Document Sample
          by :
    Tutik Juniastuti
Local ansesthetics are drugs used
 primarily to inhibit pain by preventing
 impulse conduction along sensory
They achieve this by blocking
 voltage-sensitive Na+ channels in the
 cell membrane.
Local anesthetics are also used as
 antidysrhythmics and in epilepsy
The bask eledrophysiology of neurons
 Sodium channels can exist in three states:
  resting (i.e. closed), activated (i.e. open) and
  inactivated (i.e. blocked; explained below).
 The resting cell.
   The action of the Na+ pump in cell membranes normally
    maintains a high level of K+ and a low level of Na+ within
    the cell. In the resting cell, the membrane is more
    permeable to K+ than to Na+.
   The efflux of K+ makes the cell interior negative with
    respect to the outside, giving a membrane potential
    between -60 and -90 mV.
   In the resting cell, the Na+ channels are closed.
  The action potential , When a nerve cell is
   stimulated locally (e.g. by noxious stimuli acting
   on a pain fibre or by neurotransmitter action on
   a receptor linked to a cation channel) the Na+
   channel opens, leading to a local increase in
   the membrane permeability to Na+ .
  The resultant increased influx of positive Na+
   causes membrane depolarisation and an action
   potential is generated.
  This is a regenerative process, as the action
   potential itself causes more Na+ channels to
   open, allowing its propagation along the nerve.
  Within 5 ms the Na+ channels are inactivated
   (i.e. they close and are transiently refractory to
   being opened) allowing the cell to repolarise.
   (The delayed opening of K+ channels in
   response to the membrane depolarisation also
   contributes to repolarisation.)
  The rapidity of the sequence of events means
   that repetitive firing can proceed at high
Local anaesthetics

Important examples are procaine,
 lidocaine (lignocaine), tetracalne
 (amethocaine), bupivacaine and
 prilocaine. Cocaine was the first local
 anaesthetic to be used but has few clinical
 applications now.

         Esters                         Amides

Long Short Surface               Long            Medium
Action Action Action             Action          Action
(Tetra    (Procaine) (Benzocaine) (Bupivacaine, (Lidocaine)
caine)                            Ropivacaine)
Mechanism of action
 Local anaesthetics are nearly all weak bases
  (pK. 8-9) and have similar chemical structures
  (Fig. 43.3). They act by blocking Na+ channels
  and stopping the propagation of action potentials
  in nerve. (Figs 43.1 and 43.4).
 Local anaesthetics gain access to their binding
  site either from the cell interior or by lateral
  diffusion in the cell membrane. In both cases, it
  is essential for the drug to adopt its lipid-soluble,
  uncharged form to gain access (Fig. 43.4).
 This, of course depends on pH and can explain
  the reduced activity of local anaesthetics in
  inflamed tissue, where the lower pH increases
 Many local anaesthetics show use-dependence,
  that is they am more effective in blocking
  channels once these have been activated.
 This may be because the drug's binding site is
  within the channel and accessible only when the
  channel opens or it may result from greater
  affinity for the inactivated state of the channel.
 Local anaesthetics usually block small diameter
  fibres at lower concentrations than large fibres.
  Accordingly, pain sensation is blocked before
  other sensory inputs but it is not usually possible
  to achieve local anaesthesia without loss of
  other sensory modalities or local paralysis.
 The plasma half-life of most local anaesthetics is
  1-2 h, but their action persists for longer due to
  retention at the site of administration.
 The duration of action can be increased by the
  use of a vasoconstrictor (epinephrine
  (adrenaline) or felypressin).
 The esters (tetracaine, benzocaine, procaine,
  cocaine) are hydrolysed rapidly by plasma
  esterases once they reach the bloodstream;
  whereas most amides (prilocaine, bupivacaine)
  are relatively resistant to plasma esterases and
  are subject to N-dealkylation and hydrolysis in
  the liver at a slower rate.
 The variable lipid solubility of local anaesthetics
  determines the rate at which they penetrate
  tissues to cause nerve block and also their
  suitability for action on mucous membranes.
 Table 43.1 summarises the properties of three
  local anaesthetics. Cocaine and lidocaine
  penetrate membranes readily: procaine poorly.
  Benzocaine differs from other local anaesthefics
  in lacking the amino group; this results in
  increased lipophilicity and allows rapid entry into
  tissues, a fast onset and long duration of action.
Unwanted effects
The unwanted effects of local
 anaesthetics are due to their entry into
 the systemic circulation.
CNS effects, prominent with procaine,
 less with lidocaine and prilocaine, are
 paradoxically stimulatory and include
 restlessness and tremor; though larger
 doses are depressant.
Respiratory depression may be a cause
 of death.
 Local anaesthetics also cause myocardial
  depression and vasodilatation, which may
  result in a serious lowering of blood
 Cocaine has additional effects related to its
  ability to inhibit monoamine uptake into
  nerve-endings (not shared by other local
  anaesthetics). Sympathomimetic effects
  arising in this way include a rise in blood
 Hypersensitivity reactions, manifest as
  allergic dermatitis, may occur.
Clinical use and administration of local
 Surface anaesthesia.
  Lidocalne and tetracaine are used for local anaesthesia
   of skin. coffee, etc.
 Infiltration anaesthesia.
  Most LAs are suitable. Given by Injection for minor
   surgery. Epinephrine (adrenaline) or felypressin may be
   coadministered to cause local vasoconstriction and
   reduct loss to circulation, thus prolonging action.
 Intravenous regional anaesthesia.
  A pressure cuff maintains local concentration and
   prevents entry into the general i circulation. Lidocaine
   and prilocaine are suitable.
 Nerve-block anaesthesia.
  Most LAs are suitable. Injection close to the nerve trunk
   produces regional anaesthesia for surgery or dentistry.
   Vasooonstrictors may be used to enhance duration.
 Spinal anaesthesia.
  Lidocalne or tetracalne can be injected into the
   subarachnoid space to act on spinal roots and spinal
   cord. This Is used for lower body surgery when general
   anaesthesia Is undesirable.
 EpIdural anaesthesla.
  Lidocalne or buplvacalne are injected into the-epIdural
   space. This Is used for spinal anaesthesia and also,

Shared By: