2018A12 Compare and contrast the pharmacology of neostigmine and sugammadex.

 

List:

·      Intro

·      PC

·      PK

·      PD

 

Physicochemical:

 

Neostigmine

Sugammadex

Structure

Quaternary amine

i.e. doesn’t cross blood-brain barrier

γ-cyclodextrin

Ring structure

6 sugar moieties

Hydrophilic outer (COOH substitution)

Hydrophobic inner (OH substitution)

Need for reconstitution

No (i.e. quick)

No (i.e. quick)

Stability

Requires protection from light

(or use within 5 days)

 

Pharmacokinetics:

 

Neostigmine

Sugammadex

Admin:

 

 

-Route:

IM, IV

IV only

-Profound blockade
(after induction)

Can’t

16mg/kg

-Deep blockade (TOF count 1-2)

Can’t

4mg/kg

-Moderate blockade (TOF count 3+)

0.05mg/kg

Ceiling effect 0.07mg/kg

2mg/kg

Time course:

 

 

-Onset

3 min

<1min

-Peak

10 min

 

-Duration

30-60min

 

Absorption:

 

 

-OBA

2%

 

Distribution

 

 

-Extent

Leaves plasma -> NMJ

Doesn’t cross BBB

Confined to plasma

Encapsulates drug in plasma

Create concentration gradient++

Metabolism/excretion

 

 

-Route

50% metabolized (plasma esterases)

50% excreted

100% renal unchanged

-t1/2β

1 hour

2 hours

 

Pharmacodynamics:

 

Neostigmine

Sugammadex

Effects:

 

 

MoA:

Forms reversible carbamylate complex with esteratic site of AChE

↑[ACh] at NMJ

Displacement of drug

Encapsulate relaxant

Hydrophobic inner for steroid

Hydrophilic outer for solubility

Electrostatic attraction

Effect on plasma cholinesterase

Inhibit

Nil

Effect on non-depolarisers

Augment mivacurium (inhibit PChE)

Reverse all others

Reverse roc > vec >> panc

Effect on depolarisers

Augment

Nil

Other

-Reverse any non-depolarising blockade
(but slows metabolism of mivacurium)

-Pseudo-obstruction

-Atonic bladder

-Myasthaenia gravis

(Other factors only if crossing BBB):

-Alzheimer’s disease

-Glaucoma

-Benzo overdose

-Anti-histamine overdose

-TCA overdose

Reverse aminosteroids only
(roc > vec >> panc)

 

 

 

Side effects:

 

 

Pair with antimuscarinic

Y (glycopyrrolate – similar time course)

N

Muscarinic side effects

Y

Bradycardia, bronchospasm

SLUDGE

No CNS cholinergic toxicity

N

Chelates progesterone -> failed contraception

N

Y

 

 

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