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
Difference between method of metabolism of ester- vs amide-type LA
plasma/tissue non-specific esterases vs hepatic enzymes
26
Which type of LA can patients with chronic liver disease not use?
Amide-type, metabolised by hepatic enzymes
27
What is a toxicity arsing from large dose of LA?
Systemic toxicity
28
How can we minimise LA systemic toxicity?
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
Most cardiotoxic LA
bupivacaine - use with caution in patients with heart disease
30
Cocaine toxicity
Blocks NA reuptake, increased NA in synapse and cause vasoconstriction + hypertension
31
What is the metabolite of prilocaine and what toxicity does it induce?
O-toluidine: causes methaemoglobin
32
How can we treat O-toluidine toxicity?
iv methyleneblue/ascorbic acid to convert methaemoglobin back to Hb
33
What are ester LAs hydrolysed into?
PABA derivatives
34
What kind of toxicity can PABA derivatives cause?
allergic rections in a small percentage of population
35
Which LA is most often used for ear, nose and throat procedures?
Cocaine: gives good penetration and vasoconstriction | - surface anaesthesia requires rapid penetration of the skin (mucosa) and limited tendency to diffuse away
36
Surface anaesthetics
lidocaine, tetracaine (amethocaine), dibucaine, benzocaine