Local Anaesthetics Flashcards
LA types
Weak bases
Lipophilic phenyl ring and hydrophilic tertiary amine joined by an intermediary ester- or amide- based linker
Esters
- Ester linkage (R-CO-O-R1)
- E.g procaine, amethocaine, cocaine
Amides
- Amide linkage (R-NH-CO-R1)
- E.g lignocaine, prilocaine, bupivacaine, ropivacaine, dibucaine
LA toxicity dosing
Lignocaine
- 4mg/kg
- 7mg/kg with adrenaline
- toxicity Cp >5mcg/ml
-Cp 1- 5mcg/mL -Analgesia
▪ 5-10 - light-headedness, tinnitus, numbness of tongue
▪ 10-15 - seizures, unconsciousness
▪ 15-20 - coma, resp arrest
>25 - cardiovascular depression
Ropivacaine
- 3mg/kg
- toxicity Cp >4mcg/ml
Bupivacaine
- 2mg/kg
- toxicity Cp >1.5mcg/ml
Prilocaine
- 6mg/kg
Cocaine
- 1.5mg/kg
Lignocaine
- Amide LA
- Class Ib antiarrhrythmic
- Formulated as hydrochloride (incr water solubility)
- Max dose 3-5mg/kg, 7mg/kg with adrenaline
- Lipid solubility - higher than prilocaine, lower than bupivacaine and ropivacaine
- pKa 7.9 (25% unionised at pH 7.4)
- Protein binding 70%
- Extensively metabolised in liver
=> N-de-alkylation -> mono-ethyl-glycine-xylidide (antiarrhytmic properties) -> hydroxylation to hydroxy-xylidine (main metabolite, really excreted)
-> also to acetaldehyde - T1/2B = 1.5hrs
- CC:CNS ratio = 7.1
Bupivacaine
- Amide LA
- Formulated as hydrochloride
- Racemic mixture (S- less toxic - levobupivacaine)
- Max single dose 2mg/kg, daily dose 400mg
- Lipid solubility - higher than ropivacaine, lignocaine and prilocaine
- Intrinsic vasodilator (bupiv), vasoconstrictor (levobupiv) properties
- pKa 8.1 (15% unionised at pH 7.4)
- Protein binding 95%
- Primarily hepatic N-de-alkylation in humans -> pipe-coly-xylidine (less toxic) + pipe-colic acid
- Metabolites excreted in urine
- T1/2B 2.5hrs
- CC:CNS = 3.7
Ropivacaine
- Amide LA
- Formulated as hydrochloride
- Pure S-enantiomer
- Difference with bupivacaine - propyl (-C3H7), instead of butyl (-C4H9)
- Max dose 3mg/kg
- Lipid solubility - higher than prilocaine and lignocaine, lower than bupivacaine
- Intrinsic vasoconstrictor properties
- pKa 8.1(15% unionised at pH 7.4)
- Protein binding 94%
- Primarily hepatic hydroxylation
=> 3-hydroxy-ropivacaine
=> 4-hydroxy-ropivacaine
=> Both have some LA activity - T1/2B = 2hrs
- CC:CNS = 5
Prilocaine
- Amide LA
- Formulated as hydrochloride
- Max dose 6mg/kg, 8mg/kg with felypressin
- LA of 1st choice for Biers block
- Lipid solubility - lower than bupivacaine, ropivacaine and lignocaine
- pKa 7.7 (33% unionised at pH 7.4)
- Proteinbinding 55%
- T1/2B = 1.5hrs
- Most rapidly metabolised amide - in liver, kidney and lungs
=> O-toluidine - capable of converting Hb to its oxidised metHb form -> methaemoglobinaemia -> decr O2 carrying capacity of Hb, tx with methylene blue
Skin LA
EMLA
- Eutectic mixture - mixture of substances that has the lowest possible temp of solidification (eutectic temp) than any other mixture of the same substances
- 2.5% lignocaine + 2.5% prilocaine
- Onset 45-60mins
- Duration 1-2hrs after removal
- Causes local vasoconstriction and blanching
- Avoid in pt with methaemoglobinaemia
Amethocaine (AnGel)
- 4% gel
- Onset 30mins
- Duration 2-3hrs after removal
- Causes local vasodilation and erythema
- Do not apply for longer than 60minsEMLA
- Eutectic mixture - mixture of substances that has the lowest possible temp of solidification (eutectic temp) than any other mixture of the same substances
- 2.5% lignocaine + 2.5% prilocaine
- Onset 45-60mins
- Duration 1-2hrs after removal
- Causes local vasoconstriction and blanching
- Avoid in pt with methaemoglobinaemia
Amethocaine (AnGel)
- 4% gel
- Onset 30mins
- Duration 2-3hrs after removal
- Causes local vasodilation and erythema
- Do not apply for longer than 60mins
Intralipid
Used to treat LAST
- Fat emulsion of 20% soybean oil, egg yolk phospholipids, glycerin, NaOH, water
- Initial dose 1.5ml/kg bolus every 5mins (max 3x)
- Commence infusion at 15mk/kg/hr
- Max cumulative dose 12ml/kg
- Acts as ‘lipid sink’ - draws LA out of plasma
- May actually facilitate redistribution of LA from target organs to fat stores
Mucosal LA
Lignocaine
- Comes in various forms
- 2% gel, 5% ointment, 4% solution, 10mg/dose spray
Prilocaine
- Max dose 6mg/kg
- Metabolised to O-toluidine -> oxidises Fe2+ to Fe3+ -> MetHb -> central cyanosis
Cocaine
- 1-4% paste, 1-10% solution
- Max dose 1.5mg/kg
- Uptake 1 and MAOi -> decr uptake of NA, dopamine and serotonin -> incr post synaptic conc -> CVS + CNS effects
- Dopamine depletion after chronic exposure
LA MoA
LA diffuses from site of action to axon -> crosses axon membrane in unionised form -> converted into ionised form in axoplasm -> binds to internal surface (H) gate of Na+ channels -> Na+ channels remain in inactive state -> slows rate of depolarisation -> threshold potential not reached -> AP not propagated
Other sites of action
- VGKC - LA exhibit much lower affinity
- VGCC - L-type more sensitive
- May also act on GPCRs
Frequency dependent blockade
- LA have greater access to Na+ channels when in activated (open state)
- Incr nerve firing -> easier access of LA to the binding site of Na+ channela
- May play role in differential blockade
=> B > C + A-delta > A-gamma > A-B >A-a
=> pain > cold and warm > touch > deep pressure > motor
LAST (local anaesthetic systemic toxicity)
CNS before cardiac symptoms. Both in a biphasic manner. Associated with Cp not the dose administered, hence safe dose varies depending on site of injection.
CNS
Excitation
- Numbness of tongue and circumoral tissue
- Restlessness
- Tinnitus
- Vertigo
- Shivering
- Muscular twitching and tremours
- Generalised convulsions
Depression
- Generalised depression
- Decreased LOC
- Apnoea
CVS
Initial
- HTN and tachycardia
Then
- Peripheral vasodilation, profound hypotension -> decr Q
- Sinus brady, intracardiac conduction defects (prolonged PR + QRS complex), ventricular arrhythmias, cardiac arrest
Onset of neuraxial/ LA block
Smallest diameter nerves most sensitive
Autonomic -> sensory -> motor
B (Pain) > C + A-delta (temp) > A-gamma (touch) > AB (deep pressure) > Aa (motor function)
