2015A04 A surgeon wishes to use topical local anaesthetic in the nose before surgery in a 30 year old 70kg man.
He normally uses topical cocaine 5% plus lignocaine 2% with adrenaline 1:100,000 injection.
What volumes of these drugs can be used safely?
What are the potential toxic effects of cocaine and how does lignocaine and adrenaline affect these?

 

List:

·      Numbers table

·      Purpose

·      Localised toxicity

·      CNS toxicity

·      CVS toxicity

·      Final answer

 

Numbers:

 

Concentration presented

Toxic plasma concentration

Toxic subcutaneous dose

Cocaine

5% = 50mg/mL

0.5mg/mL

2mg/kg = 140mg = ~3mL

Lignocaine

2% = 20mg/mL

5mg/mL

7mg/kg w adr = 490mg = ~25mL

Adrenaline

1:100k = 10mcg/mL

?

?

 

Purpose:

 

Mechanism of action

Function

Cocaine

Inhibit VdNaC

Monoamine reuptake

Norad : dopamine : serotonin 5:3:2

Local anaesthetic

Vasoconstriction

Lignocaine

Inhibit VDNaC

Local anaesthetic

Adrenaline

α1 agonist

Vasoconstriction

 

Localised toxicity:

Cocaine

Septal necrosis even with single use

Lignocaine

Rare

Adrenaline

Necrosis if large amount of drug

 

CNS toxicity:

LAST

·  Cause: inhibition of neuronal VDNaC

·  Initial excitation (block inhibitory interneurons): paraesthesia, peri-oral tingling, vertigo, tinnitus, inattention, slurred speech, muscle twitching, seizure

·  Then inhibition: coma, apnoea

Cocaine (non-LAST)

·  Cause: dopamine and serotonin reuptake inhibition

·  Euphoria, delirium, seizure

 

CVS toxicity:

LAST

·  Inhibit VDNaC;, also VDKC and VDCC at higher concentration

·  ECG “pulled apart” (long Q, wide QRS), tachyarrhythmia, VF arrest

·  First phase: ↑HR, ↑mAP

·  Second phase: myocardial depression, ↓mAP

·  Terminal phase: vasodilatation, arrhythmia, arrest

Cocaine (non-LAST)

·  NRI, ↑ICF Ca2+

·  Tachyarrhythmia, ↑mAP, coronary vasospasm, ischaemia, arrest

Adrenaline

·  ↑ICF Ca2+ -> tachyarrhythmia, ischaemia, stroke, arrest

 

Answer:

Considerations

·  Nasal mucosa is highly vascular -> ↑absorption rate

·  Vasoconstriction by cocaine/adrenaline -> ↓ absorption rate -> ↓peak plasma concentration

·  Interaction unclear: ? synergistic for inducing seizures

How much

·  ? Cocaine 1mL

·  ? Lignocaine with adrenaline 5mL

(I have no idea, need to find out)

 

 

 

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