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Local Anaesthetics Notes

This is a sample of our (approximately) 4 page long Local Anaesthetics notes, which we sell as part of the Neurology Notes collection, a 70-80% package written at Bristol University in 2012 that contains (approximately) 117 pages of notes across 36 different documents.

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Lecture 8 Local anaesthetics

General o Local anaesthesia: local, reversible loss of sensation without loss of consciousness
 (morphine and heroin give general loss of sensation and consciousness), o Mechanism: block nerve conduction o Many drugs have LA properties at high conc. (e.g. Propranolol & morphine)
 Have amine and aromatic moieties
 But interact with specific receptors at lower conc.
 LA drugs have NO other activities Local anaesthetic nerve block o Small-diameter nerve fibres blocked more readily (lower doses) than large fibres o Nociceptive impulses (pain info) carried by A(delta) and C fibres o Higher concentrations- other 'nerve' fibres blocked
 E.g. cardiac cells (Lidnocaine; "big nerve cell" that contracts) Susceptibility to block of types of nerve fibres o A(delta)
 Function: PAIN, prickling, touch, temperature
 High sensitivity to block o C fibres
 Function: PAIN (slow, burning), temperature, touch
 High sensitivity to block o Some other small diameter fibres also blocked, so not absolutely selective Effects of Las on events in nerve excitation o Block and inactivate (also enhance) certain parts of AP cycle o LA block the Na channels opening following depolarisation o LA enhance Na channels inactivation Na channel subunits o 4 repeat units o a-units mainly form (B sit on side, not as much function) o Each unit has 6 transmembrane domains with a loop between two of these domains o Subunits 5 & 6 of each unit contribute to the pore of the channel o Tyrosine and phenylamine (AAs of units) are important binding sites for LA
 Phenylalanine= No charge but has benzene ring with electron on either side. Nitrogen attracts electron charge from ring, pulls down arm of (F) by attaching to ring, causing conformational shape change (structure in book) LAs- chemical structure o All anaesthetics (bar 1) have 3 groups
 Aromatic group (lipophilic, hydrophobic)
 Ester/Amide (intermediate chain variable length)
 Amino group (secondary or tertiary; water soluble when protonated) o Can be in both charged or uncharged state (find both in blood) o Examples
 Procaine

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