MSS14 Neuromuscular Blocking Agents And Local Anaesthetics Flashcards
Receptor antagonism
Competitive antagonist:
% response-log[L] curve shift to right
Non-competitive antagonist:
% response-log[L] curve shift to right and downward (more agonist cannot overtake antagonist)
Neuromuscular blocking agents
Most NMB are ***competitive inhibitors
Aim: make patient immobile
Use: e.g. lax muscle to allow retractor to pull muscle apart during surgery
Succinylcholine (suxamethonium / diacetylcholine / 2 acetylcholines joined together)
- numerous side effects
- rapid onset (60 secs)
- rapid offset (10-15 mins)
- declining in popularity
- may cause initial activation of ACh receptor (since similar in structure to ACh)
ACh affected areas
- NMJ
- Ganglion in both SNS and PNS (Nicotinic ACh receptor: Ionotropic / Ligand-gated ion channels)
- Post-ganglion receptor in PNS (Muscarinic ACh receptor: Metabotropic / GPCR)
SE of succinylcholine (no need rmb)
- Cardiovascular
- arrhythmia
- sinus bradycardia - Hyperkalemia secondary to infection / trauma
- ↑ intraocular pressure
- ↑ intragastric pressure
- Myalgia
Newer NMB
Pure competitive antagonist: **NO autonomic SE since **only effective on NMJ
- Short acting (5-10 mins (=/ rapid onset)) —> more easily titratable
- ***Mivacurium - Intermediate acting (20-30 mins)
- ***Atracurium
- Cisatracurium
- Vecuronium
- Rocuronium - Long acting
- Pancuronium
- Tubocurarine
- fewer SE
- NO place for long acting
Terminating NMB effect
- Anticholinesterase (AChE inhibitor) —> increase [ACh] to overcome antagonist effect —> cannot work if NMB effect too strong
- **Neostigmine
- **Pyridostigmine
- ***Edrophonium - Metabolism and elimination of NMB
- Cannot give ACh directly since short t1/2 and actively metabolised
Neuromuscular monitoring (monitor how intense the block is)
Stimulate motor nerve using transcutaneous electrode
–> monitor finger movement
Usually **ulnar nerve: **adductor pollicis
Neuromuscular blocking =/ Anaesthetics
NMB: loss of control of movement
Anaesthetics: loss of sensation / consciousness
Mechanism of local anaesthetics
Deprotonated base (B) diffuse through epineurium and neuronal membrane
- -> Protonated (BH+) in axoplasm
- -> ***Block voltage-gated Na channels (interact with the 4 domains) (works INTRACELLULARLY: 由裡面block)
- -> Stop action potential
Therefore
- acidic environment: weaker effect (protonated —> cannot penetrate neuronal membrane)
- basic environment: improve onset, better effect
***LA may block sensory / motor / both nerve fibres, depending on dose and concentration at the area
(From internet:
Local anaesthetics work by blocking nerve impulses on sensory, motor and autonomic nerve fibres. The smallest diameter fibres are most sensitive to the effects of local anaesthetics: autonomic fibres will be blocked first, then sensory fibres and then motor fibres. Motor nerves (as well as sensory nerves) may be affected by local anaesthetics.)
SE of Anaesthetics
Lower to higher serum conc:
- anti-convulsant
- anti-arrhythmic
- muscular twitching
- unconsciousness
- ***convulsions
- ***coma
- respiratory arrest
- ***CVS depression
Notable local anaesthetics
- Lignocaine
(dose limit: 4mg/kg; 7mg/kg with adrenaline: vasoconstriction –> delay absorption of LA through capillaries; adrenaline dose limit: 1-2 ug/kg, depends on patient factors, injection site) - Bupivacaine (2.5mg/kg)
- Ropivacaine
Make sure dose not too high: otherwise absorb through capillaries
***Route of administration
- Topical
- Infiltration (needle): ***aspirate before injecting to make sure not injecting into blood vessels —> prevent systemic SE
- ***Nerve / plexus block (axillary approach: block Brachial plexus –> numb whole arm)
- Epidural / spinal
- IV (***Bier’s block: local anesthetic agent is intravenously introduced into the limb and allowed to diffuse into the surrounding tissue while tourniquets retain the agent within the desired area)
EMLA cream
Eutectic mixture of local anaesthetic (Lignocaine + Prilocaine) (homogeneous mixture of substances that melts or solidifies at a single temperature that is lower than the melting point of either of the constituents, 未到melting就溶左)
—> no need dissolve in water
—> easy to control concentration
Normal pain pathway
Spinothalamic pathway
Pain fibres in skin / tissues
- -> primary afferent neuron
- -> dorsal root ganglion
- -> second-order neuron
- -> dorsal (sensory) horn
- -> ventral (motor) horn
- -> brainstem and thalamus
Adrenaline administration
Do NOT give in sites where end arteries are (area with no other arteries supply e.g. penile block, digital block), otherwise ischaemic
