Neuromuscular blocking agents Flashcards
From which plant was Curare originally isolated
Strychnos toxifera
What are the clinical uses of NMBAs
Tracheal intubation - improves conditions, reduces change of tissue trauma and reduces incidence of vocal cord injury
Facilitate surgical exposure
Minimise possible complications of intraoperative patient movement
Which muscle is least susceptible to neuromuscular blockade and why
The diaphragm
The effect is thought to be due to differences in blood flow and different concentrations of presynaptic neurons
Describe the mature post-junctional nicotinic acetylcholine receptor
A pentamer, ligand-gated ion channel
5 subunits - 2 alpha, 1 delta, 1 beta, 1 epsilon
N- and C- terminal ends are extracellular
4 transmembrane domains (M1-M4)
M2 domain of each subunit creates the central pore
How does the nicotinic acetylcholine receptor function
Agonist binding site is located on the interface of alpha-delta and alpha-epsilon subunits where the N- terminus of each subunit interacts with the other
2 agonist molecules must bind to allow the receptor pore to open
Receptor binding sites are not identical allowing for varying affinity for each site
It is a non-selective cation channel Na=K>Ca
Describe the ED95 and its significance regarding neuromuscular blockade
ED95 is the dose at which 95% suppression of twitch response is achieved (unlike ED95 of other drugs)
An intubating dose of NMBA is typically 2x the ED95
The potency of a NMBA is inversely related to the onset of block
How are NMBAs classified
Depolarising - Succinylcholine (Suxamethonium)
Non-depolarising - Benzylisoquinoliniums - (Curiums)
Steroidals - (Uroniums)
Outline the structure of Suxamethonium
2 molecules of Acetylcholine bound at their acetate methyl groups
Why does Suxamethonium only have a short duration of action and why is it prolonged in certain people
Sux diffuses out of the NMJ into plasma where it is hydrolysed by plasma cholinesterase to succinylmonocholine and choline.
Patients with an autosomal recessive gene mutation that causes deficiency in plasma cholinesterase will have prolonged effects from Sux - Sux apnoea
Patients that have a decreased concentration or activity of PChE will have the same effect - malnutrition, chronic disease, pregnancy, medications (Lignocaine, non-penicillin ABs, B-blockers, Lithium, Metoclopramide, Ketamine, OCP, Neostigmine, Organophosphates)
What is the dose of Suxamethonium
ED95 = 0.3mg/kg, therefore dose = 0.6mg/kg
Often given as 1mg - 1.5mg/kg IV in practice
Can be given as 5-10mg/kg IM
What is the onset and duration of action of Sux
Onset 30-60 secs
Duration 3-5mins
What is the elimination half time of Sux
30-60 secs
Outline the adverse reactions of Sux
Malignant hyperthermia Anaphylaxis Rise in serum K - ~0.5-1.0mmol/L Muscarinic side effects (Bradycardia, hypersalivation, inc GIT secretion and pressure, inc uterine tone) Inc ICP (fasciculations) Inc IOP Myoglobinuria Prolonged contractions (Myotonia dystonica, masseter spasm) Tachyphylaxis and 2nd phase block Sux apnoea Myalgias
In which pt groups should Sux be avoided
Electrolyte disturbances esp K Low PChE pts Renal disease Digoxin Malignant hyperthermia or FHx of same Burns or multiple trauma Muscular dystrophy Myaesthenia gravis
Outline the mechanism of action of a Non-depolarising NMBA
2 molecules of ACh are required to activate a post-synaptic receptor
NDNMBs competitively bind to the receptor without producing a conformational change. This results in a non-functional ion channel and prevention of NMJ transmission when 80-90% of receptor sites are occupied by a NDNMB
