Valley: Neuromuscular Physiology & Pharmacology Flashcards
Motor neurons to skeletal muscle originate in the ——- of the spinal cord
anterior (ventral) horn
Sensory neurons from skeletal muscle carry action potentials to the spinal cord via the —-
dorsal horn
These motor and sensory nerves are —— nerves
somatic
Motor nerves exit the ventral cord via —-
Efferent way
Sensory nerves enter dorsal cords via —-
Afferent
5 steps process of release of ACh from 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).
What type of feedback is the release of ACh from nerve terminal?
Positive; presynaptic nicotinic receptors responds to ACh by increasing the synthesis and release of ACh to prevent depletion of ACh at neuromuscular junction.
Acetylcholine —— down a concentration gradient from the presynaptic membrane to the motor end- plate of the postsynaptic membrane.
diffuses
5 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, calcium and potassium ions diffuse through the channel.
- 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.
When both alpha subunits of the nicotinic receptor channel are occupied by ACh, the channel snaps open, and sodium, calcium and potassium ions diffuse through the channel. How do Na, Ca, and K ions diffuse?
Sodium and calcium ions diffuse into the cell and potassium ions diffuse out to the extracellular space.
3 steps to 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.
Hypocalcemia is associated with a —- in amount of neurotransmitter released.
Decrease
Hypercalcemia is associated with a —- in amount of neurotransmitter released.
Increase
Hypomagnesemia is associated with a —- in amount of neurotransmitter released.
Increase
Hypermagnesemis is associated with a —- in amount of neurotransmitter released.
Decrease
Calcium and magnesium are —— at nerve terminals.
Antagonistic
The release of neurotransmitter from all nerve terminals, including the motor nerve terminals, depend on the entry into the terminal of ——.
Calcium ions
An —— molecule must attach to each of these two identical subunits where the nicotinic receptors are located in order to open the channel
ACh
How many ACh molecules are needed to open each nicotinic acetylcholine receptor (nAChR).
2
Where do the ACh molecules attach to on the Postsynaptic receptors?
2 identical 40k subunits
5 step sequence for opening of channels by ACh:
- Two molecules of acetylcholine (represented by open triangles above) combine with two nicotinic
receptors on the channel. - The ion channel opens and becomes permeable to Na+, K+, Ca ++.
- The motor end-plate depolarizes; a local, sub-threshold depolarization occurs at the end-plate.
- When threshold is reached, an all-or-none action potential is initiated in the muscle fiber.
- An action potential passes over the muscle cell and into the transverse tubules and triggers the contraction.
Nondepolarizing agents are —— inhibitors.
Competitive
When a nondepolarizing agent binds to either ACh-binding site on a nicotinic receptor, ACh —— attach to that receptor and the channel —— open.
Cannot, cannot
Because succinylcholine is not metabolized by true acetylcholinesterase, the channels stay —— and depolarization is maintained for an extended period of time.
Open
Do nondepolarizing agents have a direct effect on the channel?
No
The nondepolarizing agent competitively blocks acetylcholine from attaching to its receptors so the channel cannot open. The channel stays closed, and the postsynaptic membrane remains ——.
Polarized
Succinylcholine (sux) is composed of two —— molecules linked together.
Acetylcholine
Because true acetylcholinesterase does not metabolize succinylcholine, the succinylcholine remains attached to the receptors, and the channels stay —— until the succinylcholine diffuses back into the circulation; depolarization is maintained for several minutes.
Open
Action potentials cannot be initiated in the skeletal muscle cell until the cell ——.
repolarizes
When an action potential cannot be initiated in the skeletal muscle cell, the —- gates are in the —— state.
Sodium, inactivated
Succinylcholine is metabolized by an enzyme in the plasma called —— ——.
plasma cholinesterase
Plasma cholinesterase is known by two other names: —— and ——.
pseudocholinesterase, butyrocholinesterase
When the channel of the motor end-plate opens, what diffuses into the cell?
