Local Anaesthetics Flashcards by Alice Spencer

What are the 2 types of anaesthesia?

1) General anaesthesia - total loss of sensation

2) Local anaesthesia

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What are the 3 types of local anaesthesia?

1) Regional anaesthesia - loss of sensation to a region or part of body
2) Local infiltration - cuts, skin incisions
3) Topical - eye, skin

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Give the 3 non pharmacological methods of achieving local anaesthesia?

1) Cold
2) Pressure
3) Hypoxia

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Give the 1 reversible and 4 not reversible pharmacological methods of achieving local anaesthesia?

Reversible = local anaesthetics

Non reversible = Phenol, ethanol, radiofrequency and surgery

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Why are phenol, ethanol, radiofrequency and surgery all non reversible methods of achieving local anaesthesia?

All methods kill the nerve
Phenol and ethanol injected around a nerve kills it
Radiofrequency waves are sugery can also destroy the nerve

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What is a local anaesthetic?

A drug which reversibly prevents the transmission of the nerve impulse, in the region to which it is applied, without affecting consciousness

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What is the mechanism of action of local anaesthetics?

They block the sodium gated ion channels on neurons

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is local anaesthetic injected into nerves?

No - if it was this would cause irreversible surgical damage to the nerve. Instead it is injected around the nerve.

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Each nerve contains many neurons, through which layers must LA pass to reach the individual neurons?

1) Whole nerve covered by epineurium
2) Bundles within the nerve covered in perineurium
3) Individual axons covered by endoneurium

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Why do LA have to be able to pass through the membrane of neurons?

Can only block the voltage gated sodium channels from within the neuron

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In which form are LAs capable of passing through the membrane of a neuron?

Unionized form (in the ionized form they would be repelled by the membrane)

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In which form are LAs capable of blocking the voltage gated sodium channels?

In the ionized form

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Voltage gated Na channels are made up of alpha and beta subunits, which sub unit does LAs bind to?

Alpha subunit

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How many domains does an alpha subunit of an voltage gated sodium channel have?

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What are the 4 ways of using local anaesthetic?

1) Topical - eg. eyes, ulcers
2) Local infiltration
3) Nerve block
4) Epidural/ spinal block

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What would be the 9 properties of an ideal LA?

1) Reversible
2) Good therapeutic index
3) Quick onset
4) Suitable duration
5) No local irritation even on repeated application
6) No side effects
7) No potential to induce allergy
8) Applicable by all rules
9) Cheap, stable, soluble

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What was the first LA ever used by who?

Cocaine - Karl Koller

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What are the 3 main components to the structure of an LA?

1) Aromatic residue (lipophilic)
2) Intermediate chain
3) Substituted amino group (hydrophilic)

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What determines whether an LA is an amide or an ester?

The chain joining the aromatic residue and intermediate chain is either an amide (contains N) group or an ester group

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What is an easy way to identify amide LAs from there name?

All LAs end in -caine, if there is the letter i at any point before the -caine then it is an amide

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What is the therapeutic index?

ED50/LD50
ED50 = dose that will be effective in 50% of patients
LD50 = dose that will be lethal in 50% of patients
The lower the therapeutic index the better

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What value determine the onset of action of a LA?

How the close the pKa value of the LA is to physiological pH

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What is the pKa value of an LA?

The pH at which the ionized form and non ionized forms are equal - the closer this is to physiological pH the fastest the onset of action

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If pKa is the same as physiological pH what will be the relative proportions of the ionized and unionized form of the LA in the body?

Equal

If the pKa is greater than physiological pH what will be the relative proportions of the ionized and unionized forms of the drug?

More ionized than unionized will be present

If the pKa is lower than physiological pH what will be the relative proportions of the ionized and unionized forms of the drug?

More unionized than ionized present

Why is the onset of action of LA longer if injected into inflamed or pus containing tissue?

pH of pus is about 6.9 thus lower than physiological pH so there is relatively more unionized drug than at physiological pH

What is physiological pH?

7.4

Why is clinical onset not the same for all LAs with the same pKa?

Thought to be due to the individual LAs ability to diffuse through connective tissue

What determines the duration of action of an LA?

