Local anaesthetics Flashcards
What is the difference between inactivation and deactivation of voltage-gated ion channels?
Inactivation: ion flow blocked by gating mechanism
Deactivation: ion flow blocked by closing of channel
MoA of local anesthetics:
- Stop axonal conduction by blocking sodium channels in axonal membrane when applied locally in appropriate concentration – prevent sodium ion entry
- Drug protonated in low pH, unable to be passed through the bilayer to enter the nerves to exert its action
- Drug is active when protonated
- non-selective modifiers of neuronal function, block action potentials in all neurons to which they have access
Factors affecting LA action:
- More lipid soluble drugs are more potent and act longer
(e. g. tetracaine, etidocaine, bupivacaine) - Acts on all nerves (small > big, circumferential > deep, myelinated > non-myelinated)
- pH dependency: increased activity in alkaline pH and decreased in acidic pH
Main differences between ester type and amide type local analgesics:
Ester type: low incidence of allergy, metabolised by plasma/tissue non-specific esterases
Amide type: very low incidence of allergy, metabolised by hepatic enzymes
Notable ester-type local analgesics:
cocaine, procaine, tetracaine, benzocaine
Notable amide-type local analgesics:
lidocaine, mepivacine, bupivacaine, etidocaine, prilocaine, ropivacaine
Cautions in use of LA:
- Unintended large dose of LA if accidentally injected IV/intra-arterially can cause systemic toxicity
- Excessive LA injected locally can result in high blood level following absorption –> onset of toxic symptoms and signs may appear late compared to direct IV scenario
Toxic effects of LA (in general) :
- CNS: sleepiness –> visual auditory disturbances –> restlessness –> nystamus –> shivering –> convulsion –> stoppage of vital functions –> death
- CVS: Cardiac contraction –> arteriolar dilatation –> hypotension –> CV collapse
Which LA has the most cardiotoxic effects?
Bupivacaine –> may combine with epinephrine and can reduce bleeding
Toxic effects of cocaine:
CNS & CVS effects,
Vasoconstriction and hypertension: due to NA reuptake blocked
Toxic effects of prilocaine. How to reverse one of the toxic effect?
CNS & CVS effects
methaemoglobin: caused by O-toluidine (prilocaine metabolite) – reversed by IV methylene blue/ascorbic acid
Toxic effects of ester LAs:
Allergic reaction due to PABA derivatives –> skin rash/anaphylactic shock
How to chose LA used:
- duration of action
- surface anaesthesia requires rapid penetration of skin and limited tendency to diffuse away (fast onset)
- cocaine gives good penetration and vasoconstriction but any amount can lead to abuse
Clinical applications of topical LA:
Skin: minor burns/wounds/inflammation
Eye: removal of foreign objects
Dental: applied to gum due to entry of injection needle
Otorhinolaryngology: insertion of endoscope for gastric ulcer
Gynecology: episiotomy cuts (lidocaine)
Common surface anaesthesia:
lidocaine, tetracaine, dibucaine, benzocaine – not effective for skin
uses of infiltration anaesthesia:
Direct injection into tissues to reach nerve branches and terminals
for minor surgery
Caution during use of infiltration anaesthetics:
epinephrine or felypressin usually added as vasoconstrictors (not with fingers or toes)
only suitable for use in small areas or will have high risk of systemic toxicity
Reason for use of nerve-block anaesthesia:
less LA needed than for infiltration anasthesia
Caution during use of nerve-block anesthetics:
- Accurate placement of needle is important
- onset of anesthesia may be slow
- duration of anesthesia may be increased by addition of vasoconstrictor
LA used in epidural anesthesia:
lidocaine, bupivacaine
How does epidural anaesthesia work, and what is it used for?
LA injected into epidural space, blocking spinal roots
used for surgery to abdomen, pelvis or leg, when GA cannot be used and for painless childbirth
side effects of epidural anaesthesia:
postoperative urinary retention
other SEs similar to spinal anaesthetics:
- bradycardia, hypotension
- respiratory depression
How spinal anaesthesia work:
- LA injected into subarachnoid space (containing CSF) to act on spinal roots and spinal cord
- used for surgery to abdomen, pelvis or leg, when GA cannot be used
How to limit spread of LA during spinal anaesthesia:
glucose can be added, tilt patient
Side effects of spinal anaesthesia:
main risks: bradycardia, hypotension owing to systemic block, respiratory depression due to effects on phrenic nerve or respiratory center, avoided by minimising cranial spread
- postoperative urinary retention (block of pelvic autonomic outflow) is common
How is intravenous regional anaesthesia administered:
LA injected IV distal to a pressure cuff to arrest blood flow, and remains effective until circulation is restored
Use of intravenous regional anaesthesia:
limb surgery
Caution for use during intravenous regional anaesthesia
risk of systemic toxicity when cuff is released prematurely – risk smaller when cuff remains inflated for at least 20 mins
drugs used as intravenous regional anaesthesia:
Lidocaine, prilocaine
Drugs used as spinal anaesthesia:
mainly lidocaine
LA dose may be reduced with:
combination with opioid (fentanyl) if epidural anaesthetics (lidocaine, bupivacaine)
Injected LA for dental use:
lidocaine is short duration, bupivacaine for longer duration
