Local Anaesthetic Agents

Question 1

what are the 7 main uses of local anaesthetics

Answer 1

1. topical anaesthesia (desensitize mucous membranes, or intact skin)
2. local infiltration (desensitize dermal or subcutaneous tissues for minor surgery)
3. instillation into cavity or wound (inter-pleural anaesthesia, intra-articular anaesthesia)
4. intravenous regional anaesthesia (bier’s block) (IV admin of lidocaine distal to tourniquet, to desensitize distal limb)
5. peripheral nerve blocks (diagnostically & therapeutically)
6. epidural (desensitive perineum, hindlimb and caudal abdomen)
7. systemic administration (IV infusion of lidocain in very painful patients)

Question 2

what is the definition of pain

Answer 2

an unpleasant sensory and emotional experience associated with actual or potential tissue damage

Question 3

what is the pain pathway

Answer 3

1. nociceptor (generates an action potention)
2. afferent fibre (conducts action potential to CNS transmission)
3. spinal cord (processing occurs at the level of the dorsal horn –> modulation)
4. brain (conscious experience of pain)

Question 4

what is nociception

Answer 4

detection of noxious stimuli that actually or potentially can cause damage to an organism

Question 5

what is the mechanism of action of local anaesthetics

Answer 5

sodium channels are blocked preventing initiation and conduction of action potentials

LA’s are weak bases

Question 6

what is use dependence

Answer 6

channels exist in 3 states

open, inactivated, closed

Question 7

what is the difference in susceptibility

Answer 7

small myelinated (A delta fibres)

small unmyelinated (C fibres)

Question 8

what is the chemical structure of anaesthetic agents

Answer 8

lipophilic aromatic group attached to hydrophilic amine side-chain by ester or amide link

Question 9

what are the physical properties

Answer 9

1. weak bases
2. largely ionized at physiological pH
3. ionization increases as pH falls
4. inflamed tissues may be resistant –> pH dependence

Question 10

what are the pharmokinetics (4)

Answer 10

1. speed of onset related to degree of ionization
2. duration related to protein-binding
3. potency related to lipid solubility
4. other drugs may be added (bicarbonate –> increases pH, adrenaline –> vasoconstricts)

Question 11

how are local anaesthetics eliminated

Answer 11

1. ester-linked drugs –> rapidly hydrolyzed by non-specific cholinesterases, short half-lives
2. amide-linked drugs –> metabolized in the liver, longer half-lives

Question 12

what are the toxicity/side effects of local anaesthetics

Answer 12

harmful effects are most likely to be seen following overdose or accidental intravenous admin

CNS: initial stimulation leading to convulsions later depression leading to coma and death

CVS: myocardial contractility & heart rate fall peripheral vasodilation

MISC: allergic reactions are rare (ester>amide) methaemoglobinaemia

Question 13

how do local anaesthetics cross through the cell membrane to block the Na channels

Answer 13

they are weak bases

they must adopt lipid soluble, uncharged form to get across

depends on pH (less effective in inflamed tissue where lower pH increases ionization)

Question 14

what is no use dependence

Answer 14

the uncharged LAs (benzocaine) and lipid soluble LAs (tetracaine) dissolve in the membrane and block the Na channel from within

Question 15

what is use dependence

Answer 15

with a weak base (lidocaine) the uncharged moitety crosses the membrane

then it becomes ionized and enters the Na channel and blocks it

Question 16

what is the susceptibility to LAs

Answer 16

1. small myelinated (A delta fibres): more susceptible, transmitt pain signals
2. small unmyelinated (C fibres): large motor axons which control movement, resistant