analgesia and anaesthesia Flashcards

local anaesthetics: explain the cellular mechanisms of action of local anaesthetics, their pharmacokinetic profiles and adverse effects

1
Q

define local anaesthetic

A

drug which reversibly blocks neuronal conduction when applied locally

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2
Q

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

A

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

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3
Q

5 examples of local anaesthetics

A

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

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4
Q

what is structure of local anaesthetic important for

A

mechanism of action, pharmacokinetics

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5
Q

3 main areas of structure of local anaesthetics

A

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

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6
Q

example of local anaesthetic with ester bond

A

cocaine

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7
Q

example of local anaesthetic with amide bond

A

lidocaine

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8
Q

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

A

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

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9
Q

describe local anaesthetic effect in motor vs sensory neurones

A

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

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10
Q

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

A

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

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11
Q

4 effects of local anaesthetics

A

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)

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12
Q

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

A

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

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13
Q

why is it more difficult to anaethetise infected tissue

A

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

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14
Q

6 routes of local anaesthetic administration

A

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

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15
Q

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

A

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

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16
Q

consequence of using high concentrations of surface local anaesthetic administration

A

systemic toxicity

17
Q

describe infiltration local anaesthetic administration (where and when)

A

directly into tissues (sensory nerve terminals) for minor surgery

18
Q

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

A

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

19
Q

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

A

i.v. distal to pressure cuff for limb surgery

20
Q

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

A

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

21
Q

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

A

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

22
Q

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

A

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

23
Q

2 consequences of spinal central anaesthetic

A

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

24
Q

why is glucose added to spinal central anaesthetic

A

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

25
Q

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

A

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

26
Q

when is epidural central anaesthetic administration used

A

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

27
Q

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

A

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

28
Q

location of injection of spinal or epidural anaesthesia

A

between L3 and L4 to avoid spinal cord

29
Q

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

A

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

30
Q

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

A

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

31
Q

bupivacaine duration of action and use

A

6 hours, so used for epidural anaesthesia

32
Q

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

A

stimulation, restlessness, confusion, tremor

33
Q

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

A

myocardial depression, vasodilation, decreased blood pressure

34
Q

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

A

euphoria, excitation

35
Q

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

A

increased cardiac output, vasoconstriction, increased blood pressure