Lecture 11: Neuromuscular agents Flashcards
What are NMBA’s?
They are a class of drugs that paralyse patients by acting at the neuromuscular junction. They present significant risk however.
Explain the sedative, analgesic and amnesic effects of NMBAs?
They have none
Clinical use of NMBAs?
For intubation of the trachea avoiding damage to the vocal cords
Prevents deleterious movements during delicate procedures
Helps to improve conditions for ventiltion by removing the work of breathing and this can allow lowered ICP
NMJ entities?
- Presynaptic - ACh is made, stored and released
- Synaptic cleft - 15nm and contins basil lamina
- Post synaptic - Has ACh receptor
*Go and review NMJ*
Structure of the Nicotinic Acetyl Choline Receptor (AChR)
- Pentameric ligand-gated ion channel
- Synthesised in muscle cells
- anchored to the endplate
Classifications if NMBAs
Mechanism of action
- depolarising vs non-depolarising
Chemical Structure
- Benzylisoquinolones vs aminosteroids
Duration of action
- Ultra-short, short, intermediate, long
Give and explain the action of a depolarising NMBA?
Succinylcholine (SCh)
Mimics the effects of ACh
one molecule binds simultaneously to the 2a subunits
Is really an agonist but blocks the NMJ after the inital stimulation as it doesnt allow for repolarisation
Is not susceptible to ACesterase but rather remains in receptor till plasma conc drops due to plasma cholinesterase or elimination by the kidneys
AE of succylcholine?
Succinylcholine (SUX) Apnoea?
- Can’t be reversed
- anaphylaxis
- Fasciculations - muscle pain in 1:5000
- Masseter spasms
- Cardiac dysrythmias - brady and tachycardia due to chatecholamine release
- increase ICP, IgastricP, IocularP
- may trigger malignant hyperpyrexia
This is what occurs in 1/3200 people that are homozygous for the deficiency.
How do Non-depolarising NMBAs work?
Effect conc relationship?
- They are + charged quaternary ammonium compounds attracted to AChR that bind to one or both a subunits preventing ACh binding.
- Compeditive interaction between ACh an d NMBA occurs
- But if only one molecule is required to block then there is an obvious bias towards the NMBA
- Effect depends on conc of the NMBA and ACh but begins when >70% occupation and is considered complete at >90%
Atracurium onset time and pathway of degradation?
AE?
Onset is 3-5 min so not that fast
Hofmann elimination at body pH and Temp that is independent of the liver or kidney
AE: CVS effects caused by histamine release, transient rash, hypotenstion or tachycardia
Mivacurium onset, potency, AE?
3x more potent than Atracurium nut slow onset of 3-4min
Has a short duration of 20-25min
Hydrolysed by plasma (pseudo)cholinesterase (like SCh) but is a non-dep. NMBA
AE: less histamine that atracurium but, conditions causing abnormal pseudocholinesterase will delay recovery
Rocuronium potency, use, duration, AE?
Intermediate duration of action around 40min
Low potency so high dose required
Rapid onset of action so useful for rapid intubation instead of SCh
Less anaphylaxis than SCh and minimal cardiac effects and low histamin release
Hepatic elimation mainly (90%) with the rest being renal
Vecuronium duration, onset, AE
Intermediate duration
slower onset but similar duration to rocuronium
Active metabolite excreted in urine - prolonged duration in renal failure patients
minimal cardiac effects with least potential for anaphylaxis
Pancuronium onset, potency, effects, removal
High potency and slow onset
longest acting (1.5-2h)
Has vagolytic effects causing increased blood pressure, HR and CO
Good for long cardiac surgical procedures
Minimal histamine release
Excreted by the Liver and Kidneys
Reversal of NMBAs?
Accelerate reversal
- increase ACh concentration at the NMJ by stoping its breakdown via acetylcholinestersae = Neostigmine and Pyridostigmine
- Decrease plasma concentration of the NMBA