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L6 MRs and Reversals finished Questions
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Which of the following MR undergo Hofmann elimination? a. Rouronium b. Vecuronium c. Succinylcholine D. cisatracurium - D What is the difference between atropine and glycopyrrolate? a. Glycopyrrolate is tertiary and crosses the BB b. Glycopyrrolate is quaternary and does not cross the BBB c. Atropine is tertiary and does not cross the BBB d. Atropine is quartenary and does cross the BBB - B T/F: A patient is in laryngospasm and you do not have an IV access, you can give succinylcholine IM - True What MR are metabolized by plasma cholinesterase? - succinylcholine and mivacurium What is the first documented paralytic? - curare What was the first synthetic MR to be used clinically? - gallamine How is the NMJ divided? - presynaptic (nerve), synaptic cleft, and post synaptic (muscle membrane)
What is the function of the presynaptic NMJ? - neurotransmitter synthesis (like ACh) uptake and storage of the neurotransmitter into the synaptic vesicles ACh release and reuptake of choline after hydrolysis (not all ACh makes it to the muscle) control of ion flow across the nerve terminal cell membrane what is the synaptic cleft? - the gas between the nerve terminal and muscular membrane What is contained in the synaptic cleft? - the basal lamina and other macromolecules like acetylcholinesterase how much ACh is either degrades by acetylcholinesterase or diffuses out of the cleft before reaching its target (muscle)? - 50% What are contained in the invaginations on the post-synaptic (muscle) membrane? - highly dense areas of ACh receptors what is the purpose of invaginations on the muscle membrane? - to increase surface area What is in-between the folds (invaginations) of the postsynaptic membrane? - Na channels which amplify depolarization
T/F: Neostigmine can always reverse succinylcholine - False, neostigmine can only reverse succ in a phase 2 block what is the only true way sux can be reversed? - when enough time has passed for the circulating concentration of succinylcholine to be gone on its own. what is the other name(s) of succinylcholine? - Anectine / Quelicin succinylcholine dosing is based on IBW or TBW? - TBW What is the onset of succinylcholine? - 30-60s What is the DOA of succinylcholine - 5-10 minutes what intubation technique is succ often used in due to its quick onset? - RSI t/f succinylcholine has a large Vd - false; its small because it has low lipid solubility succinylcholine is metabolized rapidly by pseudocholinesterase into what? - succinylmonocholine why do you need to check TOF after succinylcholine administration before you give your NDMR? - they may have pseudocholinesterase deficiency. no twitches after the DOA of succ may indicate this. Shouldn't give dose of NDMR
How can you prolong the DOA of succinycholine? - high doses, infusion, and abnormal metabolism (pseudocholinesterase deficiency, hypothermia, pregnancy, liver dz, renal dz, and some drug therapies) How do cholinesterase inhibitors prolong depolarizing phase 1 block? - prevent the breakdown of ACh in the synaptic cleft which can bind to the receptors What effects might succinylcholine have in pediatrics (5)? - hyperkalemia rhabdomyolysis cardiac arrest MH bradycardia what is an example of a reason why we may still give succinylcholine to children? - small bowel obstruction; risk of aspiration is high so RSI is needed with succ. What can you pretreat succinylcholine with to avoid bradycardia? - atropine or glycopyrrolate What effect does young age have on succinylcholine dosage? - increases What are the side effects of succinylcholine? (9) - bradycardia hyperkalemia myalgia masseter spasm triggers MH
What are all the ways you can reverse hyperkalemia? - dialysis (takes a while) kayexalate (takes a while) hyperventilate (increase RR or MV) (drives K+ back into cells) bicarbonate calcium dextrose + insulin (insulin decreases k+ and dextrose is given with it to prevent hypoglycemia) What are the muscarinic effects of succinylcholine? - bradycardia T/F: Non-depolaring MR are non-competitive antagonist - False, they are competitive antagonist What does the competitive antagonism of NDMRs depend on? - the relative concentration of the NDMR and ACh, and their affinities for each to the ACh receptor what improves the chances of NDMR binding to the receptor over ACh? - the fact that acetylcholinesterase rapidly destroys ACh in the synaptic cleft making it less available than the NDMR to bind
