2014A02 Draw and explain the characteristics of a log dose response curve
that describes the major clinical effect of rocuronium.
Describe how factors encountered in clinical practice may alter this curve.



·      Graph

·      Intro

·      Factors ↑ED95 = R shift = ↓potency

·      Factors ↓ED95 = L shift = ↑potency

·      Factors ↑duration (not relevant here)



Population, quantal curve




·   Non-depolarising relaxant

·   Competitive inhibitor at α-subunit of nAChR at NMJ

·   Must bind 70% of receptors before significant effect due to spare receptors

Measured responses

·   Onset time (time to 95% ↓single twitch height)

·   Depth (minimum post-tetanic count?)

·   Offset time (time to TOF ratio 0.9)

Muscle group differences

 Laryngeal muscle cf. adductor pollicis:

·   Physiological differences:

o ↑Blood flow

o ↑ACh vesicle release

o ↑ACh receptors

·   Clinical implication:

o Faster onset

o Less depth

o Shorter duration

Implications of inter-individual differences

·   ↑Potency and ↑duration: failure of reversal -> distress, T2RF, aspiration

·   ↓Duration: movement when dangerous e.g. neurosurgery

·   Twitch monitoring essential whenever relaxants used


Factors ↑ED95 = R shift = ↓potency:


·   ↑K+: membrane depolarisation-> ↑ACh release -> ↓drug:ACh ratio


·   Critical illness myopathy, burns -> proliferation of extrajunctional receptors -> ↓drug:ACh ratio

·   Malignant hyperthermia-> post-junctional activation

Competitive reversal

·   AChEi e.g. neostigmine: ↓drug:ACh ratio

(g-cyclodextrin chelates rocuronium in plasma, increases the gradient between effect site and plasma but does not alter the dose-response curve)


·   Tetanus toxin: ↓inhibition of a-motor neurons -> ↑NMJ activity -> ↓drug:ACh ratio


Factors ↓ED95 = L shift = ↑potency


↓ACh release -> ↑drug:ACh ratio

·   Neonate: immature NMJ

·   Respiratory acidosis

·   ↑Mg2+: ↑competition with Ca2+

·   ↓K+: membrane potential more negative -↓ACh release


·   Myasthaenia gravis: antibody against NMJ nAChR -> ↑drug:receptor ratio

·   Lambert-Eaton syndrome: antibody against pre-synaptic VDCC -> ↓competition with ACh

Pre-synaptic drugs

↓ACh release -> ↑drug: ACh ratio

·   α-motor neuron activity: volatile anaesthetic

·   ↓ axonal action potential: peripheral nerve local anaesthetic (↓Na+ flux)

·   ↓Choline uptake: hemicholinium

·   ↓ACh transport into vesicles: vesamicol

·   ↓AMP/ATP synthesis (frusemide)

·   Block pre-synaptic nAChR (volatiles)

·   Block L-Ca2+ (CCB, Mg2+, aminoglycosides, volatiles)

Post-synaptic drugs

↓Ion flux through nAChR

·   Block post-synaptic nAChR: other non-depolarisers, volatiles, aminoglycoside, quinidine

·   Desensitisation blockade (volatiles, barbiturates)

·   Inhibit peri-junctional action potential: local anaesthetic ↓Na+ flux

Post-junctional drugs

·   Dantrolene: inhibit skeletal muscle ryanodine receptor


·   Botox: cleave SNARE protein, ↓ACh release

·   Tetrodotoxin: VDNaC inhibition


Addit: factors increasing duration


*All those causing ↑potency plus…*


·   ↓Temp: ↓rate of Hoffman degradation and ester hydrolysis

·   ↑pH: ↓rate of ester hydrolysis

·   ↓pH: ↓rate of Hofmann degradation

·   Atracurium: 60% ester hydrolysis, 30%, Hoffman elimination, 10% in urine unchanged

·   Cisatracurium: 80% Hoffman elimination, 15% ester hydrolysis, 5% in urine unchanged


·   Liver failure: accumulation of bile eliminated drug (e.g. vecuronium 70%)

·   Renal failure: accumulation of drug (e.g. gallamine 100% renal), metabolite (e.g. 3-OH-panc 50% potency)




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