Neuromuscular Blockade Week 4 Flashcards
The nervous system is divided into ______
the central and peripheral nervous system
The peripheral nervous system is divided into _____
the somatic and autonomic nervous system
The autonomic nervous systems is divided into ____
the sympathetic and parasympathetic nervous system
Somatic nerves include _____
sensory and motor neurons
Sensory neurons from skeletal muscle carry ____
action potentials to the spinal cord via the dorsal (back) horn
Motor neurons to skeletal muscle originate in ____
the ventral (front) horn of the spinal cord
Acetylcholine (ACh) is __
the stimulating neurotransmitter for all cholinergic receptors
What are two major subtypes of cholinergic receptors?
muscarinic and nicotinic
Where are muscarinic receptors found?
peripherally in tissues innervated by parasympathetic postganglionic neurons such as heart, smooth muscle and exocrine glands
Exception: sweat gland
Where are nicotinic receptors found?
Locations:
- peripherally in the motor end-plate of skeletal muscle
- Cell bodies of post ganglionic (sympathetic and parasympathetic) autonomic nerves
- Central nervous system
- Adrenal medulla
- Neuromuscular junction
ACh is released from _______
Preganglionic autonomic fibers
Postganglionic parasympathetic nerve fibers
Motor neurons
Describe the Steps of the Release of Acetylcholine from the Nerve Terminal
- The motor nerve action potential arrives at and depolarizes a nerve terminal.
- Depolarization causes voltage-gated calcium channels to open.
- Calcium (Ca++) diffuses down a concentration gradient into the nerve terminal.
- Inside the nerve terminal, Ca++ causes vesicles to fuse with the nerve cell membrane and open to the exterior.
- ACh spills out into the synaptic cleft (exocytosis).
- The presynaptic nicotinic receptor responds to ACh by increasing the synthesis and release of Ach. This is a positive feedback system that prevents depletion of ACh at the neuromuscular junction
Describe the Steps: Events at the Postsynaptic Membrane
- ACh combines with nicotinic receptors of the protein channel.
- When both alpha subunits of the nicotinic receptor channel are occupied by ACh, the channel snaps open, and sodium and calcium diffuse into the cell and potassium ions diffuse out to the extracellular space.
- The diffusion of these three types of ions through the channel causes the motor end-plate to depolarize.
- At a critical level of depolarization (threshold), an action potential is initiated.
- The action potential sweeps across the skeletal muscle cell and triggers contraction.
Describe the steps: Termination of Neurotransmitter Action
- Acetylcholinesterase (AChE), also known as “true” cholinesterase, breaks down acetylcholine to choline and acetate.
- As ACh is metabolized, the motor end-plate repolarizes and the muscle cell becomes ready for another squirt of ACh from the nerve terminal.
- The choline is transported back into the nerve terminal where it is used to re-synthesize ACh
What is the Clinical use of
Neuromuscular Blocking Agents?
Facilitate tracheal intubation
Reduce risk of vocal cord damage, difficult intubations, manage difficult airways
Improve surgical working condition
Mechanical ventilation
Immobility for surgery or ICU
Remember: no hypnosis or analgesia
What are the characteristics of the ideal neuromuscular blocking agent?
Nondepolarizing Rapid onset
Rapid reliable recovery or reversal No histamine release
Does not accumulate in long cases
Not MH trigger Dose-dependent duration
No hemodynamic side-effects No placental transfer
Elimination independent of organ function
No active or toxic metabolites Cost effective
User friendly packaging and preparation
Peripheral Class of Relaxants
Acts at NMJ on nicotinic ACh receptors
Depolarizing (mimics acetylcholine)
Nondepolarizing (interferes with the action of acetylcholine)
•Short, intermediate and long acting
Central Class of Relaxants
Direct acting muscle relaxants, inhalation agents
Toxins that act at CNS (organophosphates, CNS and peripheral)
ACh central stimulants (Alzheimer’s drug, donepezil) inactivate acetylcholinesterase and increase acetylcholine circulation
Structure and Solubility of all NMBA?
