Local Anesthetics

Shane Milu

March, 27, 2007

Local Anesthetic

A drug that reversibly inhibits the propagation of signals along nerve pathways in a specific area of the body.

The first local anesthetic was cocaine, discovered in the1860s by a German, Albert Niemann, and isolated from the leaves of coca. The first clinical use was in 1884 by Sigmund Freud. It was Freud and Karl Kollar who noticed the anesthetic effect. Kollar first introduced it into ophthalmology as a topical ointment. Also around the same time Dr.William Stewart Halsted described the injection of cocaine into a sensory nerve trunk to induce surgical anesthesia.

History

General StructuresThere are two types of anesthetics amino-esters and amino-amides. All anesthetics are weak bases and are active in the cationic form.

12

34 1:Aromatic ring

2:Ester or Amide linkage

3:Hydrocarbon chain

4:Tertiary Amine group

Esters

• Examples: cocaine, procaine, tetracaine

• These get hydrolyzed in the plasma by a pseudo cholinesterase. One by-product of this reaction paraaminobenzoic acid, this is a common reason people have allergic reaction to these type of agents.

Amides

• Examples: lidocaine, mepivicaine, prilocaine, bupivacaine

• These get metabolized in the liver to inactive agents. Generally there are no allergies associated with amide anesthetics

Prilocaine

Mechanism of Action

• Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the nerve cytoplasm

– Sodium ions cannot flow in, so potassium ions cannot flow out, thereby preventing the depolarization of the nerve.

• To do this the anesthetic molecules must actually enter through the cell membrane of the nerve. This is where the differences in the time of onset and duration of the various local anesthetics lies.

Factors that affect action of local anesthetics

• pH– cationic form binds to receptor site. The

uncharged form penetrates membrane . Efficacy of drug can be changed by altering extracellular or intracellular pH

Factors that affect action of local anesthetic

• Lipophilicity

– The solubility of the lipid seems to be the main determinant of anesthetic potency. Compounds with high lipophilicity penetrate the nerve membrane more easily. This means less molecules are needed to inhibit the blockade of sodium ions. This leads to enhanced potency.

Vasoconstrictors

• Blood absorbs the unused anesthetic. In order to slow down this process many anesthetics are administered with a vasoconstrictor. These constrict the vessel and slow down the absorption of the anesthetic, by allowing less blood to enter/leave the site.

Techniques of administration

• Topical Anesthesia

• Infiltration

• Peridural

• Spinal anesthesia

Topical Anesthesia

• Done by the administering the anesthetic to mucous membranes or skin. Relieves itching, burning and surface pain, i.e. sunburns.

Infiltration

• Occurs by directly injecting a local anesthetic to block the nerve endings under the skin or in the subcutaneous tissue. Used mainly for surguries, i.e. cavities being filled.

Peridural Anesthesia

• This is accomplished by injecting a local anesthetic into the peridural space, a covering of the spinal cord

Spinal anesthesia

• Here, the local anesthetic is injected into the subarachnoid space of the spinal cord

TOXICITIES OF LOCAL ANESTHETICS

• Hypersensitivity – Someone who is allergic to one type of anesthetic may not be allergic to the other type.

Toxicity

• CNS Toxicity: If absorbed in excess systematically can lead to excitement(tremors, shivering, convulsions), and if absorbed in even higher amounts can lead to depression(coma, respiratory arrest and death)

• Cardiovascular toxicity: If absorbed in excess systematically can lead to depression of the cardiovascular system

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