Revision on neurophysiology and
Pharmacology of local anesthesia
Prepared by
Ahmed El far
Lecturer of oral and maxillofacial surgery –
Al-Azhar university
7- L.A diffusion, recovery and
Tachyphylaxis
L.A barriers
• Epinureum
• Perinureum
• endonureum
• Mantle, core fibers
Mantle, core fibers
Readmnistration of L.A
• Low dose will result in profound anesthesia
and rapid onset
• In some cases tachyphylaxis occur
Tachyphylaxis
• Increased tolerance to a drug which is administrated repeatedly if nerve
function is allowed to return before injection (pt experience pain), The
duration, intensity, and spread of anesthesia with reinjection are greatly
reduced.
• Explanation :
1- edema
2- localized hrg
3- clot formation
4- transudation
Which isolate the nerve from L.A
5- decreased PH of tissue
From the 1st injection of L.A
Pharmacokinetics of L A
Pharmacokinetics of L A
Local anesthetic drug uptake, absorption into
blood distribution to all cells and
organs (effect) elimination by (metabolism,
excretion)
Methemoglobinemia
• A metabolite of prilocaine, toluidine, can convert the iron in hemoglobin
from ferrous (Fe2+) to ferric (Fe3+).
• This form of hemoglobin is called methemoglobin, the condition is called
methemoglobinemia.
• This methemoglobin do not bind oxygen >>>>>> cyanosis
• The condition is rarely life threatening and responds to intravenous
methylene blue, which reduces (convert) the hemes to their normal state.
• Rarely, one may encounter a patient with hereditary
methemoglobinemia, which contraindicates the use of prilocaine.
Mechanism of action
Mechanism of action
specific receptor theory
Dissociation of L.A. (Pka)
• Measures affinity of molecule to H+
• Can be determined by Henderson and Hasselbelch equation
• Pka inversily proportonal to RN
RNH+ RN + H+
BH+ B + H+
Dissociation of L.A. (Pka)
Pka
• The pKa of a molecule represents the pH at
which 50% of the molecules exist in the lipid-
soluble form and 50% in the water-soluble
form.
• The pKa of all local anesthetics is >7.4
(physiologic pH), and therefore a greater
proportion the molecules exists in the water-
soluble form when injected into tissue having
normal pH of 7.4.
Impulse propagation
Unmyelinated nerve
Propagation of impulse
Sultatory conduction
Myelinated axons only allow action potentials to occur at the unmyelinated nodes
of Ranvier that occur between the myelinated internodes.
Rate of impulse propagation in myelinated nerve is higher than unmyelinated
(150 m/s compared to 0.5 to 10 m/s).
As sodium pushed into the node it creates an electrical force which pushes on the
ions already inside the axon. This rapid conduction of electrical signal reaches
the next node and creates another action potential, thus refreshing the signal.
In this manner, saltatory conduction allows electrical nerve signals to be
propagated long distances at high rates without any degradation of the signal.
Although the action potential appears to jump along the axon, this phenomenon
is actually just the rapid, almost instantaneous, conduction of the signal inside
the myelinated portion of the axon.
.
Factors affect L.A action
8- Factors affect L.A action
.
Maximum recommended dose (MRD)
Maximum recommended dose (MRD)
(MRD) articaine 4% : 7 mg/kg
Pt 50 kg
L A cartilage : 1.8 ml liter
Solution ????
Maximum recommended dose (MRD)
maximum allowable dose (mg/kg) x (weight in
kg/10) x (1/concentration of local anesthetic)
= mL .
(MRD) articaine 4% : 7 mg/kg
Pt 50 kg
L A cartilage : 1.8 ml liter
Elimination half life
Elimination half life: is the time necessary for 50%
reduction in blood level, ranging from 90
minutes for conventional agents such as
lidocaine to nearly 300 minutes for agents such
as bupivacaine.
Ex: one half life : 50% reduction
two half lives : 75% reduction
three half lives : 87.5% reduction
Question
Question
• Which of the following reflect accurate doses
contained in 5 mL (~2.5 cartridges) prilocaine
4% with 1 : 200,000 epinephrine?
• Prilocaine 20 mg.
• Prilocaine 200 mg.
Question
The maximum recommended dose is 500 mg for lidocaine with
epinephrine and 400 mg for mepivacaine. Anesthesia is difficult
to obtain, and you have administered 6 cartridges of 2% lidocaine
with epinephrine to remove third molars. Two sites remain
sensitive, and you elect to reinject with 3% mepivacaine to avoid
more epinephrine. Which of the following number of cartridges
would be the maximum number you can safely administer?
(Assume 2 mL per cartridge.)
• 1
• 3
• 5
• 7
Question
• Beckercaine is a newly released local anesthetic classified as
an ester and is compounded with epinephrine 1 : 200,000. It
has twice the lipid solubility of lidocaine, and other data are as
follows, with corresponding data for lidocaine in parentheses:
pKa = 7.5 (7.9) Protein binding 92% (65%). All of the following
are correct regarding this new wonder-drug EXCEPT:
• It is likely formulated as a 1% solution.
• It has a faster onset than lidocaine.
• It is metabolized in plasma.
• It has a shorter duration than lidocaine
THANK YOU
احمد الفار
مدرس جراحة الوجه والفكين
:ت
01093096224
Facebook: Ahmed Elfar
