LOCAL

ANESTHETICS
LEARNING OUTCOMES

1. Introduction to Local Anesthetics

2. History of Local Anesthetics
3. Classification of Local Anesthetics
4. Chemistry of Local Anesthetics
5. Properties of ideal Local Anesthetics
6. Mechanism of Action
7. Pharmacokinetics
8. Individual drugs of Local Anesthetics
LOCAL ANESTHETICS (LAS)
 “Local an anesthetics are drugs which upon topical
application or local injection cause reversible loss of
sensory perception, especially of pain in a localized
area of the body”.
 Block generation and conduction of nerve impulses
at a localized site of contact without structural
damage to neurons.
 Loss of sensory as well as motor impulses.

 LAs, do not cause the loss of consciousness when

administered correctly.
HISTORY OF LOCAL ANESTHETICS

 Albert Niemann (1860) isolated crystals from the coca

shrub – and called it “COCAINE”, he found that it
reversibly numbed his tongue.
 German chemist Alfred Einhorn (1905) produced the
first synthetic ester type local anesthetic Novocaine
(procaine) which retained the nerve blocking properties,
but lacked the powerful CNS actions of cocaine.
 Swedish chemist Nils Löfgren (1943) synthesized the
first amide-type local anesthetic - marketed under the
name of Xylocaine (Lidocaine).
CHEMISTRY OF LAS
CHEMISTRY OF LAS

 Three major parts of any Local Anesthetics:

1. Aromatic Ring (Lipophilic Moiety).
2. Intermediate Chain is of Amide or Ester, basis of
classification.
3. Amine Group (Hydrophilic Group).

 Potency = Lipid Solubility

 Higher solubility = Can use a lower concentration and
reduce potential for toxicity.
CLASSIFICATION OF LAS ON BASIS
OF DURATION OF ACTION
Duration = Protein Binding
 Short Acting (20-25 Min.) :
 Procaine
 Chloroprocaine.

 Internediate Acting (45-60 Min.) :

 Lidocaine (Lignocaine)
 Prilocaine
 Lignocaine
 Cocaine

 Long Acting (2-3 Hours) :

 Bupivacaine Etidocaine
 Ropivacaine Tetracaine
CLASSIFICATION OF LOCAL
ANESTHETICS
CLASSIFICATION ON BASIS OF CHEMICAL
NATURE:
 Esters:
 Cocaine
 Procaine
 Tetracaine
 Benzocaine

 Amides:
 Lidocaine
 Mepivacaine
 Bupivacaine
 Etidocaine
CLASSIFICATION OF LOCAL
ANESTHETICS (LAS)

AMIDE LAs ESTERS LAs

 Produce more intense &  Short duration of action

longer lasting anesthesia. and less analgesia.
 Not hydrolyzed by  Hydrolyzed by plasam

plasma esterases. esterases.

 Rarely cause  High risk of

hypersensitivity hypersensitivity.
reactions.
PROPERTIES OF IDEAL LAS
 Reversible in action
 Non irritant

 No allergic reaction

 No systemic toxicity

 Rapid onset of action

 Sufficient duration of action

 Potent

 Stable in solution

 No interfere with healing of tissues

 Should have vaso-constrictive action

 Not expensive
MECHANISM OF ACTION OF LAS
 The primary target of the LA, Voltage Activated Sodium
Channels (VASA) is one the numerous membrane proteins
which reside in phospholipids bilayer encapsulating the
neurons.
 LAs block VASA → Reduce Na+ influx → No
depolarization → No Conduction of Active Potential
(PA).
 Local anesthetics gain access to the inner axonal
membrane by:
 Traversing sodium channels while they are more
often in an open configuration.
 Pass directly through the plasma membrane.
MECHANISM OF ACTION OF LAS

 More lipid soluble (Unionized/Uncharged) form

→ More effective intracellular conc.
 Inside the neuron → Ionized form is more
effective blocking entity.
 Both ionized & unionized forms play significant
role in
 First
in reaching the receptor site.
 Second in causing the effect.
PHARMACOKINETIC OF LAS
1. ABSORPTION:
 Absorption is determined by:
 Absorption site
 Dose
 Rate of injection
 Pharmacological properties.
 Plasma Conc. After injection at various sites is:
 Intrapelural > Intercostal > Lumbar Epidural > Bracial
Plexus > Sciatic > Femoral.
 First pass Pulmonary Metabolism limits the Conc. Of
Local Anesthetics that reaches to Systemic Circulation.
PHARMACOKINETIC OF LAS

