Local Anaesthetics Flashcards
What is the propagation of action potentials?
Entry of Na+ via voltage-gated Na+ channels. Adjacent voltage fated Na+ channels open.
What are local anaesthetics?
Local anaesthetics produce a reversible blockade of action potential conduction in sensory nerves when applied locally in effective concentrations.
What is the mechanism if action of local anaesthetics?
As sensory info is conducted along nerves from the periphery to the CNS via action potentials, local anaesthetics work by producing a reversible blockade of action potential. LA blocks the initiation and propagation of action potentials by preventing the voltage dependence increase in Na+ conductance.
Network of myelinated and unmylinated nerves transmit sensory information from periphery to CNS for processing. Nonciceptive (pain) impulses are carried by small myelinated As fibres and unmylinated C fibres. The smaller the sensory fibres, the more susceptible they are to the effects of LA. This is because LA penetrates smaller fibres more readily as the diameter is much smaller. However LA would selectively block myelinated fibres if they had the same diameter as unmyelinated fibres. The shorter the myelinated fibre, the shorter the internodal distance. 3 consecutive nodes of ranvier need to be blocked by LA for action potential to be stopped.
In a voltage gated Na+ channel, LA binds to IVS6.
Chemistry of local anaesthetics?
Weak bases with pKa 7-9 and exist mainly in ionised form however can exist in both.
Effect of local anaesthetics on inflammation?
Local anaesthetics decrease effectiveness in inflamed tissues. It increase acidity of inflamed tissue limiting the formation of unionised base (B) - decreases access to nerves.
Localised vasodilation facilitates dissipation.
Inflammatory mediators increase nerve activity. Directly inhibits actions of LA. PGE2 sensitises nerve endings to pain.
What are some cardiovascular side effects of local anaesthetics?
Myocardial depression- inhibition of Na+ in cardiac muscle results in reduced ca2+ concentration stores, reduced myocardial contractility and reduced force of contraction.
Vasodilation of arterioles - direct effect on vascular smooth muscle (relaxation), inhibition of the sympathetic nervous system.
Decrease in blood pressure - sudden and life threatening.
What are some CNS side effects of local anaesthetics?
Toxic levels of LAs - stimulation due to inhibition synapses - confusion, excitement, apprehension, tremor, convulsions, CNS depression.
At very high levels:
Marked medullary depression which impairs basic functions. Cardiovascular and respiratory collapse.
Death usually results from respiratory failure
Treatment of local anaesthetic CNS side effects?
Maintain adequate ventilation Treat convulsions (diazepam)
Vasoconstrictors and their effects with local anaesthetics?
Vasoconstrictors reduce local circulation at the site of injection.
Slower diffusion from site
Lower concentrations needed
Longer duration of action
Reduced risk of systemic toxicity
Reduced bleeding and bacteraemia (bacteria in blood)
Adrenaline
Benefits of using adrenaline in combination with local anaesthetics?
Adrenaline is an endogenous catecholamine and a very effective vasoconstrictor. It can rapidly and completely metabolise.
Cardiovascular effects - increase heart rate and contraction, increased systolic blood pressure
CNS effects - stimulation of fear and anxiety, increases respiration and skeletal muscle tremor.
Describe use dependent blockade?
Most LA exhibit use-dependence. They gain access to Na+ channel more readily in the open state and the depth of nerve block increases with the frequency of action potentials. A more positive membrane potential is more sensitive to LA block.
LA selectivity for inactivated > open > resting.
Use dependent blockade is also the mechanism of anti-arrhythmic effects of LA on cardiac cells as well as epilepsy.
