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Local Anesthetics Local Anesthetics Lab


									Local Anesthetics
      Lab. 4
Local Anesthetics (LA)

• L.A. reversibly block impulse conduction
  along nerve axons and other excitable
• 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.
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.
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.
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".
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
• 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.
• 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
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
• 3- Nerve block: LA is injected in the
  vacinity of major nerve such as teeth
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
Clinical use

• 1- Systemic use as antiarrhythemic agents
  e.g. Lidocaine
• 2- Locally use to produce anesthesia
Clinical LA
• Clinical local anesthetics belong to one of two
•   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.
Classification of LA

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
Classification of LA
2-   Amide e.g. Lidocaine
•    Articaine
•    Bupivacaine
•    Cinchocaine/Dibucaine
•    Etidocaine
•    Levobupivacaine
•    Lidocaine/Lignocaine
•    Mepivacaine
•    Piperocaine
•    Prilocaine
•    Ropivacaine
•    Trimecaine
Classification of LA
3- Combinations
• Lidocaine/prilocaine (EMLA)
4- Natural local anesthetics e.g. Saxitoxin and
• 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
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
Frog’s 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
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.
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.
The time interval   Procaine   Lignocaine
       3               -           -
       6               -           +
       9               -
       12              -
       15              -
       18              +
• Negative (-)= means the presence of the
  withdrawal reflex (the drug has no
• 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

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