Local Anaesthetics Flashcards
What are local anaesthetics used for?
+ When loss of consciousness is neither necessary or desirable
+ As an adjunct to surgery to avoid high-dose general anaesthetics
+ Post-operative analgesia
+ For major surgery, with sedation
What are the two different bonds in LAs?
+ Amide (most commonly used)
+ Ester (used extremely rarely)
What are examples of amide-containing anaesthetics?
+ Lidocaine (lignocaine): medium-acting; rapid onset
+ Prilocaine: medium-acting; no vasodilation
+ Bupivacaine / Levobupivacaine: long-acting; slow onset
+ Articaine: short-acting; rapid onset
What are examples of ester-containing anaesthetics?
+ Tetracaine: long-acting; very slow onset
+ Chloroprocaine: medium-acting
+ Benzocaine: atypical mechanism of action
Why are amide-containing anaesthetics used more commonly than ones containing esters?
Esters are more unstable and can be metabolised into compounds associated with allergic reactions
How do LAs work/what is their mechanism of action?
Work by reversibly blocking voltage-gated Na+ channels:
- stabilises excitable membranes
- prevents membranes from being depolarised
What is the effect of LAs on peripheral nerves?
They consist of fibers of different function, diameter and insulation - all can be blocked by LAs but at different rates
What is order of loss, due to the effect of LAs?
- Pain
- Temperature
- Proprioception
- Skeletal muscle tone
What factors influence the probability that a local anaesthetic will block an impulse?
+ Diameter of fibre:
- smaller nerve fibers blocked more easily than large fibers
+ Myelination status:
- myelinated fibers blocked more easily than unmyelinated
+ Length of nerve exposed to drug
+ Length of time exposed to drug
+ Concentration of drug
What are the different states of the voltage gated sodium channels?
+ Resting
+ Open
+ Inactivated
What are features of LAs regarding the voltage-gated sodium channels?
Local anaesthetics are weak bases:
- can exist as neutral or protonated
- pH dependent
How do LAs block the voltage-gated sodium channels?
Block when IONISED via an intracellular binding site
HOWEVER,
Cannot pass through membrane when IONISED
What is the difference between the hydrophobic and hydrophilic pathways?
Hydrophobic: no use-dependence
Hydrophilic: use-dependent
What does pKA have to do with LAs?
As almost all LAs are weak bases, the pKA is the pH at which 50% of drug is ionised
- most LAs have pKA values 8-9
What is the Henderson-Hasselbalch equation?
pKa - pH = log10 x ( [BH+] / [B] )
What are the features of LAs that show use-dependence?
+ Bind to open air or inactive channels
+ Related to frequency of neuronal firing
- faster onset in faster firing neurones
What is the duration of action of LAs dictated by?
Rate of removal
- blood flow
- action of plasme esterases (ester-linked LAs only)
- hydrophobicity of drug
What is an effect caused by the majority of LAs?
Vasodilation
- except cocaine (vasoconstriction) and prilocaine
What is the effect of vasoconstriction on duration of action/rate of removal?
↓ blood flow to area ∴ ↓ rate of removal
Vasoconstriction (adrenaline)
- can ↑ duration ~2x
- can also ↓ bleeding during surgery
- risk of ischaemic damage at extremities
What are the routes of administration for LAs?
SURFACE: nose, mouth, bronchial tree, cornea, UT
INFILTRATION: injection into tissues to reach nerve branches/terminals
NERVE BLOCK: small or large regional block by injection around nerve
INTRAVENOUS REGIONAL: double-cuff method to contain LA to a limb
EXTRADURAL (epidural) (particulary bupovacaine): used in thoracic, lumbar and sacral regions
SUBARACHNOID (intrathecal): drug injected into the subarachnoid space (CSF)
What is a Eutectic Mixture of Local Anaesthetics (EMLA) and what is it used for?
Mixture of lignocaine and prilocaine used for dermal anaesthesia
What are features of EMLAs?
Melting point of mixture is lower than that of the individual chemicals
∴ higher concentration of both can be used
∴ increased chance more will get across skin
What causes unwanted side affects of LAs?
Entry into systemic circulation
What are the side effects of LAs on the CVS?
+ Dysrhythmias
+ Sudden fall in blood pressure due to effects on heart and vasculature
