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Y2 - PHARM > Local Anaesthetics > Flashcards

Local Anaesthetics Flashcards

1
Q

Define Local Anaesthetic

A
  • Drugs that reversibly block neuronal conduction when applied locally
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2
Q

All local anaesthetics are weak …..

A

All local anaesthetics are weak bases

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3
Q

Summarise the generation of action potential

A
  • Stimulus causes slight depolarisation away from the resting membrane potential of -70mV
  • Until it reaches a threshold potential
  • At which point there is opening of voltage-gated Na+ ion channels, so there is massive influx of sodium ion channels
  • This causes large, rapid depolarisation (phase 1)
  • Then there is inactivation of Na+ ion channels and opening of K+ channels so efflux of K+ ions - this begins repolarisation (phase 2)
  • Eventually Na+ channels are restored to the resting state but K+ channels still open so there is hyperpolarisation - the neurone is also refractory - i.e. you cannot generate another action potential at this point yet (phase 3)
  • Eventually both the sodium and potassium ion channels will return to their resting state so the cell will respond normally to further depolarising stimulus i.e. it exits the refractory state so now you can generate a new action potential (phase 4)
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4
Q

What is the rapid depolarisation stage of the action potential caused by?

A
  • Stimulus arrives causing depolarisation of the neurone, until it reaches a certain threshold
  • Voltage-gated sodium channels open causing rapid depolarisation
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5
Q

What are the three chemical structural components that make up all local anaesthetics?

A
  1. Aromatic region
  2. Basic amine side-chain
  3. Amide OR ester link
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6
Q

What are the two types of local anaesthetics and what is the basis of this grouping? Give an example of each

A
  • Grouped based on their type of links / bridging groups - either ester or amide link
  1. Ester = COCAINE (remember Ester smokes cocaine)
  2. Amide = LIDOCAINE
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7
Q

1) Name a local anaesthetic that doesn’t fit the structure of all other local anaesthetics
2) What does this mean for its properties and thus what is it useful for?

A

1)

  • Benzocaine – it has an alkyl group rather than the basic amine side chain

2)

  • This means that it is relatively weak but highly lipid soluble. It is good for surface anaesthesia and is often used in throat lozenges
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8
Q

What are the two pathways of local anaesthesia? State which one is more important

A
  1. HYDROPHILIC – most important
  2. Hydrophobic
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9
Q

Describe the hydrophilic pathway

A
  • LA is injected close to sensory neurones
  • Unionised LA from the blood is lipid soluble so crosses the axon membrane and gets into the axon
  • Within the axon it immediately forms the cation (ionised) form of the LA
  • This cation form then binds to the inside of the voltage-gated sodium channels (when they open) and block sodium entry - but the ionised LA can only enter once the sodium ion channel opens
  • This blocks action potential conduction
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10
Q

In the hydrophilic pathway, what is a prerequisite for local anaesthetics to be able to have its effect in reducing pain sensory impulses and what phenomenon is this?

A
  • The sodium ion channels must be open in the sensory neurones (the neurones must be firing and active - which occurs when detecting the pain)
  • This is use dependency within the hydrophilic pathway
  • This also helps give LAs their selectivity
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11
Q

1) Describe the hydrophobic pathway
2) Why does use dependency not occur in the hydrophobic pathway?

A

1)

  • Some very lipophilic local anaesthetics will move into the cell membrane (in unionised form) and then drop straight into the sodium channel
  • It will then become the cation form in the sodium channel
  • From here it will block sodium influx

2)

  • Because it does not require the sodium ion channels to be open - the unionised LA just goes straight through into the sodium channel and block it from the inside
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12
Q

What effect do local anaesthetics have on resting membrane potential?

A
  • No effect on resting membrane potential
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13
Q

Explain the effect of local anaesthetics on channel gating

A
  • There is some suggestion that local anaesthetics bind more strongly to the sodium channels in their inactive state
  • Once bound to the sodium channel, it then holds it in the inactive stage for longer thus increasing the refractory period and reducing the frequency of action potentials
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14
Q

Explain the effect of local anaesthetics on surface tension

A
  • They lodge into the plasma membrane and reduce surface tension of the membrane
  • This leads to non-selective expansion of the lipid membrane and leads to non-specific inhibition of ion channels
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15
Q

Describe the selectivity of local anaesthetics - 3 ways that they are selective for pain receptors

A
  • Preference for small diameter axons (useful since nociception neurones are small diameter - therefore more selective for pain)
  • Tend to block non-myelinated axons - like pain C-fibres
  • Use-dependency - when there are lots of pain impulses firing, the sodium ion channels will be open a lot in the nociceptors, therefore the local anaesthetics can enter
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16
Q

What is the pKa of all local anaesthetics?

A
  • 8-9 All local anaesthetics are WEAK BASES
17
Q

Explain why it is difficult to anaesthetise infected tissue

A
  • Infected tissue is ACIDIC
  • So the LA will be largely in its ionised form here so less will be unionised and therefore cannot cross coonnective tissue sheaths and axonal membranes as easily to have its effect
18
Q

What are the 6 methods of administration of local anaesthetics?

A
  1. Surface anaesthesia
  2. Infiltration anaesthesia
  3. Intravenous regional anaesthesia
  4. Nerve block anaesthesia (close to nerve trunk)
  5. Spinal anaesthesia
  6. Epidural anaesthesia
19
Q

What are the consequences of using high doses in local anaesthesia?

A
  • It can cause systemic toxicity
20
Q

1) What is surface anaesthesia?
2) What is a problem with surface anaesthesia?

A

1)

  • Application of local anaesthetics at mucosal surfaces
  • Often in spray form

2)

  • Problem is we need high concentrations of LA to be effective
  • However, high concentrations can lead to systemic toxicity
21
Q

What is infiltration anaesthesia?

A
  • Injection of anaesthetic subcutaneously, directly into the tissue near the sensory nerve terminals
  • It is used for minor surgery
22
Q

1) What is often coadministered with infiltration anaesthesia and what are the benefits of this?
2) Why can’t we co-administer this if the site of the infiltration anaesthesia is at the extremities?

A

1)

  • Adrenaline
  • Causes vasoconstriction - increases the duration of action of the anaesthetic meaning that a lower dose can be used
  • Reduces the amount of local anaesthetic going into the systemic circulation - so it limits the systemic side effects (thus limits toxicity)
  • It also slows bleeding at the site of injection

2)

  • If adrenaline is injected at the extremities it can lead to ischaemic damage
23
Q

What is intravenous regional anaesthesia and how can this cause systemic toxicity?

A
  • Anaesthetic is administered intravenously
  • Pressure cuff is used to cut off the blood supply downstream of it
  • Removing the pressure cuff too early can lead to a bolus of anaesthetic entering the systemic circulation
  • From here it can cause systemic toxicity - particularly dangerous as it can cause toxicity in the brain
24
Q

What is nerve block anaesthesia? Describe the dosage and onset

A
  • Inject anaesthetic close to the nerve trunks
  • Low doses and slow onset
25
Q

What is coadministered with nerve block anaesthesia?

A
  • A vasoconstrictor e.g. adrenaline
26
Q

What is another name given to spinal anaesthesia?

A
  • Intrathecal (into subarachnoid space)
27
Q

Where is the anaesthetic inserted in spinal (intrathecal) anaesthesia?

A
  • Into the subarchnoid space (into the CSF)
28
Q

Which parts of the body can be anaesthetised effectively with spinal and epidural anaesthesia?

A
  • Abdomen, pelvis, lower limbs
29
Q

How does spinal anaesthesia affect blood pressure and why does it have this effect?

A
  • It can cause a drop in blood pressure because it anaesthetises the nerve roots and the preganglionic sympathetic nerves are particularly sensitive to blockade by local anaesthetics
  • This leads to reduced sympathetic output and hence a drop in blood pressure
30
Q

1) What is epidural anaesthesia, what is it useful for?
2) Compare the onset and dosage with spinal anaesthesia
3) Give a problem and 2 advantages

A

1)

  • Anaesthesia injected into the fatty tissue in the epidural space
  • Painless childbirth

2)

  • Slower onset
  • Higher dosage requirement

3)

  • -ve: more likely to develop side effects at higher doses
  • +ve: more restricted action
  • +ve: less effects on blood pressure
31
Q

What trick can anaesthetists do to get better control over the location of the spinal anaesthesia?

A
  • Add glucose to the anaesthetic mixture
  • This increases the specific gravity of the local anaesthetic meaning that the patient can be tilted to move the bolus of anaesthetic to the right place
32
Q

Describe the difference in metabolism of lidocaine and cocaine

A
  • Lidocaine – hepatic – N-dealkylation
  • Cocaine – hepatic and plasma - non-specific cholinesterases
33
Q

Describe the difference in half-life between lidocaine and cocaine

A
  • Lidocaine – 2 hours
  • Cocaine – 1 hour
  • i.e. Lidocaine has a longer half-life than cocaine
34
Q

What are the CNS side-effects of lidocaine? Explain why it has these effects

A
  • CNS stimulation
  • Restlessness
  • Confusion
  • Tremor
  • This is because the GABA system (inhibitory effect on CNS) is very sensitive to local anaesthetics
35
Q

What are the CVS side-effects of lidocaine and what is the underlying principle behind all of them?

A
  • Myocardial depression
  • Vasodilatation
  • Decrease in blood pressure
  • Underlying priniciple: All because of sodium channel blockade
36
Q

What are the CNS side-effects of cocaine?

A
  • Euphoria and excitation
  • Because of blockade of monoamine transporters
37
Q

What are the CVS side effects of cocaine? Explain why it has these effects

A
  • Increased cardiac output
  • Vasoconstriction
  • Increased blood pressure
  • Due to increased sympathetic drive caused by blockade of monoamine transporters

Y2 - PHARM (27 decks)

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