Local anesthetics Flashcards
What is the role of voltage gated sodium channels?
It opens transiently when membrane is depolarised for sodium ions to pass through
What is the difference between inactivated and deactivated receptors?
Inactivated - ion flow blocked by a gating mechanism
Deactivated - ion flow blocked by closing of channel
What is the mechanism of action of LA?
Stops axonal conduction by blocking sodium channels in the axonal membrane when applied locally in appropriate concentration → prevent sodium entry → slow down or bring conduction to a halt
Does the protonated or non-protonated form of LAs pass through the membrane channel?
Non-protonated.
Which receptor states do LAs bind most strongly to?
Inactivated and activated channels
Why does LA work better when in a lot of pain?
Use dependency: Passage of train of action potentials cause sodium channels to cycle through open and inactivated states. During this train of action potentials, it is likely that the channel is open more often, then LA can work better
Describe use-dependency of LA
Depth of LA nerve block increase with action potential frequency because LA molecules gain access to the channel more readily when channel is open and have higher affinity for the inactivated than resting (closed) channels
Why are LAs given topical or by injection
They are non-selective modifiers of neuronal function (block action potentials in all neurons in which they have access)
Factors affecting LA action?
More lipid soluble drugs are more potent and act longer
(more hydrophobic: tetracaine, etidocaine, bupivacaine; Less hydrophobic: lidocaine, procaine, mepivacaine)
Nerve factors - size (smaller>bigger), frequency of firing (high>low), position (circumferential>deep), myelination (myelinated>non-myelinated)
pH dependency - alkaline pH → increased LA (low proportion of ionised molecules)
Types of LAs
Amide (lidocaine, mepivacaine, bupivacaine) and ester (procaine, tetracaine)
How are amide and ester LAs metabolised
Ester - plasma/tissue non-specific esterases
Amide - hepatic enzymes
Which anesthetics have the fastest onset?
Those that penetrate the axon most rapidly (small size, high lipid solubility, low ionisation)
When does toxicity occur?
When unintended large dose of LA is accidentally injected IV/intra-arterial
When there is excessive LA injected locally and subsequently lead to high and toxic blood level following absorption
How can you reduce the toxicity of LAs?
Combine with epinephrine (reduces vessel diameter, constricting it to reduce blood flow so rate of absorption of LA into systemic circulation is lower)
What kind of toxicity does LA give rise to?
CNS and CVS toxicity
CVS: reduce cardiac contraction, arteriolar dilation and hypotension, cardiovascular collapse
CNS: sleepiness, convulsion, stoppage of vital functions, death
