Local Anaesthetic Agents Flashcards by ian rowley

Structure of a local anaesthetic
Subclassification

Hydrophilic tertiary amine group linked to lipophilic aromatic group
Ester or amide based on the linking group

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What are esters and amides

Ester -C with a =O and a -O-
Amide -NH-C- with a =O on the C

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Where are local anaesthetics protonated

On the nitrogen in the amine side chain

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Henderson hasselbach equation for la

pH = PKA + log10 LA/LAH+

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Significance of protination in local anaesthetics

Only non ionised can pass through cell membrane
Only ionised has action

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How are local anaesthetics stored in solution

With HCl to make acidic environment thus protinate the local and make it soluble in water

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What do local anaesthetics block
How physically
What is the relevance of this for the type of block

Open fast sodium channels
Enter the channel itself from an intracellular direction
Use dependant - as only blocked when open

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What is intracellular ph normally

7.1

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Effect of molecular weight on local anaesthetic acitivty

No direct effect but large weight suggests increased size of side chain and thus increased lipid solubility

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Effect of lipid solubility on local anaesthetics

Higher lipid solubility greater penetration of membranes so greater potency. Also increases rate of onset and duration of action
Also more toxicity and irritancy

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Effect of PKA on local anaesthetics

Lower pKa, lower degree of ionisation at given ph so more rapid speed of onset and offset

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Effect of ph on local anaesthetics

Acidosis increases proportion of ionised drug thus reduces amount available to cross membrane thus reduced potency

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Effect of protein binding on local anaesthetics

Greater binding longer duration of action

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Examples of Esther local anaesthetic
pKa for each
Protein binding for each

Amethocaine (tetracaine) - 8.5, 76%
Procaine - 8.9, 6%

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Examples of amide local anaesthetics
pKa
Protein binding

Bupivicaine 8.1, 96%
Ropivicaine 8.1, 95%
Lidocaine 7.9, 64%
Prilocaine 7.9, 55%

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Potency of local anaesthetics vs lidocaine

Amethociane, bupicvicaine, ropivicaine all 4x
Procaine 1/2
Priolcaine same

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Lipid solubility (heptane partition coefficient) of local anaesthetics

Bupivicaine 27.5
Ropivicaine 6.1
Amethociane 4.1
Lidocaine 2.9
Prilocaine 0.9
Procaine 0.02

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Another name for Amethociane

Tetracaine

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How is Amethocaine presented

Gel 4% for topical anaesthetic to skin
Dilute solutions 1% for eyes

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What is benzocaine
What is it used for

An ester local anaesthetic with no amine component so can’t be ionised thus low potency
Used in throat lozenges or onto mouth ulcers

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What is cocaine
What is it used for

Naturally occurring ester
Topical anaesthesia of the nose

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Why does cocaine not get absorbed systemically when given intranasally
Other advantage of this

Causes vasoconstriction limiting absorbtion also reducing bleeding

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If it gets systemic how protein bound is cocaine
pKa
How is it eliminated

98%
8.7
Plasma and liver esterases

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Why does cocaine cause a stimulatory response, consequence

Inhibits catecholamine reuptake
Euphoria, hyperthermia, vasoconstriction, hypertension, mydriasis, increased resp rate, increased metabolic rate, raised o2 consumption

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What happens with very high levels of cocaine

Excitatory pathway blocking resulting in sedation, unconsciousness, resp depression and myocardial depression

Max dose of cocaine Contraindication

1.5mg/kg Porphyria

Onset and offset time of bupivicaine for large nerve block

Onset up to 60mins Can last 48hrs

Main side effect of bupivicaine

Myocardial depression

Max dose of bupivicaine to avoid toxicity When should it be avoided

2mg/kg Don’t use IV Avoid 0.75% in pregnancy

How is bupivicaine metabolised

Metabolised to pipecolylxylidine and hydroxybupivicaine Excreted in urine

What is Levobupivicaine Advantages Max dose

S enatiomer of bupivicaine Lower cardiotoxicity and CNS toxicity Remains 2mg/kg and still not for iV

Cardiotoxicity of lidocaine vs bupivicaine at equivalent CNS toxicity levels

Around 1/9th - acts as a 1b antiarrhythmic

Lidocaine metabolism

Hepatic Microsomes oxidases and amidases producing metabolites (ethylglycine, xylidide) that are excreted in urine

