Lecture 12: Local anaesthetics

Question 1

Describe the physiology of nerve conduction

Answer 1

Dendrites- nucleus - axon (myelinated), node of ranvier (with voltage sensitive ion channels) - axon terminals- new neuron

Question 2

Describe the physiology of nerve conduction (conceptual operation of voltage gated sodium channels)

Answer 2

1) Resting -Activation gate (AG) = closed -Deactivation gate (DG) = open
2) Threshold depolarisation -AG = open -DG = open
3) Automatic deactivation -AG = open -DG = closed (after miliseconds)
4) Recovering -AG = closes -DG = opens

Question 3

What is the effect of anaesthetic on Action Potentials?

Answer 3

1) depolarsiation is prevented
2) threshold and resting potential is unchanged

Question 4

Describe the structure-activity relationship of local anaesthetics

Answer 4

Ester or amide bonds determine 1) site of metabolism and 2) potential to produce allergic reactions.

Esters are more rapidly metabolised (& shorter acting) and more allergenic (Don’t really use esters anymore)

Lengthening the akyl chain increases lipid solubility.

In general, more lipid soluble = more potent

Question 5

Name 1 important ester and 4 important amides

Answer 5

Ester: Cocaine

Amide:

1) Prilocaine
2) Lignocaine
3) Bupivacaine
4) Ropivacaine

Question 6

Lengthening the akyl chain _________________. In general, more lipid soluble = ______ potent

Answer 6

Lengthening the akyl chain increases lipid solubility. In general, more lipid soluble = more potent

Question 7

What is the most important factor determining speed of onset for a local anaesthetic drug injected into health subcutaenous tissue?

Answer 7

The drug’s pKa

LAH+ -> <- LA + H+ (if pKa is high, LAH is high, if the pKa is low, LA is high)

(LA = free base. Only the free base can cross the membrane and enter cells so you want a drug with a low pKa)

Question 8

All local anaesthetics are _________

Answer 8

Weak bases

Question 9

LAs with pKa closest to physiological pH have __________

This explains ________________

Answer 9

Fastest onset of action

This explains poor quality of block when LA injected into acidic infected tissue.

Question 10

_____________ affinity for protein = increased duration of action

Answer 10

Increased

Question 11

What is the mechanism of action of local anaesthetics?

Answer 11

Prevention of voltage dependent increase in Na+ ion conductance (stop Na+ getting into the cell).

LAH and LA exists, but only the LA (non-ionised) form can cross the membrane into the intraceullar fluid. Once it crosses the memrbane, the LA ionises and blocks the ion channel from the inside.

Question 12

How are Esters and Amides metabolised?

Answer 12

Esters: plasma cholinesterases

Amides: (and some cocaine)

1) Liver metabolism
2) Most dependent on liver blood flow because of high extraction ratio.

Question 13

Describe the features of Lignocaine/Lidocaine

Answer 13

1) Amide (standard agent aginst which others are compared)
2) ‘low’ lipid solubility and low potency
3) ‘low’ pKa, highly non-ionized, fast onset
4) lowprotein binding = short duration of action
5) Ideal to cover short surgical procedures e.g. dental or mole removal

Question 14

What local anaesthetics is ideal to cover short surgical procedures?

Answer 14

Lignocaine/Lidocaine

Question 15

Describe Bupivacaine

Answer 15

1) Amide
2) High lipid solubility = more potent than lignocaine
3) High pKa = slower onset than lignocaine
4) High protein binding = Longer duration of action than lignocaine
5) May cause cardio before neurotoxicity (unlike most LA toxicity patterns)
6) Ideal for nerve blocks for analgesia

Question 16

Compare Lignocaine with Bupivacaine

Answer 16

Bupivacaine is more potent than lignocaine

Bupivacaine is slower onset than lignocaine

Bupivacaine is Longer duration of action than lignocaine

Bupivacaine is Ideal for nerve blocks for analgesia

Lignocaine is ideal for short surgical procedures

Question 17

Describe Cocaines

Answer 17

1) Ester
2) Topical to nose
3) Vasoconst.

