Local Anaesthetics Flashcards
The nerve action potential is determined by the action of 2 major currents. outline the two currents and state the ions involved
1) Sodium (Na+) current – inward, depolarizing current
2) Potassium (K+) current – outward, hyperpolarizing current
Voltage-gated Na+ and K+ channels are controlled by ‘gates’. which gates specifically activate and inactivate Na+ and K+ channels?
1) Na+ channels:
- activation m-gate
- inactivation h-gate
2) K+ channel:
- Activation n-gate
explain the ‘all-or-nothing’ principle
If that stimulus exceeds the threshold potential, the nerve or muscle fiber will give a complete response. APs have similar magnitude and duration
what happens in the absolute refactory period (ARP) and relative refractory period (RRP) of an action potential?
1) In the ARP period, Na+ channels are open or inactivated, an AP cannot be elicited
2) In the RRP period, K+ channels are open, membrane is hyperpolarized and a stronger stimuli is required to elicit an AP
describe how an action potential is propagated
generated at the axon hillock propagates as a wave along the axon. The currents flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane.
outline how Local anaesthetics work
1) LA’s reversibly block the generation and conduction of action potentials
2) LA’s are weak bases (pKa ~8-9) and largely ionised at neutral pH. they act via hydrophobic or hydrophilic pathways depending on their ionisation state.
3) Must cross membrane in unionised form (B) to act. The charged form (BH+) is thought to bind to inner pore to block conductance
4) Hydrophilic pathway: Major mode of LA action ~90% of action.
- Hydrophobic pathway: Secondary mode of mode of LA action ~10% of action
the Hydrophilic pathway is the major mode of action (90%) for local anaesthetics and is use dependent. what is meant by use dependent?
Use-dependence: the more the channel is open the greater the drug block. Due to increased access to drug binding site
outline the characteristics of local anaesthetic action
1) Different duration of action/degree of tissue penetration
2) Use-dependent block of Na+ channels
3) Preferential block of small diameter nerve fibres:
nociceptive C and Aδ fibres tend to be blocked more readily than larger Aβ fibres
4) Preferential block of the inactivated state of Na+ channels : LA’s have a higher affinity for the inactivated state rather than the resting state
Local anaesthetics action is dictated by chemical composition and rout of administration. what are the different routes local anaesthetic can be administered?
1) Surface anaesthesia
2) Infiltration anaesthesia-
3) Nerve block anaesthesia
4) Spinal anaesthesia
5) Epidural anaesthesia
6) Intravenous regional anaesthesia
what is surface anaesthesia and give examples of available products
Applied directly to mucous membrane as solution, spray, lozenge or cream:
1) lidocaine applied to mouth/pharynx, bronchial tree
2) Applied topically to the cornea e.g. oxybuprocaine and tetracaine
3) Applied directly to skin: e.g. EMLA, Ametop (tetracaine) gel
what is Infiltration anaesthesia and what are the dangers of using this method?
1) Injected directly into tissue to anaesthetize nerve ending (e.g. lidocaine/ prilocaine for wound stitching, minor surgery)
2) Danger of systemic toxicity/vascular injection (use vasoconstrictors)
what is nerve block anaesthesia?
Injected close to (but not into) nerve trunk to anaesthetize whole area of nerve distribution: e.g. bupivacaine block of mandibular nerve in dental surgery; also used to relieve neuropathic pain
1) what is spinal anaesthesia and when is it used?
2) what are the problems with using this method?
1) Injected into subarachnoid (intrathecal) space of spine (between 2nd and 5th lumbar vertebrae) e.g. bupivacaine
2) Used in caesarean section, rectal surgery due to long duration of action.
3) Great technical skill required to avoid side effects on CNS, such as infection or depressant effects causing respiratory paralysis and cardiac depression
what is epidural anaesthesia?
LA Injected directly into epidural space e.g. bupivacaine used in obstetrics (larger doses needed c.f. spinal anaesthesia)
Intravenous regional anaesthesia?
Injected into limb, LA diffuses rapidly to desired site of action
(systemic toxicity prevented by a cuff)
