Local Anesthesics Flashcards
Electrochemical gradients are maintained by
active transport (ATPase) and K+ leak channels (sets the negative membrane potential)
Depolarization causes
- opening of NaV channels, influx of cations and drive Vm to positive potentisl
- KV channels open and conduct current in opposite direction, repolarizing Vm back close to EK
What is the “m” gate and the “h” gate doing at a hyperpolarized resting membrane potential?
“m” gate is closed and the “h” gate is open
What is the “m” gate and the “h” gate doing at a depolarized membrane potential?
“m” gate opens and sodium rushes into the cell; “h” gate is still open
The two gates on the voltage-gated sodium channels
“m” gate (actual channel itself) and an “h” gate
What does the “h” gate do shortly after the sodium channel opens?
the “h” gate closes; the “m” gate remains open; closure of the “h” gate precludes the channel from conducting current - inactivated
Voltage-gated sodium channel inactivation occurs during which period?
occurs during the absolute refractory period
Structure of the voltage-gated sodium channel
tetrameric structure though a single polypeptide
Effects of Na+ channel block on the electrophysiology of a nerve cell
Na+ channel blockade will slow the upstroke rate and amplitude, sometimes to the point of abolishing the AP altogether; this slows or eliminates the conduction through nerve
Factors affecting pharmacological action
- Frequency of transmission
- Size/class of peripheral axons
- pH (acidic pH reduces efficacy of LA)
- Vascularity of target tissue
Size/class of peripheral axons related to anesthetics
small diameter axons are blocked better than large diameter axons; myelinated axons blocked better compared to unmyelinated fibers of same diameter because only a few nodes need to be blocked to halt transmission
pH of environment related to strength of anesthetics
less effective when injected into infected (acidic) tissue becasue less is non-ionized versus at physiological pH and non-ionized is the form that penetrates biological membranes
How does vascularity related to local anesthetics
greater blood flow results in faster/better absorption and higher blood concentration (an issue for toxicity)
Slow-firing nerves
lower frequency; drug completely dissociates between AP spikes, activity is preserved
Fast-firing nerves
high frequency; drug does not completely dissociate between spikes; block accumulates each spike; activity is suppressed
Hyperpolarized nerves
hyperpolarized Vm; drug completely dissociates between spikes; activity is preserved
Depolarized nerves
depolarized Vm prolongs drug interaction with channel; high percentage of channels are always blocked; activity is suppressed
Why does local anesthetic block small fibers better than large ones?
large ones have the ability to overcome blockade at low LA concentrations whereas small fibers do not
Why do you give alpha agonists with local anesthetics?
alpha adrenergic agonists are used with LA to locally constrict blood flow and prevent escape or large amounts of LA molecules into the circulation; this traps LA in the local area, increases its local concentration and can prolong its duration of action
Where should a mixture of alpha agonists and LA be avoided?
should be avoided in areas poorly vascularized due to risk of necrotic tissue damage
Why are LA often stored on the shelf at a low pH of 3 to 5 and why is bicarbonate often added immediately prior to injection of LA?
done to raise the pH closer to 7 which reduces pain on injection caused by low pH, and can enhance the onset of the LA
Local anesthetic prototypes
- Cocaine
- Procaine
- Lidocaine
What must happen to LA in order for them to cross nerve sheaths into the nerve cell membrane itself
LA must become non-ionized (this occurs better for LA with a pKa closer to 7.4)
What form of LA blocks channels?
ionized form blocks channels
Amides
- Bupivacaine
- Etidocaine
- Levobupivacaine
- Lidocaine
- Mepivacaine
- Prilocaine
- Ropivacaine
Esters
- Benzocaine
- Chloroprocaine
- Cocaine
- Procaine
- Tetracaine
Properties of Amides
fast onset; med/long duration; slow half-life; hydrolysis by CYP system
Properties of Esters
variable onset; short to long duration; rapid half life; hydrolysis by esterases
Are amides or esters more likely to have a longer duration of action?
amides
Local anesthetic cardiovascular toxicity
arrhythmias; depresses cardiac AP (rate and force, QRS spread)
Local anesthetic neurotoxicity
CNS stimulation; respiratory depression, death
Treatment of local anesthetic CNS stimulation toxicity
benzodiazepines
LA routes of administration
- Topical
- Infiltration (local injection)
- Nerve block (into neural plexus)
- Spinal (sub-arachnoid, on top of pia)
- Epidural (outside dura)
- Caudal (sacral hiatus)
Topical anesthetics
benzocaine, lidocaine, tetracaine
Infiltration (local injection) anesthetics
lidocaine, procaine, bupivacaine
Nerve block (into neural plexus) anesthetics
lidocaine, mepivacaine
Spinal (sub-arachnoid, on top of pia) anesthetics
bupivacaine, tetracaine
Epidural anesthetics
bupivacaine
Caudal anesthetics
lidocaine, bupivacaine
Infiltration route of administration used for
dental work, suturing etc
Caudal route of administration used for
rectal procedures
