Mod 3: Local Anaesthetic Pharmacological Principles Flashcards
The Plasma membrane separates the interior of all cells to the extracellular space, this membrane is full of channels which?
Control the flow of IONs and other compounds from outside the cell and vice versa.
ION channels conrtol, what?
The Voltage gradient across a plasma membrane
What does VGSC mean? and what do they do?
Voltage Gated Sodium Channel, function ad gated conduits for Sodium IONS
What is RMP?
Resting Membrane Potential. Inside cell membrane is -ve as opposed +ve outside membrane approx -70mv
What 2 activities cause RMP?
- Na/K pump pushes only 2 K+ ions into the cell for every 3 Na+ ions pushed out = net loss of charge.
- Leaky K+ channels allowing slow diffusion of K+ from high conc. to low conc.
Stimulation of the cell results in a reduction in RMP, if this reduction reaches the threshold voltage, what is generated?
An Action Potential at -50mv
Action potentials involve rapid changes in membrane potentials from -ve to +ve causing what?
The opening of VGSC which causes rapid influx of Na+ depolarizing the cell to +ve on the inside.
RMP is reestablished when?
Na+ channels are closed and K+ channels are opened allowing K+ to efflux from the cell.
LA’s block?
VGSC
Blocking Na+ influx prevents?
Depolarization required for action potential propagation and impulse conduction.
LA’s are a class off drug that?
Reversibly block the generation and conduction of action potentials in all excitable cells
Self regenerating action potential occurs when?
Cells become depolarized and VGSC are opened allowing Na+to influx into the cell leading to more VGSC to open.
Sustained depolarization causes?
- Inactivation of VGSC which shuts off influx of Na+
- concurrent opening of voltage-gated K+ channels.
- Resultant K+ efflux the K+ channels return membrane to resting potential
LA”S act by?
Selectively binding to VGSC blocking the pathway for Na+ (block channels) thus preventing depolarization necessary for action potential propagation and impulse conduction.
Once LA is stopped it…
Dissociates from the VGSC rapidly, diffusing away to be absorbed by the local circulation, impulse activity is then restored.
What are the ideal characteristics of LA’s?
- Complete reversibilty
- Low local and systemic toxicity.
- Action confined mainly to nerve tissue
- Short onset
- Duration sufficient for required procedure.
- Will not increase recovery.
- solubility in saline and lipids
- Sterilizability and storability without deterioration
- Vasoconstrictor compatible
- Non irritability to tissues.
In what order are nerves affected by LA”S
All nerves are affected by LA, however not all are affected equally, non-myelinated neurones (C fibres) are affected first, with heavily myelinated neurones (A fibres) last 1st Sympathetic function (C fibres) 2nd Pinprick and Temperature 3rd Motor function (A fibres) Nerves recover in reverse order.
Describe Activity Dependent Blockade.
- Increased nerve activity leads to increased susceptibility to LA’s
- LA’s have a greater affinity to to depolarized Na+ channels than polarized.
- therefore the more active a nerve fiber the more effective the blockade.
List the 2 types of LA’s.
- Esters
2. Amides
Describe LA’s chemical base.
Weak bases, consisting of an amide (hydrophilic) component which is connected via either an ESTER OR AMIDE link to an aromatic (hydrophobic/lipophilic) portion
Amide LA’s are chemically stable and metabolized where?
Liver