All NMBA are quaternary ammonium in structure
Water soluble in the body
Do NMBA agents cross the blood brain barrier?
Do not cross the blood brain barrier – no CNS effects
Intubating dose
NMBA Dose needed to relax a patient who is not relaxed in other ways for intubation
Rapid Sequence Intubation dose
usually 1.5x intubating dose to achieve intubating conditions in 60 sec
Relaxing dose
Dose given when succinylcholine used for intubation for surgical relaxation
Supplemental dose
Small dose (about 1/5 intubating dose) given to continue muscle relaxation during case, as indicated
Onset of Neuromuscular Block
- Diaphragm
- Orbicularis oculi
- Adductor pollicis
**Order is the same for recovery (diaphargm “wakes” up first)
Succinylcholine is composed of _____
two acetylcholine molecules linked together; thus, succinylcholine mimics the action of acetylcholine.
Succinylcholine, after it is administered intravenously, ____
diffuses into tissues from the blood.
Those succinylcholine molecules that reach the motor nerve terminal of skeletal muscle _____.
combine with nicotinic receptors and cause the channels of the motor end-plate to open; the motor end-plate depolarizes, and a single contraction occurs.
acetylcholinesterase does not metabolize succinylcholine…. describe this further..
the succinylcholine remains attached to the receptors, and the channels stay open until the succinylcholine diffuses back into the circulation; depolarization is maintained for several minutes.
Action potentials cannot be initiated in the skeletal muscle cell until the cell ______.
(MOA of succinylcholine)
repolarizes (the sodium gates are in the inactivated state). Thus, so long as the motor end-plate does not repolarize, additional action potentials and hence contractions cannot be initiated. There is skeletal muscle paralysis. This is a depolarizing block.
Succinylcholine is metabolized by _____.
an enzyme in the plasma called plasma cholinesterase.
The metabolism of succinylcholine in the plasma is rapid. As the circulating succinylcholine is metabolized, a gradient develops for succinylcholine to diffuse from the skeletal muscle motor end-plate back into the plasma, and the effect of the succinylcholine is terminated.
Plasma cholinesterase is known by what two other names?
pseudocholinesterase and butyrocholinesterase.
Class, Absorption & Clinical Use of Succinylcholine
Class: Depolarizing muscle blocking agent
Absorption: IV, IM
Clinical use: Rapid sequence induction, laryngospasm, ECT
Dosing of Succinylcholine
Induction dosing: 1 – 1.5 mg/kg
IM induction: 4 mg/kg
Laryngospasm: 20 - 40 mg
Onset, DOA, and Redistribution of Succinylcholine
Onset: 30 – 60 seconds
DOA: 5 – 15 minutes
Redistribution: Diffusion away from the neuromuscular junction into the ECF
Metabolism and Excretion of Succinylcholine
Metabolism: Plasma cholinesterases. Plasma choliesterases are made by the liver.
Metabolism is prolonged in patients with plasma cholinesterase deficiency.
Excretion: Eliminated by the kidneys
Succinylcholine can cause: ___
Bradycardia due to direct stimulation of muscarinic receptors of the SA node
Hyperkalemia risk: plasma K+ concentration may increase by 0.5 mEq/liter in normal patients and 5–10 mEq/liter in burn, trauma, or head-injury patients
Increased Pressures (ICP, IOP, gastric)
Muscular: Fasciculations/post op muscle pain (myalgias)
Rhabdomyolysis leading to hyperkalemia and cardiac arrest
Masseter spasm early sign of MH, MH trigger (malignant hyperthermia)
Why is succinylcholine riskier in pts with history of head trauma, skeletal muscle disease, TBI, burns, or spinal cord injury?
Each of those conditions is associated with proliferation of “extrajunctional postsynaptic cholinergic nicotinic receptors”.
When nerve action potentials to skeletal muscle are interrupted, post- synaptic nicotinic receptors up-regulate and spread from the neuromuscular junction to the entire muscle fiber. As you know, potassium exits the cells when the nicotinic receptor is stimulated and the channel opens. The major concern, therefore, is hyperkalemia which may occur in these patients upon administration of succinylcholine.
