phase ii block occurs after large doses (>4mg/kg). this occurs when the post-synaptic membrane action potential returns to baseline in spite of the presence of succinylcholine and causes continued activation of nicotinic acetylcholine receptors. pharmacokinetics succinylcholine is metabolised by butyrylcholinesterase (aka pseudocholinesterase or plasma cholinesterase). adverse effects of succinylcholine contraindications: malignant hyperthermia, denervating conditions, major burns after 48 hours and severe hyperkalemia hyperkalemia, malignant hyperthermia, myalgias, increased intragastric pressure, increased intraocular pressure, increased intracranial pressure, cardiac dysrhythmias and allergic reactions properties of depolarising neuromuscular blocking agent (succinylcholine). drugelimination siteclearance (ml/kg/min)approximate duration of action (min) succinylcholineplasma che2 (100%)data not found< 8 pharmacology of nondepolarising neuromuscular blocking agents the speed of onset depends on the potency of the drug, greater potency is associated with slower onset of block. rocuronium, with an ed95 of 0.3 mg/kg iv has a more rapid onset than vecuronium with an ed95 of 0.05mg/kg. steroidal compounds steroidal compounds - rocuronium and vecuronium are intermediate-acting drugs while pancuronium and pipecuronium are long-acting drugs. comparison of pharmacokinetics between nondepolarising neuromuscular blocking agents neuromuscular blocking agents dosing onset time duration pharmacokinetics, precautions and side effects rocuronium 0.6mg/kg (2 x ed95) maintenance dose: 0.1mg/kg or infusion at a dose of 5-12mcg/kg/minute 1.5-3 minutes 30-70 minutes fastest onset time, alternative to succinylcholine for rapid sequence intubation volume of distribution of 0.3-0.7l/kg, excreted mainly through biliary route vecuronium 0.1mg/kg or 2 x ed95 for 3-4 minutes maintenance dose: 0.01mg/kg or an infusion at 1-2mcg/kg/min 3-4 minutes 25-50 minutes volume of distribution of 0.4 l/kg, neuromuscular monitoring is required for patients with renal or hepatic disease that may have prolonged response to vecuroniu pancuronium 0.1mg/kg (1.5 x ed95) for 3-5 minutes maintenance dose: 0.02mg/kg 3-5 minutes 60-120 minutes rarely used due to high incidence of postoperative residual neuromuscular weakness and cause tachycardia due to direct sympathomimetic stimulation and blockage of cardiac muscarinic receptors. volume of distribution of 0.2 to 0.3 l/kg, eliminated mostly through the renal route, with 20 percent biliary excretion, avoided in patients with renal and hepatic impairment atracurium 0.5 mg/kg, or 2 x ed95 for 3-5 minutes maintenance dose: 0.1mg/kg or an infusion rate at 10-20 mcg/kg/min 3-5 minutes 30-45 minutes side effects: skin flushing, hypotension and tachycardia due to the increase in plasma histamine level volume of distribution is 0.15l/kg, metabolism of atracurium is independent of hepatic and renal function metabolised by non-specific plasma esterase-mediated hydrolysis and a nonenzymatic, ph- and temperature-dependent degradation called hofmann elimination cisastracurium 0.15-0.2 mg/kg or 3 x ed95 for 4-7 minutes maintenance dose: 0.01 mg/kg or an infusion at 1-3 mcg/kg/min guided by neuromuscular monitoring 4-7 minutes 35-50 minutes volume of distribution is 0.16 l/kg, metabolised through hofmann elimination mivacurium 0.2 mg/kg, or 3 x ed95 for 3-4 minutes maintenance dose: 0.1mg/kg or an infusion at 5 to 8 mcg/kg/min guided by neuromuscular monitoring 3-4 minutes 15-20 minutes volume of distribution of 0.2 l/kg, metabolized by butyrylcholinesterase and should not be used in patients with butyrylcholinesterase deficiency it can be reversed by neostigmine or edrophonium. comparison of properties of nondepolarising neuromuscular blocking agents. drugelimination siteclearance (ml/kg/min)approximate potency relative to tubocurarine isoquinoline derivatives tubocurarinekidney (40%)2.3-2.41 atracuriumspontaneous5-61.5 cisatracuriummostly spontaneous2.71.5 doxacuriumkidney2.76 metocurinekidney (40%)1.24 mivacuriumplasma che270-954 steroid derivatives pancuroniumkidney (80%)1.7-1.86 pipecuroniumkidney (60%) and liver2.5-3.06 rapacuroniumliver6-110.4 rocuroniumliver (75-90%) and kidney2.90.8 vecuroniumliver (75-90%) and kidney3-5.36