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45 Cards in this Set
- Front
- Back
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what do NMB's do?
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antagonize the effects of aCh
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Benzylisoquinolines [4]
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Mivacurium, Atracurium, Cisatracurium, Doxacurium
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Aminosteroids [4]
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Vecuronium, Rocuronium, Pancuronium, Pipecuronium
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Respiratory acidosis ________ blockade and _________ its reversal
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potentiates
antagonizes |
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Succinylcholine structure?
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two molecules of acetylcholine
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aCh mimetics have...
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have a quat. amine and some a second tertiary amine that is protonated at physiological pH
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prototype NMB?
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tubocurarine
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Newer NMB's– cause less toxicities (histamine release, autonomic side effects) [4]
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doxacurium, mivacurium, rocuronium, vecuronium
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There is often more than one nitrogen, if the additional are tertiary, then they add _______ character
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basic
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_________ has about the same onset and so could be used in place of succinylcholine (has many side effects) but will sacrifice for longer duration
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rocuronium
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selection of NMB's?
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Onset of Action
Rocuronium vs succinylcholine Duration of Action Short/intermediate/long Degree of changes in BP and HR Short and intermediate have minimal changes |
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Non-depolarizing- mech of action
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Competitive Antagonist
Curariform Agents Phase II Block |
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Depolarizing - mech of action
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Agonists
Succinylcholine Phase I Block |
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Nicotinic receptor is a...
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(ligand gated ion channel)
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competitive agent onset?
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Small rapidly moving muscles of eyes and face THEN 2. Larger muscles of limbs and trunk THEN 3. intercostal muscles and diaphragm (so can relax without apnea if choose)
All due to differences in blood flow, distance from central circulation and different fiber types. |
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Acetlycholine receptors are
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multi-subunit membrane spanning proteins consisting of five distinct subunits; (a,b,d,g).
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Acetylcholine binds to the ______ subunits, of which there are _____ on each of the acetylcholine receptor ion channels.
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a
2 |
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Once bound, acetylcholine causes ligand-gated ion channels in the post synaptic membrane to ______.
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open
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These channels are relatively ________, so the passage of different ions
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non-selective
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Depolarizing (succinylcholine) mechanism
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Binds to nicotinic receptor
Influx/outflux of ions leads to persistent depolarization Initially have involuntary muscle contractions (fasciculations) Paralysis sets in Time dependent gate closes but voltage gate remains open. The end plate cannot repolarize because an agonist is bound keeping upper gate open. Receptor becomes inactive and desensitized (channel will remain closed even with agonist). Mechanism is not clear we ‘exhaust’ the receptor |
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______ and ______ may change sux response.
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Hypokalemia and hypocalcemia
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Speed of onset - Most potent have _______ onset
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longer
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potency facts
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Speed of onset - Most potent have longer onset
Potency measured by ED95 ED95 is different for different muscles Takes more drug for intubation than facial relaxation Wide variability in dosages More potent so must give less, give less takes longer to get to site, longer to get to site, longer onset. |
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what is an Antagonist?
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a ligand that binds and nothing happens, we keep the membrane at its resting state
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Duration of Action
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Parallel metabolism
Succinylcholine, mivacurium Parallel elimination Usually redistribution Gradual metabolism Elimination Reversals |
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absorption for quat. amines?
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poor
Not well absorbed from gut (limits delivery, can still eat meat of animals killed) Do not cross BBB |
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NMB's hepatic metabolism [2]
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Pancuronium/Vecuronium (vecuronium active 3-hydroxy)
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Acetylcholinesterase metab [3]
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Acetylcholine (somewhat mivacurium/cisatracurium/atracurium)
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Pseudocholinesterase metab
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Non-specific cholinesterase/plasma cholinesterase/ butyrylcholinesterase
Succinylcholine (also mivacurium/cisatracurium/atracurium) Other drugs decrease psudochbolinesterase activity |
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Many not metabolized and eliminated unchanged..[4]
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Tubocurarine/Doxacurium/Rocuronium/aminosteroids
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effect of hypothermia on metabolism?
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Hypothermia
Decreased temperature decreases metabolism |
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Because of significant esterase metabolism of all of the compounds, should screen for?
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“atypical chlolinesterase”
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Drugs reducing psuedocholinesterase activity
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include echothiophate (glaucoma), neostigmine/pyridostigmine (cholinesterase inhibitors), Phenylzine (MAOI), Cyclophosphamide (antineoplastic), Esmolol (beta-blocker), Pancuronium (non-depolarizing muscle blocker), oral contraceptives.
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renal excretion [4]
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Doxacurium, Pancuronium, Vercuronium, Pipecuronium
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Biliary Excretion
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Vecuronium/Rocuronium
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renal failure/liver failure effects
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So if have renal failure and prolonged action and increased volume of distribution
Liver disease also have increased volume of distribution May need greater initial dose to compensate for increased volume of distribution but then lower maintenance doses |
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Hyperthermia delays ?
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excretion
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Toxicity
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Prolonged NM paralysis (atypical esterase levels)
Apnea Release Histamine from mast cells Curariform compounds Cause bronchospasm Block autonomic ganglia Hypotension, tachycardia Block Cardiac Muscarinic receptors |
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Less pronounced toxicities with the new drugs [4]
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doxacurium, mivacurium, rocuronium, vecuronium
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hyperkalemia effects?
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Hyperkalemia – during succinylcholine depolarization potassium is still released by muscle and raises serum potassium by 0.5 mEq/L which is ok for normal but in those patients with burn, massive trauma and other neurological and other disorders, this causes hyperkalemia. See cardiac arrest, V.fib, heart block, bradycardia
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Vecuronium
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Prolonged blockade
active metabolites or development of polyneuropathy |
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Pancuronium
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Vagal blockade and catecholamine release
Hypertesion and tachycardia Inhibits Psueodocholiesterases |
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Succinylcholine (*contraindicated for children and adolescents)
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*Hyperkalemia
*Rhabdomyolysis *Cardiac Arrest Postoperative Myalgia Bradycardia (stimulate vagal ganglia) Hypertension/tachycardia (stimulate sympathetic ganglia) Prolonged activity (atypical esterase levels) |
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Interactions
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Other drugs act at receptor (potentiate effects)
Volatile anesthetics, local anesthetics, ketamine Neostigmine, antibiotics (aminoglycoside/ tetracycline), cocaine, quinidine, calcium channel blockers. Others (table 9-4 Lange’s text) Effects pronounced with disorders (Myasthenia gravis, etc, see table 9-8, Lange’s text) Effects reversed by cholinesterase inhibitors (neostigmine) No reversal for succinylcholine |
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why no reversal for sux?
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Cholinesterase inhibitors allow for increase in Ach concentration at end plate and allow for agonism.
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