How does priolcaine toxicity compare to lidocaine Why What can it be used for as first choice

Less toxic High tissue fixation and rapid metabolism IV regional anaesthetic eg biers block

How is Prilocaine metabolised

Liver lungs and kidneys to o-toluidine then hydroxytoludine

What is the issue with priolcaine metabolism

O-toluidine causes oxidation of ferrous (2+) Fe to ferric (3+) resulting in methaemoglobinaemia

Effects of methaemoglobinaemia Who is most at risk

Cyanosis SpO2 fixes at 85% no matter true sats Kids - under developed metabolic pathways and hb more easily oxidised

Treatment of methaemoglobinaemia

If necessary methylene blue 1-2mg

Triggers for methaemoglobinaemia

Priolcaine (O-toluidine) Emla Methylene blue in high concentrationS (>7mg/kg)

What enatomer is Ropivicaine

99.5 S enatomer

Difference between Ropivicaine and bupivicaine

Less lipid soluble and thus less readily penetrates myelin sheaths causing more C fibre block than a fibre potentially sparing motor function Half as caridotoxic as bupivicaine

What protein does Ropivicaine bind to

Mainly alpha 1 acid glycoprotein

Max dose Ropivicaine

3mg/kg

What does emla stand for What does it contain

Eutectic mixture of local anaesthetic 2.5% Prilocaine and 2.5% lidocaine

What is a eutectic mixture Relevance to emla What else is in emla

A mix in which the consitiuant components are in proportions that the freezing point is as low as possible with the consituants freezing simultaneously Allows consituants not to be in aqueous solution ie in their pure form and not ionised Carboxypolymethylene and sodium hydroxide resulting in an oil water emulsion

Specific gravity of heavy bupivicaine Specific gravity of csf

1.026 1.005

What is specific gravity

The density of a solution relative to the maximum density of water (that occurs at 4oC)

Effect of adding adrenaline to local anaesthetic

Vasoconstriction resulting in Less systemic uptake thus less toxicity Increased duration Reduced surgical bleeding

Issues with adrenaline in local anaesthetic

Systemic uptake of adrenaline, esp with other agents that cause arrhythmia eg halothane Ischemia if end arteries effected too severely

Max concentration of adrenaline in local anaesthetic

<1:200,000

How much adrenaline would you put in 20ml local to make adrenaline 1:200,000

0.1ml of 1:1000

What is felypressin Relevance to local anaesthetics

Octopeptide derived from ADH Direct acting vasopressor that is safe to use with halothane

What is hyaluronidase Relevance to local anaesthetics

Causes temporary depolymerisation of hyaluronic acid Facilitates spread of drug through connective tissues following sc or IM administration

How can acid base physiology be modified to increase local anaesthetic potency

Alkalisation of the solution increases tissue ph, more non ionised LA so more enters nerves

What additives can be given with local anaesthetics that have analgesic activity

Opioids Clonidine Ketamine

When is 7.5% levobupivicaine contraindicated

Obstetrics

Why does the same dose of levobupivicaine have increased activity than bupivicaine How much

13% more Dose of Levo expressed as mg of base compound Dose of bupivicaine expressed as mg of hydrochloride salt (thus heavier)

How are bupivicain and levobupivicaine excreted differently

Bupivicaine - metabolised in liver 16% unchanged in urine Levo - non excreted unchanged, main metabolite excreted in urine

Preparations of lidocaine

Plain solution 0.5,1,2% Solutions with adrenaline 1:200,000 Gel 1, 2% with Chlorhexidine for urethral Cream 4% for topical Solution for pharynx, larynx and trachea 4% Spray for airway anaesthesia 10%

Max dose lidocaine

3mg/kg 7 with adrenaline

Metabolism lidocaine

70% dealkalation in liver 10% unchanged in urine

Max doses Prilocaine

6mg/kg 8.5mg/kg with felypressin

Presentations of Prilocaine

Plain 1,4% With felypressin 3%

Presentations of Ropivicaine

Plain solution 2,7.5 and 10mg/ml 100 and 200ml bags at 2mg/ml for epidural

Max dose Ropivicaine

250mg 150mg for C-section under epidural Cumulative dose 675mg/24o