Unit 06: Neuromuscular Blockers Flashcards
what are neuromuscular blocker agents
- obstruct transmission at the neuromuscular junction
- blockade is accomplished by structural analogues of acetylcholine that are administered intravenously in order to block transmission between motor neurons and skeletal muscle
compare Neuromuscular blocker antagonists and agonsits
antagonists = non deoplarizing block
agonists = depolarizing block
- patients are fully conscious when colinergic agetns are administered unless an anesthetic is used concurrently
- used in human surgery to increase muscle relaxation wihtout increasing anesthetic dosage, making them sake and resulting in fast recovery
what type of NM blocker agents are currently used
- only non depolarizing blockers
- can achieve complete muscle relaxation wihtout need for higher anesthetic doses making them safer with faster recovery times than using a higher anesthetic dose
- can also be used to facilitate endotrachael intubation, mechanical ventilation and manipulation of limbs during facture repaid
how were non-depolarizing blockers are used isolated and whats the active chemical
first isolated from curare from a south american poisonous vine
- active chemical isolated = d-tubocurarine
what does tubocurarine cause
- causes NM blockade and induces histamine release and lowers blood pressue
what is pancuronium
- replaced tubocurarine but tends ot be vagolytic (inhibits pSNS signaling in the vagus nerve causing increased HR)
- has been replaced with rocuronium, mivacurium and atracirium
what is atracurium
NM blocker agent
- used to prevent eye movement during ocular surgery
- chemically similar to acetylcholine and competitively blocks nicotinic receptors at neuromuscular junction
- causes intense relaxation or paralysis of voluntary muscle
- intensity of effect depends on dose
- safer than other non depolarizing blockers like tubucurauine and pancuronium and depolarizing blockers like succinyl chlone which is now barely used
describe the pharmacokinetics of atracurium
- must be injected IV bc positively charged and highly polar 9does not readily corss membranes)
- maximum block occurs in approx 3 min and duration varies with dosage (20-30min to an hour)
- emtabolized in blood by plasma esterases and can be injected to maintain relaxation wihtout extending recoery time
- main advantage = rapid reversal can be achieved with drugs that inhibit acetylcholine esterase like neostigmine and edrophonium
how can you quickly reverse effects of atracurium
rapid reversal can be achieved with drugs that inhibit acetylcholine esterase, such as neostigmine and edrophonium
disadvantage of atracurium
- can trigger histamine release and must be taken with caution in patients with asthma or cardiovascular disease
- when metabolized can trigger seizures (rarely)
- can now use cisatracurium instead- same advantages but less liekly to cause adverse effects
what do NM blcokers do?
do NOT produce analgesic effects, just immobilzie the patient
- be careful bc they can cause dose dependent paralysis of voluntaru muscles of respiration
what si the stepwise action of NM blockers?
- order of muscle paralysis following NM blockers is:
1. Extraocular (main use)
2. Neck, head, face, hands and feet
3. Abdomen, arms and legs
4. Eyeblink
5. Respiratory and diaphragm
*recovery occurs in reverse order

what are local anesthetics
- set of locally applied chemicals with similar molecular structures that can both inhibit the perception os sensations (like pain) and prevent movement
- can be topical applicationf or bruns/cute or injections during dental care, epidural and intrathecal (spinal) blocks during obstertric prodecures and major surjery
what was the first local anesthetic used
cocaine
- current agents are derivatives of cacain that do not produce euphoria - inhibit pain without causing a stimulation high or unconsciousness
what are the two main categroies of local anesthetics
esters and amides
- esters: short duration of action bc metabolized locally and in blood plasma by pseudocholinesterase
amides: newer drugs that are more stable and have longer duration of action
*local anesthetics are weak bases that are less effective in acidic tissue which would occur during inflammation or ifnection bc cant cross cell membranes to reach the cytoplasmic surface of therapeutic target: voltage sensitive Na+ channels
how do local anesthetics exert theri effects
block voltage gated sodium channels so Na+ cannot enter the cell, inhibits the propogation of action potentials along neurons
- sall fibers such as those assocaited with pain re lbocked at lower concentrations and motor fibers are blocked last
analgesics vs local anesthetics
- analgesics inhibt the generation of pain signals (opioids) while local anesthetics inhibt the transmission of signals related to all sensation and motor activity (ex: lidocaine)
MOA of local anesthetics
- act by binding to cytoplasmic (intracellualr) side of voltage gated Na+ channel
- hydrophobicity determines how efficiently it diffuses across lipid membranes and how tightly it binds to Na+ channel (governs the potency
poorly hydrophobic LA are unable to cross lipid bilayer efficiently
compare local anesthetics hydrophobicity of poorly hrdrophobic, moderately hydrophobic and extremely hydrophobic
Poorly Hydrophobic
- unable to corss lipid bilayer efficiently
- (1) Neutral La cannot absorb to or enter the neuronal cell membrane bc the LA is very stable in the extracellualr solution and hs high activation energy for entering hydrophobic membrne
Moderately hydrophobic
- most effective agents
- (1) neutral La absorbs to extracellular side of neuronal cell membrane
- (2) La diffuses throguh the cell membrane to the cytoplasmic side
- (3) La diffuses and binds to its bidnign site on voltage gated sodium channel
- (4) once bound can switch between neutral and protonated forms by bidning and realsing proteons
Extremely hydrophobic
- become trapped in lipid bilayer
- (1) neutral La absorbs to neuronal cell membrane
- (2) it is so stablized that it cannot dissociate from or trnaslocate across the membrane

vasconstrictors and local anesthetics
- local anesthetics block sodium gated ion channels until they diffuse into the sytem circulation
- vasocontrictors like epinephrine can be sued in combination with local anesthetics to slow down removal of the drug and prolong its action
- this can delay tissue healing due to reduced blood flow
- vasoconstrictors are also not used where an end-artery supplies an organ (sug as in digits, ears, noe and penis) bc they could cause ischemia which can lead to tissue necrosis
what is skin necrosis
- tissue death
- can occur when lidocaine and epinephrine are administered in combination subcutaneously
- some practitioners will not use these products together bc of this risk
systemic effetcs of local anesthetics
- occur if level in circualtion are high enough
- occur primarily in the CNS and the cardiovascular system
- in CNS as the dose increases local anesthetics can cause rowsiness then excitation which may or may not induce seizures
- decreased excitability of the myocardium can occur, may cause an atrioventricular block and arrhythmias
- in extream cases cardiac arrest an result- requires plasma drug conc that would noly arise form accidental bolug delivery to the heart
cocaine as an anesthetic current use
- still used topically in more than 50% of rhinolaryngologic (nose and thraod) cases for examination and repair wound of children
- applied to the oral/nasal muscosa for the nose and throat procuedures due to ecellent penetration and sympathomimetic action inhibits NE re-uptake causing vasoconstriction amkign it easier to see
- cocaine is evry irritating to tissues and can rpoduce severe cardiovascular toxicity including hypertension, arrhythmias and cardiac arrest