Lecture # 06_Fall Flashcards
When a nerve depolarizes, ___ ions enter the neuron and ___ is released from vesicles and binds to ___ receptors on the motor-end plate of the muscle fiber
Ca ions enter, Ach is released, binds to nicotinic cholinergic receptors
Ach is hydrolyzed by ____ into ____ and ____.
Acetylcholinesterase, acetate and choline
Select the correct option.
Depolarizing NMBAs act as Ach receptor _____ (agonist or competitive antagonist).
agonist
Select the correct option.
Non-depolarizing NMBAs act as Ach receptor _____ (agonist or competitive antagonist).
competitive antagonist
T or F. Phase I and Phase II blocks are seen with non-depolarizing NMBAs.
False. They refer to the blocks seen with depolarizing NMBAs.
NMBAs are quaternary ______ compounds with afinity for _____ Ach receptors.
ammonium, nicotinic
A Phase II block resembles a ___ block.
non-depolarizing
What % of receptors must be blocked before you observe fade with a twitch monitor?
> 70%
What % of receptors must be blocked for complete twitch suppression?
> 90%
What is responsible for the metabolism of sux?
plasma pseudocholinesterase
What happens if you try to reverse a Phase I block with an AchE inhibitor?
can lead to prolonged depolarization
What is Dibucaine
it is a local anesthetic that inhibits pseudocholinesterase
What is A Dibucaine Number?
It is the % of pseudocholinesterase that is inhibited by dibucaine
What is a normal Dibucaine number?
80 = normal
What would a dibucaine number of 0-20 indicate?
a homozygous abnormal pseudocholinesterase gene that will result in prolonged NMB with Sux, lasting 4-8hrs
What would a dibucaine number of 40-60 indicate?
a homoheterozygous abnormal pseudocholinesterase gene that will result in prolonged NMB with Sux, lasting 20-30min
Pesticide toxicity resembles the effects of what drugs?
resembles the SLUDGE effects of AchE Inhibitors like Neostigmine
T or F. Pancuronium can prolong the depolarizing block of Sux.
True - Pancuronium inhibits pseudocholinesterase
T or F. Low doses of Sux causes tachycardia.
False. It binds to muscarinic cardiac Ach receptors - causes bradycardia and decreased myocardial contractility. Opposite at high doses
Why is hyperkalemia a side effect of Sux?
Due to the sustained opening of ion channels and membrane depolarization
Sux increases serum K+ levels by ___ mEq/L
0.5 mEq/L
How does neural injury lead to significant K+ release with Sux?
Rapid proliferation of extrajunctional ACh receptors with neural injury (trauma, denervation) - Widespread depolarization leads significant K+ release
Which of the following side effects associated with Sux can be attenuated with a defasciculating does of non-depolarizering MRs? (select all that apply)
A. Myalgias B. Increased ICP C. Increased IOP D. Hyperkalemia E. Increased Gastric Pressure
A. Myalgias - Yes B. Increased ICP - Yes C. Increased IOP - NO!! D. Hyperkalemia - NO!! E. Increased Gastric Pressure - Yes
A Phase II block will be seen after ___mg/kg IV Sux.
7-10 mg/kg or 30-60 min
- or after a single dose in pts with atypical plasma cholinesterase
Which of the following increases risk of succinylcholine induced hyperkalemia (Potential risk within 96 hours, peaks ~7-10 days after injury, lasts 6 months or longer)?
A. 3rd degree burn injury B. Massive skeletal trauma C. Upper motor neuron injury D. Denervation muscle atrophy E. Myopathies (myotonia, muscular dystrophy)
All of them
Inhalational anesthetics ____ the onset of a Phase II block.
accelerate
Succinylcholine-induced MMR can lead to _____.
rhabdomyolysis
What are the 6 ABSOLUTE contraindications for succinylcholine?
ABSOLUTE contraindications include: 1, MH 2. dangerously elevated serum K+ 3. known myotonia or muscular dystrophy 4. >2-4 days after CNS injury (stroke, cord injury) 5. massive musculoskeletal injury 6. major burn
What are 2 signs of rhabdomyolysis?
myoglobinuria and myoglobinemia
What are the 2 classes of Non-Depolarizing Neuromuscular Blocking Agents?
Benzoisoquinolines (“-acurium”) or steroidals (“-curonium”)
What is the Priming dose of Non-Depolarizing Neuromuscular Blocking Agents?
Priming dose: give 10% of intubating dose 5 min before induction
What is the Defasciculating dose of Non-Depolarizing Neuromuscular Blocking Agents?
Defasciculating dose: give 10% of intubating dose 5 minutes before succinylcholine
___, ____, ___, and ___ potentiate the action of Non-Depolarizing NMBAs.
- inhalational anesthetics (DES > SEVO > ISO > HAL)
- antibiotics (aminoglycosides – prolong
steroidal NMBs) - phenytoin
- Mg
___, ____, ___, and ___ prolong the action of Non-Depolarizing NMBAs.
hypothermia, acidosis, hypokalemia, and hypocalcemia
Muscles of glottis, face, airway, diaphragm are ___ sensitive to NMB than the thumb (adductor pollicis) so the dose to block diaphragm is ___ the dose needed to block adductor pollicis.
less, twice
Cisatracurium is metabolized by _____.
