Term
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Definition
Non-depolarizing NM blocking Agent
-long-acting agent
-charged (can't cross BBB so won't effect CNS)
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
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Term
|
Definition
Non-depolarizing NM blocking Agent
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
|
|
Term
|
Definition
Non-depolarizing NM blocking Agent
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
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Term
|
Definition
Non-depolarizing NM blocking Agent
-short acting
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
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|
Term
|
Definition
Non-depolarizing NM blocking Agent
-longest acting agent
charged (can't cross BBB so won't effect CNS)
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
|
|
Term
|
Definition
Non-depolarizing NM blocking Agent
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
|
|
Term
|
Definition
Non-depolarizing NM blocking Agent
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic |
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|
Term
|
Definition
Depolarizing NM blocking Agent
-ultrashort acting agent
-it's two ACH molecules linked together
-binds to M and N receptor
-acts like ACH but produces longer effect at the NMJ
-resistant to hydrolysis by AChE in the NMJ
-metabolized by butyrylcholinesterase in plasma and liver
2 phases of block:
1. phase 1 block (prolonged depolarization
2. phase 2 block (desensitizing)
Clinical use:
-relax skeletal m. for surgical procedures and tracheal intubation
-prevent fracture and dislocations associated with ECT (electroconvulsive shock therapy)
-control muscle spasms of tetanus
-sustained NM blockade in critically ill patients
*good to use when patient needs to be intubated quickly*
-doesn't enter CNS, doesn't affect sensory neurons (so can feel pain), NOT anesthetic or analgesic
adverse effects:
-rapidly metabolized by plasma and liver butyrylcholinesterase (genetic variants or poisioned enzyme may give prolonged effects)
-bradycardia (initial agonistic muscarinic effect)
-post-op muscle pain (can stop fasiculations and thus pain by giving small dose non-depolarizing muscarinic blocker before give succinylcholine
-stimulates histamine release
-hyperkalemia (if increase K a lot then can get cardiac arrhythmia and die)
-malignant hyperthermia
-excessive Ca+2 release from the SR |
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Term
| what's the MOA for the non-depolarizing NM blocking agents? |
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Definition
| competitive antagonists of the nAChR in the NMJ (Nm) |
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Term
| What's the sequence of paralysis in the non-depolarizing NM blocking agents? |
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Definition
flaccid paralysis of muscles:
1. eyes-->face
2. limbs-->abdominal-->intercostals-->diaphragm (last)
*function recovered in reverse order |
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Term
| How can you reverse the effects of pancuronium? |
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Definition
AChE inhibitor
-get more ACH in NMJ when want it there; if gave nicotinic agonist would be stimulating the receptor all the time |
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Term
| what happens to the muscle if there is a prolonged depolarization at the NMJ? |
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Definition
fasiculations; can't repolarize; EC coupling requires end plate repolarization and repetitive firing to maintain muscle tension
end result: flaccid paralysis |
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Term
| what's the MOA of phase 1 block for succinylcholine? |
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Definition
-initial action
-depolarizes the membrane by opening the channel in the same manner as ACh
-resistant to AChE so persists for a longer duration
-brief period of repetitive excitation that may elicit transient m. fasiculations
-followed by depolarization block of NM transmission and flaccid paralysis |
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Term
| will neostigimine (reversible AChE inhibitor) reverse the effects of succinylcholine? |
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Definition
NO
don't want to add more ACH?
..later in phase 2 succinylcholine acts like non-depolarizing blocker and neostigmine might reverse the effects of succinylcholine |
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Term
| what's the MOA for phase 2 block for succinylcholine? |
|
Definition
continual exposure-->membrane gradually depolarizes, but it's also desensitized--> can't easily be depolarized again
later in phase 2 it acts like a non-depolarizing blocker
-with high doses or continuous exposure
-initial depol is followed by a gradual repol
-this repol, in many respects resembles receptor desensitization
-more like competitive inhib in phase 2
-cholinesterase inhibitors MAY reverse
-can directly stimulate muscle by electrical input |
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Term
| Adverse effects of non-depolarizing blockers? |
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Definition
*variable depending on agent used
histamine release, block autonomic ganglia, block muscarinic receptors |
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Term
| what effect can histamine have on the CV system? |
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Definition
| hypotension (b/c causes VD via NO bindin to endothelial cells) |
|
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Term
| what effect can histamine have on the lungs (especially in asthmatics)? |
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Definition
bronchoconstriction
(bronchial smooth m. receptors-->Gq--> increase Ca+2, etc) |
|
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Term
| what effect can ganglionic blockade have on the CV system? |
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Definition
| Hypotension (block sym to BV and get lots of VD) |
|
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Term
| what effect can muscarinic blockade have on the CV system? |
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Definition
|
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Term
| Summarize the NMJ in healthy muscle |
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Definition
when the nAChR opens, it allows the passage of K and Na ions across the membranes; this generates Na and K currents, but since the Na current predominates, an excitatory postsynaptic potential is generated
(succinylcholine binds to the nAChR and net effect is inward Na+ current) |
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Term
| Summarize the hyperkalemic effect of succinylcholine |
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Definition
occurs most often in patients with burns, severe muscle trauma, upper or lower moter neuron denervation (e.g. stroke or spinal cord injury, respectively) and prolonged ICU care (bed rest, steroids, prolonged NM blockade)
-this causes denervation sensitivity: -->upregulation of the nAChR, which results in an increase in their density and they spread over the muscle surface outside of the motor endplate area; there is also a change in the subunit type
-->when the NMJ is exposed succinylcholine, more ion channels become available to release K during depolarization
-when large muscle groups are involved, there can be massive efflux of K ions from the muscle cells causing marked hyperkalemia
-this can precipitate severe cardiac events, including cardiac arrest (be careful with heart failure patients on digoxin or diurietics) |
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Term
| Describe the adverse effect of malignant hyperthermia in succinylcholine |
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Definition
-genetic disorder of skeletal m.(e.g. mutated RyR)
-one of the main causes of death due to anesthesia
-triggered most often by a combination of anesthetics and succinylcholine |
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Term
| What are the side effects involved with the adverse effect of excessive Ca+2 release from the SR with succinylcholine? |
|
Definition
-rapid hyperthermia and metabolic acidosis
-tachycardia
-muscle rigidity
-accelerated muscle metabolism and contractures
-potentially fatal
-treat symptomatically and with DANTROLENE |
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Term
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Definition
RyR inhibitor (prevents Ca+2 release from SR)
-used to counteract the adverse effect of excessive Ca+2 release from the SR with succinylcholine use |
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