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
