LOCAL ANESTHETIC AGENTS

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LOCAL ANESTHETIC AGENTS
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History of local anesthesia

• 1500s Accounts referring to Peruvian Indians
  chewing on leaves of the coco plant are found
• 1884 Cark Koller demonstrated the usefulness of
  the extract from these leavescocaineas a
  topical anesthetic for the eyes, and earned
  distinction as the father of local anesthesia
• 1884 Willium Halsted used cocaine in the first
  nerve block Inferior alveolar nerve block. The
  use of cocaine for anesthesia produced several
  unwanted side effects including cardiac problem
  and addiction
• 1885 James Corning demonstrated the use of a
  tourniquet to slow absorption of cocaine

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History of local anesthesia

• 1901 Heinrich Braun demonstrated the use of
  epinephrine to retard local anesthetic absorption
  from the site of injection
• 1904 Alfred Einhorn introduced procaine .
  Epinephrine was needed to constrict the vessels
  in the area of administration to lengthen the
  duration of anesthesia. It was common to see a
  150,000 concentration for many years
• 1943 Nils Lofgren introduced lidocaine
• 1947 Novocol company made the dental aspirating
  syringe available
• 1959 Disposable sterile needles made available by
  Cook- Waite, Roehr Company

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Physiology of nerve conduction
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Sodium-potassium Pump
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Channel Entry
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Local anestheticsamides vs. esters
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Classification of local anesthetics
Amides Ester
Bupivacaine Benzocaine
Lidocaine Cocaine
Mepivacaine Procaine
Prilocaine
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Absorption

• Site of injection
• The dose of local anesthetic
• Physicochemical properties of local anesthetic
• The addition of epinephrine

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Distribution

• Site of injection

Systemic absorption
heart
brain
Skeletal muscle
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Biotransformation and Elimination

• Aminoester Aminoamide
• Plasma esterase Hepatic enzyme
• Renal excretion

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• ???? ???????????????????????????????
• ?????? ????? half life ????????????
• cardiac output ????? cardiac output ???
  ???????????????????

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• Potency lipid solubility
• Onset pKa, concentration of local anesthetic

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What is pKa?

• pKa pH log RNH
• RN
• (modified Henderson- Hasselbalch equation)
• pKa is the dissociation constant, represents
  the
• pH at which the concentration of the
• ionized base(RNH) and the non-ionized
  
• base (RN) are equal.

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• RNH RN H

Outside membrane
Inside membrane

• RNH RN H

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Anesthetic pKa RN at pH 7.4 Onset min
Mepivacaine 7.6 40 2-4
Etidocaine 7.7 33 2-4
Articaine 7.8 29 2-4
Lidocaine 7.9 25 2-4
Prilocaine 7.9 25 2-4
Bupivacaine 8.1 18 5-8
Procaine 9.1 2 14-18
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Example at physiologic pH (7.4)
Lidocaine Procaine
pKa 7.9 31 ionized to non-ionized 8.9 321, ionized to non-ionized
onset 2 to 3 minutes 6 to 12 minutes

• if lidocaine (pKa 7.9) is administered into an
  area of infection (pH 4.9) resulting 1,0001
  ionized to non-ionized indicates a poorer
  penetration into the nerve tissue and therefore a
  less effective nerve block

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Quinn and Malamed (1990) and Haegerstam(1990)
suggested of administer L.A.

• AWAY from the area of inflammation (nerve block)
  especially in the area of EXTENSIVE CELLULITIS
• Malamed. Handbook of LOCAL ANESTHESIA 1990.
• Haegerstam, Introduction to Dental Local
  anesthesia 1990.

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• Duration of action
• Differential sensory/ motor blockade
• Adverse reaction

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Clinical use of local anesthesia

• Topical anesthesia
• Infiltration
• Peripheral nerve block
• Epidural block
• Spinal block
• Intravenous regional anesthesia

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Toxicity
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Clinical sign and symptom LA toxicity
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CNS toxicity

• Potency
• The rate of intravenus administration
• Acid base status and PaCO2

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Cardiovascular toxicity
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CC/CNS Ratio

• i.e. the ratio of the LA dosage required for
  irreversible cardiovascular collapse and the
  dosage that produces CNS toxicity (convulsions)
• the higher the CC/CNS ratio the better the safety
  margin

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Prevention

• Aspiration before injection
• Inject slowly
• Use smallest quantity of solution and lowest
  concentration of vasoconstrictor
• Observe the patient after injection
• Choose another anesthetic if the patient has
  tendency for allergic reaction

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The signs and symptoms of allergic reaction
include

• generalized body rash or skin redness
• itching, urticaria (hives)
• bronchospasm (difficulty breathing)
• swelling of the throat
• asthma
• abdominal cramping
• irregular heartbeat
• hypotension (low blood pressure)
• swelling of the face and lips (angioneurotic
  edema)

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Adverse reactions of commonly usedlocal
anesthetics

• Methemoglobinemia
• associated with prilocaine, articaine,
  benzocaine
• Local tissue toxicity

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epinephrine
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• Receptor Response
• Alpha stimulation Vasoconstriction
• Peripheral resistance
• Beta 1 stimulation Heart rate
• Force of cardiac contraction
• Cardiac output
• Beta 2 stimulation Vasodilatation
• Bronchodilation
• 
  Coronary blood flow

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Adverse reactions of vasopressor drugs

• Signs
• Elevated BP, HR
• Symptoms
• Fear
• Anxiety
• Restlessness
• Throbbing headache
• Tremor
• Dizziness
• Pallor
• Respiratory difficulty
• Palpitations

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Contraindication for Epinephrine

• Blood pressure over 200 torr systolic or 115 torr
  diastolic
• Uncontrolled hypertension
• Severe cardiovascular disease including less than
  6 months after a myocardial infarction or
  cerebrovascular accident
• Daily episodes of angina pectoris or unstable
  angina
• Cardiac dysrhythmias despite appropriate therapy
• Medicated with beta blocker,monoamine oxidase
  inhibitor , or tricyclic antidepressant or
  general anesthesia with a halogenated anesthetic
  like halothane

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New York Heart Association

• ?????????????? epinephrine ?????? 3 ug. / kg.
  Body weight ????????????? 0.2 mg. (200 µg)
• ?????????????????????????? ??????????????????
  ???????? ?????? Epinephrine ?????? 40 ug
  ????????? ?????????? 54 µg ?????????????????????

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?????????????????? Epinephrine

• Epinephrine ???? 1 200,000
• 1 gm / 200,000 ml
• 1,000 mg / 200,000 ml
• 1 mg / 200 ml
• 0.005 mg / 1 ml

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??????????????? 2 ?? ???? 12 ???????? ????????????
??????????? ??????????? ???????????????? ?????????
?????????????????
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?????????????? 25 ?? ??????? 60
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