Core pharmacology

Class Group

Cholinesterase Inhibitor

Legacy Cicm Level

Level 2

Indications Uses

- Reversal of NDMR (0.05mg/kg)
- Myasthenia gravis (PO 15-30mg)
- Urinary retention
- Paralytic ileus

Chemical Pharmaceutics

Carbamate ester Acetylcholinesterase inhibitor

Presentation

PO or IV (IV preparations may contain glycopyrolate)

Mechanism of action

reversible acid transferring cholinesterase inhibitor that binds to the esteratic site of AChE and is hydrolyzed but at a much slower rate than Ach. Leads to increase in Ach in the synapse.

Physiological effects

CVS: Bradycardia. In high doses a central effect may precipitate hypotension

Resp: Bronchoconstriction in asthmatic. Increased bronchial secretion

Renal: Increased ureteric peristalsis leading to involuntary micturition

GIT:
- Salivation
- Increased LOS tone and GIT motility (cramps)
- N/V
- Increased gastric acid output

CNS: Miosis and failure to accommodate

Other: Sweating and lacrimation

Adverse Effects Toxicity

(SLUDGE-BM)
- Salivation
- Lacrimation
- Urination
- Diaphoresis
- GI upset
- Emesis
- Bradycardia and bronchoconstriction
- Miosis

- Prolongs suxamethonium duration of action

Absorption

Poorly absorbed orally (bioavailability 1%)

Distribution

Highly ionized so does not cross BBB

Protein binding

10% PB

Volume of distribution

Vd 0.5-1L/Kg

Metabolism

- Predominantly plasma esterases
- Some hepatic metabolism with biliary excretion

Excretion

65% renally excreted

Half-life

T1/2= 15-80min (increased in renal failure)