Neuromuscular blocking drugs Flashcards
The main site of action of neuromuscular blocking agents (muscle relaxants) is on the?
Nicotinic cholinergic receptors at the endplate of muscles
Is a blocking agent that produces depolarization
at the endplate and binds to extrajunctional receptors..
Succinylcholine
The TOF fade is difficult to evaluate manually or visually during recovery when TOF ratio is >
0.4
When using mivacurium, reversal with anticholinesterases should be attempted only when all four twitches in response to TOF stimulation are visible at what muscle?
Adductor pollicis muscle
Most widely used measurement for awareness
Bispectral index
Threshold for complete neuromuscular recovery is a train-of-four (TOF) ratio of?
0.9
The terminal portion of the axon is a specialized structure, designed for the production and release of acetylcholine.
Synapse
The synapse is separated from the endplate of the muscle fiber by a narrow gap, called?
Which is approximatelywhich is approximately how wide (nm or um)
Synaptic cleft
50 nm or 0.05 um
Under resting conditions, the electrical potential of the inside of a nerve cell is negative with respect to the outside which is how much mV?
-90 mV
Acetycholine is released in?
Quanta or packets
Acetylcholine is synthesized from choline and acetate and packaged into __ vesicles
When an action potential invades the nerve terminal, approximately ____ quanta are released, unloading approximately ____ acetylcholine molecules?
45 nm
200 to 400 quanta
1 to 4 million
Each vesicle contains ____ acetylcholine molecules.
5,000 to 10,000
Some of these vesicles cluster near the cell membrane opposite the crests of the junctional folds of the endplate, in areas called?
active zones
Neuromuscular blocking agents functions (3)
- Improve conditions for tracheal intubation
- Provide immobility for surgery
- Facilitate mechanical ventilation
Suggamadex is a selective binding agent for NMBAs such as (2)
- Rocuronium
2. Vecuronium
The main site of action of NMBAs is on the?
Nicotinic cholinergic receptor
Is a specialized portion of the membrane of the muscle fiber where nicotinic acetylcholine receptors are concentrated
Endplate (especially at the crest of the folds)
Calcium, which enters the nerve terminal through channels that open in response to depolarization, is required for ____________ and ________.
Vesicle fusion and release
Each impulse releases ___% to ____ % of the 75,000
to 100,000 vesicles in the nerve terminal.
0.2% to 0.5%
The receptors at the endplate are of the nicotinic cholinergic type.
They are members of the class of _____ ion channels, to which glycine, 5HT3, and GABA receptors belong.
Cysloop ligand gated
The nicotinic subtype present at the neuromuscular junction is made up of two identical subunits, designated _, and three others, called _, _, and _.
a, and three others, called B, S, and E
The muscle action potential has a duration of ___ ms?
5 to 15
Early in development, receptors are slightly different from those found at the adult endplate: They have a ___ subunit instead of an E subunit.
y subunit (fetal receptors) instead of an E subunit
As maturation continues, the y subunit is substituted by an E subunit, which is characteristic of the adult type, junctional receptor. In humans, the switch occurs in the ___ trimester of pregnancy.
third
Is determined by constructing dose-response curves, which describe the relationship between twitch depression and dose
Potency
Or time to maximum blockade, can be shortened if the dose is increased. When two or more drugs are compared, it is meaningful to compare only equipotent doses and usually clinically relevant doses (2 × ED95) are considered.
Onset time
Is the time from injection of the neuromuscular
blocking agent to return of 25% twitch height (compared with control).
Duration time
Is the time interval between 25% and 75% twitch height.
Recovery time
After 30 to 60 minutes of administration of succinylcholine, tetanic fade becomes apparent. However neostigmine or edrophonium can antagonize this block which is termed as?
nondepolarizing, dual, or phase II block
2 effective defasciculating agents for succinylcholine
- Rocuronium (0.03 - 0.04 mg/kg)
2. Atracurium (0.02 mg/kg)
Intraocular pressure increases by ___ to ___ mmHg after succinylcholine administration
5 to 15
Serum potassium increases by ___ mEq/L after succinylcholine administration
0.5 mEq/L
Plasma cholinesterase activity is reduced by what 2 drugs?
Neostigmine and pyridostigmine
Cholinesterase gene is located in?
chromosome 3 at q26
Nondepolarizing neuromuscular blocking drugs bind to the ______receptor in a competitive fashion, by binding to one of the ___ subunits of the receptor
postsynaptic
a
The volume of distribution of non-depolarizing agents is equivalent o the ECF volume which is about?
0.2 to 0.4 L/kg
Is determined by the time required for drug concentrations at the site of action to reach a critical level, usually that corresponding to 100% block
Onset time
This delay reflects the time required for drug transfer between plasma and neuromuscular junction and is represented quantitatively by a rate constant (keo). This rate constant corresponds to half-times of 5 to 10 minutes for most nondepolarizing drugs and is determined by all the factors that modify access of the drug to, and its removal from, the neuromuscular junction. These include cardiac output, distance of the muscle from the heart, and muscle blood flow. Thus, neuromuscular blockade usually occurs sooner at well-perfused centrally located muscles (diaphragm or vocal
cords) than at peripheral locations (hand or foot).
Is determined by the time required for drug concentrations at the site of action to decrease below a certain level, usually corresponding to 25% first twitch blockade.
Duration of action
A nonenzymatic degradation with a rate that increases as temperature and/or pH increases.
Hoffman elimination
The enzymes involved in the metabolic pathway of atracurium involves?
The same in the degradation of what two drugs?
Tissue esterases
Esmolol and ramifentanil
The end products of the degradation of atracurium are:
laudanosine (seizures) and acrylate fragments
Main degradation pathway of gantacurium?
cysteine
Most potent metabolite of vecuronium
3-OH vecuronium
