P10: Local Anaesthetics

Question 1

What is the synthetic substitute of cocaine

Answer 1

Procaine

Question 2

What are the major local anaesthetics in use

Answer 2

Lidocaine
Prilocaine
Articaine
Mepivacaine

Question 3

What is the Infiltration method of local anaesthetic

Answer 3

Injection into tissues to reach nerve branches and terminals for minor surgery

Question 4

What is the nerve block method of local anaesthetic

Answer 4

Injection close to the nerve trunk causes loss of peripheral sensation, used for surgery or dentistry - lidocaine, prilocaine

Question 5

What is the surface method of local anaesthetic

Answer 5

Applied as a spray (lidocaine) or powder (benzocaine) to mucus membrnae of the nose, mouth and cornea

Question 6

What is the spinal method of local anaesthetic

Answer 6

Injected into the subarachnoid space to act on spinal roots and cord - lidocaine

Question 7

What is the epidural method of local anaesthetic

Answer 7

injected into the epidural space to block spinal roots.

Question 8

What kind of molecule is lidocaine and describe its features

Answer 8

Amide, slow onset, medium duration of action, widely used

Question 9

What kind of molecule is prilocaine and describe its features

Answer 9

Amide, rapid onset, low toxicity but can cause methaemoglobinaemia

Question 10

Effects of cocaine on NA and DA

Answer 10

Blocks the uptake of these amines

Question 11

What kind of molecule is bupivacaine and describe its features

Answer 11

Amide, slow onset, long duration of action, used for epidural anaesthesia

Question 12

What kind of nerve fibres as more easily blocked

Answer 12

smaller myelinated fibres like Adelta fibres

Question 13

Do local anaesthetics bind more strongly to active or inactive channels

Answer 13

Inactive

Question 14

What is the order of nerve type blockade by increasing concs of LA

Answer 14

Autonomic
Pain
Temperature
Touch
Proprioception
Skeletal muscle tone

Question 15

Why are myelinated fibres easier to block than unmyelinated

Answer 15

Myelinated (autonomic etc) express clustered Na+ channels at nodes of ranvier

Unmyelinated (C fibres etc) expressed Na+ channels along length and yh

Question 16

After voltage gated Na+ channels open what is used to close them

Answer 16

Slow acting inactivation gate that is refractory for 1-5ms

Question 17

What side of an Na+ channel do LAs work on

Answer 17

Intracellular

Question 18

As an LA must enter a neuron to work, what increases LA potency

Answer 18

Increased lipophilicty

Increased non-ionised fraction

Question 19

What is a use dependent block

Answer 19

This means that the more a nerve is stimulated, the faster the onset of the anaesthesia will be

Question 20

Where do all biological reaction take place

Answer 20

Aqueous solution

Question 21

What indicates whether a drug is protonated or not

Answer 21

If environmental pHpKa the drug will dissociate and release a proton

Question 22

Roughly what is the pKa of most LAs

Answer 22

Most LAs are weak bases with pKa - 8.9

Question 23

Are LAs often ionised at physiological pH

Answer 23

Mainly but not completely ionised as the physiological pH is below the pKa.

Question 24

What are the 2 main pathways that LAs can block Na+ channels with

Answer 24

Use Dependent - Hydrophilic

Use Independent - Hydrophobic

Question 25

Why do LAs need to have a weakly basic pKa

Answer 25

It is the ionised form of the drug that binds to the channel interior but only non-ionised forms of the drug can cross the membrane

Question 26

What happens to an LA is the pKa is too low

Answer 26

Drug will stay deionised inside and outside the cell - no blocking

Question 27

What happens to an LA is the pKa is too high

Answer 27

Drug will be ionised - no entry into the axon

Question 28

Due to a combo of pKa and lipophilicity what is a low potency LA

Answer 28

Procaine

Question 29

Due to a combo of pKa and lipophilicity what is an intermediate potency LA

Answer 29

Mepivacaine Prilocaine Chloroprocaine Lidocaine

Question 30

Due to a combo of pKa and lipophilicity what is a high potency LA

Answer 30

Tetracaine Bupivacaine Etidocaine Levobupivacaine

Question 31

What effect does vasodilation have on LAs

Answer 31

Enhanced blood flow at site of action leads to more rapid clearance of administered LA

Question 32

How do LAs cause vasodilation

Answer 32

blockade of sympathetic vasoconstrictive a1 stimulation

Question 33

Why is a low dose of adrenaline given with LAs

Answer 33

To cause vasoconstriction (activation of a1 receptors) preventing loss of anaesthetic

Question 34

Why shouldnt LAs be injected intravenously

Answer 34

Risk of systemic effects

Question 35

What are the 2 classes of LAs based on their structures

Answer 35

Amides or Esters

Question 36

Describe ester LAs metabolism, duration of action and toxic potential

Answer 36

- Rapidly hydrolysed, short t1/2 - Hydrolysed by plasma pseudocholinesterase - Almost no potential for accumulation - Toxicity is either by direct IV injection or repeated exposure

Question 37

Describe amide LAs metabolism, duration of action and toxic potential

Answer 37

- More stable of hydrolysis - Primarily hepatic metabolism - Can accumulate on repeated dosage - Dose related toxicity, may be delayed by minutes to hours

Question 38

What is the easiest way to remember LAs are esters or amides

Answer 38

Amides have an 'i' before the 'caine' suffix

Question 39

What are the benefits and risks of amide LAs compared to esters

Answer 39

Amides have longer t1/2 | Greater risk of toxicity

Question 40

What are early signs of CNS toxicity by LAs

Answer 40

Tinnitus Dizziness Light-headedness

Question 41

What are the symptoms of cardiovascular toxicity by LAs

Answer 41

- Hypotension - Negative inotropism (reduced cardiac contractile force) - Vasodilation by direct actions on smooth muscle and blockade of SNS (except cocaine) - Bradycardia leading to asystole through block of cardaic Na+ channels (not always bad - lidocaine is anti-dysrhythmic cus of this)

Question 42

What usually occurs first CNS or CVS toxicity

Answer 42

CNS

Question 43

What is the key response method to acute toxicity

Answer 43

Maintain oxygenation and normal CO2

Question 44

What factors can increase risk of seizure and/or cardiovascular collapse with acute toxicity

Answer 44

- Cold temperature (slows metabolism) - Metabolic or respiratory acidosis - Hypoxia - Pregnancy