Transcript Uses of Genomic Information in the Diagnosis of Disease Bethany

Local Anesthetics
Shane Milu
March, 27, 2007
Local Anesthetic
A drug that reversibly inhibits the
propagation of signals along nerve
pathways in a specific area of the
body.
History
The first local anesthetic was cocaine, discovered
in the1860s by a German, Albert Niemann, and
isolated from the leaves of coca. The first clinical
use was in 1884 by Sigmund Freud. It was Freud
and Karl Kollar who noticed the anesthetic effect.
Kollar first introduced it into ophthalmology as a
topical ointment. Also around the same time
Dr.William Stewart Halsted described the injection
of cocaine into a sensory nerve trunk to induce
surgical anesthesia.
General Structures
There are two types of anesthetics
amino-esters and amino-amides. All
anesthetics are weak bases and are
active in the cationic form.
2
1
4
3
1:Aromatic ring
2:Ester or Amide linkage
3:Hydrocarbon chain
4:Tertiary Amine group
Esters
• Examples: cocaine, procaine, tetracaine
• These get hydrolyzed in the plasma by a
pseudo cholinesterase. One by-product of
this reaction paraaminobenzoic acid, this
is a common reason people have allergic
reaction to these type of agents.
Amides
• Examples: lidocaine,
mepivicaine, prilocaine,
bupivacaine
• These get metabolized in
the liver to inactive
agents. Generally there
are no allergies
associated with amide
anesthetics
Prilocaine
Mechanism of Action
• Local anesthetic drugs act mainly by inhibiting
sodium influx through sodium-specific ion
channels in the nerve cytoplasm
– Sodium ions cannot flow in, so potassium ions
cannot flow out, thereby preventing the
depolarization of the nerve.
• To do this the anesthetic molecules must
actually enter through the cell membrane of the
nerve. This is where the differences in the time
of onset and duration of the various local
anesthetics lies.
Factors that affect action of local
anesthetics
• pH
– cationic form binds to receptor site. The
uncharged form penetrates membrane .
Efficacy of drug can be changed by altering
extracellular or intracellular pH
Factors that affect action of local
anesthetic
• Lipophilicity
– The solubility of the lipid seems to be the
main determinant of anesthetic potency.
Compounds with high lipophilicity penetrate
the nerve membrane more easily. This means
less molecules are needed to inhibit the
blockade of sodium ions. This leads to
enhanced potency.
Vasoconstrictors
• Blood absorbs the unused anesthetic. In order to
slow down this process many anesthetics are
administered with a vasoconstrictor. These
constrict the vessel and slow down the
absorption of the anesthetic, by allowing less
blood to enter/leave the site.
Techniques of administration
•
•
•
•
Topical Anesthesia
Infiltration
Peridural
Spinal anesthesia
Topical Anesthesia
• Done by the administering the anesthetic
to mucous membranes or skin. Relieves
itching, burning and surface pain, i.e.
sunburns.
Infiltration
• Occurs by directly injecting a local
anesthetic to block the nerve endings
under the skin or in the subcutaneous
tissue. Used mainly for surguries, i.e.
cavities being filled.
Peridural Anesthesia
• This is accomplished
by injecting a local
anesthetic into the
peridural space, a
covering of the spinal
cord
Spinal anesthesia
• Here, the local
anesthetic is injected
into the subarachnoid
space of the spinal
cord
TOXICITIES OF LOCAL
ANESTHETICS
• Hypersensitivity – Someone who is allergic
to one type of anesthetic may not be
allergic to the other type.
Toxicity
• CNS Toxicity: If absorbed in excess
systematically can lead to excitement(tremors,
shivering, convulsions), and if absorbed in even
higher amounts can lead to depression(coma,
respiratory arrest and death)
• Cardiovascular toxicity: If absorbed in excess
systematically can lead to depression of the
cardiovascular system
Sources
http://en.wikipedia.org/wiki/Local_anesthetic
http://www.emedicine.com/ent/topic20.htm
http://www.doctorspiller.com/local_anesthetics.htm#History
http://web.ebscohost.com/ehost/pdf?vid=2&hid=106&sid=04226761-8aaa-4a5c-b5dd-dadfe10396e4%40sessionmgr107
http://patft.uspto.gov/netacgi/nphParser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6413961.PN.&OS=
PN/6413961&RS=PN/6413961
http://springer.metapress.com/content/m5g694v83500k565/fulltext.pdf
http://www.drugs.com/MMX/Lidocaine_Hydrochloride.html
http://www.emedicine.com/ent/topic20.htm
www.med.howard.edu/pharmacology/handouts/Local%20Anesthetics2.ppt
http://library.med.utah.edu/pain_center/education/outlines/local_anes.html
http://www.pharmacology2000.com/Central/Local_Anes/LAobj1.htm
http://www.moleculeoftheday.com
http://sci-toys.com/ingredients/benzocaine.html