Tubocuraine, atracurium, mivacurium, gallamine

Question 1

What is Tubocuraine (dTC)?

Answer 1

Monoquaternary alkaloid with a tertiary amine group. Largely protonated at body pH

Question 2

Tubocuraine presentation and uses

Answer 2

Colourless solution 10mg.ml-1
0.5m/kg can intubate in 3 mins
lasts 40 mins

Question 3

CV/GI etc effects of tubocuraine

Answer 3

Greatest degree of autonomic ganglion blockade and histamine release= fall in BP. Reflex tachycardia uncommon due to ganglion blockade. Protects against arrhythmias.

Increases salivation

Associated with anaphylaxis

Question 4

Kinetics of tubocuraine

Answer 4

30-50% protein bound.
Under acidic conditions the tertiary amine group (pKA 8) becomes increasingly protonated, resulting in increased potency.
PH varies K+ concentration and may alter membrane potential and alter potency.

Elimination independent of metabolism. 70% excreted in the urine and 30% in bile
Accumulates in renal failure

Question 5

What is atracurium

Answer 5

Benzylisoquinolinium compound. Mixture of 10 stereoisomers, resulting from the presence of 4 chiral centres

Question 6

Atracurium presentation and use

Answer 6

Colourless solution 10mg/ml in 2.5, 5 and 25ml vials
store at 4 degrees
0.5mg/kg intubate in 90-120 seconds

Question 7

CVS effects of atracurium

Answer 7

Release of histamine following rapid administration- could cause bronchospasm and hypotension. Give slowly

Question 8

Atracurium and myopathy

Answer 8

Associated with critical illness myopathy

Question 9

Metabolism of atracurium

Answer 9

Esterhydrolysis: non-specific esterases account for 60% of metabolism. Breakdown products are a quaternary alcohol, a quaternary acid and laudanosine. Unlike Hofmann elimination, acidic conditions accelerate this metabolic pathway. PH changes probably don’t alter ester hydrolysis.

Hofmann elimination: Spont breakdown to laudanosine and a quaternary monoacrylate when at normal body temp and pH. Acidosis and hypothermia will slow process. High concs of breakdown products could cause seizures. Laudenosine is a glycine antagonist but has no NMB properties and is cleared by the kidneys.

Drug independent of hepatic or renal function.

Question 10

What is cis-atracurium?

Answer 10

One of the 10 stereoisomers

Question 11

Presentation and uses of cis-atracurium

Answer 11

Colourless solution 2 or 5mg/ml. Store at 4 degrees. 3-4 times more potent than atracurium and therefore has a slower onset time. Can increase dose to shorten onset time as potential for histamine release is very low

Question 12

Kinetics of cis-atracurium

Answer 12

Does not undergo direct hydrolysis by plasma esterases. Predominant pathway is Hofmann elimination then hydrolysis to monoquaternary alcohol and acrylic acid. Can be used safely after 2 years age. Safe in hepatic/ renal failure

Question 13

What is mivacurium?

Answer 13

Benzylisoquinolinium ester- similar to atracurium.
Chiral mixture of 3 stereospecific isomers (36% cic trans, 58% trans trans 6% cis cis)

Ciscis isomer has 10% of the potency of the other 2 isomers and is not metabolised enzymatically. Half life is 10x that of the other two.

Short duration of action as rapid enzyme metabolism. Neostigmine inhibits plasma cholinesterase and may prevent its breakdown. Edrophonium is a better reversal agent.

Question 14

Mivacurium presentation and uses

Answer 14

Acidic (3.5-5) aqueous solution 2mg/ml in 5 and 10ml amps. Lasts 18 months when stored below 25 degrees

Question 15

Kinetics of mivacurium

Answer 15

Plasma cholinesterase is responsible for the metabolism of cis trans and trans trans isomers therefore if low plasma cholinesterase then prolonged block.

Duration of action prolonged with end stage liver disease due to reduced plasma cholinesterase activity.

Question 16

CVS effects of mivacurium

Answer 16

High doses release histamine resulting in hypotension and bronchospasm.