Local Anaesthetic Agents

T.C. Smith

STRUCTURE

Pharmacokinetics

MECHANISM OF ACTION FACTORS INFLUENCING ACTIVITY Molecular weight Lipid solubility pKa pH

Protein binding

CLINICAL EFFECTS

Systemic effects TOXICITY

Factors affecting local anaesthetic toxicity ESTER-LINKED AGENTS

Amethocaine

Benzocaine

Cocaine

AMIDE-LINKED AGENTS

Bupivacaine Lidocaine (lignocaine) Prilocaine Ropivacaine ADDITIVES Glucose

Vasoconstrictors

Additives with analgesic activity

SPECIFIC PHARMACOLOGY

Bupivacaine hydrochloride Lidocaine hydrochloride Prilocaine hydrochloride Ropivacaine hydrochloride

Local anaesthetic agents are used directly to block neuronal transmission. They also stabilize other electrically excitable membranes, and some examples, such as lignocaine, have clinically useful anti-arrhythmic activity.

Structure

Local anaesthetic agents comprise a lipophilic tertiary amine group linked to a hydrophilic aromatic group. They are divided into esters and amides based on the linking group. Figure LA.1 shows examples of these two types of local anaesthetic agent. Protonation of the highlighted amine nitrogen atom confers activity on the molecule once it is inside the cell.

Ester Amide Lidocaine
Figure LA.1 Chemical structure of an ester (procaine) and an amide (lidocaine)

Local anaesthetic agents exist in two states, acid (protonated) and basic (non ionized) in equilibrium according to their pKa and ambient pH, as determined by the Henderson-Hasselbach equation (Figure LA.2).

Local anaesthetic agents are weak bases. At physiological pH, there exists a mixture of non ionized and ionized drug. This is important as only the non ionized drug passes through the membrane, yet it is only the ionized drug that is active. Small changes in pH have marked effects on the proportion of drug that is ionized and, therefore, markedly influence the effect.

Pharmacokinetics

Injectable local anaesthetics must be soluble and stable in water, which is achieved by creating hydrochlorides of the drug. These drugs exist within ampoules in acid solution with a high degree of ionization that maintains solubility.

Was this article helpful?

0 0
Defeat Drugs Death

Defeat Drugs Death

This Book Is One Of The Most Valuable Resources In The World When It Comes To Helpful Info On Avoiding And Beating A Fatal Drug Addiction!

Get My Free Ebook


Post a comment