Local Anaesthetics Flashcards
What is an LA?
reversibly block neuronal conduction when applied locally
How are APs generated?
- Depolarising stimulus – Na+ channels open, Na+ enters cell
- Inactivation – Na+ channels close, K+ channels open, K+ leaves cell
- Cell refractory state – Na+ channels restored to resting state but K+ channels still open so cell is refractory
- Resting state – Na+ and K+ channels restored to resting state
What are the components of LAs?
- Aromatic region – very lipid-soluble/hydrophobic
- Amine side-chain – hydrophilic
- Ester or Amide bond
- Cocaine – ester
- Lidocaine – amide
- benzocaine doesn’t have a basic amine group -> weaker potency
Describe the hydrophillic pathway of LAs on VGSCs
- The drug remains in equilibrium between ionised and unionised forms (as all LAs are weak bases)
- Unionised form – can pass across membranes but CANNOT have any action
- Ionised form – is needed to have an action but CANNOT pass across membranes
- This pathway is use-dependent as the channels need to be open for the cation drug to access the VGSCs
- The ionised form binds to the inside of the VGSCs and stereochemically hinders the influx of Na ions - In order for the ionised form of the LA to be able to bind to its target site, the channel has to be open
What is the hydrophobic pathway?
more important for the more lipid-soluble LAs. As the unionised form crosses the axonal membrane, some can drop into the ion channel and convert into the cation ionised form to block the ion channel
- This means that, by the hydrophobic route, the LAs can drop into a closed channel AS WELL AS an open channel
What are the effects of LAs?
- Prevent generation and conduction of APs
- Do not influence resting membrane potentials
- May influence:
- Channel gating – e.g. hold an inactivated state in a channel
- Surface tension – lower surface tension - Selectively block:
- Small diameter fibres – e.g. nociceptive pain fibres
- Non-myelinated fibres – pain fibres are often small (Ad(delta)-fibres) and unmyelinated (C-Fibres)
Why are LAs less effective in infected tissues?
LAs are weak bases (pKa 8-9) and so are mostly ionised and so less pass into the axons of neurones. As they have a high pKa, this means they are use-pH-dependent
- INFECTED TISSUES are normally slightly acidic and so the LA is less effective as more will be ionised
What are some routes of administration?
- surface anaesthesia - spray or powder form e.g sore throat relief
- infiltration anaesthesia - SC injection e.g post surgery sutra LA analgesia
- IV regional anaesthesia - IV injection distal to pressure cuff e.g trigger finger repair
- nerve block anaesthesia - injection e.g tooth extraction
- spinal anaesthesia - intrathecal (sub-arachnoid space injection) e.g hip replacement
- Epidural anaesthesia – injection into epidural space e.g lower limb surgery, painless childbirth
Where is surface anaesthesia used?
mucosal surfaces e.g mouth/ bronchial tree
Whys is adrenaline co-administered with infiltration anaesthesia?
to vasoconstrict to:
- Slow down diffusion of LA away from the site of injection – lower concentration of LA needed
- Reduce systemic toxicity
What is the downside to spinal anaesthesia?
Reduces BP and so can cause prolonged headache
- Glucose can be added to increase specific gravity so the LA doesn’t travel up the CSF to the brain
What are the pros and cons of epidural anaesthesia?
Cons – slower onset and higher doses required
Pros – more restricted action, less effect on BP
What are the pharmacokinetics of cocaine and lidocaine?
Lidocaine (amide) - T1/2 = 2h
- Good absorption
- 70% PPB
- Hepatic metabolism – N-dealkylation
Cocaine (ester) - T1/2 = 1h
- Good absorption
- 90% PPB
- Hepatic and plasma metabolism – non-specific esterases
What are the unwanted side effects of lidocaine?
CNS – paradoxical effects:
- Stimulation
- Restlessness, confusion
- Tremor
CVS – due to Na+-channel blockade:
- Myocardial depression
- Vasodilation
- Reduction in BP
What are the unwanted side effects of cocaine?
SNS actions:
CNS:
- Euphoria, excitation – due to blocking effects in re-uptake of NA
CVS:
- Increased CO
- Vasoconstriction
- Increased BP
