all about local anesthetic.

1. Presentation
on
Local anesthetic

2. – Presented by
Elvin akter mim
Tasfia tabassum
roshny
Tania akter
Keshob kumer Ghose
– Presented to
yesmin Begum
Assistant professor
Department of pharmacy
Southeast university

3. Local
anesthetic
All about local anesthetic

4. Definition
– Drugs that causes loss of sensation to pain in specific area of the body without
loss of consciousness.

5. History
Cocaine
– Isolated by Niemann in 1860.
– Introduced by koller In 1884 as topical optical anesthetic.
Procaine
– Synthesized by Einhorn in 1905.
Lidocaine
– Synthesized by Lofgren in 1943.

6. Ideal criteria
– Non irritating.
– Water soluble.
– Serializable.
– Inexpensive.
– Rapid onset of action.

7. Ideal criteria
– Should not produce permanent damage to the nerve tissue.
– Potent.
– Effective whichever route is given.
– No post anesthetic side effect.

8. Classification (according to
duration of action)
– Short acting (30 to 60 minutes)
 Procaine (30 mins)
 Amethocaine (1 hour)
– Intermediate acting (60 to 120 minutes)
 Lidocaine (1-1.5 hour)
 Pilocaine (2 hours)
– Long acting (>2 hours)
 Bupivacaine (3 hours)
 Tetracaine

9. structure
procaine
lidocaine
bupivacaine

10. Classification(according to
chemical structure)
– Ester group
 Procaine
 Cocaine
 Benzocaine
– Amide group
 Lidocaine
 Etidocaine

11. Some drugs used as LA
Cocaine
– Used as surface anesthetic.
– Topical or parenteral.
– Duration-1 to 2 hours.

12. Some drugs used as LA(contd.)
Procaine
– Used as infiltration anesthetic and in dental procedure.
– Parenteral.
– Duration: 15 to 30 minutes.

13. Some drugs used as LA(contd.)
Lidocaine
– Used as epidural and spinal anesthetic.
– Parenteral.
– Duration: 30 to 60 mins.

14. Some drugs used as LA(contd.)
Bupivacaine
– Used as infiltration and spinal anesthetic.
– Parenteral.
– Duration: 2 to 4 hours.

15. Tasfia tabassum roshny
2016000300006

16. pharmacokinetics
– Soluble surface anesthetics are rapidly absorbed from mucous membrane and
abraded areas but absorption from intact skin is poor.
– Rate of absorption depends on the blood flow to the area of application or
injection.
– Procaine is negligibly bound to plasma proteins, but amide local anesthetics are
bound to plasma α1acid glycoprotein.

17. Pharmacokinetics(contd.)
– Amide linked Las (lignocaine) are degraded only in liver macrosomes by
dealkylaiton and hydrolysis.
– Ester linked Las (procaine) are rapidly hydrolyzed by plasma pseudo
cholinesterase and remaining by esterase in the liver.
– After oral ingestion both procaine and lignocaine have high first pass
metabolism in the liver. Thus they are not effective orally for anti-arrhythmic
purpose.

18. indications
– LAs are used for
 Minor surgery
 Dental procedure
 Suturing small wounds
 Making an incision in a small area for removing superficial tissue sample for biopsy.
 During labor and delivery
 Gastrointestinal endoscopy
 Wart treatment
 Vasectomy
 Neonatal circumcision.

19. Adverse effect
– Adverse effect may be classified as:
– Those associated directly with blocking ion channels in cell membranes, such as
cardiovascular and CNS toxicity.
– Those due to other effects of drug or vehicle (mainly peripheral nerve
complications).
– Allergic reactions (often a mistaken diagnosis).
– Mechanical or other effects of technique, such as needle trauma or introduction
of infection. Signs and symptoms of CNS toxicity include convulsions, followed
by coma and respiratory depression.

