· Intro
· PC
· PK
· PD
|
|
Neostigmine |
Sugammadex |
|
Structure |
Quaternary amine |
Modified γ-cyclodextrin 8-sugar ring structure Side chains extend the molecule Hydrophobic inner (OH) for steroid Hydrophilic outer (COOH) for solubility |
|
Pre-mixed |
Yes |
Yes |
|
Stability |
Yes |
Light protection (or use in 5 days) Shelf life 3 years |
|
|
Neostigmine |
Sugammadex |
|
Admin: |
|
|
|
-Route: |
IM, IV |
IV only |
|
-Immediate: |
- |
16mg/kg |
|
-PTC 1-2: |
- |
4mg/kg |
|
TOF 2+: |
0.05mg/kg Ceiling 0.07mg/kg |
2mg/kg |
|
Time course: |
|
|
|
-Onset |
3 min |
2-3 mins (to TOF 0.9) |
|
-Peak |
10 min |
? Mins |
|
-Duration |
30-60min |
? Hours |
|
Absorption: |
|
|
|
-OBA |
2% |
- |
|
Distribution |
|
|
|
-Extent |
ECF – acts mostly at NMJ Doesn’t cross BBB |
ECF – acts mostly in plasma |
|
Metabolism/excretion |
|
|
|
-Metabolism |
50% (plasma esterases) |
- |
|
-Excretion |
50% (renal) |
100% (renal unchanged) Contraindicated if CrCl <30 |
|
-Rate: |
t1/2β 1 hour |
t1/2β 2 hours Cl 1.5mL/kg/min |
|
|
Neostigmine |
Sugammadex |
|
Effects: |
|
|
|
MoA: |
Displacement: -Forms carbamylate complex with esteractic site of AChE -↑[ACh] at NMJ
|
Encapsulation: -Van Der Waal / electrostatic attraction -Form complexes with relaxant in plasma -Create concentration gradient for removal from NMJ
|
|
Non-depolarising block |
Reversal of all (but augment mivacurium - inhibit PChE) |
Reversal of aminosteroids |
|
Depolarising block |
Augment |
- |
|
Plasma cholinesterase |
Inhibit |
- |
|
Other clinical uses |
-Pseudo-obstruction -Atonic bladder -Myasthaenia gravis (Other factors only if crossing BBB): -Alzheimer’s disease -Glaucoma -Benzo overdose -Anti-histamine overdose -TCA overdose |
- |
|
|
|
|
|
Side effects: |
|
|
|
Failed reversal / recurarisation |
More common |
Less common |
|
Hypersensitivity |
Rare Anaphylaxis – case reports only |
Overall 5-10% Anaphylaxis up to 1:3500 |
|
Muscarinic |
Bradycardia, bronchospasm Salivation / Lacrimation / Urination / GIT upset / Defecation / Emesis (No CNS effects) |
Bradyarrhythmias 1% (? mechanism) -Rx atropine |
|
Chelation |
No |
Progesterone -> failed contraception -Need other protection next 7 days Clotting factors -> INR/aPTT ↑20% -Lasts 30-60 mins -Not clinically significant |
Feedback welcome at ketaminenightmares@gmail.com