local anaesthetics

Question 1

what are local anaesthetics?

Answer 1

drugs that reversibly block neuronal conduction when applied locally

Question 2

describe the generation of an action potential

Answer 2

1. Depolarising stimulus – Na+ channels open, Na+ enters cell.
2. Inactivation – Na+ channels close, K+ channels open, K+ leaves cell.
3. Cell refractory state – Na+ channels restored to resting state but K+ channels still open so cell is refractory.
4. Resting state – Na+ and K+ channels restored to resting state.

Question 3

what are the 3 components of a local anaesthetic?

Answer 3

o Aromatic region – very lipid-soluble/hydrophobic.

o Amine side-chain – hydrophilic. derivatives of ammonia

o Ester (COO)or Amide (NHCO) bond. bridge the two other groups together 
--> give rise to the 2 classes 

eg cocaine- ester
lidocaine (xylocaine)-amide

Question 4

describe the hydrophilic pathway MOA of local anaesthetics

Answer 4

LA is injected close to connective sheath

equilibrium is created between ionized and unionized form of the LA

the unionized version can defuse through the sheath and enter the inside of the neurone

then once within the neurone, the cationic (ionised) form of the anaesthetic will bind to the inside of the VG Na channels

this reduces Na influx which therefore reduce the action potential stimulation

Question 5

what are the effects of local anaesthetics?

Answer 5

They:

Prevent generation and conduction of APs

Do NOT influence resting membrane potential

May also influence channel gating

Selectively block:

• small diameter fibres
• non myelinated fibres (LA can get into the neurone more effectively and quicker)

all are weak bases so action is pH dependent

Question 6

what are the different methods/routes of administration?

Answer 6

1. surface
   - mucosa surface
   - spray or powder
   - requires high concentrations as not very efficient –> can give rise to systemic complications
2. infiltration anaesthesia
   - directly into tissues subcutaneously –> acts on sensory nerve terminals
   - used for minor surgical procedures
   - may be given adrenaline co-injection to minimise risk of systemic concentrations (vasoconstrictor so confines LA to site and minimises LA that escapes into systemic circulation)
3. intravenous regional anaesthesia
   - IV distal to pressure cuff (restricts blood flow)
   - limb surgery
   - may get systemic toxicity if cuff is released too soon
4. nerve block anaesthesia
   - eg. dental anaesthesia
   - injected close to nerve trunks
   - widely used- low doses (becuase injecting close to nerve), but slow onset
   - vasoconstrictor co injection
5. spinal anaesthesia
   - injected in the CSF of the sub arachnoid space and enters spinal roots (aka intrathecal)
6. epidural anaesthesia
   - injected into fatty tissue of epidural space
   - more restricted action as it doesnt dissolve in the CSF

Question 7

what does the addition of glucose do to the LA

Answer 7

increases its specific gravity which means you can control the localisation of the anaesthesia

used for spinal anaesthesia

Question 8

what are some unwanted effects of lidocaine? also common SE of LAs

Answer 8

CNS:
stimulation
restlessness, confusion, irritability
tremor

CVS:
myocardial depression
vasodilatation
↓ b.p.

Question 9

what are some unwanted effects of cocaine?

Answer 9

CNS:
euphoria, excitation

CVS:
↑ C.O.
vasoconstriction
↑ b.p.