Local Anesthetics

1
Local Anesthetics

• Lab. 5

2
Local Anesthetics (LA)

• L.A. reversibly block impulse conduction along
  nerve axons and other excitable membrane.
• A local anesthetic is a drug that causes
  reversible local anesthesia and a loss of
  nociception. When it is used on specific nerve
  pathways (nerve block), effects such as analgesia
  (loss of pain sensation) and paralysis (loss of
  muscle power) can be achieved.

3
Mechanism of action of LA

• They act by blockade of sodium channels so that
• 1- The threshold for excitation increase
• 2- Impulse conduction slow
• 3- The rate of rise of the action potential
  declines, and
• 4- The ability to generate an action potential is
  abolished or canceled.

4
Mechanism of action of LA

• When the influx of sodium is interrupted, an
  action potential cannot arise and signal
  conduction is inhibited. LA drugs bind more
  readily to sodium channels in activated state,
  thus onset of neuronal blockade is faster in
  neurons that are rapidly firing. This is referred
  to as state dependent blockade.

5
Effect of PH

• Local anesthetics are weak bases and are usually
  formulated as the hydrochloride salt to render
  them water-soluble. At the chemical's pKa the
  protonated (ionized) and unprotonated (unionized)
  forms of the molecule exist in an equilibrium but
  only the unprotonated molecule diffuses readily
  across cell membranes. Once inside the cell the
  local anesthetic will be in equilibrium, with the
  formation of the protonated (ionized form), which
  does not readily pass back out of the cell. This
  is referred to as "ion-trapping".

6
Effect of PH (cont.)

• LA are weak bases and their activity increases by
  increasing PH
• This because if large amount of a drug is
  unpolar, it will facilitate its penetration
  through the cell membrane
• Once the drug has penetrated the lipid barrier
  and reach its site of action it ionized and the
  ionized form is responsible for LA activity

7

• Acidosis such as caused by inflammation at a
  wound partly reduces the action of local
  anesthetics. This is partly because most of the
  anesthetic is ionized and therefore unable to
  cross the cell membrane to reach its
  cytoplasmic-facing site of action on the sodium
  channel.

8

• Local anesthetics block conduction in the
  following order small myelinated axons (e.g.
  those carrying nociceptive impulses),
  non-myelinated axons, then large myelinated
  axons. Thus, a differential block can be achieved
  (i.e. pain sensation is blocked more readily than
  other sensory modalities).

9
Methods of Administration

• 1- Surface anesthesia direct application of the
  drug on the surface such as skin and wounds.
• 2- Infiltration anesthesia injection of LA in
  subcutaneous tissue in order to paralyze nerve
  endings at the site of action.
• 3- Nerve block LA is injected in the vacinity of
  major nerve such as teeth

10
Methods of Administration

• 4- Epidural anesthesia injection of LA into the
  epidural space.
• 5- Sympathetic block inject LA around
  sympathetic nerves
• 6- Spinal anesthesia injection of LA into
  subarachnoid space in the lumber region

11
Clinical use

• 1- Systemic use as antiarrhythemic agents e.g.
  Lidocaine
• 2- Locally use to produce anesthesia

12
Clinical LA

• Clinical local anesthetics belong to one of two
  classes
• 1- aminoamide and 2- aminoester
• Synthetic local anesthetics are structurally
  related to cocaine. They differ from cocaine
  mainly in that they do not produce hypertension
  or local vasoconstriction, with the exception of
  Ropivacaine and Mepivacaine that do produce weak
  vasoconstriction.

13
Classification of LA

• 1-Esters
• A- esters of P- amine benzoic acid e.g. Procaine
• B- Esters of benzoic acid e.g. Cocaine
• Benzocaine
• Chloroprocaine
• Cyclomethycaine
• Dimethocaine/Larocaine
• Propoxycaine
• Procaine/Novocaine
• Proparacaine
• Tetracaine/Amethocaine

14
Classification of LA

• 2- Amide e.g. Lidocaine
• Articaine
• Bupivacaine
• Cinchocaine/Dibucaine
• Etidocaine
• Levobupivacaine
• Lidocaine/Lignocaine
• Mepivacaine
• Piperocaine
• Prilocaine
• Ropivacaine
• Trimecaine

15
Classification of LA

• 3- Combinations
• Lidocaine/prilocaine (EMLA)
• 4- Natural local anesthetics e.g. Saxitoxin and
  Tetrodotoxin
• Naturally occurring local anesthetics not derived
  from cocaine are usually neurotoxins, and have
  the suffix -toxin in their names. Unlike cocaine
  produced local anesthetics which are
  intracellular in effect, saxitoxin tetrodotoxin
  bind to the extracellular side of sodium channels.

16
Potency LA

• The potency of LA is vary from one to another
  where the potency and duration of action are
  increased with decreased water solublility of the
  agent for example
• Procaine ???? 1 more water soluble
• Lidocaine ???? 4
• Tetracaine ???? 16

17
Frogs plexus method

• Foot withdrawal reflex of frog
• Principle
• The skin of the frog is very sensitive to diluted
  HCL and will reflex by withdrawing its leg when
  immersed in HCL

18
Procedure

• 1- Decapitaion the frog (avoid pithing the spinal
  cord)
• 2- Make a transverse incision in the abdominal
  wall just below the xiphoid cartilage and
  eviscerate the abdomen carefully to form
  abdominal sac and expose the lumbar plexus
  without damaging it
• 3- suspend the frog in a stand and test the
  withdrawal reflex with 0.1 N HCL by immersing one
  foot in HCL and avoid touching the bottom of the
  beaker.
• 4- remove the acid and wash immediately with tap
  water
• N.B. the withdrawal reflex time should not exceed
  10 seconds and the contact with HCL too.

19

• 5- Administer 1 ml of LA solution in the
  abdominal sac of the frog and observe the zero
  time.
• 6- Test the withdrawal reflex at 3 minutes
  interval and wash with tap water after each
  exposure to the acid, observe the time at which
  the absence of withdrawal reflex occurs
• Onst time is the time from adding LA untill the
  acid fails to provoke withdrawal of the foot
• Recovery time is the time in minutes from
  washing the LA till the appearance of the
  withdrawal reflex in response to HCL.
• 7- Tabulate your results and determine which of
  LA is more rapid in its action than the other.

20
Lignocaine Procaine The time interval
- - 3
- 6
- 9
- 12
- 15
18
21

• Negative (-) means the presence of the
  withdrawal reflex (the drug has no activity).
• Positive () means the absence of the withdrawal
  reflex (the drug has activity and blocks sodium
  channels)
• Conclusion
• From the table we conclude that lignocaine is
  more rapid in inducing local anesthesia than
  procaine