Which NDMRs are benzylisoquinoliniums? - atracurium (tracrium) cisastracurium (Nimbex) mivacurium (mivacron) D-tibocurarine (curare) doxacurium (nuromax) Which NDMRs are aminosteroids? - pancuronium (pavulon) (usually only used in long cases or when pt needs to stay intubated) pipecuronium (arduran) vecuronium (Norcuron) rocuronium (zemuron) can sugammadex reverse benzylisoquinoliniums? - no What effect do volatiles have on MRs? - dose-dependent enhancement in magnitude and duration of NMB (potentiates both NDMR and DMR). VAs induce skeletal muscle relaxation at the level of the spinal cord via nAChR What effects do aminoglycoside antibiotics have on MRs? - stimulates pre-synaptic receptors causing decreased release of ACh; potentiates NDMR and DMR What effects do LAs have on MRs? - interfere with prejunctional release of ACh. directly depress skeletal muscle fibers. esters compete for plasma cholinesterase. potentiates DMR & NDMR at high doses only
What effects does hypothermia have on MRs? - decreased clearance slows the rate of effect site equilibrium; prolong DOA of MR What effect does a burn injury (>30%) have on MRs? - altered affinity of receptor for ACh; potentiates increased hyperkalemic response to DMR and inhibits NDMR prior succinylcholine does what to NDMR? - increases the dose of NDMR needed???? review this pic: - What is the trade name for cisatracurium? - Nimbex what muscle relaxant is commonly used with ESRD patients? - cisatracurium What is the onset of cisatracurium? - 3-5 minutes What is the DOA of cisatracurium? - 30-50 minutes How is cisatracurium metabolized? - Hoffman elimination Renal clearance 10-30% What effect does cisatracurium have on the CV system? - no change in HR or BP
T/F: Cisatracurium does not produce a consistent, dose- dependent increase in plasma histamine levels following administration - True What is the standard concentration of Cisatracurium? - 2 mg/cc cisatracurium besylate What is the dose of cisatracurium? - 0.08-0.12 mg/kg What is the trade name for pancuronium? - Pavulon Explain the structure of pancuronium and how it relates to its function - resembles ACh enough to bind but not activate nAChR What is the onset of pancuronium? - 3-5 minutes What is the DOA of pancuronium? - 60-90 minutes (considered long) How is pancuronium metabolized? - 10-20% hepatic How is pancuronium excreted? - 60-80% renal, 10% biliary What effect does pancuronium have on the CV system? - stimulant via blocking mAChR; increases HR What is the standard concentration of pancuronium? - 2 mg/cc pancuronium bromide What is the IV dose of pancuronium? - 0.1-0.2 mg/kg
How is rocuronium excreted? - 30-40% renal and 60% biliary What is the standard concentration of rocuronium? - 10 mg/cc rocuronium bromide What is the dose of rocuronium? - 0.6-1.2 mg/kg What is the max induction dose of rocuronium? - 50 mg when may we give more than 50 mg of Roc? - a true RSI where we want a fast onset T/F: Rocuronium has active metabolites - False Which patient population may have prolonged DOA with rocuronium? - elderly patients due to decreased liver mass 0.1 mg/kg of rocuronium has shown to be what? - a rapid and effective agent decreased fasciculations and postoperative myalgias; but needs time to take effect before pushing succ. most people push one after the other and then it's not very effective What effect do cholinesterase inhibitors have? - increased the amount of ACh by reversibly binding and inactivating acetylcholinesterase; increasing the amount of ACh available to compete with the NDMR What can anticholinesterases be used to diagnose? - myasthenia gravis
what is myasthenia gravis? - autoimmune disease where antibodies attack ACh receptors therefore decreasing the amount of them myasthenia gravis has what effect on MRs? - resistance to succ sensitive to NDMR what is the anti-cholinesterase tx for myasthenia gravis? - pyridostigmine what cholinesterase inhibitor is most commonly used in the OR?