Sodium and calcium
When the channel of the motor end-plate opens, what diffuses out of the cell?
Potassium
As long as succinylcholine maintains the —— state, the voltage-gated sodium channels remain ——, and action potentials cannot be elicited.
depolarized, inactivated
When the gated sodium channel is in the inactivated state, another action potential —— be fired no matter how intense the stimulus.
cannot
The —— —— ——corresponds to the time when the fast voltage-gated sodium channels are in the inactivated state. Depolarization of the motor end-plate by succinylcholine causes the voltage-gated sodium channels to become inactivated, thereby electrically arresting skeletal muscle.
absolute refractory period
At the neuromuscular junction, does the presynaptic action of succinylcholine enhance or antagonize its postsynaptic action?
presynaptic action of succinylcholine enhances its postsynaptic action.
Which neuromuscular blockers are very short?
Succinylcholine; anectine
Which neuromuscular blockers are short?
Mivacurium; mivacron
Which neuromuscular blockers are intermediate?
Atracurium (tracrium), cisatracurium (nimbex), vecuronium (norcuron), Rocuronium (zemuron)
Which neuromuscular blockers are long?
D-tubocurarine (tubarine), metocurine (metabine), pancuronium (pavulon), gallamine (flaxedil), pipecuronium (arduan), doxacurium (nuromax)
Physiological Properties of Neuromuscular Relaxants A. 100% —— at physiologic pH
B. —— —— protein bound
C. —— cross the blood-brain barrier (ions do not cross lipid bilayers)
D. —— cross the placental barrier (ions do not cross lipid bilayers)
E. Trapped in the —— —— after filtration because of high degree of ionization (NB: muscle relaxants can be excreted by the kidney if other routes are unavailable)
A. Ionized
B. Very highly
C. Do not
D. Do not
E. renal tubule
Route of elimination for succinylcholine?
Metabolism
Route of elimination for mivarcurium?
Metabolism
Route of elimination for atracurium?
Metabolism
Route of elimination for cisatracurium?
Metabolism
Route of elimination for vecuronium?
Biliary excretion
Route of elimination for rocuronium?
Biliary excretion
Route of elimination for d-tubocurarine?
Renal excretion
Route of elimination for metocurine?
Renal excretion
Route of elimination for pancuronium?
Renal excretion
Route of elimination for gallamine?
Renal excretion
Route of elimination for pipecuronium?
Renal excretion
Route of elimination for doxacurium?
Renal excretion
Atracurium is eliminated by —— ——(nonspecific esterases, unrelated to plasma cholinesterase, perform ester hydrolysis) and —— —— (pH and temp dependent degradation)
ester hydrolysis , Hofmann elimination
Cisatracurium is eliminated by —— —— only
Hofmann elimination
Mivacurium is eliminated by —— ——.
Plasma cholinesterase
Which 2 neuromuscular blockers produce autonomic ganglionic blockade?
D-tubocurarine and metocurine
Which 5 neuromuscular blockers elicit the release of histamine?
Sux, Mivacurium, atracurium, d-tubocurarine, and metocurarine
Which 3 neuromuscular blockers produce reflex tachycardia?
Atracurium, d-tubocurarine, and metocurine
Which 2 neuromuscular blockers cause direct vagolytic (antimuscarinic) by competitively antagonize ACh?
Pancuronium and gallamine
Which 3 neuromuscular blockers produce hypotension?
Sux, d-tubocurarine, and metocurine
Which 2 neuromuscular blockers produce HTN?
Pancuronium and gallamine
How does rocuronium affect peds?
Increase HR
How does sux effect plasma K?
Increase 0.5 mEq/L in normal pts and 5-10 mEq/L in burn, trauma, or head-injury pts
How does sux effect muscles?
Muscle pain (myalgia)
How does sux effect HR?
Bradycardia
How does sux effect heart conduction?
AV conduction block
How does sux effect eyes?
Increase intraocular pressure
How does sux effect MH?
Can cause it
How does sux effect intracranial pressure?
Increase it
How does sux effect pts with atypical plasma cholinesterase?
Prolonged respiratory paralysis
How does sux effect urine?
Myoglobinuria
How does sux effect muscle movement at induction?
Fasciculations
How does sux effect intragastric pressure?
Increase
What are the 4 conditions that accentuate sux-induced hyperkalemia?
- Burn
- Paraplegia or hemiplegia
- Skeletal muscle trauma
- Upper motor neuron injury (head, cerebrovascular, Parkinson’s disease)
If you use a nerve-muscle stimulator on the right wrist of the patient with right-sided hemiplegia, will the twitch be less than, the same as, or greater than the twitch on the left?
The twitch on the right will be greater than on the left!! Nicotinic receptors are up-regulated on the right, hemiplegic side.
What are the 5 diagnosis of MH?
- Pyrexia (fever)
- Tachycardia
- Cyanosis
- Rigidity
- Failure of masseter to relax (trismus)
What are the 5 chances in serum composition that are found in MH?
Increased: protons, potassium, calcium and CO2
Decreased: O2
The defect in malignant hyperthermia is in the —— —— of skeletal muscle.
sarcoplasmic reticulum
In MH, the sarcoplasmic reticulum fails to sequester ——, so sustained contractions with increased metabolism result.
calcium
—— is used to treat malignant hyperthermia.
Dantrolene
Dantrolene acts on the sarcoplasmic reticulum to decrease the release of —— to contractile proteins.
calcium
One of the earliest and most sensitive signs of malignant hyperthermia is an unexplained doubling or tripling in —— ——.
end-expiratory CO2
In MH, the initial signs of tachycardia and tachypnea result from —— nervous system stimulation secondary to underlying —— and ——.
sympathetic , hypermetabolism and hypercarbia
In MH, sympathetic hyperactivity manifested by increased —— is also an early sign of increased
——.
heart rate , metabolism
In MH, an increase in end-tidal CO2 —— the increase in heart rate.
precedes
In MH, increased PaC02 (possibly > —— mmHg) and decreased pH (possibly < ——)
100 , 7.0
What 2 things can trigger MH?
Sux and halogenated inhalational agents (iso, des, halothane, enflurane, sevo)
Factors that alter the degree of NDMB: antibiotics
Block increased EXCEPT for penicillin, chloramphenicol, and cephalosporins
Factors that alter the degree of NDMB: local anesthetics
Block increase by amides
Factors that alter the degree of NDMB: volatile inhalational agents
Block increased
Factors that alter the degree of NDMB: hypokalemia
Block increased
Factors that alter the degree of NDMB: mypermagnesemia
Block increased
Factors that alter the degree of NDMB: respiratory acidosis
Block increased
Factors that alter the degree of NDMB: hypothermia
Block increased
Factors that alter the degree of NDMB: anti-arrhythmic agents
Block increased
Factors that alter the degree of NDMB: renal disease
Block increase for those agents that are eliminated by renal excretion (gallamine)
Factors that alter the degree of NDMB: hepatic disease
Block increased for those agents that are eliminated in the bile (vec and roc)
Factors that alter the degree of NDMB: myasthenia gravis
Block increased
Factors that alter the degree of NDMB: age
Block increased (>60-65) bc organs of elimination are less effective
Factors that alter the degree of NDMB: lithium
Block increased
Factors that alter the degree of NDMB: diuretics
Block increased
Factors that alter the degree of NDMB: calcium channel blockers
Block increased
Factors that alter the degree of NDMB: corticosteriods
Block unchanged
Factors that alter the degree of NDMB: anticonvulsants
Block decreased in pts treated chronically with anticonvulsants
Factors that alter the degree of NDMB: thermal (burn) injury
Block decreased; manifests 10 days after injury, peaks at 40 days and declines after 60 days
Factors that alter the degree of DMB: antibiotics
Block increased EXCEPT with penicillin, chloramphenicol, and cephalosporins
Factors that alter the degree of DMB: local anesthetics
Block increased by amides
Factors that alter the degree of DMB: volatile inhalational agents
Block unchanged
Factors that alter the degree of DMB: anticholinesterase agents
Block increased
Factors that alter the degree of DMB: hyperkalemia
Block increased
Factors that alter the degree of DMB: hypermagnesemia
Block increased
Factors that alter the degree of DMB: inherited pseudocholinesterase defect (atypical pseudocholinesterase)
Block increased
Factors that alter the degree of DMB: lithium
Block increased
Factors that alter the degree of DMB: calcium channel blockers
Block increased
Characteristics of NDMB: Amplitude of single twitch contractions —— with increasing intensity of block.
decreases
Characteristics of NDMB: Fade occurs during ——stimulation and —— stimulation.
Train of four and tetanic
Characteristics of NDMB: The train-of-four ratio (amplitude of fourth beat to amplitude of first beat) is less than ——%.
70
Characteristics of NDMB: (T4/T1 < ——%).
70
% Receptors occupied with NDMB: Complete paralysis - flaccid patient (no twitches in train-of- four)
99-100
% Receptors occupied with NDMB: Diaphragm moves (no twitches in train-of-four)
95
% Receptors occupied with NDMB: Abdominal relaxation adequate for most intra-abdominal procedures (one twitch present in train-of-four)
90
% Receptors occupied with NDMB: Tidal volume returns to normal (>5 mL/kg); single twitch as strong as baseline (not an indicator of recovery)
75-80
% Receptors occupied with NDMB: No palpable fade in TOF, useful as gauge of recovery; sustained tetanus at 50Hz for 5 seconds, reliable indicator of recovery
70-75
% Receptors occupied with NDMB: No palpable fade in double burst stimulation, more sensitive than TOF as indicator
60-70
% Receptors occupied with NDMB: Passes inspiratory pressure test, at least -40 cm H 20; head lift for 5 seconds; sustained strong handgrip; sustained bite, very reliable indicator of recovery.
50
Data suggest that conditions for intubation with NDMB are appropriate if greater than ——% of nicotinic receptors at the motor end-plates are occupied.
95
Characteristics of DNMB: Block is —— by cholinesterase inhibitors (edrophonium, neostigmine, pyridostigmine).
enhanced (augmented)
Characteristics of DNMB: Fade —— occur during tetanic stimulation or train-of-four stimulation, although the amplitudes of the tetanic contraction and train-of-four beats are reduced.
does not
Characteristics of DNMB: The train-of-four ratio (amplitude of fourth beat to amplitude of first beat) is greater than ——% (T4/T1 >——% = T4/T1 >——).
70 , 70 , 0.7
Characteristics of DNMB: Post-tetanic facilitation (post-tetanic potentiation) is ——.
absent
Characteristics of DNMB: Block is —— by nondepolarizing muscle relaxants.
antagonized
Which phase block is this? The motor end-plate is depolarized; succinylcholine has activated the nicotinic receptors of the motor end-plate and the ion channels have opened and remained open.
phase I block
Treatment with higher doses of succinylcholine and/or prolonged exposure of the motor end-plate to
succinylcholine leads to the development of ——.
phase II, or desensitization, block.
very complex phenomenon; ion channels of the motor end-plate close for reasons that are unknown, and the motor end-plate repolarizes.
Phase II (desensitization) block
Phase II block has the characteristics of a nondepolarizing block; use of a peripheral nerve stimulator during phase II block will show —— and ——.
fade and post-tetanic facilitation
Refers to simultaneous existence of both depolarizing (Phase I) and Phase II blockade.
Dual Blockade
“Antagonism of neuromuscular blockade should normally not be attempted when blockade is intense because reversal will often be inadequate, regardless of the dose of antagonist administered?’ Reversal can be attempted when —— twitch is elicited.
One
In general, antagonism should not be initiated before at least ——, preferably —— or ——, responses are observed?
2 , 3 , 4