20. Adverse effect(contd.)
– Adverse effect include
 Restlessness
 Dizziness
 Disorientation
 Light-headedness
 Rhythmical oscillation of the eyeballs
 Psychosis
 Slurred speech
 Slow heart rate
 Cardiac arrest

21. contraindications
– Local anesthetics are contraindicated in patient with known anesthetics are
contraindicated in patient with known hypersensitivity, in the elderly, severe
hemorrhage deformities, blood dyscrasias and hypertension.

22. Drug interactions
– Barbiturates may decrease activity of lidocaine. Increased effects of lidocaine
may occur if taken with beta blockers, cimetidine and quinidine.
– If lidocaine is used on a regular basis Its effectiveness may diminish when used
with other medications.

23. Factors affecting the reaction of
LA (lipid solubility)
– All local anesthetics have weak bases. Increasing the lipid solubility leads to
faster nerve penetration, block sodium channels, and speed up the onset of
action.
– The more tightly local anesthetics bind to the protein, the longer the duration
of onset action.
– Local anesthetics have two forms, ionized and nonionized. The nonionized form
can cross the nerve membranes and block the sodium channels.
– So, the more no ionized presented, the faster the onset action.

24. Factors affecting the reaction of
LA (pH influence)
– Usually at range 7.6 – 8.9
– Decrease in pH shifts equilibrium toward the ionized form, delaying the onset
action.
– Lower pH, solution more acidic, gives slower onset of action

25. Factors affecting the reaction of
LA (vasodilation)
– Vasoconstrictor is a substance used to keep the anesthetic solution in place at a
longer period and prolongs the action of the drug
– vasoconstrictor delays the absorption which slows down the absorption into the
bloodstream
– Lower vasodilator activity of a local anesthetic leads to a slower absorption and
longer duration of action
– Vasoconstrictor used the naturally hormone called epinephrine (adrenaline).
Epinephrine decreases vasodilator.

26. Tania akter
201600030007

27. Routes of administration
– There are five major routes for applying local anesthetics. These routes are
summarized as follows:
 Topical
 Nerve block
 Infiltration
 Spinal
 Epidural

28. Topical anesthesia
– Act as nerve blocking agent. E.g., lidocaine.
– This procedure can provide anesthesia on
 Skin and the mucus membrane of the rectum.
 Urethra and vagina.
 available in creams, ointments, aerosols, sprays, lotions, and jellies.

29. Nerve block anesthesia
– Often a group of nerves, called a plexus or ganglion, that causes pain to a
specific organ or body region can be blocked with the injection
of medication into a specific area of the body. The injection of this nerve-
numbing substance is called a nerve block.
– Affect the bundle of nerves serving the area to be operated upon.
– This anesthesia used to block sensation in a limb or large area such as face.

30. How are nerve block uses?
– Therapeutic nerve blocks are used to treat painful conditions. Such nerve blocks
contain local anesthetic that can be used to control acute pain.
– Diagnostic nerve blocks are used to determine sources of pain. These blocks
typically contain an anesthetic with a known duration of relief.
– Preemptive nerve blocks are meant to prevent subsequent pain from a
procedure that can cause problems including phantom limb pain.
– Nerve blocks can be used, in some cases, to avoid surgery.

31. Types of nerve block
– Trigeminal nerve blocks (face)
– Ophthalmic nerve block (eyelids and scalp)
– Supraorbital nerve block (forehead)
– Maxillary nerve block (upper jaw)
– Sphenopalatine nerve block (nose and palate)
– Cervical epidural, thoracic epidural, and lumbar epidural block (neck and back)
– Cervical plexus block and cervical paravertebral block (shoulder and upper neck)
– Brachial plexus block, elbow block, and wrist block
– Subarachnoid block and celiac plexus block (abdomen and pelvis)

32. Local infiltration anesthesia
– Uses for infiltrative anesthetics are as follows:
– Blocks a specific group of nerves in a small area.
– Subcutaneous infiltration (IV placement, superficial/shave biopsy, suturing)
– Submucosal infiltration (dental procedures, laceration repairs)
– Wound infiltration (postoperative pain control at incision site)
– Intraarticular injections (postsurgical pain control, arthritic joint pain control)
– Infiltrative nerve blocks (ankle block, scalp block, digit block)

33. Dosage administration guidelines
– Lower concentrations of local anesthetics are typically used for infiltration
anesthesia.
– Variation in local anesthetic dose depends on the procedure, the degree of
anesthesia required, and the individual patient's circumstances.
– Reduced dosage is indicated in patients who are debilitated or acutely ill, in
patients who are very young or very old, and in patients with liver disease,
arteriosclerosis, or occlusive arterial disease.

