Local Anesthetics

Question 1

What is the difference between LA and GA?

Answer 1

LA is as effective but safer than GA!

Question 2

What is a local anesthetic?

Answer 2

A local anesthetic is a drug that causes reversible local anesthesia and a loss of nociception by blocking afferent activity in the peripheral and CNS produced by stimulation of specialised nociceptors or “pain receptors” that only respond to tissue damage caused by intense chemical, mechanical or thermal stimulation.

Question 3

What are the various techniques of local anesthesia?

Answer 3

Administered to the site of action using:

1. Topical Anesthesia (surface)
2. Infiltration (into subcutaneous tissue)
3. Plexus block (bundle of nerves)
4. Epidural (Extradural) block
5. Spinal anesthesia (subarachnoid block)

4 and 5 are for lower limb/abdomen

Question 4

Which technique of local anesthesia is most commonly used by dentist?

Answer 4

Infiltration

Question 5

What are the effects of LA?

Answer 5

Analgesia (loss of pain sensation) and Paralysis (loss of muscle power)

Question 6

What are the adverse effects of LA?

Answer 6

Depends on: LA, method, site of administration

1. Localised prolonged anesthesia or Paresthesia
   Caused by Infection, hematoma, excessive fluid pressure in a confined cavity, severing of nerves and support tissue during injection
2. Systemic reactions - when LA is accidentally injected into the bloodstream
   Causes depressed CNS syndrome, allergic reaction, vasovagal episode, and cyanosis due to local anesthetic toxicity

Question 7

What is the pKa of LA?

Answer 7

8-9 (weak base)

Question 8

What are examples of LA which are part of the amide group?

Answer 8

Lidocaine
Mepivacaine
Bupivacaine
Etidocaine
Prilocaine

Question 9

What are examples of LA which are part of the ester group?

Answer 9

Cocaine
Procaine
Chloroprocaine
Tetracaine

Question 10

What is the chemical structure of LA?

Answer 10

A lipophilic group connected via an amide or ester link to an ionisable group

Question 11

Why do ester LAs have a shorter duration of action?

Answer 11

This is because ester links are more prone to hydrolysis

Question 12

Which form of LAs is most active

Answer 12

The charged form of LAs are the most active, as it cannot readily exit closed Na channels

Question 13

What is the uncharged form of LA good for?

Answer 13

The uncharged form of LAs is important for rapid penetration of the lipid membranes.

Question 14

Why are LAs less effective when injected into acidic tissues? (Inflamed or ischemic tissues)

Answer 14

This is because a smaller proportion of it will be unionsed and available for diffusion into nerves. Only uncharged forms of LAs can rapidly penetrate into lipid membranes.

Question 15

What does absorption and distribution of LA determine?

Answer 15

Offset of action and systemic toxicity

This is because LA is usually injected around nerves.

Question 16

What is systemic absorption dependent on?

Answer 16

1. Dosage
2. Site of injection (increase blood supply in highly vascular areas eg. trachea increases absorption and distribution)
3. Tissue binding
4. Local blood flow
5. Use of vasoconstrictors eg. epinephrine (decreases blood flow) to prolong the action
6. Drug properties

Question 17

How are Esther type LAs metabolised?

Answer 17

Esther type LAs are rapidly hydrolysed in the blood by circulating butyrylcholinesterases to inactive metabolites (very short plasma life)

Question 18

How are Amide type LAs metabolised?

Answer 18

Amide type LAs are metabolised in the liver by microsomal cytochrome P450 isoenzymes

Question 19

What medical conditions result in a reduced metabolism of Amide type LAs?

Answer 19

1. Liver Disease
2. Reduced hepatic flow (patients anaesthetised with volatile anaesthetics)
3. Under concomitant medications competing for OR inhibiting cytochrome P450 enzymes

Question 20

How are the metabolites of both Esther and Amide type LAs excreted?

Answer 20

Kidney

Question 21

What is the mechanism of action of LAs?

Answer 21

They bind to receptors near the intracellular end of sodium channels to increase the threshold for excitation. This is a voltage and time dependent blockage (effect is more marked in rapidly firing fibres eg. pain fibres). There is hence a reduction of depolarisation and prolongation of repolarisation. Thus it has anti-inflammatory effects.

