analgesia and anaesthesia

Question 1

define local anaesthetic

Answer 1

drug which reversibly blocks neuronal conduction when applied locally

Question 2

describe process of generation of neuronal action potential (“all or nothing” response in 10-15ms)

Answer 2

depolarisation (from -70mV) -> resting voltage-sensitive Na+ channels open -> Na+ enters cell -> Na+ channels close (inactivation), K+ channels open (start at depolarisation but take longer) -> K+ leaves cell -> Na+ channels restored to resting state, but K+ channels still open, so cell refractory (can create new depolarisation if greater stimulus) -> Na+ and K+ channels restored to resting state, so cell will respond normally to further depolarising stimuli

Question 3

5 examples of local anaesthetics

Answer 3

procaine, cocaine, lidocaine, bupivacaine, benzocaine (doesn’t have amine side-chain so surface anaesthetic as weak but more lipid soluble)

Question 4

what is structure of local anaesthetic important for

Answer 4

mechanism of action, pharmacokinetics

Question 5

3 main areas of structure of local anaesthetics

Answer 5

aromatic region, ester or amide bond, basic amine side-chain

Question 6

example of local anaesthetic with ester bond

Answer 6

cocaine

Question 7

example of local anaesthetic with amide bond

Answer 7

lidocaine

Question 8

mechanism of action of local anaesthetics with Na+ channels of sensory neurone: hydrophilic pathway (main)

Answer 8

applied close to trunk -> ionised and unionised form reach equilibrium -> unionised form crosses connective tissue sheath -> crosses neurone -> ionised and unionised form reach equilibrium -> ionised (cation) form binds inside voltage-sensitive Na+ channel (channel must be open, so if firing more rapidly, local anaesthetic has greater effect - use dependency so gives degree of selectivity) -> prevent Na+ influx

Question 9

describe local anaesthetic effect in motor vs sensory neurones

Answer 9

block of motor neurone not as effective as sensory neurone (due to myelination)

Question 10

mechanism of action of local anaesthetics with Na+ channels of sensory neurone: hydrophobic pathway

Answer 10

increased lipid solubility: diffuse in membrane -> ionised and unionised form reach equilibrium -> ionised (cation) form binds inside voltage-gated Na+ channels (channels don’t need to be open) -> prevent Na+ influx

Question 11

4 effects of local anaesthetics

Answer 11

prevent generation and conduction of action potentials, don’t influence resting membrane potential, may influence channel gating (e.g. binding preferentially to inactivated voltage-gated Na+ channels, increasing refractory period), selectively block small diameter (ad and C-fibres) and non-myelinated fibres (as well as firing rate)

Question 12

what are local anaesthetics (acid or base), and effect on mechanism of action

Answer 12

weak bases (pKa 8-9), so mechanism of action is pH dependent

Question 13

why is it more difficult to anaethetise infected tissue

Answer 13

tends to be more acidic, so more is ionised so less can enter neurone

Question 14

6 routes of local anaesthetic administration

Answer 14

surface, infiltration, i.v. regional, nerve block, spinal, epidural

Question 15

describe surface local anaesthetic administration (where, how and dose)

Answer 15

mucosal surface (mouth, bronchial tree) by spray (or powder), requiring high concentration

Question 16

consequence of using high concentrations of surface local anaesthetic administration

Answer 16

systemic toxicity

Question 17

describe infiltration local anaesthetic administration (where and when)

Answer 17

directly into tissues (sensory nerve terminals) for minor surgery

Question 18

why does infiltration local anaesthetic require co-injection of adrenaline (not for extremities to avoid ischaemic tissue damage)

Answer 18

vasoconstrictor so limits distribution (lower dose, reduce risk of systemic toxicity)

Question 19

describe i.v. regional local anaesthetic administration (where and when)

Answer 19

i.v. distal to pressure cuff for limb surgery

Question 20

when can systemic toxicity occur with i.v. regional local anaesthetic administration

Answer 20

premature cuff release (leave it on for at least 20 minutes, so most diffused into tissue)

Question 21

describe nerve block local anaesthetic administration (where, what does this require, dose, onset)

Answer 21

close to nerve trunks e.g. dental nerves, with vasoconstrictor co-injection, with low doses and slow onset (wait to diffuse across connective tissue)

Question 22

describe spinal central anaesthetic administration (dose, where, and when)

Answer 22

low doses into CSF in sub-arachnoid space for spinal roots in abdominal, pelvic and lower limb surgery

Question 23

2 consequences of spinal central anaesthetic

Answer 23

blood pressure drop (preganglionic SNS neurones are narrow diameter, so blocked as well), prolonged headache (CSF into brain or leakage)

Question 24

why is glucose added to spinal central anaesthetic

Answer 24

increase specific gravity, so can move bolus around spinal cord to localise anaesthesia

Question 25

describe epidural central anaesthetic administration (where, onset, dose)

Answer 25

into fatty tissue of epidural space to effect spinal roots, with slower onset so requires higher doses

Question 26

when is epidural central anaesthetic administration used

Answer 26

same as spinal (spinal roots in abdominal, pelvic and lower limb surgery), and painless childbirth

Question 27

why is systemic toxicity of epidural central anaesthetic less than spinal central anaesthetic

Answer 27

more restricted action as doesn't diffuse into CSF (less effect on blood pressure drop)

Question 28

location of injection of spinal or epidural anaesthesia

Answer 28

between L3 and L4 to avoid spinal cord

Question 29

pharmacokinetics: absorption, distribution (plasma protein binding %), metabolism and plasma half life of lidocaine (amide)

Answer 29

good absorption, 70% plasma protein binding, hepatic metabolism (N-dealkylation), plasma half life of 2 hours (more stable)

Question 30

pharmacokinetics: absorption, distribution (plasma protein binding %), metabolism and plasma half life of cocaine (ester)

Answer 30

good absorption, 90% plasma protein binding, liver and plasma metabolism (non-specific esterases), plasma half life of 1 hour (less stable)

Question 31

bupivacaine duration of action and use

Answer 31

6 hours, so used for epidural anaesthesia

Question 32

paradoxical CNS unwanted effects of lidocaine (more normal for local anaesthetics) due to GABA receptors (inhibition) being sensitive at low doses

Answer 32

stimulation, restlessness, confusion, tremor

Question 33

CVS unwanted effects of lidocaine due to Na+ channel blockade on cardiac myocytes

Answer 33

myocardial depression, vasodilation, decreased blood pressure

Question 34

2 CNS unwanted effects of cocaine (less normal for local anaesthetics) due to central sympathetic actions (blocks monoamine reuptake)

Answer 34

euphoria, excitation

Question 35

3 CVS unwanted effects of cocaine due to central sympathetic actions (blocks monoamine reuptake)

Answer 35

increased cardiac output, vasoconstriction, increased blood pressure