Local Anaesthetics

Question 1

What is the definition of an anaesthetic drug?

Answer 1

A drug that induces partial or total loss of sensation

Question 2

What are the 2 main types of anaesthesia?

Answer 2

General anaesthesia:

• this involves total loss of sensation

Local anaesthesia:

• this involves partial loss of sensation

Question 3

What are the 3 different types of local anaesthesia?

Answer 3

Regional anaesthesia:

• involves the loss of sensation to a region or part of the body

Local infiltration:

• Involves infiltration into cuts or skin incisions
• it is more confined to the area around the wound

Topical anaesthesia:

• this involves eye drops or topical skin creams
• it does NOT involve a needle

Question 4

What are the 2 different methods of local anaesthesia?

Answer 4

Non-pharmacological:

• cold
• pressure
• hypoxia

Pharmacological:

• reversible - local anaesthetics
• irreversible - phenol, ethanol, radiofrequency, surgery
• involves complete destruction of the nerve carrying sensation from an area to the brain

Question 5

What are the fundamental characteristics of a local anaesthetic agent?

Answer 5

It is a drug which:

1. Reversibly prevents transmission of a nerve impulse
2. In the region to which it is applied
3. Without affecting consciousness

Question 6

What are the different ways in which local anaesthetics can be administered?

Answer 6

• Can be applied topically - e.g. eye drops, on mouth ulcers or skin
• local infiltration around the skin edges of a wound
• nerve block
• epidural or spinal block

Question 7

Which 2 major systems are affected in local anaesthetic toxicity?

What symptoms may result?

Answer 7

If you give someone too much local anaesthetic, it will work on the brain and the specialised conduction system within the heart

this results in neurological and cardiovascular symptoms

Question 8

What are the 3 layers of a nerve?

Where does the local anaesthetic work?

Answer 8

The nerve is surrounded by the epineurium

Individual nerve bundles are surrounded by the perineurium

An individual nerve fibre is surrounded by the endoneurium

the LA is injected into the epineurium and takes time to diffuse into the nerve fibre

Question 9

Why are local anaesthetics sometimes called “blocks”?

What is their general mechanism of action?

Answer 9

They block voltage gated sodium channels along the axon

this means that action potentials cannot be generated and passed on

they work on different domains of the sodium channel and prevent Na⁺ ions from moving into the cell

Question 10

What are the characteristics of an ideal local anaesthetic?

Answer 10

• Reversible
• quick onset
• suitable duration
• no local irritation on repeated application
• no side effects
• no potential to induce allergy
• applicable by all routes
• cheap, stable and soluble

Question 11

From which aspect do local anaesthetics block sodium channels?

What type of block does this provide?

Answer 11

LAs work by blocking sodium channel conduction

they block sodium channels from the inside

they provide reversible conduction block

Question 12

What are the main local anaesthetic agents?

Answer 12

• Procaine
• Lidocaine
• Prilocaine
• Mepivacaine
• Bupivacaine
• Levo bupivacaine
• Ropivacaine
• Articaine

Question 13

What is the structure of a local anaesthetic like?

Answer 13

All LAs have 2 components connected with an intermediate chain

they have a lipophilic part - an unsaturated benzene ring

and a hydrophilic part - tertiary amine

Question 14

What structural component determines which type of local anaesthetic it is?

Answer 14

The link between the intermediate chain and the benzene ring determines the type of LA

it is either ester or amide

Question 15

What do the names of all LAs end in?

How can you tell if they are ester or amide?

Answer 15

“Caine”

If there is an i before the Caine, they are amides

if there is NOT an i before the Caine, they are esters

Question 16

What are examples of ester local anaesthetics?

Answer 16

• Benzocaine
• chloroprocaine
• cocaine
• procaine
• tetracaine

Question 17

What are examples of amide local anaesthetics?

Answer 17

• Bupivacaine
• etidocaine
• levobupivacaine
• lidocaine
• mepivacaine
• prilocaine
• ropivacaine

Question 18

What characteristic of local anaesthetics determines their onset of action?

Answer 18

The pKa value

LAs can exist in the ionised or unionised form

in order to get into the cell, they have to be in the unionised form

once they are within the cell, they have to become ionised in order to bind to the channel

Question 19

What does the pKa value of a local anaesthetic tell you?

Answer 19

The pKa value shows that ionised and non-ionised forms of local anaesthetics are equal

if pKa > pH then unionised form > ionised form

if pKa < pH then ionised form > unionised form

Question 20

What would the ratio be like if one local anaesthetic had a pKa of 10 and another had a pKa of 7?

Answer 20

The LA with a pKa value of 7 will have more unionised form and will work quicker

body pH is 7.4

the closer the pKa value of the local anaesthetic to 7.4, the faster it will work

Question 21

What happens if body pH is lowered?

What does this mean about where local anaesthetic can be injected?

Answer 21

If the pH is lowered, there will be even less unionised form of LA and there is a greater difference between pH and pKa

if you inject LA around an abscess or inflamed tissue, it will not work due to local acidosis and lowered pH

Question 22

What are the rules around ionised and non-ionised forms of local anaesthetic?