Question 22

At physiologic pH, which form of LA is favoured?

Answer 22

The charged cationic form, which is the active form at the receptors (Na+ channels).

Question 23

Why does LA need to cross the cell membrane?

Answer 23

This is because the drugs can only access the receptors from the inside of the cell, and only the uncharged (hydrophobic) form can cross the cell membrane.

Question 24

Why is LA a use dependent drug?

Answer 24

It has a use dependent block due to better access of drug to the binding site only when the channel opens frequently.

Question 25

Where are sodium channels found?

Answer 25

Along the axon of the nerves inside and outside of the CNS

Question 26

What are the 3 factors which affect the susceptibility of nerve fibres to LA blockade?

Answer 26

1. Fibre diameter Smaller fibre diameter (eg. pain) which are unmyelinated can only passively propagate electrical impulses over a short distance (easier to block the propagation) Larger myelinated fibre diameters need at least 2 or 3 nodes of ranvier to be blocked to halt impulse propagation (more difficult to block propagation) 2. Firing frequency Sensory (pain) fibres have a higher firing rate than motor fibres 3. Fibre position on nerve bundle For large nerve trunks, fibres located circumferentially are the first to be exposed to local anesthetics injected into surrounding tissues. Hence proximal sensory is lost first before distal sensory

Question 27

What is the diameter of pain fibres (Type C)

Answer 27

0.4 to 1.2 um

Question 28

Are pain fibres (type C) myelinated?

Answer 28

No.

Question 29

What are the usual routes of administration of LA?

Answer 29

1. Topical Eg. Nasal mucosa, wound margins. perineural 2. Major Nerve Trunks (blocks) Eg. Brachial plexus 3. Spinal Eg. Sympathetic ganglion Epidural (extradural) blockade Subarachnoid (spinal) blockade 4. Intravenous * exception to injecting into blood Injected into distal vein of limb isolated by proximal tourniquet (Bier block - prevents LA from becoming systemic) 5. Tigger points - to locate where/what is causing pain

Question 30

What are the different duration of effects for LAs plus an example of each

Answer 30

``` Short Acting: Procaine (Less hydrophobic) Medium Acting: Lidocaine Long Acting (120-240 mins): Bupivacaine (more hydrophobic) ```

Question 31

How do you prolong the effect of LA?

Answer 31

1. Increasing the dose | 2. Adding a vasoconstrictor (less blood flow so less absorption into systemic hence slower offset)

Question 32

How do you accelerate the onset of action of LA?

Answer 32

1. Add sodium bicarbonate (less acidic) into solutions - more unionised forms of LA hence more diffusion through cell membrane to get to intracellular end of Na+ receptor hence faster onset 2. Choose local anesthetic with rapid penetration of skin

Question 33

What are the possible direct toxic effects of LA?

Answer 33

Direct neurotoxicity | High concentrations in close proximity to spinal cord or nerve trunks)

Question 34

What are the possible systemic toxic effects of LA?

Answer 34

Systemic toxicity from rapid absorption or accidental IV administration 1. CNS a. Sleepiness, light headedness, visual and auditory disturbances, restlessness b. Circumoral and tongue numbness, metallic taste c. Nystagmus and muscle twitching d. Seizures e. Coma 2. Cardiovascular (direct effect on cardiac and smooth muscle + indirect effect on autonomic nervous system) a. Depress myocardial contractility, produce arteriolar dilation and hence systemic hypotension b. Arrhythmias 3. Haematology Accumulation of prilocaine (amide) metabolite may cause methemoglobinema d. Allergic reactions Metabolites of ester type LAs

Question 35

If patient is allergic to procaine, should lidocaine be used?

Answer 35

Yes. Procaine is esther LA while lidocaine is amide LA hence allergic reactions are unlikely.

Question 36

What does tonic-clonic movements of a patient signify?

Answer 36

Systemic toxicity

Question 37

What is the treatment for a patient who is experiencing systemic toxicity from LA?

Answer 37

1. Stop LA 2. Maintain Airway 3. Check Breathing 4. Administer a small dose of benzodiazepine - for seizure control with minimal potential for causing cardiac depression.