Local Anaesthetics Flashcards
What are the two groups of local anaesthetics?
Amides
Esters
Both consist of an aromatic ring which is lipophillic. This is connected by a link (determining group) and then a hydrophilic amine
What is a local anaesthetic?
Drug that produces temporary reversible blockage of AP/ neuronal transmission when applied to a nerve fibre.
Depending on volume and concentration, small autonomic to large motor fibres are affected.
List 3 amide LA?
Lidocaine (xylocaine)
Prilocaine (Biers block use)
Bupivicane (Marcaine)
Ropivicaine (Naropin)
List 3 ester LA?
Cocaine, procaine and amethocaine
What are the differences between amides and ester LA?
Structural link -O-CO-, -NH-CO-
Functional - stability in solution
Esters are unstable but amides can remain stable for up to 2 years
Pharmacokinetics - distribution varies as esters are minimally bound to proteins and amides are extensively bound to protein
Metabolism - esters are rapidly hydrolysed by pseudocholinesterases in the plasma to inactive compounds, amides are hepatic
Allergy - higher with amides due to para-aminobenzoate metabolite
How do LA work?
Block influx of sodium at VG Na channels inside nerve axons/ nerve cell membrane preventing depolarisation and propagation of neuronal actions potential. Higher affinity for open or inactived Na channels. Block from inside of neurone by crossing lipid membrane positive ion binding receptor.
What is pKa?
pH at which 50% of drug is ionised and 50% unionised
What is the Henderson hassellbach equation?
Acid: pH = pKa + log (ionised form)/ (unionised form)
Base: pH = pKa + log (unionised)/(ionised)
What is the significance of pKa in LA?
LA exist in equilibrium between unionised and ionised forms
Their pKa and pH DETERMINE percentage ionised v unionised
Weak base pH below pKa - a greater proportion of base exists in ionised form (acidic)
pKa determines speed of onset of action, lower pKa = quicker due to high unionised proportion of drug
List pKa of lidocaine, bupivicaine and cocaine
Lidocaine 7.9 (2-4min onset of action)
Bupivicaine 8.1 ( 5-8mins onset of action)
Cocaine 8.6
What is physiological pH and why is this important in LA mechanism of action?
pH of body 7.4 - below LA pKa therefore exist as greater proportion unionised form the lower the pKa (lidocaine higher proportion unionised therefore quicker onset of action!)
Lipid solubility is related to what?
Potency of a drug
Bupivicane is 95% protein bound
Lidocaine is 75% protein bound
What else affects potency of a drug?
Tissue distribution and vasodilatation (control volume available at membrane)
What affects duration of action of LA?
Protein binding - highly bound = longer duration
Drug potency
Vasodilation reduces duration of action
What LA vasoconstricts?
Cocaine
Other agents in high concentrations of with adrenaline
What are toxic doses for common LA?
Lidocaine 3- 5mg/kg, 7mg/kg with adrenaline
Bupivicaine 2mg/kg in any state
What is the elimination half life of lidocaine?
Plasma cholinesterases break down lidocaine into inactive PABA metabolite, 100 minutes
This is compared to 160 mins bupivicaine
What LA would be suitable for a sciatic nerve block?
Ropivicaine
slower onset of action due to reduced lipid solubility and therefore lower penetration of large myelinated nerve fibres
reduced potency and shorter duration of action
Less cardiotoxic due to higher toxic plasma level of 4ug/ml
How do LA affect the heart?
Block sodium channels therefore phase 0 of cardiac AP increases more slowly . This delays arrival at threshold for spontaneous depolarisation. Prolong refractory period.
PR and QRS prolonged
Bupivicaine takes 10x longer to move away from the myocardium leading to arrythmias and VF
Ropivicaine is structurally different and diffuses away more quickly
Why does LA not work in infected tissue?
Acidic environment
Low pH reduced unionised fragment making diffusion across lipid membrane longer.
Vasodilatation of surrounding tissue and increased blood supply takes away LA more quickly
What concentrations of LA are used in spinal anaesthesia?
- 5% bupivicaine spinal
0. 1% in epidurals as no motor block required
What is heavy Marcaine?
Bupivicaine contains glucose 80mg/ml to provide a denser block that descends with gravity and sits above CSF
What are features of LA toxicity?
CNS - tingling, dizziness, tinnitus, visual disturbance, seizures, coma
CVS - chest pain, sob, arrythmias VF
What factors increase risk of LA toxicity?
Highly vascular area
- brachial, intercostal, caudal, epidural, paracervical
Higher concentration or volume
Acidic or hypoxic environment a protein binding decreases
Vasoconstrictor added aid prevention of systemic absorption
Adipose helps to protein bind LA reducing toxicity risk
