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
what is procaine
- first cocaine substitute
- main local anesthetic until lidocaine
- known as Novocain and still used but less frequently
- problem is that its an ester which is cleaved by plasma esterases and has a short duration of action (15-60min)
esters are more allergenic then amides but are sometimes still use wen rapid onset but short duration is desired
what is lidocaine
- most widely used local anesthetic
- numerous routes of administration and applications
- overdose can cause drowsiness or seizures, muscle twitching, possible cardiac arrest and death
- usualy administered via injection and has duration of action of 30-60 min
- onset following infiltration is approx 3 min
what is bupivacaine
- antoher widely used local anesthetic
- slower onset (15min) but logner duration (2-4 hours)
- longer effects come with greater cardiovascular toxicity if an IV bolus forms, can cause severe ventricular arrhythias
- lecobupivacaine is the s(-) enantiomer and does not dsitribute well to CNS and heart
- **levobupivacaine has replaced bupivacaine for regional, IV use in human medicine.
describe clinical use for local anesthetics
- used for local loss of sensation rather than unconsciousness
- they are safer then general anesthetics
- can be administers numberous ways
what ir surface anesthesia
refers to a topical gel that lasts less than an hour and can penetrate a few millimeters.
Without epinephrine, they increase blood flow to skin which improves perfusion of burned skin and results in better healing.
what is infiltration anesthesia
involves subcutaneous injection, and epinephrine doubles the duration. Large doses may be toxic but it is uncommon.
what is a field block
very similar to infiltration anesthesia, but the goal is to prevent pain signals coming from “upstream” sites.
During a nerve block, the drug is injected in the vicinity of the nerve which may be superficial or deep.
Less drug is needed compared to infiltration anesthesia, however the technique requires good anatomical knowledge.
describe intravenous injection of local anesthetic
involves a tourniquet to keep the drug in a limb.
This is often used during bovine digit surgery or human arm/hand surgery.
what is an epidural
- way to use lcoal anesthetic
injection into the epidural space and commonly used agents are lidocaine, mepivacaine, bupivacaine or opioids.
This blocks action potentials approaching the spinal cord in peripheral nerves.
The agent will also diffuse across the dura into subarachnoid space and is used for the management of pain in caudal body structures.
what is a paravertebral procedure
involves injecting the drug where the nerve leaves the vertebral foramen, and is used during bovine standing surgery.
describe systemic IV lidocaine
inhibits depolarization of cardiac myocytes.
“Premature” action potential that originates in damaged cardiac muscle is blocked at low drug concentrations based on a use-dependent blockade.
An excessively high dose may cause arrhythmias which can result in death.
It is also used as a component of mixed anesthesia protocols, however not in combination with epinephrine-containing products to avoid arrhythmias.