- neostigmine t/f neostigmine is lipid soluble and crosses the BBB - False; lipid insoluble and can't cross the BBB What is the maximum recommended dose of neostigmine? - 0.08 mg/kg (up to 5 mg in adults) what is the neostigmine concentration? - 0.5mg/mL or 1mg/mL What is neostigmine used to treat? - myasthenia gravis urinary bladder atony paralytic ileus t/f: quantitative neuromuscular monitoring devices can measure TOF ratio and qualitative devices can't - true; qualitative can only measure TOFc What causes central anticholinergic syndrome? - atropine or scopolamine overdose
pyridostigmine What anticholinesterases have good lipid solubility? - physostigmine organophosphates How are anticholinesterases metabolized? - hepatic hydrolysis and conjugation to inactive metabolites How are anticholinesterases excreted? - renal clearance 50-75% What is the onset of edrophonium? - 1-2 minutes What is the onset of neostigmine? - 5-10 minutes (need to wait for peak effect before extubation) What is the onset of pyridostigmine? - 10-12 minutes What is the DOA of edrophonium? - 30-60 minutes What is the DOA of neostigmine? - 45-60 minutes What is the DOA of pyridostigmine? - 90-120 minutes What is the standard concentration of neostigmine? - 0.5- mg/cc neostigmine methylsulfate What is the standard concentration of edrophonium? - 10 mg/cc edrophonium chloride
What is the standard concentration of pyridostigmine? - 1 mg/cc pyridostigmine chloride What is the dose of neostigmine? - 0.04-0.08 mg/kg; max 5 mg What is the dose of edrophonium? - 0.5-1 mg/kg What is the dose of pyridostigmine? - 0.2-0.5 mg/kg dose of neostigmine for 4 twitches - 30mcg/kg dose of neostigmine for 2-3 twitches - 60 mcg/kgz dose of neostigmine for 1 twitch - not indicated What are the muscarinic side effects? - SLUDGE salvation lacrimation urination diaphoresis GI upset emesis How do antimuscarinics work? - competitively block binding by ACh and prevents muscarinic receptor activation What are common anticholinergics? - atropine, scopolamine, and glycopyrrolate Which anticholinergics are lipid-soluble tertiary amines? - atropine and scopolamine
What are the respiratory effects of anticholinergics? - inhibits secretion of the respiratory tract mucosa (antisialagogue); relaxation of the bronchial smooth muscle reducing AW resistance and increases anatomic dead space What are the cerebral effects of anticholinergics? - can cause stimulation to depression; excitation, restlessness, and hallucinations sedation and amnesia (especially with scopolamine) When is scopolamine used? - in trauma cases (used more now for PONV though as a patch) What are the GI effects of anticholinergics? - salivary and gastric secretions are reduced: decreased intestinal motility and peristalsis prolonged gastric emptying time: lower esophageal sphincter pressure reduced *opposite of SLUDGE What are the ophthalmic effects of anticholinergics? - pupillary dilation (mydriasis) and cycloplegia What is cycloplegia? - an inability to accommodate to near vision
What are the genitourinary effects of anticholinergics? - urine retention bc of decreased ureter and bladder tone Which anticholinergic causes bronchodilation? - ipratropium (as an inhaler) What is the trade name for ipratropium? - atrovent What is used to prevent PONV? - scopolamine patch (1.5 mg behind the ear - wear gloves when applying) What is the standard concentration of atropine? - 0.1 or 0. mg/cc atropine sulfate What is the standard concentration of glycopyrrolate? - 0. mg/cc glycopyrrolate HCl What is the dose for atropine? - 0.01-0.03 mg/kg What is the dose for glycopyrrolate? - 0.01-0.02 mg/kg What is the standard concentration of scopolamine? - 0.2 mg/cc What is the dose for scopolamine? - 0.2 mg IVP What is used to reverse rocuronium and vecuronium? - sugammadex What is the trade name for sugammadex? - bridion How long does sugammadex take to reverse patients? - 2 mins
