L13: SA Neuromuscular Blocking Agenst (Granone) Flashcards
NMJ
Interface b/w large myelinated nerve fiber and muscle that innervates it
Composed of pre-jx motor nerve ending, synaptic cleft filled with ECF, and membrane of post-jx skeletal m. Fiber
Ach goes across cleft
Physiology of the NMJ
- nicotinic cholinergic receptors lie on pre and post-junctional areas of the NMJ, which bind Ach
- synthesis and mobilization of Ach from pre-junctional neuron
- resting transmembrane potential -90 mV due to unequal distr. of K and Na
Extrajunctional vs. junctional post-synaptic receptors
Junctional: end plates of normal adult animals; interact w/ Ach resulting in m. Contraction
Extrajunctional: synthesized w/ less than normal nerve stimulation; increased after spinal cord injury or muscle disuse
NM transmission summary
1) muscle cells depolarized by end-plate potential –> m. Contraction
- potential cause by binding of Ach to receptor
2) M. Cells repolarized as Ach removed from receptor by AchE
- Ach hydrolyzed and repackaged
- m. Relaxes
Ach binding is competitive and reversible
2 Ach must bind to each alpha subunit receptor to have an effect
A NM antagonist must only bind to 2 subunit to prevent normal fx
NM transmission dependent on:
Conc. Of Ach vs. concentration of antagonist
NMB agent MOA
Competitive binding of Ach receptor
-can be polarizing (ie. Atracurium) or depolarizing (succinylcholine)
Depolarizing NMB agents and MOA
- competitively bind to receptor like Ach and stimulates it
- causes depolarization of post-jx membrane
- NOT degraded by AchE, so repolarization doesn’t repolarize
- causes inexcitability and flaccid paralysis
- ie: succinylcholine
Nondepolarizing NMB agents and MOA
- bind to Ach receptor but don’t activate it
- causes progressive m. Weakness –> flaccid paralysis
- Atracurium, pancuronium, rocuronium, vecuronium
Properties of atracurium
- short-acting nondepolarizing NMB drug
- DOA 20-30 min
- few CV effects
- eliminated by Hoffman elimination (spontaneous molecular degradation that is pH and temp. Dependent)
- can cause HA release –> hypotension
Properties of Pancuronium
Long-acting nondepolarizing NMB drug
- DOA 40-60 mins
- excreted by kidneys, met. By LIV
- Vagolytic effect: inhibits cardiac muscarinic receptors –> tachycardia
Uses of NMB drugs
- ophtho sx
- dec. resistance to controlled ventilation
- facilitate sx access
Order of paralysis
1) muscles of face, jaw, tail
2) neck, distal limbs
3) proximal limbs
4) pharynx, larynx
5) abdomen
6) intercostal muscles
7) diaphragm
Monitoring while using NMB drugs
- PPV
- Peripheral n. Stim.
- reversal agent
- watch for signs of full blockade: loss of jaw tone, pedal withdrawal, palpebral, central eye, apnea
- ensure good plane of anesthesia b/c p may not be able to move if light
Peripheral nerve stimulator
- monitors evoked motor response
- degree of NM blockade
- applied to peripheral motor nn.
- presence of NMB agent –> absence of movement
- TOF most often used
Normal T4:T1 ratio
1.0
What percent of receptors need to be occupied before twitches start to fade? In what order? ***
70%
1) T4
2) T3
3) T2
4) T1
Will return in reverse order as drug wears off
Blockade reversal
1) Normal: AchE (hydrolyzes ACh)
2) AchE inhibitors
-increase ACh concentration, which take place of NMB drug at receptor
-indirectly restores NM transmission
Drugs: Edrophonium, Neostigmine, Pyridostigmine
ACh is the NT at which receptors?
Nicotinic and muscarinic receptors
-sinus node, smooth muscle, glands, skeletal and cardiac m.
Increased Ach at muscarinic receptors –>
Bradycardia Sinus arrest Bronchospasm Miosis Inc. intestinal peristalsis Salivation
Prevention of muscarinic stimulation effects
- administer anticholinergic (antimuscarinic) prior to NMB reversal
- blocks muscarinic receptors
- causes inc. HR, bronchodilation, dec. GI peristalsis
NMB drug action must wane before antagonism with reversal agent - why?**
- premature reversal –> blockade refractory to reversal
- 3 twitches of TOF should be present first
- depolarizing NMB drugs cannot be reversed!!
Neuromuscular blocking drugs are peripheral muscle relaxants. MOA:
-interfere w/ NM transmission
- anesthetic adjunct only
- lack sedative, hypnotic, analgesic, amnestic properties
