Local anaesthetics Flashcards
Describe the structure of local anaesthetics
Each has an aromatic region (benzene ring, non-olar) and a basic amino side chain (hydrophilic) then a bridging group which is either an ester or an amide.
Cocaine- ester
Lidocaine- amide
Describe the hydrophilic pathway
So most local anaesthetics are weak bases which means they are ionised in the acidic blood. Only unionized chemicals can cross the connective tissue and myelin sheath that covers the axon. However the chemical then needs to be cataionic to enter the sodium channel to acces the bidning site.
Describe the MOA of local anaesthetics
They are generally sodium chanell blockers, which prevents propogartion of APs.
They are selective for small diameter fibres and non-myelinated fibres (can enter in an ionised form). These are commonly nociceptive fibres. They also have use-depenedcy- e.g. selectivity for rapidly firing neurons because their axons are opening more frequently, increasing oppuruntities of rth chemical to access and hence block the channel.
NB local anaesthetics do NOT influence RMP (mianted by pumps)
Why are local anaesthetics less effective in infected tissue?
The fluid surrounding infected tissue tends to be more acidic, shifts the dynamic equialibrium, hence a smaller proportion of the drug is unionized and able to corss the connective tissue sheath to access the axon and its sodium channels.
Name 6 routes of administration for local anaesthetics
Surface anaesthesia, infiltration anaesthesia, IV regional anaesthesia, nerve block anaesthesia, spinal anaesthesia and epidural anaesthesia.
How does surface anaesthesia work? What is the drawback?
Applied to a mucosal surface, usually by a spray or powder. High concentrations used- can lead to systemic toxicity.
How does infiltration anaesthesia work? What would you co-inject and why?
The local anaesthetic is injected directly into sensory nerve terminals. Useful for minor surgery. Co-inject with adrenaline to 1) stop any coincident wound bleeding 2) vasoconstriction increases concentration of the anaesthetic at the site, increasing efficacy and 3) vasoconstriction also limits systemic toxixicty. DO NOT CO-INJECT ADRENALINE INTO EXTREMITIES- peripheral capillaries prone to vasospasm, could lead to limb ischemia.
How does IV regional anaesthesia work? What do you need to be careful of?
Give anaesthetic IV distal to a pressure cuff. Useful for limb surgery. Be careful not to release pressure cuff too early- could lead to systemic toxicity.
How does nerve block anaesthesia work? What would you co-inject?
Anesthetic is injected close to nerve trunks. Commonly used for dental surgery. Low doses- slow onset. Vasoconstrcitor co-injection like adrenaline.
Which two modes of admisnitration would you co-inject a vasoconstrictor?
Infiltration anaesthesia and nerve block anaesthesia.
How does spinal anaesthesia work, when would you use it, what problems can it cause and how can you prevent this?
Injection into subarachnoid space, around the spinal roots. Would use it for abdominsal, pelvic or lower limb surgery. It can cause hypotension and a headache from dispersion of the anaesthetic in the CSF. You can prevent this by co-injecting glucose. This increases the specific gravity of the local CSF and allow you to mainipulate the position of the bolus of anaesthetic.
How does an epidural work? Compare to spinal anaesthesia
Injection of anaesthetic into the fatty tissue of the epidural space. Used for adominal surgery, pelvic surgery, lower limbs surgery and painless childbirth. Higher doeses needed than for spinal anaesthesia because absorption required but ut is not dispersed to sympathetic neurones so less effect on BP than a spinal.
Comapre PP binding, metabolism and half life of lidocaine and cocaine
PP binding: lidocaine 70% and cocaine 90%
Metabolism: lidocaine hepatic N-dealkylation and cocaine liver + plasma esterases
Half life lidocaine 2 hrs , cocaine 1 hr.
Compare the unwanted effects of lidocaine and cocaine
Lidocaine- paradoxical CNS stimualation (inhibits inhibitory neurones) followed by resp depression. CVS depression, vasodilation, hypotension etc
Cocaine cuase CNS AND CVS excitation because of increased NA levels (reuptake 1 blocker)
