Paralytics Flashcards
What receptors are the receptors for ACh on the neuromuscular end plate of skeletal muscle and preganglionic autonomics?
Nicotinic
What do drugs that cross the BBB result in? How about drugs that dont?
Central side effects, drugs that do not result in paralysis only
What are the two types of MOAs for drugs acting on the nicotinic receptor?
Direct = stimulate or block the receptor; Indirect = AChE inh increase the ACh at the receptors
What is the nicotinic ACh receptor?
A ligand gated Na+ channel that leads to membrane depolarization, 2 AChs required for activation
What are NMDs used for?
Muscle paralysis, NOT ANALGESIA therefore use for intubation or orthopedic procedures, also IV only
How do you test the extent of paralysis/durability of drug action?
By sending a current down the ulnar nerve and monitoring the electrical activity of the muscle twitch of the Adductor Pollicis (Or twitch of the eyebrow if facial nerve stimulated; or plantar flexion of great toe if Posteror Tibial stimulated)
Describe what happens during peripheral nerve stimulation and what fade is.
A train of four of sequential stimuli are sent and each causes a release of ACh; in absesne of NMB the first is as strong as the last; with NMB the fourth will be less than the first until eventually it does not twitch with the fourth stimulation. This is fade.
At what percent occupation will only the first twitch happen?
85-90%
At what percent occupation will 2-4 twitches happen?
70-85%
What is the desired number of twitches?
2-3; NMBs are titrated to this goal
What does use of Peripheral nerve stimulators do for ICU?
Reduces the amount of drugs used
What is Post-tetanic Potentiation (PTP)?
It is caused by prolonged stimulation which results in Ca2+ depended activation of PKC that can overcome paralysis by increased ACh vesicle release but it fades rapidly
What are the off target effects of paralytics?
Autonomic ganglionic effects (N, Cardiac M2, and Histamine release)
What is malignant hyperthermia?
It is genetic and AD, caused by uncontrolled release of Ca2+ from SR that causes rigor, increased CO2, increased lactic acidosis, very increased body temp and caused by succinylcholine and volatile anesthetics
How do you treat malignant hyperthermia?
Give the patient Dantrolene
What are some DDRs with NMBs?
Can interact with local and general anesthetics (malignant hyperthermia), ABX can cause prolonged blockade (aminoglycosides)
What is the MOA of all the Nondepolarizing paralytics? and what are they derived from?
They prevent the opening of the ACh receptor Na channel preventing the depolarization from occuring; it is competitive antagonist and are derived from Isoquinolone and Steroids
What drugs are classified as nondepolarizing?
Atracurium, Pancuronium, Vecuronium
What do nondepolarizing parylitics show on peripheral nerve stimulation?
With TOF stimulation these cause stepwise diminution of muscle twitch = fade, titrated to 2-3 twitches
How are nondepolarizing paralytics (other than DTC) distributed and eliminated?
Rapid distrubution, slow elimination (nonenzymatic elimination) and about 20-45 minutes
What drug are the potencies of all the other NMBs based off of?
D-Tubcurarine
How is DTC eliminated?
Renally, >50 minutes
What are the off-target effects of DTC?
Weak autonomic ganglion blockade and moderate histamine release
How is Atracurium metabolized/eliminated? and what are the consequences of it’s metabolite?
Hepatically metabolized into Laudanosine = seizures and histamine release and Hofmann elimination
What are the Nondepolarizing paralytics and what are they derived from? How are they all eliminated?
Pancuronium, Vecuronium; steroid derived; Hepatically and Renally
What is the off target effect of Atracurium?
Slight histamine release
What are the elimination time/route potency, elimination, and side effects of Pancuronium?
> 35 min, 6x DTC, 80% renal, and Moderate M2 cardiac blocking
What are the elimination time/route, potency, and side effects of vecuronium?
20-35 min, 90% hepatic, 6x DTC, and no off target effects
What is the MOA of the depolarizing paralytics?
Activates the channel causing a depolarization (contraction); but the drug persists on the binding site and blocks the channel from closing; inhibits repolarization which leads to paralysis
What will be seen with Peripheral nerve stimulation and depolarizing agents?
Phase 1: causes initial fasciculation (depol) that shows no fade then Phase 2 is a fade like non-depolarizing with flaccid paralysis
What do you not give depolarizing paralytics with?
A non-depolarizing agent
What is the sole depolarizing paralytic and what is it’s duration of action?
Succinylcholine; 5-10 minute duration
How is Succinylcholine metabolized?
Rapid hydrolysis by butyrylcholinesterase in liver and high capacity pseudocholinesterase in plasma therefore genetic variations in these cause changes in duration
How do you test the enzymes that metabolize Succinylcholine?
Dibucaine test
What is the potency of Succinylcholine and what are the off target effects?
.4x DTC and stimulation of autonomic nicotinic N-receptors and cardiac M2, slight histamine release
What are the ADE of Succinylcholine?
Arrythmias, HTN, hyperkalemia in large traume and neuromuscular dz (increase ACh receptor), prolonged paralysis (dibucaine test) increase ocular/cranial pressure (mannitol), Myalgia/Myoglobinuria, Anaphylaxis, and Malignant hyperthermia
What are the reversal agents MOA?
They are AChE inhibitors so ACh increases so it can outcompete the blockers.
What do you give reversal agents with?
Anti-cholinergic so you dont get SLUDGEBBB
What are the reversal agents?
Pyridostigmine, Neostigmine
What is the onset, duration, and coadministered drug with pyridostigmine?
20 min onset; 2 hr duration; Glycopyrrolate; NO BBB
What is the onset, duration, and coadministered drug with Neostigmine?
10 min onset; 1 hr duration; Glycopyrrolate; NO BBB
What do paralytic agents actually do and not do?
They only paralyze muscles by blockade of Nm receptor, they DO NOT provide pain or anxiety relief
How does succinylcholine differ from all of the other drugs?
It produces initial muscle contraction then flaccid paralysis and has distinct adverse effects
What are the two ways reversal is achieved?
Inhibition of AchE or through encapsulation of steroids (Sugammedex) which shifts the balance in favor of restoration of skeletal muscle function