Answer 22

• Clinical onset is not the same for all local anaesthetics with the same pKa
• this may be due to the individual LAs ability to diffuse through connective tissue
• the closer the pKa to physiological pH, the faster the onset

Question 23

What characteristic determines the duration of action of a local anaesthetic?

Answer 23

Protein binding

the more protein binding, the longer the duration of action

the drug is released from the protein over a longer period of time

the length of the intermediate chain joining aromatic and amide groups also has an influence

Question 24

What is meant by potency?

What does it depend on?

Answer 24

The dose required to produce the desired effect

this depends on lipid solubility

a more lipid soluble drug will penetrate the cell membrane, meaning a smaller amount is required to produce a given effect

Question 25

What does the ability to block neuronal conduction depend on?

Answer 25

**Type of nerve fibre:** * the larger the fibre, the slower the onset **Location of the nerve fibre:** * is it outside or in the mantle? * it will take longer for the LA to reach the nerve fibre if it is in the centre of the nerve, opposed to just under the membrane

Question 26

When local anaesthetic is applied, what is one of the first sensations that is lost?

Answer 26

Pain pain nerve fibres have a small diameter

Question 27

What is the effect called that describes how the smaller the nerve fibres are, the more quickly they become numb?

Answer 27

**Differential block**

Question 28

What is the % protein binding of lignocaine, bupivacaine and procaine?

Answer 28

Procaine - 65% bupivacaine - 95% procaine - 6% bupivacaine will have the longest duration of action

Question 29

What does the ability to block neuronal conduction depend on? In which order is sensory function lost?

Answer 29

Ability to block neuronal conduction depends upon the **type of nerve fibre** sensory function is lost in the following order: * cold, warmth * pain * touch, deep pressure * motor function

Question 30

Why are local anaesthetics frequently given with a vasoconstrictor?

Answer 30

* To prolong action * to reduce plasma levels so there is less risk of CNS effects * 'greater anaesthesia' or reduced dose * reduced operative haemorrhage (bleeding)

Question 31

When should vasoconstrictors not be used with local anaesthetics?

Answer 31

They are not used when a structure is supplied by end-vessels e.g. Fingers, toes, penis, ear lobule or ala of nose

Question 32

What are two common vasoconstrictors that are used alongside local anaesthetics?

Answer 32

**Adrenaline:** * stimulates a-adrenoceptors that constrict blood vessels **felypressin:** * this is an analogue of vasopressin * it causes vasoconstriction but is less effective than adrenaline * it has no effect on heart conduction/contraction

Question 33

What are common combinations of local anaesthetics and vasoconstrictors?

Answer 33

* Lignocaine with adrenaline * prilocaine with felypressin

Question 34

What are the 2 main adverse effects of local anaesthetics?

Answer 34

* Hypersensitivity (allergic response) * methaemoglobinaemia

Question 35

What are the characteristics of a hypersensitivity reaction associated with local anaesthetics?

Answer 35

The anaphylactic reaction can range from a skin rash to full anaphylactic shock it is common with **ester LAs**, but rare with amides is often a reaction to **preservatives**, rather than the LA itself

Question 36

Why does methaemoglobinaemia occur? What are the associated symptoms?

Answer 36

It is the main toxic effect of **prilocaine** due to its metabolite *0-*toludine this oxidises ferrous to ferric ions **symptoms:** * cyanosis * lethargy * respiratory distress, which does not respond to oxygen **treatment:** * IV methylene blue - 1.5 mg per kg

Question 37

How does the severity of side effects of LA toxicity change with plasma concentration?

Answer 37

At very low doses, LAs can stabilise the heart and be anti-arrhythmic as plasma concentration increases, the severity of side effects increase

Question 38

What are the side effects of local anaesthetics in order of increasing severity?

Answer 38

As plasma concentration of LA increases, the severity of the side effects increases from: 1. Circumoral and tongue numbness 2. Lightheadedness and tinutis 3. Visual disturbances 4. Muscular twitching 5. Convulsions 6. Unconsciousness 7. Coma 8. Respiratory arrest 9. CVS depression

Question 39

What are the first stages in treatment of local anaesthetic toxicity?

Answer 39

* Stop injecting the local anaesthetic * call for help **A:** * maintain the airway * if necessary, secure it with a tracheal tube **B:** * give 100% oxygen and ensure adequate lung ventilation **C:** * confirm or establish intravenous access * Assess cardiovascular status throughout*

Question 40

What are the further steps involved in treatment of LA toxicity?

Answer 40

**D:** * control seizures * benzodiazepine, thiopental or propofol **Consider drawing blood for analysis** **In circulatory arrest:** * Start cardiopulmonary resuscitation * use standard protocols **Give intravenous lipid emulsion**

Question 41

What are the toxic doses of lidocaine and bupivacaine?

Answer 41

**Lidocaine:** * 3 mg/kg * 7 mg/kg with adrenaline **Bupivacaine:** * 2 mg/kg * 2 mg/kg with adrenaline also

Question 42

What is the toxic dose of prilocaine?

Answer 42

6 mg/kg or 8 mg/kg with adrenaline