Local Anaesthesia Flashcards
What precautions are required for safe analgesia?
- Thorough and concurrent medical history taking including LA history and experience, anxiety levels
- Good patient cooperation and consent
- Safe disposal/single use
- Needle guards/safety systems
- Sharps boxes
- Semi-recumbent position
- Self aspirating syringe
What are the constituents of Local Anaesthetics?
- Aromatic region (lipid soluble)
- Ester/amide bond (determines biotransformation)
- Basic amine side chain (water solubility)
- Weak bases with a pKa rof 8-9 = mainly ionised at physiological pH (7.4) – important as it determines their ability to penetrate the nerve sheath and axon membrane
How is presence of an ester or amide bond an important factor to consider when choosing an LA?
- Ester containing compounds are fairly rapidly inactivated in the plasma and liver by non-specific esterases
- Amides* are more stable and these analgesics generally have longer plasma half-lives
- Low potential for producing allergic effects and the breakdown is more complex = slower = superior analgesia
What’s the importance of having a lipophilic and water soluble groups?
- Lipophilic part of the compound helps the LA pass through neuron membrane
- The fat soluble form of LA penetrates the lipid part of the neuron membrane
- The strength of LA is directly related to its lipid solubility - Once inside the lipophilic part is inside the cell and a new equilibrium with the water soluble part will be established and is responsible for the analgesic effect
Rank amide LA’s (H-L) by their lipid solubility
- Articaine
- Lidocaine
- Prilocaine
- Mepivacaine
What’s the general mechanism of action for LA’s?
- Block the initiation and propagation of action potentials by preventing the voltage-dependent increase in Na+ conductance
- At low concentrations it decreases the rate of rise action potential - increasing its duration an increases the refractory period thus reducing firing rate
- High concentrations they prevent action potential firing
- Physically plug the transmembrane pore of Na+ channels - interacting with amino acid residues of the S6 transmembrane helical domain of the channel protein (at the nodes of ranvier)
Where is the main site of action for LA’s?
Small-diameter nerve fibres
- Block conduction in small-diameter nerve fibres more readily than large fibres
- Nociceptive impulses are carried by Aδ and C fibres which are relatively small in diameter = pain sensation is blocked more readily than other sensory modalities (touch etc)
Before administering LA, why should you consider the pH of the environment you’re administering it into?
- LA activity is strongly pH-dependent, being increased at alkaline extracellular pH (when proportion of ionised molecules is low)
In an alkaline environment** There is no electrical charge so they have lipophilic activity and adequate tissue penetration
- Activity is reduced at acid pH
- Extracellular fluid of inflamed tissue depends to be relatively acidic = somewhat resistant to LA
How does LA cause in increase in perfusion of blood and what are the 2 resulting effects of this?
Increased perfusion due to Vasodilation effect
- Direct effect on vascular smooth muscle and partial inhibition of symapthetic nervous system = fall in blood pressure
- Drug is carried away from the site of admission = less effective
- Suppression of cardiovascular system
- Absorption into systemic circulation causes myocardial depression, conduction block and vasodilation
- Reduction in myocardial contractility via indirect inhibition of Na+ current in cardiac muscle – reduces intracellular Ca2+ stores = reduces force of contraction
How can LA effect the CNS?
Both depressant and stimulant
- Depressant at lower levels
- High levels cause restlessness/tremors/confusion/extreme agitation
- Profoundly high concentrations cause severe CNS depression and death due to respiratory depression
How can do we counter the vasodilation effect of LA?
Addition of a vasoconstrictor (epinephrine/adrenaline)
- Maintains effective concentrations of LA at the site of injection
What’s the significance of protein binding in relation to LA’s duration time?
- LA in solution binds to both plasma and tissue proteins
- Protein binding effects duration time = higher the binding to plasma proteins the longer it will be active (isn’t free to be metabolised)
- Articaine = >90% plasma binding
- Lidocaine = 60%
- Prilocaine = 50%
What factors determine onset and duration of LA?
- Alkaline tissue = higher the alkaline the tissue pH the quicker the onset (ability to diffuse across the phospholipid bilayer increases)
- Total dose = volume determines spread - high dose = high spread
- Concentration = strength of effect = higher the concentration the stronger the effect
- Duration = diffusion form the site of administration followed by redistribution in the tissue - low diffusion = increased duration
- Total dose
What’s the primary factor determining local elimination of LA?
The degree of vascularisation of the tissue - determines the amount and velocity of loss
- Additionally, LA’s vasodilation effect influences the rate of local elimination
Pharmacokinetics: how are amide-linked drugs eliminated from circulation?
- Primarily metabolised in the liver (70-90%) via N-dealkylation rather than cleavage of amide group
- Excreted by the kidney (10-30% unchanged)
Your patient has liver disease/impaired function, what should you consider when administering LA?
- They degrade amide-type LA’s at a delayed rate which increases the risk of toxicity in these patients (toxic in the sense that it still exhibits LA characteristics)
What is Lidocaine and what are its properties?
- Gold standard LA
Onset = Rapid (2-3 min)
Duration = Medium (1-1.5hrs pulpal + 3-4hr tissue)
Tissue penetration = good
MRD = 7mg/kg of body weight (500mg max)
- Combined with Epinephrine to increase pulpal anaesthesia (1:80,000 conc)
- Dissoolved in solution as hydrochloride salt
What is Prilocaine and what are its properties?
Onset = Medium
Duration = Medium
Tissue penetration = moderate
- Large doses - methemoglobinemia - reduces 02 carry capacity of the blood
- More rapidly metabolised than Lidocaine = less toxic
- Can be found in the form of EMLA cream - topical analgesic cream to numb an area before injection