Hoffman Elimination
Atracurium (isomer of cisatracurium) is degraded by ___ AND _____ by
non-specific plasma esterases
Hoffman elimination AND ester hydrolysis
What is the must common paralytic used in renal failure patietns and for ICU infusions?
Cistatracurium
Which paralyzing agent is metabolized by pseudocholinesterase but no longer available?
Mivacurium
Which paralyzing agent should be used with caution in renal failure patients and why?
Pancuronium - 40% renally cleared – caution in renal failure
What CV effect does Pancuronium have?
Increases in HR, BP, CO (block cardiac
muscarinic ACh receptors)
What is the best non-depolarizer for rapid sequence intubation?
Rocuronium
What is the onset time and duration of Vecuronium?
Onset = 3-4 min Duration = 35-45min
What is the onset time and duration of Rocuronium?
Onset = 2 min Duration = 30-40min
What is the onset time and duration of Nimbex
Onset = 2-4 minutes Duration = 35-40 minutes
What percent of Vecuronium is renally cleared?
25%
How do reversal agents work?
Cholinesterase (AChE) Inhibitors (“Anticholinesterases”) - Indirectly increase amount of ACh in the NMJ which can compete with the non-depolarizing NMB agent
T or F> Organophosphates (pesticides) are also anticholinesterases.
True
AChE inhibitors are used in the diagnosis of ____.
myasthenia gravis
In excessive doses, AChE inhibitors can cause_____ leading to ____.
ACh-mediated blockade, weakness
T or F. Bronchospasm is a side effect of AChE inhibitors.
True
___ is the only AChE inhibitor that crosses the Blood-Brain Barrier.
physostigmine
Which anticholinergic agent crosses the BBB?
Atropine
A pt with TOF with fade should get a ___ reversal dose.
Full
A pt with TOF without fade should get a ___ reversal dose
partial
When would you consider giving no reversal?
If the pt has sustained 5 sec tetanus or clinical evidence of adequate strength
List the clinical signs of adequate strength in order from best to least acceptable.
Sustained head lift / leg lift > negative inspiratory force > vital capacity > tidal volume
A p with post-tetanic twitch or no tetanic response should get a ___ reversal dose.
They should not get any reversal - they are unreversible at this point
Post-tetanic count correlates with ____.
time until spontaneous recovery
Reversal agents have ____% Hepatic and ____% renal clearance.
Hepatic (25-50%) and Renal (50-75%)
What is the max dose of Neostigmine for adults?
5mg
Which reversal agent should be given with atropine and why?
Edrophonium: rapid onset of action (1-2 minutes) and short duration of effect - Give with atropine – better match with onset, duration
When would you consider using atropine with neostgmine instead of glycopyrrolate?
When you are concerned about it crossing the placenta
_____ is a tertiary amine that crosses blood-brain barrier and is used as treatment for central cholinergic toxicity
Physostigmine
T or F. You do not have to give atropine / glycopyrrolate with Physostigmine.
True
Physostigmine is metabolized by ____.
plasma esterases
_____ can be used to reverse deep NMB from non-depolarizing agents, although it is not currently approved for use in the US.
Sugammadex
Sugammadex only works on non-depolarizing NMBAs with a ____ nucleus, such as ___, ____, and ___.
Steroid, Rocuronium, Vecuronium, and Pancuronium
______ could be used with rocuronium for RSI – replace succinylcholine- which would be a huge benefit due to all the contraindications associated wit Sux.
Sugammadex
If you couldn’t tell by my 3 flashcards, this is sort of important to know!
___is an autoimmune neuromuscular disease where circulating antibodies block Ach receptors at the postsynaptic NMJ and cause muscle weakness.
Myasthenia Gravis
What should you remember about NMBAs in patients with Myasthenia Gravis?
They are Resistant to Sux and Sensitive to non-depolarizers (like Roc)
so you can remember this with:
“R to S and S to R”
What is Myotonia?
abnormal delay in muscle relaxation after contraction
What should you remember about NMBAs in patients with Myotonia (many types)?
They will have:
SUSTAINED contracture leading to hyperkalemia with SUX
A Normal response to Non-depolarizers
so you can remember this with:
“S with S and N with N”
What should you remember about NMBAs in patients with Muscular Dystrophy, a disease that causes loss of muscle mass?
First, it is often latent and undiagnosed in patients <10y old (esp. males)
They have a normal response to non-depolarizers
BUT Sux can cause hyperkalemic cardiac arrest
This is why we avoid using sux in children
What should you remember about NMBAs in patients with Upper Motor Neuron Lesions: hemiplegia, quadriplegia?
starting ~2-4 days after injury for up to 6-12 months use of Sux will cause hyperK
And they have a resistance to non-depolarizers below the level of the lesion
What should you remember about NMBAs in burn patients?
They are Sensitive to Sux b/c they have a proliferation of extra-junctional Ach receptors
(sux will cause hyperK starting ~2-4 days after the burn for at least 12 months)
They are Resistance to non-depolarizing agents (Roc)
so you can remember this with:
“S to S and R to R”
