Local Anesthetics Flashcards
Local anesthetics: are _________, with pKa values of ∼7.7 – 9
weak bases
The LA intermediate chain is key determinant for:
onset speed, duration, potency
LA general structure
aromatic moiety- (lipophilic)
intermediate chain
amino group- (hydrophilic)
*Note: amides have ______ in their names, esters have one
two i’s
Cocaine:
a natural product first employed as LA in 1884
• Still used clinically, for procedures on nasal passages and lachrymal glands
• Procaine (Novocain): synthetic LA developed, first employed in 1904
Local anesthetics work by blocking ___________and
consequently, action potentials
NaV channels
faster onset, lower pKa,
more potent, have:
higher lipid solubility,
longer-lasting LAs and greater protein binding
Correlation of potency, speed and duration of LA action
with physico-chemical properties of LAs
Esters are hydrolyzed in the
plasma (primarily by pseudocholinesterase) and in the liver.
Amides are metabolized only in the
liver
patients with hepatic insufficiency, use of ________ local anesthetics may be contraindicated.
amide-linked
Describe the role of pH in determining the effectiveness of local anesthetics.
Weak bases (neutral). Can be protonated (cationic). Need both forms for drug action.
lower pKa = better (↑ neutral LA%, more drug can get into the nerves)
The NaV channels gate (on the intracellular side) must open to allow ___________, thereby obstructing Na+ flux through the channel.
LA+ to enter the channel and bind within
NaV channels must first open in order to allow LA block, LA action is said to
be:
“use-dependent.”
LA fx?
Enters the nerve
LA+ fx?
Blocks Na channel
Use-dependent block:
the more NaV channels are used, the more they become blocked
LA strongest block?
C fiber- no myelin
LA weakest block?
Aa, AB- heavy mylin
Excretion of (primarily the charged form of) local anesthetics occurs via the
kidney.
plasma level of _________ binds much of the injected LA-
α1-acid glycoprotein
–> amount of amide delivered to the liver for metabolism is variable–> variable degree
of local anesthetic toxicity.
Topical anesthesia
application directly onto skin/cornea/mucous membranes of
nose, mouth, throat.
Infiltration anesthesia
injection of LA into tissue without consideration of the
location of cutaneous nerves
Lidocaine, procaine and bupivacaine .
Nerve block anesthesia:
injection of a LA near peripheral nerve
Intravenous regional anesthesia (Bier’s Block):
blood is squeezed out of a limb using a tight elastic bandage, and a tourniquet is placed proximally. LA is injected via a catheter, and limb anesthesia develops within 5-10 minutes.
Lidocaine is most commonly employed in this technique.
more cardiotoxic drugs, such as bupivacaine,
are contraindicated.
Spinal anesthesia
LA injection into CSF bathing lumbar spinal cord
Lidocaine for shorter procedures, bupivacaine for intermediate procedures, and
tetracaine (a long-lasting ester-linked drug)
Epidural anesthesia:
LA injection just outside dura-enclosed spinal canal.
Lidocaine for shorter duration procedures, bupivacaine for longer procedures.
EMLA cream
a eutectic mixture of lidocaine and prilocaine that exists as an oil at room temperature and can thereby penetrate intact skin, producing anesthesia up
to a depth of 5 mm
Co-application of the vasoconstrictor epinephrine w/ LA
LAs can block sympathetic activity, causing vasodilatation.
Coapplication of epinephrine reduces this action, helping retain LA near injection site.
LAs can block NaV channels and action potentials ___________,
including brain and heart.
in all nerve and muscle tissue
LA overdose can produce ______ via action on inhibitory interneurons of the
CNS.
convulsions
LAs often interfere with :
autonomic nervous system function.
LAs block cardiac NaV channels, causing ________;
cardiac arrhythmia
bupivacaine is particularly cardiotoxic.
Para-aminobenzoic acid (PABA) is a metabolic product of ester-linked LAs; this is
the primary culprit in:
local anesthetic hypersensitivity.
In patients allergic to both amide and ester LAs, high doses of__________
can be used as a local anesthetic.
promethazine
antihistamine at lower doses
Tetrodotoxin and saxitoxin:
block NaV channels by
plugging the extracellular channel entrance
_________ is a small organic toxin found in some kinds of fish (Japanese puffer fish), newts and frogs (Atelopus).
Tetrodotoxin
__________ is produced by marine dinoflagellates, which are consumed by, and retained in the flesh of, clams and other shellfish.
Saxitoxin
Although chemically
distinct from one another, tetrodotoxin and saxitoxin both act by binding to and blocking the
extracellular entrance of voltage-gated Na+ channels
Tetrodotoxin and saxitoxin
therefore cause death by paralyzing:
respiratory muscles, and not by an action on the heart
Drug List
Esters
tetracaine
benzocaine
procaine
cocaine
Amides Drug List
lidocaine
bupivacaine
prilocaine