34. Spinal anesthesia
– In this anesthesia, an anesthetic agent is injected into the subarachnoid space
through spinal needle.
– Drugs affect large regional areas such as lower abdomen and leg.

35. Epidural anesthesia
– It involves injection of the local anesthetic into the epidural (lumbar or caudal)
space via a catheter that allows repeated infusions.
– It absorb slowly in to the cerebrospinal fluid.
– Used in labor and delivery.

36. Keshob K. Ghose
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37. Mechanism of LA
– The resting neuronal membrane potential is -60 to -70 millivolts. During an
action potential, the resting channels move through several closed
conformation and finally open briefly to allow sodium channel.

38. Voltage gated sodium channel
1 2 3 4 5 6 1 2 3 4 5 6
1 2 3 4 5 6
h
1 2 43 5 6
p

39. LA binding site
– The LA lidocaine is shown docked to two of these residues for formation of the
local anesthetic binding site.
F
I
Y

40. Frequency and voltage
dependence of LA
– The degree of block by a given concentration of LA depends on how the nerve
has been stimulated and on its resting membrane potential.
– Due to this effect its charged form gain access to the membrane.

41. Different stage of the voltage
gated sodium channel
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Resting
conformations S4
regions
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Intermediate
closed
conformation
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Open
conformation
Inactivated
conformation

42. Affinity of LA to different stage.
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v
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v
L
A L
A
L
A
Resting conformation
(low affinity for LA)
Intermediate closed
conformation
(high affinity for LA)
Opening
conformation
(high affinity for LA)
Inactivated
conformation
(high affinity for LA)

43. Entry in to the membrane
Na
+
Na
+
Na+

44. Use of vasoconstrictor
– Increase duration of action.
– increase intensity of nerve block.
– Decrease systemic toxicity.

45. Use of vasoconstrictor
– Added to the LA to delay absorption of the anesthetic from its injection site.
– Administration of lidocaine 1% with epinephrine results in the same degree of
blockade as that produce by lidocaine 2% with out vasoconstrictor.

46. clinical pharmacology of LA
– Central nervous system
central nervous system effects at low doses include sleepiness, light-headness,
visual and auditory disturbances and restlessness. at higher concentrations
nystagmus and muscular twitching may occur.
- Cardiovascular system
The cardiovascular effects of local anesthetics result partly from direct effects
upon the cardiac and smooth muscle membranes and partly from indirect effects
upon the autonomic nerves. Local anesthetics block cardiac sodium channels and
thus depress abnormal cardiac pacemaker activity, excitability and conduction.

47. clinical pharmacology of LA
– Blood
The administration of large doses of prilocaine during regional anesthesia may
lead to accumulation o the metabolite 0-toluidine, an oxidizing agent capable of
converting hemoglobin to methemoglobin that lead to pulmonary disease.
- Allergic reaction
The ester type local anesthetics are metabolized to p-aminobenzoic acid
derivatives. These metabolites are responsible for allergic reaction. amides are not
metabolized to p-aminobenzoic acid that’s why no allergic reaction occur.

48. Reference
– Goodman and Gillman’s “the pharmacological basis of therapeutics” by
Hardman, Limbird, and Gilman.
– “Principles of pharmacology” by David E. Golan.
– Essential of medical pharmacology by K.D. Tripathi.
– https://www.youtube.com/watch?v=lHIvBFPM0Ps.
– https://www.youtube.com/watch?v=h7wHS7IOT4M&t=463s.
– https://en.wikipedia.org/wiki/Local_anesthetic.