PHARM Modulation of Nerve Conduction Local Anaesthetics Flashcards
Myelination & size of A-alpha fibres.
Large, myelinated.
Myelination & size of A-beta fibres.
Large, myelinated.
Myelination & size of A-delta fibres.
Small, myelinated.
Myelination & size of C fibres.
Small, unmyelinated.
What fibres carry nociceptive information?
A-delta & C fibres.
What fibres is anaesthetic most active on?
Small nerves, lacking in myelination (= C type).
If the dosage was increased, then medium sized nerves (= A-delta fibres) would be targeted and then larger nerves (=A-beta fibres).
MOA Local Anaesthetic.
Reversibly bind directly to the intracellular part of voltage-dependent Na+ channels.
NB: Inhibiting the ability of Na+ to influx into the cell for a portion of a nerve results in all downstream impulses & conduction being blocked…
Factors affecting local anaesthetic action.
• Lipophilicity – more lipophilic agents are more potent as local anaesthetics.
• Ionisation status – local anaesthetics are weak bases (approx. pKa 8-9)
o At physiological pH -> largely ionised
o Inflamed tissue (acidic) -> even more ionised
o (alkaline/basic) -> non-ionised
NB: Anaesthetic must be in the non-ionised form to cross cell membranes and cause action, however it is the ionised form/cationic form of the anaesthetic that binds to receptor sites inside the channel to cause a loss of function.
• Absorption
o Dependent on:
Dosage
Site of injection
Drug-tissue binding
Blood flow
Vasoconstriction factors (e.g., adrenaline & felypressin ) – prolongs anaesthetic effect & limits circulation of anaesthetic.
Classification of local anaesthetics.
Amides – metabolism tends to be slow and thus higher duration of action (metabolised via liver microsomal enzymes like P450).
Esters – metabolism tends to be faster (due to breakdown commenced by esterase enzymes in tissue) and thus short duration of action (metabolised by tissue-associated esterases).
Classify lignocaine/lidocaine as an amide/ester.
Amide.
(Remember: has ‘I’ early in its name)
Classify tetracaine/amethocaine as an amide/ester.
Ester.
Lignocaine administration.
Topical, infiltration, nerve block epidural, intrathecal.
Amethocaine administration.
Topical.
Unwanted effects of local anaesthetics.
CNS effects: restlessness/shivering/tongue numbness/metallic taste, respiratory depression.
Cardiovascular effect: myocardial depression, vasodilation.
How inflammatory mediators cause symptoms of inflammation.
Many of the inflammatory mediators produce pain (e.g., histamine) and some potentiate (e.g., eicosanoids ).