 FACTORS AFFECTING THE ABSORPTION

OF LAs:

1. Site of Injection (Intrapelural > Intercostal >

Lumbar Epidural > Bracial Plexus > Sciatic >
Femoral).
2. Dose
3. Physicochemical Properties ( Lipid
Solubility & Protein Binding).
4. Addition of Epinephrine.
PHARMACOKINETIC OF LAS

2. DISTRIBUTION:
 Tissue distribution of LA is proportional to:
 Lipidsolubility of drug
 Blood supply to that tissue

 LA drugs are distributed rapidly in:

 Brain, Heart, Liver, Lung.
 But more slowly distributed…..which have lower blood
supply:
 Muscles & Adipose Tissues.
 Patient age, cardio-vascular status and hepatic function
influence the tissue blood flow.
PHARMACOKINETIC OF LAS
3. METABOLISM:

 Amide:
 Metabolism is dependent on hepatic blood flow.
 Toxicity of amides is more likely with:
 Prolonged infusions in sick, elderly patients.
 Postoperative increase in AAG(Acute Angle Glaucoma)
attenuates the rise in plasma concentrations
 Esters:
 Hydrolyzed rapidly in plasma by pseudo cholinesterase to the
metabolite
 Para-aminobenzoic acid (PABA), which can generate an allergic
reaction.
PHARMACOKINETIC OF LAS
4. EXCRETION:
 Kidneys are primary excretory organs of LA drugs &
their metabolites.
 Esters appears in very small conc. of parent compound
in urine.
 Excretion of amide local anesthetics is dependent on
hepatic metabolism metabolites may accumulate in
renal failure.
 Metabolism is fastest in the rank order:
 Prilocaine > Lidocaine > Bupivacaine.
 Most of the LA drugs cross the placenta.
LIDOCAINE

 Concentration 2%
 Potency is 2X than Procaine

 Toxicity is 2X than Procaine

 Metabolized in Liver

 Excreted via Kidney

 Time to onset: 2-3 min.

 Half life: 90 min.

MEPIVACAINE
 Concentration - 2% or 3%
 Potency is 2X than Procaine

 Toxicity is 1.5-2X than Procaine

 Metabolized in Liver

 Excreted via Kidney

 Time of onset of action: 1.5-2 min.

 Half life: 1.9 Hours

 Max. safe dose: 3% without Vasoconstrictor & 2% with

Vasoconstrictor.
BUPIVACAINE
 Concentration: 0.5%
 Potency: 8X Procaine (4X Lidocaine)

 Toxicity:8X Procaine (4X Lidocaine)

 Metabolized: Liver

 Excreted: Kidney

 Onset of action: 5-10 min.

 Half life: 2.7 Hours

 Max. Recorded Dose: 1.3 mg/Kg

 Max. Safe Dose: 90 mg

PROCAINE

 Concentration - 2-4%
 Potency - 1

 Toxicity - 1

 Metabolized: Hydrolyzed in plasma by pseudo-

cholinesterase to PABA
 Excreted: Kidney

 Onset of action: 6-10 min.

 Duration of action: 2-3 hours in tissues.

 Max. Recorded Dose: 6.6 mg/Kg

 Max. Safe Dose: 400 mg

PROCAINE

 Strong vasodilatation.
 Very short duration of anesthesia.

 High incidence of allergic reactions.

 Drug of choice for Tx of inadvertent intra-arterial

injection (relieves pain and spasm).
 Consider for Amide allergic patient.
IMPORTANCE OF ADDING
VASOCONSTRICTOR IN LAS

 Vasoconstrictors Constrict blood vessels

 Decrease blood flow

 Decrease the blood level of the drug

 Increase the concentration of drug at the site

 Decrease bleeding at site

 Increase the duration of drug.