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1  Anesthetic Pharmacology: Local  Aneathesia CN S Phar macol ogy 3XX  

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 Anesthetic Pharmacology: Local

 Aneathesia

CNS Pharmacology 3XX  

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Local Anesthetic

 A local anesthetic is an agent that interruptspain impulses in a specific region of thebody without a loss of patient

consciousness.

Normally, the process is completelyreversible--the agent does not produce any

residual effect on the nerve fiber.

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History of Local Anesthetics

Cocaine isolated 1856

1884 cocaine used in occular surgery

1880’s Regional anesthesia plexus 

1898 cocaine used in spinalanesthesia

1905 1st synthetic LA (procaine)introduced

1943 lidocaine synthesized Mepivacaine (1957), Bupiv (’63),

Ropiv (’96) Erythroxylon coca

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Chemistry

Common structure – Aromatic ring

 – Tertiary amine

 – Alkyl chain

Linking bond – Amide bond (see

lidocaine)

 – Ester bond (seeprocaine)

Esters versus Amides

 – Affectmetabolism

 – Affect toxicity

 – Allergic potential

All local anestheticsare weak bases,

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Chemistry of Local Anesthetic… 

Esters:

These include cocaine, procaine, tetracaine,and chloroprocaine.

They are hydrolyzed in plasma by pseudo-cholinesterase.

One of the by-products of metabolism is

para-aminobenzoic acid, the common causeof allergic reactions seen with these agents

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Chemistry of Local Anesthetic… 

 Amides:

These include lidocaine, mepivicaine,prilocaine, bupivacaine, and etidocaine.

They are metabolized in the liver to inactiveagents.

True allergic reactions are rare (especiallywith lidocaine)

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Mechanism of action

Generally, local anesthetics interfere with Na+ ion channel passageacross the nerve cell membrane.

The greatest effect is on small, unmyelinated nerves. Myelinated nerves are also susceptible due to access at the nodes of 

Ranvier.

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Mechanism of action….. 

The unionized form of local anesthetics diffusesthrough the nerve cell membrane to a specifichydrophobic binding site on the Na+ ion channel.

The ability to exist in an ionized form improveswater solubility and there may be polarinteractions between the drug and the binding site.

 All the injectable anesthetics exist as a equilibrium

mixture of ionized and unionized forms.

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Mechanism of action….. 

O

O

O

OCH3

CH3 N

O

O

O

OCH3

CH3 N+

H

H+

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Factors affecting

local anesthetic action.....

Effect of pH 

charged (cationic) form binds to receptorsite uncharged form penetrates membrane,efficacy of drug can be changed by

altering extracellular or intracellular pH

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Factors affecting local anesthetic action..... :

Effect of lipophilicity on ANESTHETIC POTENCY 

Lipid solubility appears to be the primarydeterminant of intrinsic anesthetic potency.

Chemical compounds which are highly lipophilic

tend to penetrate the nerve membrane moreeasily, such that less molecules are required forconduction blockade resulting in enhancedpotency.

more lipophilic agents are more potent aslocal anesthetics 

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Factors affecting local anesthetic action.....

Effect of protein binding – 

 – increased binding increases duration of 

action

Effect of diffusibility –  – increased diffusibility = decreased time of 

onset

Effect of vasodilator activity –  – greater vasodilator activity = decreased

potency and decreased duration of action

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Properties of Local Anesthetic Agents

PROPERTIES  AMINOESTERS  AMINOAMIDES 

Metabolism rapid by plasmacholinesterase 

slow, hepatic 

Systemictoxicity 

less likely  more likely 

Allergicreaction 

possible - PABA derivativesform 

very rare 

Stability in

solution 

breaks down in ampules

(heat,sun) very stable

chemically 

Onset of action  slow as a general rule  moderate to fast 

pKa's higher than PH = 7.4 (8.5-

8.9) close to PH = 7.4

(7.6-8.1) 

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Types of Local Anesthesia

Local Infiltration (Local Anesthesia). – Local infiltration occurs when the nerve endings in the skin and

subcutaneous tissues are blocked by direct contact with alocal anesthetic, which is injected into the tissue.

• Local inf i l t rat ion is used p r imar i ly fo r surg ical pro cedures 

invo lv ing a small area of t issue (for example, sutu r ing a cu t).

Topical Block. – A topical block is accomplished by applying the anesthetic

agent to mucous membrane surfaces and in that way blockingthe nerve terminals in the mucosa.

•This techniqu e is of ten u sed dur ing examinat ion p rocedures invo lv ing th e respiratory tract .

• The anesthet ic agent is rapid ly absorbed in to the bloodstream.

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Types of Local Anesthesia…. 

Surface Anesthesia

 – This type of anesthesia is accomplished by the

application of a local anesthetic to skin or mucous

membranes.

• Surface anesthesia is used to rel ieve itchin g, burnin g, and 

su rface pain (for example, as seen in m inor s unb urns ).

Nerve Block.

 – In this type of anesthesia, a local anesthetic is

injected around a nerve that leads to the operative

site.

• Usual ly mo re con centrated forms of local anesthet ic 

so lut ions are used for this typ e of anesthesia.

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Types of Local Anesthesia…. 

Peridural Anesthesia

 – This type of anesthesia is accomplished by

injecting a local anesthetic into the peridural

space

Spinal Anesthesia

 – In spinal anesthesia, the local anesthetic is

injected into the subarachnoid space of thespinal cord

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The use Vasoconstrictors in Local anaesthesia

 Vasoconstrictors decrease the rate of vascularabsorption which allows more anesthetic to reachthe nerve membrane and improves the depth of 

anesthesia. 1:200,000 adrenaline is the commonly used

vasoconstrictor.

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Local Anesthetic Toxicity

Central nervous system – initially-- lightheadedness, circumoral

numbness, dizziness, tinnitus, visual change

 – later-- drowsiness, disorientation, slurredspeech, loss of consciousness, convulsions

 – finally-- respiratory depression

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Local Anesthetic Toxicity

Cardiovascular

 – myocardial depression and vasodilation--

hypotension and circulatory collapse

 Allergic reactions-- rare (less than 1%)

 – preservatives or metabolites of esters

 – rash, bronchospasm

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RESUME: Clinical applications of local

anesthetic agents:

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Clinical applications of local anesthetic

agents…….: 

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Clinical applications of local anesthetic

agents………: 

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