Pharm Quiz #3 Flashcards
What is the pharmacologic effect of neuromuscular blocking agents?
interrupt nerve impulse transmission at neuromuscular junction
What are the two classifications of NMB agents?
- depolarizing
2. non-depolarizing
How does depolarizing agent provide NMB?
by mimicking acetylcholine (acetylcholine makes the muscle contract)
How does non-depolarizing agents provide NMB?
by blocking the actions of acetylcholine
The non-depolarizers in use today are primarily _____ acting and the two categories of them are….?
intermediate;
- benzylisoquinolinium
- aminosteroid compounds
What are some examples of benzylisoquinolinium NMB agents?
- nimbex
2. atricurium(nibex’s daddy)
What are some examples of amino steroid compounds?
- pancuronium
- rocuronium
- vecuronium
What are the 3 types of blocks?
- phase I
- phase II
- non-depolarizing block
How are NMB agents potency measured?
by ED 95; equal potency between NMB agents measured by dose required to suppress 95% of single twitch responses.
- ED95 measured under nitrous-barb-opioid anesthesia
- ED95 greatly reduced under volatile anesthesia
So the onset and duration of NMB is monitored by?
PNS
What are the principle sites of PNS and what are the characteristics of each?
- adductor pollicis(slow twitch)
2. obicularis oculi(fast twitch)
NMB affects _____ first and the _____ last.
- small, rapidly moving skeletal muscles first(eye lids)
- diaphragm last
What is the first muscle to return after NMB?
diaphragm
Non-depolarizing NMB onset is more rapid yet less intense at _____ muscle than the _____.
laryngeal; diaphragm
Laryngeal muscles(fast twitch) equilibrate more _____ with plasma NMB {} than slow twitch muscles(adductor pollicis).
rapidly
- acetylcholine receptor density greater with fast twitch muscles
- laryngeal muscle relaxation is brief(is declining by time of maximal diaphragmatic relaxation occurs)
Dose required to produce a degree of NMB at diaphragm is 2 X that required for an equal block at adductor pollicis or obicularis oculi. The _____ muscle the _____ it takes.
bigger, more
What muscle does PNS at the adductor pollicis best monitor?
diaphragm; poor indicator of laryngeal relaxation
What muscle does PNS at the obicularis oculi best monitor?
laryngeal
Single twitch response give?
POST-junctional data
Tetanus and TOF give?
data on POST-juctional membranes
Do you have fade with TOF using depolarizing NMB agents?
nope
What is the PNS indicator that differentiates between depolarizing NMB agents and non-depolarizing NMB agents?
TOF-NOT SINGLE TWITCH
What is Wedensky inhibition?
- a positive TOF fade seen when using non-depolarizing NMB agents.
- continous refractory state preventing repolarization; occurs when nerve is stimulated with high electrical frequencies and ends when application of current stops
NMB agents have quaternary ammonium groups which makes them(4)?
- unable to cross the BBB
- highly ionized
- water soluble at physiologic pH
- poorly lipid soluble
Poor lipid solubility gives NMB _____ volume of distribution.
small
What 4 lipid membranes are NOT crossed by NMB?
- BBB
- renal tubular epithelium
- GI
- placenta
So what is the summary of pharmacokinetics of NMB?
- no CNS effects(dosent cross BBB)
- oral absorption very poor
- not crossing renal tubular epithelium causes poor tubular reabsorption
- no placental crossing-no effects to the newborn
- plasme clearance, Vd, elimination 1/2 times influenced by: age, volatile agent, hepatic/renal disease
Are the pharmacokinetics altered by long acting NMB agents in patients with ESRD?
yes
Are NMB bound to plasma proteins?
NOT highly bound to plasma proteins
Describe the rate of disappearance of long acting NMB.
rapid initial decline by REDISTRIBUTION followed by a slower decline via CLEARANCE
What type of effects does inhaled anesthetics have on NMB?
minimal effects
With hypovolemia, equal drug doses produce _____ effects to due to greater plasma {}.
exaggerated
What are the 4 clinical uses of NMB agents?
- provide optimal conditions for laryngeal intubation
- improve surgical conditions during GA
- management of patients undergoing mechanical ventilation
- treatment of laryngospasm
What percent single twitch response is required for optimal surgical conditions with NMB?
90% suppression of single twitch response
-if patient has no twitches they are over paralyzed
How much ED95 dose of non-depolarizing NMB is required to aid laryngeal intubation?
2 X ED95(typically dose we give)
For laryngospasm, doses as small as _____ mg/kg of succinylcholine are effective.
0.1 mg/kg
TOF > then _____ provides adequate return of skeletal muscle strength for spontaneous ventilation.
Quiz Question
- 7
- if you wait until you have 4 twitches before reversing you will never take the “walk of shame”
4 additional indicators of muscle strength.
- grip strength
- sustained head lift
- VC
4 NIF
What is the only non-depolarizer NMB with onset similar to succinylcholine, by at an intermediate duration?
Rocuronium
reasons to use: securing airway, break laryngospasm, lead chest(maybe)
What factors determine depolarizer vs non-depolarizer?
speed of onset
duration of action
drug effects at other than NMJ
rapid onset-brief duration may indicate succinylcholine
What are 2 situations where a non-depolarizer might be used instead of a depolarizer.
- sustained NMB is needed
2. for GA when rapid intubation is not required
Neuromuscular blockers affect _____ moving muscles before muscles of the _____ & _____.
small rapidly moving muscles(eyes & digits) before muscles of the trunk and abdomen.
*the last muscles paralyzed are the intercostals and the diaphragm(skeletal muscle recovery occurs in reverse order with the diaphragm first)
Pre-treatment of NMB agents can produce:
- difficulty focusing
- mandibular weakness
- ptosis
- diplopia
- dysphagia
- decreased hearing due to middle ear muscle relaxation
Which NMB most resembles acetylcholine and how?
succinylcholine-2 molecules of acetylcholine linked by acetate methyl groups
What do quaternary ammonium compounds bind to?
Quaternary ammonium compounds with at least 1+ charged nitrogen atom binds to alpha subunit of post-synaptic cholinergic receptors.
Describe the structure of succinylcholine.
long, flexible, slender structure binds to and activated cholinergic receptors
Describe the structure of Non-depolarizing NMB.
bulky and rigid molecules that contain acetylcholine structures but can’t bind to & activate cholinergic receptors
Quaternary ammonium groups are found in _____ NMB.
all
Describe the structure of acetylcholine.
acetylcholine has a + charged quaternary ammonium group(4 carbons attached to a nitrogen) that attaches to negative charged cholinergic receptors.
Most NMB have bisquaternary ammonium structures. What does that mean?
Bisquaternary ammonium structures give electrical attractions between the 2+ charged areas of the NMB molecule and anionic groups at:
- NMJ cholinergic receptors
- Cholinergic receptors not @ NMJ(cardiac muscarinic & autonomic ganglia nicotinic receptors)
Is the pre-junctional nerve ending myelinated or non-myelinated?
non-myelinated
What do the non-myelinated pre-junctional nerve endings contain?
- mitochondria
- endoplasmic reticulum
- synaptic vesicles which make acetylcholine
What is the resting membrane potential across nerve/skeletal muscle membranes?
What maintains this resting membrane potential?
-90 mv;maintained by unequal distribution of K+ and Na+ ions across the membrane
Describe the 3 types of cholinergic nicotinic receptors found at the NMJ.
Two are at the post-synaptic on skeletal muscle surfaces
- post-synaptic junctional
- post-synaptic extra junctional
- pre-synaptic on the nerve ending
Where are post-synaptic receptors located?
in the junctional folds; opposite nerve ending sites where acetylcholine is released
What are some characteristics of extra-junctional receptors?
- not normally involved in nerve impulse transmission
- may proliferate in nerve or muscle damage
What is the characteristic of TOF twitches in phase 1 NMB in a depolarizing block?
constant by diminished twitches
What is the characteristic of TOF twitches in phase 2 NMB in a depolarizing block?
twitches with fade
What is a depolarizing phase II block related to?
usually due to a large dose or repeated dose of succinylcholine
What is the characteristic of TOF twitches NMB using a non-depolarizing block?
fade
What is the characteristic of tetanus twitches in phase 1 of NMB in a depolarizing block?
constant but diminished
What is the characteristic of tetanus twitches in phase 2 of NMB in a depolarizing block?
fade
What is the characteristic of tetanus twitches NMB using a non-depolarizing block?
fade
What is the characteristic of post-tetanic potentiation twitches of a phase I depolarizing block?
NO TWITCHES(absent)
What is the characteristic of post-tetanic potentiation twitches of a phase 2 depolarizing block?
present
What is the characteristic of post-tetanic potentiation twitches of a non-depolarizer block?
present
Should a phase 2 block be reversed?
typically don’t try to reverse a phase 2…its important to check twitches before giving a ND agent to make sure its not a phase 2 block
The neuromuscular junction neurotransmitter is?
acetylcholine
What is the classification of acetylcholine?
Quaternary ammonium ester
Acetylcholine in the motor nerve endings is made by what and controlled by what?
quiz question
made by acetylation of choline;controlled by the enzyme choline acetylase
Where is acetylcholine stored?
in the synaptic vesicles in motor nerve endings
How is acetylcholine released?
always on quiz
Released in synaptic cleft as packets or quanta-1000 molecules
How does acetylcholine cause a muscle contraction?
- nerve impulse arrives causing release of 100’s of quanta to bind to nicotinic cholinergic receptors on post-synaptic membranes causing membrane permeability change in ions.
- permeability change decreases transmembrane potential from -90 to -45 mV(threshold potential)
- at threshold potential, action potential spreads causing contraction
What is the receptor acetylcholine binds to on the post-synaptic membrane
nicotinic receptors
Where are nicotinic receptors located and what are they made up of?
- present in large numbers on post-junctional membranes
- proliferate in skeletal muscle with deficient nerve stimulation
- are 250K Dalton weight glycoproteins
Post-junctional nicotinic cholinergic receptors consist of how many subunits concentrically arranged?
5
What are the names of the 5 post-junctional nicotinic cholinergic receptors?
- alpha(x2)
- beta
- gamma
- delta
Where specifically at the post-synaptic junction are nicotinic cholinergic receptors located?
-located mainly on the shoulders of post-junctional membrane folds, exactly opposite pre-junctional acetylcholine release
Each neuromuscular junction has _____ of post-junctional receptors and a burst of acetylcholine opens at least how many receptors?
millions; at least 400K receptors
-currents flows through open receptors, depolarizes endplates, starting action potentials
What is the basis for neuromuscular transmission?
the flow of ions
In addition to binding acetylcholine, the 2 alpha units(alpha, beta, gamma, delta) are the sites of what?
sites of action for NMB drugs
Non-depolarsing NMB show preference for 1 of 2 alpha subunits
What is the result of occupation of the 1 of 2 alpha subunits by non-depolarizing NMB?
causes ion channel formed by receptors to remain closed
when we pretreat with a non-depolarizer(preventing fascinations)
-ion flow ends and depolarization can not occur
If 2 alpha subunits are occupied simultaneously, what happens?
ion channels opens and fasciculations occur
