBD?
Mivacurium
Which NMBDs are aminosteriods?
Rocuronium
Vecuronium
Pancuronium
Which NMBDs are benzylisoquinoline?
Cisatracurium
Atracurium
Mivacurium
d-Tubocurarine