Protein binding (given as a percentage) - the higher the protein binding the longer the duration of action as, as the LA is used up more is released from the binding proteins

What feature of the structure of an LA determines the extent of protein binding?

The length of the aromatic chain joining the aromatic and amine groups

What is meant by the potency of an LA?

Dose required to produce the desired effect

What determines the potency of an LA?

The lipid solubility

Will a more lipid soluble drug be more or less potent?

More potent - more lipid soluble drug penetrates the cell membrane, smaller amount is required to produce the desired effect

What is meant by differential block?

Blocking different sensations

What 2 things does the ability to block neuronal conduction by a particular nerve depend on?

1) The type of nerve fibres - the larger the fibre, the slower the onset 2) Location of the never fibre - outside or in the mantle (location within the bundle)

What are the 6 types of nerve fibres?

``` A alpha A beta A delta A gamma B C ```

Sensory function is lost in what general order?

1) Cold, warmth 2) Pain (first pain - A delta fibres - then second pain - C fibres) 3) Touch, deep pressure 4) Motor function

What other drug are LAs often given with?

Vasoconstrictor

What are the 4 advantages of giving LA with a vasoconstrictor?

1) Prolong action 2) Reduce plasma levels - less risk of CNS effects 3) Greater anaesthesia or reduced dose needed 4) Reduced operative haemorrhage

When are vasoconstrictors not given with an LA?

With LAs which are applied to body parts which are supplied by end vessels eg. fingers, toes, penis, ear lobule and ala of nose

Which 2 vasoconstrictors are used with LAs?

1) Adrenaline | 2) Felypressin

How does adrenaline cause vasoconstriction?

Stimulation of alpha adrenoreceptors (this also stimulates cardiac beta 1 receptors)

What kind of surgery uses a lot of vasoconstrictor?

Dental - very vascular

What is the advantage and disadvantage of using felypressin over adrenaline?

Advantage - no effect on heart conduction or contraction | Disadvantage - causes vasoconstriction but less effective than adrenaline

Felypressin is an analogue of what?

Vasopressin

What are the 2 main adverse effects of LAs?

1) Hypersensitivity (allergic response) - skin rash to full anaphylactic shock (may be a reaction to preservatives) 2) Methaemaglobinaemia

What kind of LAs are hypersensitivity reactions more common with?

Ester LAs

Which LA tends to cause methaemaglobinaemia, what is the process?

Prilocaine | Has a metabolite called 0-toluidine which oxidises ferrous to ferric ions - thus Hb can not carry oxygen

What are the 3 symptoms of methaemaglobinaemia?

1) Cyanosis 2) Lethargy 3) Respiratory distress

What is the treatment for methaemaglobinaemia?

Methylene blue

The order that symptoms of local anaesthetics toxicity present relates to the extent of nerve supply to tissues, what is the order of symptoms? 9

1) Circumoral and tongue numbness 2) Lightheadedness and tinnitus (structures of the face have big nerve supply) 3) Visual disturbances 4) Muscular twitching 5) Convulsions 6) Unconciousness 7) Coma 8) Respiratory arrest 9) CVS depression

Why do patients with local anaesthetic toxicity become unconscious before they experience cardiac arrest?

Cardiac tissue is not nerves but is a specialised conductive tissue which is much more resistant to LA

What is a last resort treatment for LA toxicity?

Give IV lipid emulsion - mops up the LA and the conc of LA goes down

What are the 8 steps in treating LA toxicity?

1) Stop injecting LA 2) Call for help 3) A: airways - make sure patent 4) B: breathing - give 100% oxygen 5) C: confirm or extablish IV access 6) D: control seizures - benzodiazepine, thiopental, propofol 7) Consider drawing blood for analysis 8) In circulatory arrest - start CPR, use standard protocols

What is the toxic dose of Lidocaine, with and without adrenaline?

Without: 3mg/kg | With adrenaline: 7mg/kg

What is the toxic dose of Bupivicaine/ lipobupivicaine with and without adrenaline?

Without = 2mg/kg | With adrenaline = 2mg/kg

What is the toxic dose of prilocaine with and without adrenaline?

Without = 6mg/kg | With adrenaline = 8mg/kg