T3 Komiskey - Neuromuscular Blocking Agents

Front 1

name the main ingredient that was used in curare blow dart poison; it is the prototype neuromuscular blocking drug.

Back 1

tubocurarine

Front 2

what neurotransmitter is responsible for eliciting a muscle contraction on striated muscle?

Back 2

Ach

Front 3

what type of receptors are in the somatic nervous system (on muscle)?

Back 3

nictoinic ACh receptors

Front 4

an influx of what causes the depolarization and releases the vesicles full of ACh?

Back 4

Ca2+

Front 5

there are two types of nicotinic ACh receptors (neural nicotinic and muscular nicotinic), what makes them different from eachother?

Back 5

subunit composition, affinity for drugs, use different ligands (but must be cations);

Front 6

describe the shape of almost all agonist and antagonist to the nicotinic Ach receptor.

Back 6

quaternary ammounium compounds

Front 7

how many subunits make up the nicotinic receptor?

Back 7

five (usually the types of subunits are mixed - alpha, beta, etc.)

Front 8

in muscle there are four types of subunits with alpha repeated twice; which subunits do Ach bind to?

Back 8

Ach binds to each alpha subunits (in nerve there may only be alpha, or a mix of alpha and beta)

Front 9

explain how the nicotinic receptors work.

Back 9

at rest the gate is closed; when ACh attaches to its alpha subunits, the gate opens and allows ions to pass

Front 10

there are two major subdivisions of neuromuscular blocking agents, nondepolarizing and depolaring blocking agents. what is the difference in their MOA?

Back 10

NONDEPOLARIZING (tubocurarine, pancuronium, atracurium, vecuronium): competitively block ACh from binding; (antagonists at the nico. receptor; all or none: dose response curves are very steep) and DEPOLARIZING: drug directly binds and opens Na+ channels causing depolarization followed by flaccid paralysis; it also desensitizes the receptor to ACh (SUCCINYLCHOLINE is the only depolarizing agent)

Front 11

are all muscles equally effected?

Back 11

no. the muscles of the eye and face are affected first and respiratory are affected last. thus muscles of respiration have the greatest "receptor reserve"

Front 12

released ACh acts retrogradely on presynaptic neuronal nicotinic receptors. can these presynaptic receptors be blocked?

Back 12

yes; (also, know that the amount of Ach that is released in the nerve terminal is finite and each subsequent release of ACh is not in the same amount)

Front 13

list some adverse effects of tubocurarine (nondepolarizing agent).

Back 13

blocks ganglia and lose control of BP; affects muscarinic receptors - lose parasympathetic control and get tachycardia; releases histamine (hypotension, bronchoconstriction, anaphylaxis); long duration of action (over 30 min) this is too long to use for short procedures such as RSI (rapid sequence intubation)

Front 14

when choosing a muscle relaxant, what do you think of?

Back 14

1)Class of muscle relaxant; 2)onset time; 3)duration of action; 4)pharmacokinetic profile; 5)cardio effects; 6)need for reversal

Front 15

what is the shortest acting muscle relaxant?

Back 15

succinylcholine

Front 16

list the physio-chemical properties that make up a good muscle relaxer.

Back 16

highly ionized at physiologic pH; positively charged (since the cholinergic receptor is neg); resemble ACh and are quaternary ammounium compounds; they are highly WATER SOLUBLE/relatively HYDROPHILIC (easily excreted in urine, don't cross BBB, placenta, small Vd, and not actively metabolized in the liver since the cyP-450 system requires lipophilic substrates)

Front 17

describe the shape and size of nondepolarizing agents.

Back 17

heavy, bulky, rigid molecules that block but don't activate cholinergic receptors

Front 18

name an alkaloid curare drug that releases histamine.

Back 18

benzylisoquinolines

Front 19

name a drug that promotes a muscarinic block.

Back 19

aminosteroids (muscarinic receptors are located on the post-synaptic cleft in the parasympathetic ANS) -

Front 20

name an aminosteroid nondepolarizing blocking agent that has an onset of 3-5 minutes and 12 min recovery of twitch.

Back 20

vecuronium

Front 21

name an aminosteriod nondepolarizing blocking agent that has a very short (60-70sec) onset but a duration of action of 28 minutes.

Back 21

rocuronium (min. CV side-effects)

Front 22

name two short-acting nondepolarizing blocking agents that degrade spontaneously or are metabolized by plasma cholinesterase.

Back 22

ATRACURIUM (release histamine and good for renal failure pts) and MIVACURIUM (eliminated by plasma cholinesterase)....side note: depolarizing succinyl. is also eliminated by plasma Cholinesterase

Front 23

describe pancuronium.

Back 23

bis-quaternary aminosteriod; slow onset, long acting, little BP effects, vagolytic, renal clearance

Front 24

cis-atracurium is a stereoisomer of atracurium; it is eliminated by ___________ and its major differences from atracuirum are what?

Back 24

eliminated by Hoffman degradation; it doesn't release histamine therefore it doesn't have the CV effects of hypotension like atracurium

Front 25

the duration of action of NDMR in pediatrics is generally _______________; and ______________ in elderly, renal failure and hepatic failure.

Back 25

shorter in peds and longer in elderly, renal and hepatic failure (exception - atracurium and cis-atracurium is the same in elderly, renal and liver failure)

Front 26

the only depolarizing agent, succinylcholine differs from ACh how?

Back 26

it can't be broken down by SYNAPTIC acetylcholinesterase (only by plasma AChE)

Front 27

what will you see on initial depolarization with depolarizing succinylcholine?

Back 27

fasciculations and twitches

Front 28

there are two phases in depolarizing agent succ; phase I is the binding of succ and opening the Na+ channels and getting depolarizations - fasciculations followed by flaccid paralysis; explain phase II.

Back 28

Phase II: eventually the membrane will partially repolarize. however, the membrane is desensitized to Ach and further action potentials are prevented.

Front 29

there is a deficiency that may cause a prolonged blockade of succinylcholine. name it.

Back 29

pseudocholinesterase deficiency (dibucaine is a local anesthetic that inhibits normal pseudocholinesterase)

Front 30

explain malignant hyperthermia and name a drug used to treat it.

Back 30

uncontrolled Ca++ release from the sarc. reticulum leads to muscle contracture and a rise in body temperature; succinylcholine (esp. with halothane has been known to do this). dantrolene will block the release of Ca++

Front 31

name some anticholinesterases. what does this mean?

Back 31

an anticholinesterase is a way to reverse the blockade (it inhibits the cholinesterase enzyme from breaking down ACh and thus increases the action of ACh); edrophonium and neostigmine