Neuromuscular Blocking Agents Flashcards
what are the purposes of using muscle relaxants
- to offset muscle hypertonicity with ketamine (BZPs, alpha-2s)
- to relieve muscle spasms (BZPs)
- to facilitate smooth induction of anaesthesia in large animals (GGE)
- to improve surgical conditions –> deep general anaesthesia, local anaesthesia, centrally acting muscle relaxants, neuromuscular blocking drugs (muscle relaxants or NMBs)
how does blockade of transmisstion at the NMJ
3 ways
- local anaesthetics
- magnesium ions, aminoglycosides –> block Ca entry –> blocks Ach release
- neuromuscular blocking drugs target nicotinic acetylcholine receptors
what is competitive antagonist at the nicotinic Ach receptor
binds at same site at dynamic way and will compete
rigid bulky molecules with quaternary N (central N with 4 branches –> always +ve charged)
what needs to occur in competitive antagonists that block the nicotinic Ach receptor
need to block ~80% of receptor sites
in order to have a clinical effect
spare receptors –> more than needed to have action because there is excess amount of them
lots of Ach –> lots of competition
what are other methods of blockade
- nerve impulses blockade
- muscle can still respond to direct stimulation (electrically)
- some may block ion channels (at high conc. can block ion channels but not at normal therapeutic doses)
what is degree of blockade
blockade within a muscle cell is “all or nothing”
the degree of blockade represents the proportion of fibres blocked
if degree of increase tension is because of increased recruitment of muscle fibres
what are the effects of NMB
- flaccid motor paralysis
- respiratory muscles last to be affected and first to recover
*consciousness and perception of pain are normal –> never use alone always use anaesthesia + analgesia
what are unwanted side effects of NMB
- fall in BP: ganglion block/histamine release
- tachycardia: muscarinic receptor block –> increase HR due to decrease in BP and also because because muscarinic blockade can occur which decreases parasympathetic stimulation to heart
ANS coupling receptors = Ach (adrenergic + muscarinic) but nicotinic as well, can decrease tone and noradrenaline + adrenaline
histamine –> vasodilation
what is the pharmacokinetics of NMB (structure, administration, rate of onset, metabolization, distribution)
- most quaternary ammonium compounds
- administered IV
- rate of onset and duration vary
- generally metabolized by liver or excreted unchanged by kidney
- small volume of distribution (do not cross into protected organs –> CNS or placenta)
what are the two main groups of NMBs
- aminosteroids (-onium)
- benzylisoquinolines
what are the practical uses of muscle relaxants
- administered IV only
- will induce apnea –> mechanically ventilated
- only administered to anaesthetized patients
- no anaesthetic or analgesic effects
- can be topped up or given by IV infusion
what are the implications with respiratory muscles
respiratory muscles (diaphragm and intercostal muscles) are most resistant
last to become affected and first to start working again
muscle of control entrance to airway area highly sensitive –> possible for patient to start breathing again as relaxant effects wear off but not be able to maintain patient airway
what are the indications of use of muscle relaxants
- facilitate endotracheal intubation
- to relax skeletal muscle for easier surgical access
- control ventilation during anaesthesia
- ophthalmic surgery
how does recovery occur from NMBs
will occur spontaneously –> as plasma concentration of relaxant declines, drug will move down its concentration gradient from NMJ into plasma
eventually sufficient relaxant will have left to restore NM transmission
what are anticholinesterases
inhibit acetylcholinesterase (neostigmine, edrophonium)
Ach concentrations increase not only at the NMJ but throughout the body
what effect does anticholinesterases
bradycardia
salivation
bronchoconstriction
urination and defacation
what receptor does anticholinesterase act on
muscarinic
what are antimuscarinic drugs
because anticholinesterases have muscarinic effects they are often combined with antimuscarinic drugs (atropine, glycopyrrolate)
sometimes called anticholinergic drugs
what is sugammadex
novel antagonist to rocuronium/vecuronium
cyclodextrin molecule
surrounds relacant, rendering it inactive
no antimuscarinic needed
but expensive
what factors affect NM blockade
- other drugs –> anaesthetics, antibiotics, anticholinesterases
- pathophysiological conditions –> hepatic/renal impairment, age, temperature, acid base balance, electrolyte disturbances, myasthenia gravis (can affect NM blockade, autoimmune which destroys nicotine receptors)
what are centrally acting muscle relaxants
- benxodiazepines (diazepam, midazolam)
- guaifenesin (glycerol gualacolate) –> blocks impulse transmission at internuncial neurons within spinal cord and brain-stem –> relaxes limb > respiratory muscle, mild sedation, no analgesia
what are physiochemical factors
distribution influences how/where you give a particular drug –> the drug needs to get from the site of admin to its site of action
what are physiochemical factors of local anaesthetics
ionization status
ability to cross membranes (internal access to ion channel required)
what are physiochemical factors of NSAIDs
highly plasma protein bound
ability to cross membranes (intracellular enzyme target)
interspecies variability in metabolism
what are physiochemical factors of NMBs
charged so don’t cross membranes
must be given parenterally
don’t cross placenta or CNS
