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 ).
Eicosanoid
Inflammatory mediators which result from the breakdown of cellular membranes/phospholipids.
Eicosanoids are involved in:
- Platelet aggregation
- Uterine motility
- Vasconstriction/vasodilation
- Bronchodilation/bronchoconstriction
- Inflammation
- Gastric ulcers
- Allergic responses
3 examples of NSAIDs.
Aspirin, ibuprofen, diclofenac.
Aspirin-sensitive asthma symptoms arise due to
Increase leukotriene conc. because of blocked COX function.
NSAIDs MOA.
Interfere with COX function.
COX 1 vs COX 2
‘Housekeeper’ maintaining platelet aggregation/vascular flow vs Inflammation mediators.
Selective COX 2 inhibiting NSAID
Meloxican.
Side effects of aspirin
Salicylism:
• Tinnitus
• Deafness
• Headache
• Mental confusion
• Convulsions
• Coma
• Death
How is salicylism treated?
Administration of sodium bicarbonate (as aspirin is well absorbed in an acidic environment).