Question 18

Describe Prilocaines

Answer 18

1) Amide
2) Safest agent, used in IV regional anaesthesia (e.g. Bier’s block)

Question 19

What are Bier’s block?

Answer 19

Intravenous regional anesthesia (IVRA) or Bier block anesthesia is an anesthetic technique for surgical procedures on the body’s extremities where a local anesthetic is injected intravenously.

(Often use Prilocaine)

Question 20

Describe Ropivavaine

Answer 20

1) Amide
2) Slow onset
3) Long acting
4) Less cardaic toxicity compared with bupivacaine.

Question 21

Describe Local Anaesthetic Toxicity

Answer 21

1) Allergic reactions- rare with amides
2) Dose dependent CNS toxicity (seizures, periordal paraesthesiae, tinnitus)
3) Dose dependent Cardiac toxicity (ventricular fibrillation and heart block)
- If you give a large LA into a vein- likely to get a siezure first before the cardiac arrest
- Lignocaine CC: CNS ratio is 7
- Bupivacaine CC: CNS ratio is 3 (therefore both are more likely and more dangerous with bupivacaine).
4) Dose dependent toxicity is usually because of inadvertent IV administration. (= accidently administer into the vein and not the muscle)

Question 22

What are the maximum safe doses of lignocaine and bupivacaine?

Answer 22

5mg/Kg (LEAN body weight) - Lignocaine

2mg/Kg (LEAN body weight) - Bupivacaine

Question 23

What does it mean by “Topical Administration”?

Answer 23

Most often topical administration means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin.

Question 24

Describe Topical Administration and uses

Answer 24

Topical to skin

• EMLA- eutectic mexture of LAs
• Mexure of lignocaine and prilocaine as an oil preparation that allows most to be free base and therefore able to cross skin
• For insertion of IV cannulae in children

Topical to mucous membranes

• Cocaine (added advantage of vasocontriction)
• Lignocaine spray and viscous preparations
• For instrumentaion of the nose/mouth/pharynx

Question 25

Describe the Soft tissue infiltration way of administrating LA

Answer 25

For minor interventions e.g. mole removal

(Fast acting, short duration agent)

For post operative pain relief (slow acting, long duration agent)

Question 26

Name the 4 types of Administration and uses

Answer 26

1) Topical
2) Soft tissue infiltration
3) Block nerve conduction (peripheral, spinal)
4) Epidural anaesthesia

Question 27

Describe the Block nerve conduction type of administration

Answer 27

2 Classifications (neuro and spinal)

1) Peripheral nerve block:

• LA is infiltrated around a specific nerve(s), e.g. a brachial plexus block for surgery on the arm (without general anaesthersia)
• In a mixed nerve, smaller sensory fibre more susceptible, but motor fibres can be affected
• For surgery without general anaesthesia, or for post-operative pain relief (or both)

2) Spinal Anaesthesia

• LA injected into the intrathecal space. Only below L2 where spinal cord terminates- so you don’t damage the SC.
• Profound distal motor and snensory blockade (below the level of injection)
• Allows major surgery (e.g. hip and knee replacement, C section), in awake patients.

Question 28

Describe the Epidural Anaesthesia

Answer 28

• Small catheter inserted into epidural space and LA infused through catheter. Affects spinal nerves passing through space. Can be done at any level
• Distal sensory +-motor blockade
• Excellent post op/labour analgesia if inserted at correct level.
• Hit epidural space at any level. Put the needle in and put the catheter in and insert local anaesthesia. If this goes into the epidural sapce, it can cause a band of numbness. Epidural catheter allow infusion of anaesthesia and can cause prolonged analgesia

Question 29

If you wish to achieve rapid onset of local anaesthesia for insertion of a large intravenous catheter. What local anaesthetic would you choose to infiltrate into the skin.

Answer 29

Lignocaine.

Question 30

What is the difference between spinal nerve block and epidural?

Answer 30

It is easy to confuse a spinal block and spinal epidural because they are both injections into the spinal area.

For a spinal block, narcotics or anesthetic is injected once with a needle.

For a spinal epidural or combined spinal epidural, a catheter is placed in the epidural space to allow continuous anesthesia.