local anaesthesia- pharmacology

Question 1

What is analgesia?

Answer 1

Loss of pain alone

Question 2

What is anaesthesia?

Answer 2

Loss of all forms of sensation

Question 3

What is local anaesthesia?

Answer 3

Loss of sensation in circumscribed areas of body by a depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerves

Question 4

What are the contents of a local anaesthetic cartridge?

Answer 4

Anaesthetic 
Vasoconstrictor 
Vehicle- Ringers solution- isotonic
Reducing agent- sodium metabisulphite (prevents oxidation of adrenaline) brown discolouration
Fungicide- thymol
Preservative- not anymore due to allergy

Question 5

What is the anaesthetic agent?

Answer 5

Weak organic base w general formula
Aromatic group, intermediate chain and amino terminal

Aromatic ring- lipophilic so dissolves in lipid sheath around nerve
Intermediate chain- amides
Amino terminal- hydrophilic, soluble in water so transfers through interstitial fluids

Question 6

Why are amides used instead of esters as intermediate chains?

Answer 6

Ester (cocaine, procaine, amethocaine, benzocaine)
~unstable in solution, not autoclavable, antigenic/allergy

Amides (lidocaine, prilocaine etc)
~stable, autoclavable, v rarely antigenic

Question 7

What are the durations of anaesthetics?

Answer 7

Intermediate-
Lidocaine, prilocaine, mepivacaine, articaine

Long acting-
Bupivocaine

Short acting-
Procaine (but it’s an ester)

Question 8

How does the chemistry of anaesthetics help its function?

Answer 8

For administration- drug dispensed as salt (hydrochloride) to make soluble
In solution- uncharged free base/+ve charge

Uncharged- penetrate membrane so more= faster onset
Charged- binds to specific receptors

Question 9

How does the chemistry of anaesthetics help its function?

Answer 9

Log(ionised/unionised)=pKa-pH

7.4pH (extracellular fluid) needs high  conc of unionised form for faster action
Lower pH (eg infection) less will be unionised so slow action

Question 10

What is the specific mode of action of local anaesthetic?

Answer 10

At rest- nerve membrane largely impermeable to sodium ions

Stimulus reduces electronegative charge to -55mV (firing level) so membrane is highly permeable to sodium ions- action potential

Binding site inside cell so unionised anaesthetic must penetrate epineurium, perineurium and endoneurium

Then reequilibrates to mixed charged and +ve binds to receptor

Question 11

What is the non-specific mode of action of local anaesthetic?

Answer 11

Lipophilic portion causes swelling of membrane to block voltage-gated sodium channels

Initially high threshold for excitation then conduction block

Question 12

What is the effect of anaesthetic?

Answer 12

Affect all nerve fibres
Small (pain and temp) first
Large (motor, proprioceptive) last
Inc. vasomator (blood vessel wall)
~blocks sympathetic vasoconstrictors so dilates
~smooth muscle of vessels varies (cocaine- constricts, lidocaine-dilates

Question 13

How is the anaesthetic detoxified/ broken down?

Answer 13

Esters- esterases in blood and liver broken down into benzoic acids and alcohol- urine (but people lack pseudocholinesterase)

Amides- broken down in liver, oxidised, conjugated w glucuronic acid- urine
Must take care w patients w severe liver disease
Lidocaine half life= 90 mins
However articane, initial breakdown by esterases in plasma, half life= 20 mins

Question 14

What is the ideal anaesthetic?

Answer 14

Compete local analgesia w/o damage
Rapid onset
Predictable
Appropriate duration
Isotonic
Non-toxic
Readily soluble and stable in solution
Adequate shelf life 2-2 1/2 yrs
Sterilisable 
Non addictive

Question 15

Why are vasoconstrictors used?

Answer 15

E.g adrenaline

Delay removal from site
Rapid onset
Prolongs and enhances effect
Reduces operative bleeding

However,
Longer anaesthetic can be unpopular w patients
Potential systemic effects w intravascular injection

Question 16

How does the vasoconstrictor- adrenaline affect the patient in 2 LA cartridges?

Answer 16

Used as 1:80000 in lidocaine
Affects alpha and beta receptors
\+ve inotropic and chronotropic effects
Affects-
Slight reduction in diastolic BP
Vasodilation of muscles
Vasoconstriction of skin
Increases rate and force of heart contractions 
Increases glucose
Reduces potassium
So higher potential for arrhythmias

Question 17

How do the vasoconstrictors- noradrenaline and felypressin affect the patient?

Answer 17

Noradrenaline- high BP can lead to stroke (don’t use in UK)

Felypressin (octapressin)- synthetic polypeptide, usually w prilocaine, less cardiovascular effects than adrenaline
However, affects uterus so pregnancy avoid

Question 18

What is lidocaine?

Answer 18

2% solution (20mg/ml), 1:80000 adrenaline
Max total dose- 4.4mg/kg in healthy adult (approx 7 cartridges)
Rapid onset, good penetration
Also, 5% ointment, 4%/10% spray and 2% gel for topical

Kg of person x 4.4mg= ?mg
?/20= ??ml of 2%
??/2= ??? x 2ml cartridges

Question 19

What is mepivacaine?

Answer 19

3% plain w/o vasoconstrictor better than lidocaine, good for short procedures

2%, 1:80000 adrenaline, indistinguishable from lidocaine

Question 20

What is bupivocaine?

Answer 20

0.5% solution, 1:200000 adrenaline
Slow onset but v long
Used for major surgery/ short term relief for trigeminal neuralgia

Question 21

What is prilocaine?

Answer 21

4% plain or 3% w felypressin
Rapid onset, good penetration
Use if avoiding adrenaline
Used w lignocaine as Eutectic Mixture of Local Anaesthetics for venepucture in kids