Local anesthetics' Adrenergic transmission' Anaphylactic shock

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• Local anesthetics. Adrenergic transmission.
  Anaphylactic shock

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LOCAL ANESTHETICS
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Local anesthetics (LA) Are substances inducing
local desenzitisation, it means they reversibly
inhibit generation and propagation of excitement
in nervous fibers
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Chemical aspects
Aromatic part
Ester (amid) part
Basic side chain
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All LA are weak basis with values of pK 8-9, so
at physiologic pH are partlially, but not
absolutely ionisied. The more acid surrounding
(inflammation), the more they are ionisied.
EFFECT ionisied form PENETRATION TO THE SITE OF
EFFECT nonionised form
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kreslila N. Hlavacova
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MECHANISM OF ACTION
Block generation of action potential through
blocking Voltage dependend Na channels
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MECHANISM OF ACTION
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• Na ionic channels can be in state
• Steady, not permeable
• Activated, open
• Inactive
• automatically traverse to it from open state,
  also if depolarisation still remains

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LA block initiation and propagation of action
potential 1. Non specific effect on membranes
( ? surface potential, similarity with
inhalational anestetics) 2. Specific effect on
Na channels - use-dependence the
higher frequency of AP, the stronger
blockade - LA influence state 2. and 3. -
importance for antidysrrhytmic effect
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OLDER SUBSTANCES
COCAINE - history PROCAINE, NOVOCAIN TETRACAINE,
AMETHOCAINE LIDOCAINE, LIGNOCAINE,
XYLOCAINE TRIMECAINE, MESOCAIN CINCHOCAINE not
used BENZOCAINE only surface anesthesia
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• EFFECTS OF LA
• dependence from thickness and myelinisation of
  nerve fibers
• SEQUENCE OF DESENSITIZATION
• pain ? cold ? heat ? touch ? deep pressure

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RISK OF TOXIC EFFECTS mainly if they get to
blood (purposely accidentaly) heart slowing
down of excitement propagation, stopping CNS
restlessness, spasms, at last breathing
depression (allergic reactions) Therapy
thiopental, diazepam, i.v., assisted breathing
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Important role play speed of
administration concentration of solution
Effect and toxicity raises with LA
concentration faster, than corresponds to total
dose. At low concentration can be exceeded
maximal doses. On the other hane, at high
concentrations are administered lower doses.
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VAZOKONSTRICTOR ADDITIVES LA slower reaches
circulation, result longer effect
lower toxicity epinephrine, corbadrine,
norepinephrine If epinephrine is contraindicated
- felypressin, derivate of VP - a little
toxic LA without additive No at anesthesia of
acral parts ischaemia!
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Types of Local Anesthesia

• Surface anesthesia
• Infiltration anesthesia
• Conduction anesthesia
• Spinal (subdural) anesthesia

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• Surface anesthesia
• mucosa, no skin
• but not crystalic (eutectic) mixtures of LA
• can be used at skin (e.g. lidocaine
  prilocaine)
• Infiltration anesthesia
• injection to the region to be desensitized
• special type at limbs interventions
• intravenous regional anesthesia cuff

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• Conduction anesthesia
• higher concentrations of LA with higher addition
  of vasoconstrictor
• substance
• near nerve branch
• high conduction anesthesia paravertebral and
  epidural

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• Spinal (subdural) anesthesia
• Difference between subdural and epidural
  (sometimes listed as spinal)

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Subdural anesthesia
Solution lighter than liquor (hypobaric) in
liquor goes up, hyperbaric goes down can be
influenced with NaCl and glucosa, important for
the region of desensitization By paralysis of
vasomotoric nervs occurs vasodilation in
anesthetised region blood pressure goes down No
vasoconstrictor additives
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Use of Local Anesthetics
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• Other Indications of Local Anesthetics
• 5. prevention and therapy of some arrhytmias
• - lidocaine and trimecaine, i.v.
  administration, usually 50 100 mg
• Vinevskýs blockade
• 7. analgesia postherpetic neuralgias
• - lidocaine patches (concentration 5 )

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• Sympathic Nervous System (Thoracolumbal)
• Mediator is norepinephrine (NE) in ganglions
  acetylcholine
• Receptors a a1 vessels vasoconstriction
  mydriasis, ejaculation
• a2 GIT - ? motility
  and secretion, CNS central hypotension
• Receptors ß ß1 heart increases frequency,
  contractility, conductivity and
• excitability
  kidneys - ? excretion of renin
• ß2 bronchi
  dilation, skeletal muscle vasodilation,
• uterus
  tocolysis
• ß3 adipocyts
  lipolysis
• Sympathomimetics
• Direct
• endogenous catecholamines and their derivates
  (NE more a1, a2, ß1 epinephrine a1,
• a2, ß1, ß2 isoprenaline only ß1, ß2)
• a1 phenylephrine, nafazoline,
  oxymetazoline (mydriasis, decongestion of mucosa)
• a2 clonidine, corbadrine (? a-metyldopa),
  guanfacin (hypertension)
• ß1 nonglycoside cardiotonics dopamine,
  dobutamine (heart failure)
• ß2 short lasting effect salbutamol,
  fenoterol, terbutalin
• long lasting effect salmeterol,
  formoterol, klenbuterol

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• Indirect
• amphetamine, metamphetamine budivé amines
  (penetration to CNS, abuse)

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• Anaphylaxis
• acute generalised allergic reaction with
  simultaneous affection of more
• organ systems, usually CVS, resp. GIT
• - sensibilizing antigen, repeated exposition
  to Ag
• Ag IgE ? histamine, leucotriens ?
  bronchoconstriction, vasodilation
• - foreign proteins often bee, gad-bee, snake
• - hormones, enzymes, fine dust, polysacharids,
  dg preparations, blood derivates, drugs
  (antibiotics) low-molecular substances ?
  haptens ? bond to blood plasma proteinst
• occurrence seconds to minutes after allergen
  penetration usually in parenteral
• form
• Anaphylactoid reaction
• missing reaction AgAb
• - toxically-idiosyncratical mechanisms
• - after first application of Ag!
• - opioid analgetics, polymyxine, RTG contrast
  substances

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• Anaphylactic shock
• anaphylactic reaction ? BP /-
  unconsciousness
• - symptom of anaphylactic reaction to
  esposition of specific antigen
• shock condition
• bronchoconstriction
• acute respiratory insuficiency
• Quinckes edema, edema 1 mm skin fold 1 liter
  in IST
• dermal symptoms urticaria, pruritus
• GIT nausea, vommiting, abdominal spasms,
  diarrhoea
• Treatment
• - stop penetration of Ag to organism
• vein cannulation
• ensure breathing
• immediate administration of epinephrine
• i.v. glucocorticoides hydrocortisone 200 mg and
  more,
• methylprednisolone 40-80 mg and more

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• H1-antihistaminics (bisulepine Dithiaden),
  Calcium gluconicum
• epinephrine fysiologic antagonist of chemical
  mediators effects of an. reaction on smooth
  muscles, vessels,...
• shock dose 0,5-1,0 mg i.v. in bolus doses by
  0,1 mg, than repeat according to patients
  condition and its reaction to therapy
• continual infusion in saline solution at speed
  2-4 µg/min
• alternative routes of administration
  intratracheal, sublingual
• if persistance of bronchospasm ? aminophyline 6
  mg/kg (Syntophyllin inj.)
• patient should be after anaphylactic episode
  examined by allergologist!
• prevention before RTG investigation
  antihistaminic substance and glucocorticoid
  according to risk category