L8 Local Anesthetics Flashcards

1
Q

For ion channels: inactivation vs deactivation

A

ion flow blocked by a gating mechanism vs closing of the channel

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2
Q

What is the MOA of LA?

A

Stop axonal conduction by blocking sodium channels in axonal membrane

  • when applied locally in appropriate concentration
  • prevent sodium ion entry
  • slow down or bring conduction to a halt
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3
Q

Many LAs bind most strongly to the

A

inactivated and activated states

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4
Q

Passage of train of action potentials causes the sodium channel to

A

cycle through open and inactivated states

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5
Q

depth of LA nerve block increases with action potential frequency because LA molecules

A
  • gain access to the channel more easily when channel is open
  • have higher affinity for the inactivated than for the resting (closed) channels
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6
Q

Depth of LA nerve block increases with action potential frequency because LA molecules

A
  • gain access to the channel more easily when channel is open
  • have higher affinity for the inactivated than for the resting (closed) channels
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7
Q

Are LAs selective/non-selective modifiers of neuronal function?

A

non-selective ie. they will block action potentials in all neurons to which they have access

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8
Q

How to achieve selectivity for LAs?

A

by delivering LA to a limited area: topical dosage form or superficial injection

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9
Q

Factors affecting LA action (3)

A

lipid solubility, nerve types (size, frequency, position, myelination), pH dependency

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10
Q

Are more/less lipid soluble drugs more potent and act longer?

A

More

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11
Q

Examples of more hydrophobic LA

A

Tetracaine, etidocaine, bupivacaine

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12
Q

Examples of less hydrophobic LA

A

Lidocaine, procaine, mepivacaine

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13
Q

Does more potent or longer of duration equate to better efficacy?

A

Depending on applications!

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14
Q

Is size or myelination a more important factor affecting LA action?

A

size

  • small myelinated axons > small non-myelinated axons > large myelinated axons
  • nociceptive and sympathetic transmission is blocked first
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15
Q

LA molecules are

A
weak bases (pKa 8-9)
- mainly (but not completely) ionized at physiological pH
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16
Q

LA binding site

A

inner end of the sodium channel

- must penetrate nerve sheath and axon membrane to reach

17
Q

Does LA work better in acidic or alkaline pH?

A

Alkaline, low proportion of ionized molecules, increased LA activity

18
Q

Examples of LA in the esters class

A

cocaine, procaine, pontocaine, benzocaine

19
Q

short acting ester LA

A

procaine (Novocain)

20
Q

long acting ester LA

A

pontocaine

21
Q

Examples of LA in the amides class

A

lidocaine, mepivacaine, bupivacaine

22
Q

long acting amide LA

A

bupivacaine (Marcaine)

23
Q

medium acting amide LA

A

lidocaine, mepivacaine

24
Q

Does ester- or amide-type LA have a lower incidence of allergic reactions?

A

Amide-type

25
Q

Difference between method of metabolism of ester- vs amide-type LA

A

plasma/tissue non-specific esterases vs hepatic enzymes

26
Q

Which type of LA can patients with chronic liver disease not use?

A

Amide-type, metabolised by hepatic enzymes

27
Q

What is a toxicity arsing from large dose of LA?

A

Systemic toxicity

28
Q

How can we minimise LA systemic toxicity?

A

Combine LA with epinephrine (vasoconstrictor, blood flow at area of application reduced, hence reduced rate of absorption into systemic circulation)
- prevent LA systemic distribution from the site of action

29
Q

Most cardiotoxic LA

A

bupivacaine - use with caution in patients with heart disease

30
Q

Cocaine toxicity

A

Blocks NA reuptake, increased NA in synapse and cause vasoconstriction + hypertension

31
Q

What is the metabolite of prilocaine and what toxicity does it induce?

A

O-toluidine: causes methaemoglobin

32
Q

How can we treat O-toluidine toxicity?

A

iv methyleneblue/ascorbic acid to convert methaemoglobin back to Hb

33
Q

What are ester LAs hydrolysed into?

A

PABA derivatives

34
Q

What kind of toxicity can PABA derivatives cause?

A

allergic rections in a small percentage of population

35
Q

Which LA is most often used for ear, nose and throat procedures?

A

Cocaine: gives good penetration and vasoconstriction

- surface anaesthesia requires rapid penetration of the skin (mucosa) and limited tendency to diffuse away

36
Q

Surface anaesthetics

A

lidocaine, tetracaine (amethocaine), dibucaine, benzocaine