Lec 32 Drugs Acting at the NMJ Flashcards
What is function of acetylcholinesterase inhibitors?
increase conc of ACh in cholinergic synapses [including NMJ]
What is pathology of myasthenia gravis?
autoimmune attack on postsynaptic NMJ
- against nicotinic ACh receptors
- against MuSK [kinase involved in AChR clustering
What is rate limiting step of AChE?
hydrolytic cleavage of acetyl enzyme bond = only 40 u-sec
What are the 3 classes of anticholinesterases?
- competitive: interact with ACh binding site
- carbamates: reversible inhibitors
- organophosphates: irreversible soon after binding, little clinical use, include sarin + insecticides
What are two different mechs of NMJ blockers?
non-depolarizing = competitive antagonists at ACh binding sites of nicotinic receptors
depolarizing = provide sustained membrane depolarization –> inactivation of voltage gated Na and Ca channels
What is the train of four?
- stimulation test to assess degree of paralysis induced by NMJ blocker
- calculate strength of 4th contraction divided by that of first
- non-depolarizing NMJ inhibit autoreceptors –> fade
- succinylcholine = no fade in phase 1, but does in phase 2
What is interaction general anesthetics and NMJ blockers?
- can potentiate NMJ blockers
What is malignant hyperthermia?
rare life threatening consequence of succinylcholine when administered with inhaled anestthetics
- treat wtih dantrolene
What is interaction NMJ blockers and antibiotics?
- antibiotics reduce stimulation-induced ACh release –> potentiate effect of non-depolarizing NMJ blockers
What are adverse effects of NMJ blockers?
- histamine release –> hypotension
- effect ANS ganglia
- effect cardiac muscarinic
- increase IOP –> contraindicated when anterior chamber of eye is open b/c of trauma
- post op muscle pain
Which NMJ in particular known to cause hypotension?
mivacurium
What should you pay attention to when giving NMJ blocker to pt with myasthenia gravis?
- more sensitve to NMJ blocker since fewer nAChR present
What should you pay attention to when giving NMJ blocker to pt with motor neuron disease?
- need higher dose of NMJ blocker due to denervation-induced up regulation of nAChR
What should you pay attention to when giving NMJ blocker to pt with reduced kidney or liver function?
recover more slowly
need lower dose for non-depolarizing drugs that are cleared by kidney/liver
How do you reverse non-depolarizing blockade?
- cholinesterase inhibitors + antimuscarinics to counter PNS side effects
- sugammadex for rocuronium
